Study on the Mechanism of Gastrodiae Rhizoma, Lycii Fructus, and Ziziphi Spinosae Semen in Sedation and tranquilizing mind

Study on the Mechanism of Gastrodiae Rhizoma, Lycii Fructus, and Ziziphi Spinosae Semen in Sedation and tranquilizing mind | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Study on the Mechanism of Gastrodiae Rhizoma, Lycii Fructus, and Ziziphi Spinosae Semen in Sedation and tranquilizing mind Chenghao Zhu, Zhengru Zhang, Zhirong Sun This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3133115/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 02 Nov, 2023 Read the published version in Molecular Diversity → Version 1 posted 9 You are reading this latest preprint version Abstract Method The chemical constituents and therapeutic targets of Gastrodiae Rhizoma, Lycii Fructus, and Ziziphi Spinosae Semen were acquired from TCMSP, HERB, and ETCM databases. Active components were identified using ADME criteria, while the primary targets associated with sedation and mental tranquility were obtained from GENECARDS, OMIM, and DRUGBANK databases. To investigate potential functional protein modules within the network, a protein-protein interaction (PPI) network analysis was conducted using the STRING platform. The METASCAPE platform was employed for the analysis of the "component-target" and its associated biological processes and pathways. Subsequently, the construction of the "component-target" network was accomplished using Cytoscape 3.9.1 software. Finally, the validation of molecular docking was conducted through AUTODOCK. Results: The findings revealed that Quercetin, Atropine, dauricine, (S)-Coclaurine, and other active ingredients were identified as the core constituents of Gastrodiae Rhizoma, Lycii Fructus, and Ziziphi Spinosae Semen. Additionally, PTGS2, PTGS1, MAOB, GABRA1, SLC6A2, ADRB2, CHRM1, HTR2A, and other targets were identified as the core targets. The results of the molecular docking analysis demonstrated that Quercetin, dauricine, and (S)-Coclaurine exhibited strong binding affinity towards PTGS2. The predominant biological pathways associated with sedation and tranquilization primarily involved neuroactive ligand-receptor interaction and activation of receptors involved in chemical carcinogenesis. This study provides initial findings on the multi-component, multi-target, and multi-pathway mechanism underlying the sedative and tranquilizing effects of Gastrodiae Rhizoma, Lycii Fructus, and Ziziphi Spinosae Semen. These findings have the potential to serve as a foundation for the future development and utilization of Gastrodiae Rhizoma, Lycii Fructus, and Ziziphi Spinosae Semen. Gastrodiae Rhizoma Lycii Fructus and Ziziphi Spinosae Semen insomnia network pharmacology sedation and tranquilizing mind Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Introduction Gastrodia elata Bl. (Orchidaceae), a perennial parasitic herbaceous plant, the rhizome of Gastrodia elata (Gastrodiae Rhizoma), as a superior herb, has been used for thousands of years. Modern pharmacological studies have shown that Gastrodiae Rhizoma contains substances such as phenols, polysaccharides, sterols, and organic acids [ 1 ], which have a wide range of biological activities, including sedation, hypnosis, antiepileptic, anticonvulsant, anti-anxiety, antidepressant, neuroprotective, antipsychotic, anti-vertigo, circulatory regulation, anti-inflammatory, analgesic, antioxidant, memory improvement, anti-aging, antiviral, and anti-tumor effects[ 2 – 4 ], in clinical practice, it is mainly used for neurasthenia, insomnia, dizziness, epilepsy, convulsions, nervous headache, Alzheimer's disease, hypertension, etc. Lycium barbarum L. (Solanaceae), a perennial herbaceous plant, mainly distributed in arid to semi-arid environments in North and South America and Africa, with a few in the Eurasian temperate zone[ 5 ]. The mature dried fruit (Lycii Fructus) of Lycium contains polysaccharides, carotenoids, polyphenols, phenolic acids, flavonoids, alkaloids, and fatty acids [ 6 ], and has been recognized as a functional food for treating various diseases, including waist and knee pain, tinnitus, impotence, spermatorrhea, blood deficiency and eye weakness [ 7 ]. Ziziphus jujuba M. belongs to Rhamnaceae [ 8 ]. The fruit (Ziziphi Spinosae Semen) of Ziziphus jujuba contains flavonoids, phenolic acids, terpenes, alkaloids, polysaccharides, and other substances. Modern pharmacological research shows that Ziziphi Spinosae Semen has antibacterial, antioxidant, sedative, liver protective, anti-hyperglycemic, anti-hyperlipidemic and other effects [ 9 ]. Insomnia and the tension, anxiety, and neurasthenia it causes are common sleep disorders [ 10 ]. It is a common form of neurasthenia caused by various situational, medical, emotional, environmental and behavioral factors [ 11 ]. Insomnia is a serious health problem that affects millions of people worldwide, with an estimated prevalence rate ranging from 4–22%[ 12 ]. Consequently, the presence of insomnia may potentially contribute to the onset of depression. In comparison to individuals without insomnia, there is a twofold increase in the likelihood of developing this sleep disorder. Insomnia has the capacity to significantly impact one's overall well-being, and in more severe instances, it can precipitate mental health conditions such as anxiety, depression, and even suicidal ideation[ 13 , 14 ]. The synergistic effects of Gastrodiae Rhizoma, Lycii Fructus, and Ziziphi Spinosae Semen have been found to contribute to the unification of the liver and kidney, promotion of blood circulation, and nourishment of the heart, resulting in sedation and tranquilization of the mind. This herbal combination has demonstrated significant therapeutic efficacy in addressing insomnia, anxiety, and neurological weakness associated with liver yang hyperactivity in patients. Xiao et al. (2015) have documented research findings on the efficacy of combining Gastrodiae Rhizoma and Ziziphi Spinosae Semen for enhancing sleep. Additionally, traditional medicine literature posits that the kidney plays a crucial role in brain function. Specifically, the kidney is responsible for storing essence and generating marrow, thereby suggesting that the brain marrow originates from the essence of the kidney. The fluctuation in kidney essence levels directly impacts the replenishment of brain marrow and consequently influences normal brain function [ 15 ]. If the renal essence is abundant, the cerebral medulla is replete, and the faculties of memory, cognition, thinking, and regulation of the five viscera and six viscera are unimpaired, in addition to stable sleep patterns and sound mental well-being, the inclusion of Lycii Fructus alongside Gastrodiae Rhizoma and Ziziphi Spinosae Semen may confer advantageous effects on the kidneys, replenishing essence, nurturing the liver and kidneys, enriching the blood, and pacifying the nerves. However, a comprehensive understanding of its precise mechanism of action necessitates further investigation. Therefore, this study employs the network pharmacology approach to investigate the molecular mechanism of Gastrodiae Rhizoma, Lycii Fructus, and Ziziphi Spinosae Semen. It adopts a comprehensive perspective to analyze the material basis and conducts preliminary functional verification of its effective ingredients and targets using molecular docking and other technologies. The study aims to offer novel insights and a theoretical foundation for the advancement of sedative drug research and development. Materials and methods 1.1 Screening of active ingredients and related targets The chemical constituents of Lycii Fructus and Ziziphi Spinosae Semen were investigated using the TCMSP database ( https://old.tcmsp-e.com/ ). Active constituents and target protein information were filtered based on criteria of oral bioavailability (OB) ≥ 30% and drug-likeness (DL) ≥ 0.18. Similarly, the chemical constituents of Gastrodiae Rhizoma were explored using the HERB ( http://herb.ac.cn/ ) and ETCM ( http://www.tcmip.cn/ ) databases, the smile number from the SwissTarget database ( http://www.swisstargetprediction.ch/ ) was utilized to filter ADME values. Subsequently, the active ingredients of Gastrodiae Rhizoma were screened based on indicators of oral bioavailability and drug-likeness. The protein target information was then predicted using SwissTarget. Following the screening process, the protein target information was standardized and unified within the Uniprot protein database ( https://www.uniprot.org ). 1.2 Screening of disease target The disease targets related to sedation and tranquilizing mind were searched in the GeneCards database ( https://www.genecards.org/ ), Drugbank database( https://go.drugbank.com/ ), and OMIM database ( https://omim.org/ ). The retrieved keywords were insomnia, anxiety, neuritis, and epilepsy. In the Genecards database, a higher score value indicates a close relationship between the target and the disease. If there are too many targets, target targets with a score value greater than the median are set as potential targets. After merging three disease database targets, remove duplicate disease targets related to sedation and tranquilizing mind. 1.3 PPI network construction of active ingredient-disease target To clarify the interaction between the relevant targets of Gastrodiae Rhizoma, Lycii Fructus, and Ziziphi Spinosae Semen and the related diseases targets of sedation and tranquilizing mind, the intersection targets were obtained through the venny2.1.0 online platform ( https://bioinfogp.cnb.csic.es/tools/venny/ ). Then submit the intersection targets to the STRING11.5 database( https://string-db.org ) to build a protein interaction (PPI) network model, the biological species were "Homo sapiens" and the minimum interaction threshold was "highest confidence" (> 0.4), Further analysis of PPI network was conducted using the MCODE plugin in Cytoscape 3.9.1 to identify potential protein functional modules and their functions were described by analyzing the biological processes involved. 1.4 Enrichment analysis of intersection target functions and pathways The target points of Gastrodiae Rhizoma, Lycii Fructus, and Ziziphi Spinosae Semen were analyzed on the Metascape platform( http://metascape.org/gp/index.html ) (P < 0.01), the main biological processes and metabolic pathways were analyzed and visualized the data using OriginPro 2015. 1.5 Construction of component target network diagram CytoScape 3.9.1 was used to build a network diagram of active ingredients - sedation and tranquilizing mind, the network topology parameters of active ingredients and targets were analyzed by the built-in tools of CytoScape 3.9.1, including degree, betweenness, closeness, etc., and the core targets and the main active ingredients that play their effects were judged according to the network Topology parameters. 1.6 Molecular docking verification The sdf files of the key active ingredients structure were downloaded in Pubchem ( https://pubchem.ncbi.nlm.nih.gov/ ). The minimum energy was run in chemdraw3D and a mol2 format file was converted, the most critical targets were screened out in the protein interaction network, the entry number was found in the UniProt database( https://www.uniprot.org/ ), and the PDB format file of the structure was download in the Pdb database( https://www.rcsb.org/ ) and we optimized it in Pymol, the mol2 files and pdb files were converted in the autodock tools file, and the score of their docking Binding energy was got. The docking results were visualized in Pymol. Results 2.1 Screening of active ingredients and related targets 43 chemical components of Gastrodiae Rhizoma (Herb), 188 chemical components of Lycii Fructus (TCMSP), and 33 chemical components of Ziziphi Spinosae Semen (TCMSP) were preliminarily extracted. After screening by TCMSP (OB ≥ 30%, DL ≥ 0.18) and SwissADME, 25(Gastrodiae Rhizoma), 45 (Lycii Fructus) and 9 (Ziziphi Spinosae Semen) active components were obtained, including quercetin, dauricine, cyanin, and sanjoinenine (Tables 1 and 2 ). At the same time, four active ingredients, Betaine (Lycii Fructus), jujuboside A (Ziziphi Spinosae Semen), Spinosin (Ziziphi Spinosae Semen), and Gastrodin (Gastrodiae Rhizoma), which are not screened by the above conditions but have been reported to have sedative and sedative effects, are added to the table. After predicting the active ingredient targets, it was found that there were 389 active ingredient targets in Lycii Fructus, 47 active ingredient targets in Ziziphi Spinosae Semen, and 173 active ingredient targets in Gastrodiae Rhizoma. After merging, a total of 303 active ingredient targets were obtained by deleting duplicate values. Table 1 Main active ingredients in Gastrodiae Rhizoma Drug Ingredient ID Mark Ingredient name GI absorption Druglikeness (yes༞3) Gastrodiae Rhizoma HBIN009937 TM1 4,4'-dihydroxy dibenzyl ether High 4 HBIN009938 TM2 4,4'-dihydroxy diphenyl methane High 5 HBIN009959 TM3 4-(4'-hydroxybenzyloxy)benzyl methyl ether High 5 HBIN009960 TM4 4-(4'-hydroxybenzyloxy)benzyl nethyl ether High 5 HBIN010380 TM5 4-ethoxymethylphenyl-4'-hydroxybenzylether High 5 HBIN010513 TM6 4-hydroxybenzylamine High 3 HBIN010518 TM7 4-hydroxybenzyl mathyl ether High 3 HBIN010519 TM8 4-hydroxybenzyl methyl ether High 3 HBIN018559 TM9 bis(4-hydroxybenzyl)ether High 5 HBIN018560 TM10 bis(4-hydroxybenzyl)ether mono-beta-d-glucopyranoside High 5 HBIN020993 TM11 citronellal High 3 HBIN022781 TM12 dauricine High 3 HBIN025849 TM13 ethoxysanguinarine High 5 HBIN027383 TM14 gastrodamine High 5 HBIN027384 TM15 Gastrodin High 4 HBIN029268 TM16 hexadecanoic acid High 3 HBIN035490 TM17 m-hydroxybenzoicacid High 3 HBIN039671 TM18 p-hydroxybenzaldehyde High 3 HBIN039681 TM19 p-hydroxybenzyl alcohol High 3 HBIN039682 TM20 p-hydroxy benzyl ethylether High 3 HBIN040911 TM21 protocatechuic aldehyde High 3 HBIN045062 TM22 succinic acid High 3 HBIN045071 TM23 suchilactone High 5 HBIN047744 TM24 vanillin High 3 HBIN047745 TM25 vanillin acetate High 5 HBIN047752 TM26 Vanillyl alcohol High 3 Table 2 Main active ingredients in Lycii Fructus, and Ziziphi Spinosae Semen Drug Ingredient ID Mark Ingredient name OB(%) DL Lycii Fructus MOL001323 GQZ1 Sitosterol alpha1 43.28 0.78 MOL003578 GQZ2 Cycloartenol 38.69 0.78 MOL001494 GQZ3 Mandenol 42 0.19 MOL001495 GQZ4 Ethyl linolenate 46.1 0.2 MOL001979 GQZ5 LAN 42.12 0.75 MOL000449 GQZ6 Stigmasterol 43.83 0.76 MOL000358 GQZ7 beta-sitosterol 36.91 0.75 MOL005406 GQZ8 atropine 45.97 0.19 MOL005438 GQZ9 campesterol 37.58 0.71 MOL006209 GQZ10 cyanin 47.42 0.76 MOL007449 GQZ11 24-methylidenelophenol 44.19 0.75 MOL008173 GQZ12 daucosterol_qt 36.91 0.75 MOL008400 GQZ13 glycitein 50.48 0.24 MOL010234 GQZ14 delta-Carotene 31.8 0.55 MOL000953 GQZ15 CLR 37.87 0.68 MOL009604 GQZ16 14b-pregnane 34.78 0.34 MOL009612 GQZ17 (24R)-4alpha-Methyl-24-ethylcholesta-7,25-dien-3beta-ylacetate 46.36 0.84 MOL009615 GQZ18 24-Methylenecycloartan-3beta,21-diol 37.32 0.8 MOL009617 GQZ19 24-ethylcholest-22-enol 37.09 0.75 MOL009618 GQZ20 24-ethylcholesta-5,22-dienol 43.83 0.76 MOL009620 GQZ21 24-methyl-31-norlanost-9(11)-enol 38 0.75 MOL009621 GQZ22 24-methylenelanost-8-enol 42.37 0.77 MOL009622 GQZ23 Fucosterol 43.78 0.76 MOL009631 GQZ24 31-Norcyclolaudenol 38.68 0.81 MOL009633 GQZ25 31-norlanost-9(11)-enol 38.35 0.72 MOL009634 GQZ26 31-norlanosterol 42.2 0.73 MOL009635 GQZ27 4,24-methyllophenol 37.83 0.75 MOL009639 GQZ28 Lophenol 38.13 0.71 MOL009640 GQZ29 4alpha,14alpha,24-trimethylcholesta-8,24-dienol 38.91 0.76 MOL009641 GQZ30 4alpha,24-dimethylcholesta-7,24-dienol 42.65 0.75 MOL009642 GQZ31 4alpha-methyl-24-ethylcholesta-7,24-dienol 42.3 0.78 MOL009644 GQZ32 6-Fluoroindole-7-Dehydrocholesterol 43.73 0.72 MOL009646 GQZ33 7-O-Methylluteolin-6-C-beta-glucoside_qt 40.77 0.3 MOL009650 GQZ34 Atropine 42.16 0.19 MOL009651 GQZ35 Cryptoxanthin monoepoxide 46.95 0.56 MOL009653 GQZ36 Cycloeucalenol 39.73 0.79 MOL009656 GQZ37 (E,E)-1-ethyl octadeca-3,13-dienoate 42 0.19 MOL009660 GQZ38 methyl (1R,4aS,7R,7aS)-4a,7-dihydroxy-7-methyl-1-[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-1,5,6,7a-tetrahydrocyclopenta[d]pyran-4-carboxylate 39.43 0.47 MOL009662 GQZ39 Lantadene A 38.68 0.57 MOL009664 GQZ40 Physalin A 91.71 0.27 MOL009665 GQZ41 Physcion-8-O-beta-D-gentiobioside 43.9 0.62 MOL009677 GQZ42 lanost-8-en-3beta-ol 34.23 0.74 MOL009678 GQZ43 lanost-8-enol 34.23 0.74 MOL009681 GQZ44 Obtusifoliol 42.55 0.76 MOL000098 GQZ45 quercetin 46.43 0.28 MOL000430 GQZ46 Betaine 40.92 0.01 Ziziphi Spinosae Semen MOL001521 SZR1 ceanothic acid 33.41 0.77 MOL001522 SZR2 (S)-Coclaurine 42.35 0.24 MOL001525 SZR3 Daucosterol 36.91 0.75 MOL001527 SZR4 jujuboside A_qt 34.96 0.62 MOL001532 SZR5 phytosterol 36.91 0.75 MOL001539 SZR6 sanjoinenine 67.28 0.79 MOL001542 SZR7 swertisin 31.83 0.75 MOL001546 SZR8 zizyphusine 41.53 0.55 MOL000211 SZR9 Mairin 55.38 0.78 MOL001526 SZR10 jujuboside A 8.04 0.02 MOL001540 SZR11 Spinosin 6.31 0.72 2.2 Screening of disease targets related to sedation and tranquilizing mind In the GeneCards database target information, target targets with a Score > 1.5 are identified as potential targets for insomnia, while target targets with a Score > 7.0 are identified as potential targets for any entity. Combining the target information related to sedation and tranquilizing mind in GeneCards, OMIM, and Drugbank databases, the duplicate values were deleted after merging, and finally, 492 related targets were obtained. 2.3 Construction of active ingredient-disease target PPI network A total of 81 common targets were obtained for both component targets and disease targets (Fig. 1 ). Furthermore, the target was submitted to the STRING11.5 platform to obtain a PPI network (Fig. 2 ). To analyze the mechanism of action of Gastrodiae Rhizoma, Lycii Fructus, and Ziziphi Spinosae Semen more accurately, the PPI network was obtained and its intrinsic modules were further identified. After obtaining the PPI network, the MCODE plugin in Cytoscape 3.9.1 was used to analyze the interaction relationship through the molecular complex detection algorithm, and the module was obtained (Fig. 3 ). According to the P-value, the biological processes with the three best scores in the PPI network and Module were retained for functional description (Table 2 ). Table 3 Description of PPI network functions for three modules MCODE1 biologic function GO ID Description P value 0.0159 Biological processes GO:0060559 Positive regulation of calcidiol 1-monooxygenase activity GO:0002874 regulation of chronic inflammatory response to antigenic stimulus GO:0030730 sequestering of triglyceride Molecular function GO:0070851 growth factor receptor binding GO:0005125 cytokine activity GO:0005126 cytokine receptor binding MCODE2 Biological processes GO:0051932 synaptic transmission, GABAergic 1.88e-10 GO:1904862 inhibitory synapse assembly GO:0007214 gamma-aminobutyric acid signaling pathway Molecular function GO:0008503 benzodiazepine receptor activity GO:0022851 GABA-gated chloride ion channel activity GO:0005237 inhibitory extracellular ligand-gated monoatomic ion channel activity MCODE3 Biological processes GO:0001993 regulation of systemic arterial blood pressure by norepinephrine-epinephrine 9.39e-10 GO:0071880 adenylate cyclase-activating adrenergic receptor signaling pathway GO:0007200 phospholipase C-activating G protein-coupled receptor signaling pathway Molecular function GO:0004935 adrenergic receptor activity GO:0008227 G protein-coupled amine receptor activity GO:0004993 G protein-coupled serotonin receptor activity 2.4 Enrichment analysis of intersection target functions and pathways The functions of multiple targets were closely related to their sedation and tranquilizing mind effects. The main biological processes involved in the Gastrodiae Rhizoma, Lycii Fructus, and Ziziphi Spinosae Semen: cellular response to organic cyclic compound, regulation of tube diameter, and response to xenobiotic stimulus, the main cellular components were postsynaptic membrane, membrane raft, GABA-ergic synapse, the main molecular functions included G protein-coupled amine receptor activity, neurotransmitter receptor activity, catecholamine binding (Fig. 4 ). The main pathways were neuroactive ligand-receptor interaction, chemical carcinogenesis-receptor activation, serotonergic synapse, and Lipid and atherosclerosis (Fig. 5 ). The enrichment results of the target pathway (Table 4) indicated that Gastrodiae Rhizoma, Lycii Fructus, and Ziziphi Spinosae Semen significantly acted on the neuroactive ligand-receptor interaction to exert sedation and tranquilizing mind effects. 2.5 Construction of component target network diagram Active ingredient sedation and tranquilizing mind network were constructed using Cytoscape 3.9.1 (Fig. 6 ). By analyzing the network Topology parameters that play a calming role through the built-in Network Analyzer of CytoScape 3.9.1, the core components and core action targets were obtained. Cytoscape network analysis showed that GQZ45 (Quercetin) had a connectivity degree of 34, betweenness centrality of 0.4017, and a closeness centrality of 0.4232. It was predicted that Quercetin was the main component of Gastrodiae Rhizoma, Lycii Fructus, and Ziziphi Spinosae Semen which played a calming role. Secondly, GQZ34 (Atropine) (connectivity: 27, betweenness: 0.1314, compactness: 0.4021), SZR2 (mydrine) in Ziziphi Spinosae Semen was the main component (connectivity: 14, betweenness: 0.0494, compactness: 0.3610), and TM12 (Dauricine) in Gastrodiae Rhizoma was the main component (connectivity: 8, betweenness: 0.0723, compactness: 0.3029) (Table 5 ). The connectivity of PTGS2 in the network was 16, the mediation was 0.1250, and the tightness was 0.4232. It was predicted that PTGS2 was the main target for the calming effect of Gastrodiae Rhizoma, Lycii Fructus, and Ziziphi Spinosae Semen. PTGS1, MAOB, GABRA1, SLC6A2, ADRB2, CHRM1, HTR2A, and ADRA1A were also relatively important targets (Table 6 ). Table 5 Main active ingredient network node characteristic parameters Mark ID Compound name Connectivity Betweenness Compactness GQZ45 quercetin 34 0.401702098 0.423220974 GQZ34 Atropine 27 0.131435047 0.402135231 GQZ7 beta-sitosterol 23 0.133755168 0.385665529 TM12 dauricine 8 0.072296565 0.302949062 TM5 4-ethoxymethylphenyl-4'-hydroxybenzylether 6 0.042675336 0.372937294 TM3 4-(4'-hydroxybenzyloxy)benzyl methyl ether 5 0.027101405 0.370491803 SZR2 (S)-Coclaurine 14 0.049455498 0.361022364 SZR8 zizyphusine 6 0.012606377 0.331378299 SZR6 sanjoinenine 3 0.003918413 0.325648415 Table 6 Main active ingredient target network node characteristic parameters Mark ID Compound name Connectivity Betweenness Compactness PTGS2 Prostaglandin G/H synthase 2 16 0.12501423 0.423220974 PTGS1 Prostaglandin G/H synthase 1 12 0.086957031 0.410909091 MAOB Amine oxidase 9 0.066102002 0.388316151 GABRA1 Gamma-aminobutyric acid receptor subunit alpha-1 7 0.0491451 0.385665529 SLC6A2 Sodium-dependent noradrenaline transporter 6 0.020399725 0.331378299 ADRB2 Beta-2 adrenergic receptor 6 0.041484238 0.383050847 CHRM1 Muscarinic acetylcholine receptor M1 6 0.00886712 0.320113314 HTR2A 5-hydroxytryptamine receptor 2A 6 0.018837197 0.345565749 ADRA1A Alpha-1A adrenergic receptor 6 0.028127314 0.352024922 2.6 Molecular docking verification The active ingredients (quercetin, dauricine, (S) - Coclaurine) ranking first in each main drug in Table 5 were used as ligand compounds, and the core target (PTGS2) ranking first in Table 6 was used as receptor protein for molecular docking. The Binding energy of PTGS2 with quercetin, dauricine, and (S) - Coclaurine was − 9.8 kcal/mol, -10.0 kcal/mol, and − 8.9 kcal/mol, respectively. The smaller the binding energy of ligand and receptor, the more stable the molecular binding conformation. It was generally believed that the ligand and receptor could bind at Binding energy<-5 kcal/mol. Among them, quercetin bound to PTGS2 through four hydrogen bonds formed by HIS-39, TYR-130, ARG-44, ASP-125, dauricine bound to PTGS2 through one hydrogen bond formed by APG-376, and (S) - Coclaurine bound to PTGS2 through two hydrogen bonds formed by GLY-45 and HIS-39. Therefore, it could be concluded that Gastrodiae Rhizoma, Lycii Fructus, and Ziziphi Spinosae Semen could effectively exert sedation and tranquilizing mind effects. Discussion The study found that Quercetin and Luteolin, present in Hemerocallis citrina , were identified as the primary active compounds responsible for improving sleep in Drosophila melanogaster[ 16 ]. Furthermore, lower concentrations of Quercetin were observed to have positive effects on shoaling behavior and anxiety in Zebrafish[ 17 ]. Quercetin, known for its mitochondrial protective properties, shows potential in treating anxiety induced by methylamphetamine (MA) [ 18 ] and can also mitigate anxiety resulting from hypoxia-induced neonatal seizures (HINS) [ 19 ] by down-regulating the inflammatory response through the TLR4/NF kappa B pathway. Atropine, an anticholinergic drug, has the potential to serve as adjunctive therapy for Ketamine sedation[ 20 ]. Dauricine, an alkaloid, exhibits promise as an Acetylcholinesterase inhibitor for the treatment of epilepsy, a nervous system disease [21]. Additionally, (S) - Coclaurine found in Ziziphi Spinosae Semen may have a significant impact on the treatment of insomnia induced by p-chlorophenylalanine (PCPA) in rats[ 22 ]. The aforementioned research findings indicate that quercetin, atropine, dauricine, and (S) - coclaurine demonstrate efficacy in addressing insomnia, anxiety, epilepsy, neurasthenia, and other neurological disorders. Sleep disorders have been found to potentially occur in the central pain inhibition pathway, Cyclooxygenase (COX) pathway, and endogenous Cannabinoid (eCB) pathway[ 23 ]. A case study reported the development of symptoms such as anxiety, irritability, lethargy, insomnia, aggression, impulsivity, and hypomania in a patient with depression and Spondylolisthesis after taking Celecoxib, a cyclooxygenase-2 inhibitor [ 24 ]. Prostaglandin peroxylactone synthase (PTGS), also known as cyclonenenebb oxygenase (COX), is a crucial enzyme involved in the biosynthesis of Prostaglandin, serving as both a double Oxygenase and peroxidase [ 25 ]. PTGS encompasses two distinct isozymes, namely constitutive PTGS1 and inducible PTGS2, both of which serve as targets for Nonsteroidal anti-inflammatory drugs (NSAIDs) [ 26 ]. Based on our molecular docking findings, it is postulated that quercetin, dauricine, and (S) - Coclaurine present in Gastrodiae Rhizoma, Lycii Fructus, and Ziziphi Spinosae Semen possess the potential to effectively interact with PTGS2, thereby mitigating the adverse effects of NSAIDs such as insomnia, anxiety, and irritability. Hence, we present a potential schematic representation (Fig. 8 ) elucidating the plausible mechanism underlying the sedative and anxiolytic effects of Gastrodiae Rhizoma, Lycii Fructus, and Ziziphi Spinosae Semen. Through functional analysis of the convergence between constituents and disease targets, it was observed that the neuroactive ligand-receptor interaction pathway may also facilitate the sedative and anxiolytic properties of other constituents. This finding has been substantiated by numerous research reports [ 27 – 29 ], such as the neuroactive ligand-receptor interaction and the upregulation of Oxytocin signal transduction, which have emerged as the foremost regulatory processes in the efficacy of Mongolian medical warm acupuncture for insomnia treatment [ 30 ]. In contrast to synthetic pharmaceuticals, traditional Chinese medicine possesses the attributes of "multi-component", "multi-target", and "multi-pathway" [ 31 ]. The field of network pharmacology, an emerging discipline in systematic drug investigation, endeavors to comprehend the mechanisms and interactions of drugs with multiple targets. This novel approach has revolutionized the conventional paradigm of one-drug-one-target, ushering in a new era of highly efficacious multi-target drugs [ 32 ]. However, this prediction holds a prominent position in the field, although it relies on several assumptions that need to be verified. Consequently, it is susceptible to potential false positive outcomes and necessitates rigorous experimental validation. Moreover, it may not provide a comprehensive and reliable understanding of the treatment mechanism. Given the limitations and challenges, this approach additionally provides scientific researchers with guidance in designing and investigating pharmaceuticals from a prospective and analytical standpoint. This has significantly contributed to the reduction of drug consumption rates [ 33 ] and has further enhanced the composition and effectiveness of medications. In the future, it is imperative to integrate machine learning, experimental validation, and clinical application to enhance the rationality of drug design. Conclusion The core active ingredients of Gastrodiae Rhizoma, Lycii Fructus, and Ziziphi Spinosae Semen were quercetin, atropine, dauricine, and (S) - coclaurine, etc. The core targets were PTGS2, PTGS1, MAOB, GABRA1, SLC6A2, ADRB2, CHRM1, HTR2A, etc. Molecular docking verification showed that quercetin, dauricine, and (S) - coclaurine can work well with PTGS2. The biological pathways of sedation and tranquilizing mind mainly include neuroactive ligand-receptor interaction, chemical carcinogenesis receptor activation, serotonin synapse, lipid, and atherosclerosis, etc. This study preliminarily revealed the multi-component, multi-target, and multi-pathway mechanism of the sedation and tranquilizing mind effect of Gastrodiae Rhizoma, Lycii Fructus, and Ziziphi Spinosae Semen, which can provide a basis for the development and utilization of Gastrodiae Rhizoma, Lycii Fructus, and Ziziphi Spinosae Semen. Declarations Author Contributions: Data analysis: CHZ, ZRZ; Draft the first draft: CHZ; Literature research: CHZ; Review final draft: ZRS. Funding This work was supported by the Ministry of Finance and Ministry of Agriculture and Rural Areas: special subsidy of national modern agricultural industrial technology system (CARS-21) and Shaanxi Ningqiang Gastrodia elata Product Development (KJ2022—001) Conflict of interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. References Ojemann LM, Nelson WL, Shin DS, Rowe AO and Buchanan RA (2006) Tian ma, an ancient Chinese herb, offers new options for the treatment of epilepsy and other conditions. Epilepsy Behav 8:376-83. doi: 10.1016/j.yebeh.2005.12.009 Zhan HD, Zhou HY, Sui YP, Du XL, Wang WH, Dai L, Sui F, Huo HR and Jiang TL (2016) The rhizome of Gastrodia elata Blume - An ethnopharmacological review. 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Breast Cancer Res 8:R71. doi: 10.1186/bcr1629 Gong L, Thorn CF, Bertagnolli MM, Grosser T, Altman RB and Klein TE (2012) Celecoxib pathways: pharmacokinetics and pharmacodynamics. Pharmacogenetics and Genomics 22:310-318. doi: 10.1097/FPC.0b013e32834f94cb Jin D, Zhang J, Zhang Y, An X, Zhao S, Duan L, Zhang Y, Zhen Z, Lian F and Tong X (2021) Network pharmacology-based and molecular docking prediction of the active ingredients and mechanism of ZaoRenDiHuang capsules for application in insomnia treatment. Comput Biol Med 135:104562. doi: 10.1016/j.compbiomed.2021.104562 Weng XJ, Jiang JM, Li HL and Tan Y (2023) Network pharmacology strategy to investigate the pharmacological effects of Suanzaoren Decoction on insomnia. Brazilian Journal of Pharmaceutical Sciences 59. doi: ARTN e21182 10.1590/s2175-97902023e21182 Zheng P, Liang Y, Wang LL, Zhang YM, Liu XY, Li JQ, Zhao LZ and Zhang MW (2022) Network Pharmacology Based and Molecular Docking Prediction of the Active Ingredients and Mechanism of Ziziphi spinosae semen-Schisandrae chinensis fructus for Application in Insomnia Treatment. Indian Journal of Pharmaceutical Sciences 84:29-41. doi: 10.36468/pharmaceutical-sciences.spl.450 Xu Y, Li X, Man D, Su X and A G (2020) iTRAQ-based proteomics analysis on insomnia rats treated with Mongolian medical warm acupuncture. Biosci Rep 40. doi: 10.1042/BSR20191517 Jiashuo WU, Fangqing Z, Zhuangzhuang LI, Weiyi J and Yue S (2022) Integration strategy of network pharmacology in Traditional Chinese Medicine: a narrative review. J Tradit Chin Med 42:479-486. doi: 10.19852/j.cnki.jtcm.20220408.003 Noor F, Asif M, Ashfaq UA, Qasim M and Tahir Ul Qamar M (2023) Machine learning for synergistic network pharmacology: a comprehensive overview. Brief Bioinform 24. doi: 10.1093/bib/bbad120 Hao da C and Xiao PG (2014) Network pharmacology: a Rosetta Stone for traditional Chinese medicine. Drug Dev Res 75:299-312. doi: 10.1002/ddr.21214 Additional Declarations No competing interests reported. Supplementary Files Graphicalabstract.tif Highlights.docx Cite Share Download PDF Status: Published Journal Publication published 02 Nov, 2023 Read the published version in Molecular Diversity → Version 1 posted Editorial decision: Major revision 07 Oct, 2023 Reviews received at journal 06 Oct, 2023 Reviews received at journal 16 Jul, 2023 Reviewers agreed at journal 16 Jul, 2023 Reviewers agreed at journal 16 Jul, 2023 Reviewers invited by journal 15 Jul, 2023 Editor assigned by journal 03 Jul, 2023 Submission checks completed at journal 03 Jul, 2023 First submitted to journal 02 Jul, 2023 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-3133115","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":215200849,"identity":"97c6ac5a-7ac9-4b37-acb2-8710586b4046","order_by":0,"name":"Chenghao Zhu","email":"","orcid":"","institution":"Beijing University of Chinese Medicine","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Chenghao","middleName":"","lastName":"Zhu","suffix":""},{"id":215200851,"identity":"e4aece0a-1841-4487-b6b1-d3c2cc3c8c0c","order_by":1,"name":"Zhengru Zhang","email":"","orcid":"","institution":"Beijing University of Chinese Medicine","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Zhengru","middleName":"","lastName":"Zhang","suffix":""},{"id":215200852,"identity":"4bf7b3fd-eecd-48b7-935b-9388c1193a05","order_by":2,"name":"Zhirong Sun","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAwElEQVRIiWNgGAWjYHACNhAhZ3+8sfHhB1K0GDOcOdxsLEGKlkSGG+ltAjzEqJfvP/vsMU/NtgTGmQ/bGCQY7OR0GwhoMThw3NyY59jtPGbpxLYHBQzJxmYHCGlhbGOT5m24XcwmndhuIMFwIHEbIS3yzWxgLYk9kgfbJHiI0cJwDKplhgQjkVoMzrCxG845dtvYgCcRGMgGRPhFvv8Y24M3NbflDNiPP3z4ocJOjqAWdEtJUz4KRsEoGAWjAAcAAH0rPq8TN0YVAAAAAElFTkSuQmCC","orcid":"","institution":"Beijing University of Chinese Medicine","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Zhirong","middleName":"","lastName":"Sun","suffix":""}],"badges":[],"createdAt":"2023-07-02 15:29:16","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-3133115/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-3133115/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s11030-023-10756-x","type":"published","date":"2023-11-02T15:00:56+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":39585979,"identity":"a84c008c-eaa8-49dc-82e7-dd248f9f8719","added_by":"auto","created_at":"2023-07-05 15:15:26","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":159588,"visible":true,"origin":"","legend":"\u003cp\u003eVenn Diagram of Gastrodiae Rhizoma-Lycii Fructus-Ziziphi Spinosae Semen - Sedation and tranquilizing mind targets\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-3133115/v1/8c7edd8e74df9bf504e27751.png"},{"id":39587101,"identity":"a79a37ec-b91b-425c-85a4-f98a8a7497d0","added_by":"auto","created_at":"2023-07-05 15:23:26","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":167170,"visible":true,"origin":"","legend":"\u003cp\u003ePPI Network of Gastrodiae Rhizoma-Lycii Fructus-Ziziphi Spinosae Semen - Sedation and tranquilizing mind targets\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-3133115/v1/9f347145f4f66babe221e497.png"},{"id":39585987,"identity":"b5d49593-a862-4d25-bc87-5073bbc5e9bf","added_by":"auto","created_at":"2023-07-05 15:15:26","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":202911,"visible":true,"origin":"","legend":"\u003cp\u003eModule in PPI network\u003c/p\u003e","description":"","filename":"floatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-3133115/v1/0c78588ffcdb1f320baae109.png"},{"id":39588743,"identity":"9c69c9ac-f141-4a95-a965-397e0126258f","added_by":"auto","created_at":"2023-07-05 15:31:26","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":88302,"visible":true,"origin":"","legend":"\u003cp\u003eGO analysis of intersection targets\u003c/p\u003e","description":"","filename":"floatimage4.png","url":"https://assets-eu.researchsquare.com/files/rs-3133115/v1/61fccd6f0c06c2fc5f69ca4c.png"},{"id":39587102,"identity":"a47df244-6a7a-4951-bf91-d0728725bba5","added_by":"auto","created_at":"2023-07-05 15:23:26","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":45408,"visible":true,"origin":"","legend":"\u003cp\u003eKEGG analysis of intersection targets\u003c/p\u003e","description":"","filename":"floatimage5.png","url":"https://assets-eu.researchsquare.com/files/rs-3133115/v1/878ae9517d404c23d5f0180a.png"},{"id":39585985,"identity":"eae3f354-e50a-404d-adcd-41a1b2faf3b7","added_by":"auto","created_at":"2023-07-05 15:15:26","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":857741,"visible":true,"origin":"","legend":"\u003cp\u003eComponent target network diagram\u003c/p\u003e","description":"","filename":"floatimage6.png","url":"https://assets-eu.researchsquare.com/files/rs-3133115/v1/a0c53075f0e7843266aac87c.png"},{"id":39588744,"identity":"3fcf10b2-1e31-44b1-9d95-a311f12d6d76","added_by":"auto","created_at":"2023-07-05 15:31:26","extension":"png","order_by":7,"title":"Figure 7","display":"","copyAsset":false,"role":"figure","size":1035941,"visible":true,"origin":"","legend":"\u003cp\u003eMolecular docking results of quercetin, dauricine, (S) - Coclaurine and PTGS2\u003c/p\u003e","description":"","filename":"floatimage7.png","url":"https://assets-eu.researchsquare.com/files/rs-3133115/v1/49c6896e978b778c43504038.png"},{"id":39585981,"identity":"8755eb85-f18f-49a8-96e6-44e49daf7128","added_by":"auto","created_at":"2023-07-05 15:15:26","extension":"png","order_by":8,"title":"Figure 8","display":"","copyAsset":false,"role":"figure","size":172476,"visible":true,"origin":"","legend":"\u003cp\u003ePossible mechanisms of quercetin, dauricine, and (S) - Coclaurine in sedation and tranquilizing mind effects\u003c/p\u003e","description":"","filename":"floatimage8.png","url":"https://assets-eu.researchsquare.com/files/rs-3133115/v1/c3501689d86524f5634c5553.png"},{"id":45943118,"identity":"f5e45498-390b-49cc-939c-b7b4392e7437","added_by":"auto","created_at":"2023-11-06 15:08:03","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2072546,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3133115/v1/89164908-dcf5-4eff-8496-57aa997752b9.pdf"},{"id":39585986,"identity":"4d1b94de-a03f-4de8-855e-f7ddd1e2dcb6","added_by":"auto","created_at":"2023-07-05 15:15:26","extension":"tif","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":3012488,"visible":true,"origin":"","legend":"","description":"","filename":"Graphicalabstract.tif","url":"https://assets-eu.researchsquare.com/files/rs-3133115/v1/52fc68d5ddda1d0a34c898f3.tif"},{"id":39585978,"identity":"a40759d0-ab75-4098-9b66-016bd7e39d32","added_by":"auto","created_at":"2023-07-05 15:15:26","extension":"docx","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":15121,"visible":true,"origin":"","legend":"","description":"","filename":"Highlights.docx","url":"https://assets-eu.researchsquare.com/files/rs-3133115/v1/7716adc01213bd62ad4e10db.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Study on the Mechanism of Gastrodiae Rhizoma, Lycii Fructus, and Ziziphi Spinosae Semen in Sedation and tranquilizing mind","fulltext":[{"header":"Introduction","content":"\u003cp\u003e \u003cem\u003eGastrodia elata\u003c/em\u003e Bl. (Orchidaceae), a perennial parasitic herbaceous plant, the rhizome of \u003cem\u003eGastrodia elata\u003c/em\u003e (Gastrodiae Rhizoma), as a superior herb, has been used for thousands of years. Modern pharmacological studies have shown that Gastrodiae Rhizoma contains substances such as phenols, polysaccharides, sterols, and organic acids [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e], which have a wide range of biological activities, including sedation, hypnosis, antiepileptic, anticonvulsant, anti-anxiety, antidepressant, neuroprotective, antipsychotic, anti-vertigo, circulatory regulation, anti-inflammatory, analgesic, antioxidant, memory improvement, anti-aging, antiviral, and anti-tumor effects[\u003cspan additionalcitationids=\"CR3\" citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e], in clinical practice, it is mainly used for neurasthenia, insomnia, dizziness, epilepsy, convulsions, nervous headache, Alzheimer's disease, hypertension, etc. Lycium barbarum L. (Solanaceae), a perennial herbaceous plant, mainly distributed in arid to semi-arid environments in North and South America and Africa, with a few in the Eurasian temperate zone[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. The mature dried fruit (Lycii Fructus) of Lycium contains polysaccharides, carotenoids, polyphenols, phenolic acids, flavonoids, alkaloids, and fatty acids [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e], and has been recognized as a functional food for treating various diseases, including waist and knee pain, tinnitus, impotence, spermatorrhea, blood deficiency and eye weakness [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Ziziphus jujuba M. belongs to Rhamnaceae [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. The fruit (Ziziphi Spinosae Semen) of Ziziphus jujuba contains flavonoids, phenolic acids, terpenes, alkaloids, polysaccharides, and other substances. Modern pharmacological research shows that Ziziphi Spinosae Semen has antibacterial, antioxidant, sedative, liver protective, anti-hyperglycemic, anti-hyperlipidemic and other effects [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Insomnia and the tension, anxiety, and neurasthenia it causes are common sleep disorders [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. It is a common form of neurasthenia caused by various situational, medical, emotional, environmental and behavioral factors [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Insomnia is a serious health problem that affects millions of people worldwide, with an estimated prevalence rate ranging from 4\u0026ndash;22%[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Consequently, the presence of insomnia may potentially contribute to the onset of depression. In comparison to individuals without insomnia, there is a twofold increase in the likelihood of developing this sleep disorder. Insomnia has the capacity to significantly impact one's overall well-being, and in more severe instances, it can precipitate mental health conditions such as anxiety, depression, and even suicidal ideation[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. The synergistic effects of Gastrodiae Rhizoma, Lycii Fructus, and Ziziphi Spinosae Semen have been found to contribute to the unification of the liver and kidney, promotion of blood circulation, and nourishment of the heart, resulting in sedation and tranquilization of the mind. This herbal combination has demonstrated significant therapeutic efficacy in addressing insomnia, anxiety, and neurological weakness associated with liver yang hyperactivity in patients. Xiao et al. (2015) have documented research findings on the efficacy of combining Gastrodiae Rhizoma and Ziziphi Spinosae Semen for enhancing sleep. Additionally, traditional medicine literature posits that the kidney plays a crucial role in brain function. Specifically, the kidney is responsible for storing essence and generating marrow, thereby suggesting that the brain marrow originates from the essence of the kidney. The fluctuation in kidney essence levels directly impacts the replenishment of brain marrow and consequently influences normal brain function [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. If the renal essence is abundant, the cerebral medulla is replete, and the faculties of memory, cognition, thinking, and regulation of the five viscera and six viscera are unimpaired, in addition to stable sleep patterns and sound mental well-being, the inclusion of Lycii Fructus alongside Gastrodiae Rhizoma and Ziziphi Spinosae Semen may confer advantageous effects on the kidneys, replenishing essence, nurturing the liver and kidneys, enriching the blood, and pacifying the nerves. However, a comprehensive understanding of its precise mechanism of action necessitates further investigation. Therefore, this study employs the network pharmacology approach to investigate the molecular mechanism of Gastrodiae Rhizoma, Lycii Fructus, and Ziziphi Spinosae Semen. It adopts a comprehensive perspective to analyze the material basis and conducts preliminary functional verification of its effective ingredients and targets using molecular docking and other technologies. The study aims to offer novel insights and a theoretical foundation for the advancement of sedative drug research and development.\u003c/p\u003e"},{"header":"Materials and methods","content":"\u003cp\u003e1.1 Screening of active ingredients and related targets\u003c/p\u003e \u003cp\u003eThe chemical constituents of Lycii Fructus and Ziziphi Spinosae Semen were investigated using the TCMSP database (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://old.tcmsp-e.com/\u003c/span\u003e\u003cspan address=\"https://old.tcmsp-e.com/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e). Active constituents and target protein information were filtered based on criteria of oral bioavailability (OB)\u0026thinsp;\u0026ge;\u0026thinsp;30% and drug-likeness (DL)\u0026thinsp;\u0026ge;\u0026thinsp;0.18. Similarly, the chemical constituents of Gastrodiae Rhizoma were explored using the HERB (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttp://herb.ac.cn/\u003c/span\u003e\u003cspan address=\"http://herb.ac.cn/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e) and ETCM (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttp://www.tcmip.cn/\u003c/span\u003e\u003cspan address=\"http://www.tcmip.cn/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e) databases, the smile number from the SwissTarget database (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttp://www.swisstargetprediction.ch/\u003c/span\u003e\u003cspan address=\"http://www.swisstargetprediction.ch/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e) was utilized to filter ADME values. Subsequently, the active ingredients of Gastrodiae Rhizoma were screened based on indicators of oral bioavailability and drug-likeness. The protein target information was then predicted using SwissTarget. Following the screening process, the protein target information was standardized and unified within the Uniprot protein database (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.uniprot.org\u003c/span\u003e\u003cspan address=\"https://www.uniprot.org\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e1.2 Screening of disease target\u003c/p\u003e \u003cp\u003eThe disease targets related to sedation and tranquilizing mind were searched in the GeneCards database (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.genecards.org/\u003c/span\u003e\u003cspan address=\"https://www.genecards.org/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e), Drugbank database(\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://go.drugbank.com/\u003c/span\u003e\u003cspan address=\"https://go.drugbank.com/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e), and OMIM database (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://omim.org/\u003c/span\u003e\u003cspan address=\"https://omim.org/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e ). The retrieved keywords were insomnia, anxiety, neuritis, and epilepsy. In the Genecards database, a higher score value indicates a close relationship between the target and the disease. If there are too many targets, target targets with a score value greater than the median are set as potential targets. After merging three disease database targets, remove duplicate disease targets related to sedation and tranquilizing mind.\u003c/p\u003e \u003cp\u003e1.3 PPI network construction of active ingredient-disease target\u003c/p\u003e \u003cp\u003eTo clarify the interaction between the relevant targets of Gastrodiae Rhizoma, Lycii Fructus, and Ziziphi Spinosae Semen and the related diseases targets of sedation and tranquilizing mind, the intersection targets were obtained through the venny2.1.0 online platform (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://bioinfogp.cnb.csic.es/tools/venny/\u003c/span\u003e\u003cspan address=\"https://bioinfogp.cnb.csic.es/tools/venny/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e). Then submit the intersection targets to the STRING11.5 database(\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://string-db.org\u003c/span\u003e\u003cspan address=\"https://string-db.org\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e) to build a protein interaction (PPI) network model, the biological species were \"Homo sapiens\" and the minimum interaction threshold was \"highest confidence\" (\u0026gt;\u0026thinsp;0.4), Further analysis of PPI network was conducted using the MCODE plugin in Cytoscape 3.9.1 to identify potential protein functional modules and their functions were described by analyzing the biological processes involved.\u003c/p\u003e \u003cp\u003e1.4 Enrichment analysis of intersection target functions and pathways\u003c/p\u003e \u003cp\u003eThe target points of Gastrodiae Rhizoma, Lycii Fructus, and Ziziphi Spinosae Semen were analyzed on the Metascape platform(\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttp://metascape.org/gp/index.html\u003c/span\u003e\u003cspan address=\"http://metascape.org/gp/index.html\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e) (P\u0026thinsp;\u0026lt;\u0026thinsp;0.01), the main biological processes and metabolic pathways were analyzed and visualized the data using OriginPro 2015.\u003c/p\u003e \u003cp\u003e1.5 Construction of component target network diagram\u003c/p\u003e \u003cp\u003eCytoScape 3.9.1 was used to build a network diagram of active ingredients - sedation and tranquilizing mind, the network topology parameters of active ingredients and targets were analyzed by the built-in tools of CytoScape 3.9.1, including degree, betweenness, closeness, etc., and the core targets and the main active ingredients that play their effects were judged according to the network Topology parameters.\u003c/p\u003e \u003cp\u003e1.6 Molecular docking verification\u003c/p\u003e \u003cp\u003eThe sdf files of the key active ingredients structure were downloaded in Pubchem (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://pubchem.ncbi.nlm.nih.gov/\u003c/span\u003e\u003cspan address=\"https://pubchem.ncbi.nlm.nih.gov/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e). The minimum energy was run in chemdraw3D and a mol2 format file was converted, the most critical targets were screened out in the protein interaction network, the entry number was found in the UniProt database(\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.uniprot.org/\u003c/span\u003e\u003cspan address=\"https://www.uniprot.org/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e), and the PDB format file of the structure was download in the Pdb database(\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.rcsb.org/\u003c/span\u003e\u003cspan address=\"https://www.rcsb.org/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e) and we optimized it in Pymol, the mol2 files and pdb files were converted in the autodock tools file, and the score of their docking Binding energy was got. The docking results were visualized in Pymol.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e2.1 Screening of active ingredients and related targets\u003c/p\u003e\n\u003cp\u003e43 chemical components of Gastrodiae Rhizoma (Herb), 188 chemical components of Lycii Fructus (TCMSP), and 33 chemical components of Ziziphi Spinosae Semen (TCMSP) were preliminarily extracted. After screening by TCMSP (OB\u0026thinsp;\u0026ge;\u0026thinsp;30%, DL\u0026thinsp;\u0026ge;\u0026thinsp;0.18) and SwissADME, 25(Gastrodiae Rhizoma), 45 (Lycii Fructus) and 9 (Ziziphi Spinosae Semen) active components were obtained, including quercetin, dauricine, cyanin, and sanjoinenine (Tables \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e and \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e). At the same time, four active ingredients, Betaine (Lycii Fructus), jujuboside A (Ziziphi Spinosae Semen), Spinosin (Ziziphi Spinosae Semen), and Gastrodin (Gastrodiae Rhizoma), which are not screened by the above conditions but have been reported to have sedative and sedative effects, are added to the table.\u003c/p\u003e\n\u003cp\u003eAfter predicting the active ingredient targets, it was found that there were 389 active ingredient targets in Lycii Fructus, 47 active ingredient targets in Ziziphi Spinosae Semen, and 173 active ingredient targets in Gastrodiae Rhizoma. After merging, a total of 303 active ingredient targets were obtained by deleting duplicate values.\u003c/p\u003e\u0026nbsp;\u003ctable id=\"Tab1\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eMain active ingredients in Gastrodiae Rhizoma\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eDrug\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eIngredient ID\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eMark\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eIngredient name\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eGI absorption\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eDruglikeness\u003c/p\u003e\n \u003cp\u003e(yes༞3)\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" rowspan=\"26\"\u003e\n \u003cp\u003eGastrodiae Rhizoma\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHBIN009937\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTM1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4,4\u0026apos;-dihydroxy dibenzyl ether\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHigh\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHBIN009938\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTM2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4,4\u0026apos;-dihydroxy diphenyl methane\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHigh\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHBIN009959\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTM3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4-(4\u0026apos;-hydroxybenzyloxy)benzyl methyl ether\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHigh\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHBIN009960\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTM4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4-(4\u0026apos;-hydroxybenzyloxy)benzyl nethyl ether\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHigh\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHBIN010380\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTM5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4-ethoxymethylphenyl-4\u0026apos;-hydroxybenzylether\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHigh\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHBIN010513\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTM6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4-hydroxybenzylamine\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHigh\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHBIN010518\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTM7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4-hydroxybenzyl mathyl ether\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHigh\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHBIN010519\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTM8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4-hydroxybenzyl methyl ether\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHigh\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHBIN018559\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTM9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ebis(4-hydroxybenzyl)ether\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHigh\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHBIN018560\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTM10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ebis(4-hydroxybenzyl)ether mono-beta-d-glucopyranoside\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHigh\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHBIN020993\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTM11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ecitronellal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHigh\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHBIN022781\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTM12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003edauricine\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHigh\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHBIN025849\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTM13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eethoxysanguinarine\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHigh\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHBIN027383\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTM14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003egastrodamine\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHigh\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHBIN027384\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTM15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGastrodin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHigh\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHBIN029268\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTM16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ehexadecanoic acid\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHigh\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHBIN035490\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTM17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003em-hydroxybenzoicacid\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHigh\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHBIN039671\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTM18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ep-hydroxybenzaldehyde\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHigh\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHBIN039681\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTM19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ep-hydroxybenzyl alcohol\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHigh\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHBIN039682\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTM20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ep-hydroxy benzyl ethylether\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHigh\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHBIN040911\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTM21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eprotocatechuic aldehyde\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHigh\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHBIN045062\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTM22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003esuccinic acid\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHigh\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHBIN045071\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTM23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003esuchilactone\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHigh\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHBIN047744\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTM24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003evanillin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHigh\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHBIN047745\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTM25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003evanillin acetate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHigh\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHBIN047752\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTM26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eVanillyl alcohol\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHigh\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n \u003cdiv align=\"left\" class=\"colspec\"\u003e\u003cbr\u003e\u003c/div\u003e\n \u003cdiv align=\"left\" class=\"colspec\"\u003e\u003cbr\u003e\u003c/div\u003e\u0026nbsp;\u003ctable id=\"Tab2\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eMain active ingredients in Lycii Fructus, and Ziziphi Spinosae Semen\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eDrug\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eIngredient ID\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eMark\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eIngredient name\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eOB(%)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eDL\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" rowspan=\"46\"\u003e\n \u003cp\u003eLycii Fructus\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMOL001323\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGQZ1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSitosterol alpha1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e43.28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.78\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMOL003578\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGQZ2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCycloartenol\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e38.69\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.78\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMOL001494\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGQZ3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMandenol\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e42\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.19\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMOL001495\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGQZ4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eEthyl linolenate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e46.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMOL001979\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGQZ5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLAN\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e42.12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.75\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMOL000449\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGQZ6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eStigmasterol\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e43.83\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.76\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMOL000358\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGQZ7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ebeta-sitosterol\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e36.91\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.75\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMOL005406\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGQZ8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eatropine\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e45.97\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.19\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMOL005438\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGQZ9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ecampesterol\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e37.58\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.71\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMOL006209\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGQZ10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ecyanin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e47.42\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.76\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMOL007449\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGQZ11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e24-methylidenelophenol\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e44.19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.75\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMOL008173\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGQZ12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003edaucosterol_qt\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e36.91\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.75\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMOL008400\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGQZ13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eglycitein\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e50.48\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.24\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMOL010234\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGQZ14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003edelta-Carotene\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e31.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.55\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMOL000953\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGQZ15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCLR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e37.87\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.68\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMOL009604\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGQZ16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e14b-pregnane\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e34.78\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.34\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMOL009612\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGQZ17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e(24R)-4alpha-Methyl-24-ethylcholesta-7,25-dien-3beta-ylacetate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e46.36\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.84\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMOL009615\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGQZ18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e24-Methylenecycloartan-3beta,21-diol\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e37.32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.8\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMOL009617\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGQZ19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e24-ethylcholest-22-enol\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e37.09\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.75\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMOL009618\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGQZ20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e24-ethylcholesta-5,22-dienol\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e43.83\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.76\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMOL009620\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGQZ21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e24-methyl-31-norlanost-9(11)-enol\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e38\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.75\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMOL009621\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGQZ22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e24-methylenelanost-8-enol\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e42.37\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.77\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMOL009622\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGQZ23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFucosterol\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e43.78\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.76\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMOL009631\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGQZ24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e31-Norcyclolaudenol\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e38.68\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.81\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMOL009633\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGQZ25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e31-norlanost-9(11)-enol\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e38.35\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.72\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMOL009634\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGQZ26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e31-norlanosterol\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e42.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.73\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMOL009635\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGQZ27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4,24-methyllophenol\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e37.83\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.75\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMOL009639\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGQZ28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLophenol\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e38.13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.71\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMOL009640\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGQZ29\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4alpha,14alpha,24-trimethylcholesta-8,24-dienol\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e38.91\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.76\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMOL009641\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGQZ30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4alpha,24-dimethylcholesta-7,24-dienol\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e42.65\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.75\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMOL009642\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGQZ31\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4alpha-methyl-24-ethylcholesta-7,24-dienol\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e42.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.78\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMOL009644\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGQZ32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6-Fluoroindole-7-Dehydrocholesterol\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e43.73\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.72\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMOL009646\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGQZ33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7-O-Methylluteolin-6-C-beta-glucoside_qt\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e40.77\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMOL009650\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGQZ34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAtropine\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e42.16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.19\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMOL009651\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGQZ35\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCryptoxanthin monoepoxide\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e46.95\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.56\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMOL009653\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGQZ36\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCycloeucalenol\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e39.73\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.79\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMOL009656\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGQZ37\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e(E,E)-1-ethyl octadeca-3,13-dienoate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e42\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.19\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMOL009660\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGQZ38\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003emethyl (1R,4aS,7R,7aS)-4a,7-dihydroxy-7-methyl-1-[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-1,5,6,7a-tetrahydrocyclopenta[d]pyran-4-carboxylate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e39.43\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.47\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMOL009662\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGQZ39\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLantadene A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e38.68\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.57\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMOL009664\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGQZ40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePhysalin A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e91.71\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.27\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMOL009665\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGQZ41\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePhyscion-8-O-beta-D-gentiobioside\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e43.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.62\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMOL009677\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGQZ42\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003elanost-8-en-3beta-ol\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e34.23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.74\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMOL009678\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGQZ43\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003elanost-8-enol\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e34.23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.74\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMOL009681\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGQZ44\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eObtusifoliol\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e42.55\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.76\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMOL000098\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGQZ45\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003equercetin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e46.43\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.28\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMOL000430\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGQZ46\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBetaine\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e40.92\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" rowspan=\"11\"\u003e\n \u003cp\u003eZiziphi Spinosae Semen\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMOL001521\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSZR1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eceanothic acid\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e33.41\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.77\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMOL001522\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSZR2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e(S)-Coclaurine\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e42.35\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.24\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMOL001525\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSZR3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDaucosterol\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e36.91\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.75\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMOL001527\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSZR4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ejujuboside A_qt\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e34.96\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.62\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMOL001532\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSZR5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ephytosterol\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e36.91\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.75\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMOL001539\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSZR6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003esanjoinenine\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e67.28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.79\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMOL001542\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSZR7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eswertisin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e31.83\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.75\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMOL001546\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSZR8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ezizyphusine\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e41.53\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.55\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMOL000211\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSZR9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMairin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e55.38\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.78\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMOL001526\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSZR10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ejujuboside A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8.04\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.02\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMOL001540\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSZR11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSpinosin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6.31\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.72\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e2.2 Screening of disease targets related to sedation and tranquilizing mind\u003c/p\u003e\n\u003cp\u003eIn the GeneCards database target information, target targets with a Score\u0026thinsp;\u0026gt;\u0026thinsp;1.5 are identified as potential targets for insomnia, while target targets with a Score\u0026thinsp;\u0026gt;\u0026thinsp;7.0 are identified as potential targets for any entity. Combining the target information related to sedation and tranquilizing mind in GeneCards, OMIM, and Drugbank databases, the duplicate values were deleted after merging, and finally, 492 related targets were obtained.\u003c/p\u003e\n\u003cp\u003e2.3 Construction of active ingredient-disease target PPI network\u003c/p\u003e\n\u003cp\u003eA total of 81 common targets were obtained for both component targets and disease targets (Fig. \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e). Furthermore, the target was submitted to the STRING11.5 platform to obtain a PPI network (Fig. \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e). To analyze the mechanism of action of Gastrodiae Rhizoma, Lycii Fructus, and Ziziphi Spinosae Semen more accurately, the PPI network was obtained and its intrinsic modules were further identified. After obtaining the PPI network, the MCODE plugin in Cytoscape 3.9.1 was used to analyze the interaction relationship through the molecular complex detection algorithm, and the module was obtained (Fig. \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e). According to the P-value, the biological processes with the three best scores in the PPI network and Module were retained for functional description (Table \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e).\u0026nbsp;\u003c/p\u003e\u0026nbsp;\u003ctable id=\"Tab3\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eDescription of PPI network functions for three modules\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" rowspan=\"8\"\u003e\n \u003cp\u003eMCODE1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003ebiologic function\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eGO ID\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eDescription\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eP value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" rowspan=\"7\"\u003e\n \u003cp\u003e0.0159\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" rowspan=\"3\"\u003e\n \u003cp\u003eBiological processes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGO:0060559\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePositive regulation of calcidiol 1-monooxygenase activity\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGO:0002874\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eregulation of chronic inflammatory response to antigenic stimulus\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGO:0030730\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003esequestering of triglyceride\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" rowspan=\"3\"\u003e\n \u003cp\u003eMolecular function\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGO:0070851\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003egrowth factor receptor binding\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGO:0005125\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ecytokine activity\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGO:0005126\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ecytokine receptor binding\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" rowspan=\"6\"\u003e\n \u003cp\u003eMCODE2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" rowspan=\"3\"\u003e\n \u003cp\u003eBiological processes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGO:0051932\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003esynaptic transmission, GABAergic\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" rowspan=\"6\"\u003e\n \u003cp\u003e1.88e-10\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGO:1904862\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003einhibitory synapse assembly\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGO:0007214\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003egamma-aminobutyric acid signaling pathway\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" rowspan=\"3\"\u003e\n \u003cp\u003eMolecular function\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGO:0008503\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ebenzodiazepine receptor activity\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGO:0022851\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGABA-gated chloride ion channel activity\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGO:0005237\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003einhibitory extracellular ligand-gated monoatomic ion channel activity\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" rowspan=\"6\"\u003e\n \u003cp\u003eMCODE3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" rowspan=\"3\"\u003e\n \u003cp\u003eBiological processes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGO:0001993\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eregulation of systemic arterial blood pressure by norepinephrine-epinephrine\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" rowspan=\"6\"\u003e\n \u003cp\u003e9.39e-10\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGO:0071880\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eadenylate cyclase-activating adrenergic receptor signaling pathway\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGO:0007200\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ephospholipase C-activating G protein-coupled receptor signaling pathway\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" rowspan=\"3\"\u003e\n \u003cp\u003eMolecular function\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGO:0004935\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eadrenergic receptor activity\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGO:0008227\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eG protein-coupled amine receptor activity\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGO:0004993\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eG protein-coupled serotonin receptor activity\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003c/p\u003e\n\u003cp\u003e2.4 Enrichment analysis of intersection target functions and pathways\u003c/p\u003e\n\u003cp\u003eThe functions of multiple targets were closely related to their sedation and tranquilizing mind effects. The main biological processes involved in the Gastrodiae Rhizoma, Lycii Fructus, and Ziziphi Spinosae Semen: cellular response to organic cyclic compound, regulation of tube diameter, and response to xenobiotic stimulus, the main cellular components were postsynaptic membrane, membrane raft, GABA-ergic synapse, the main molecular functions included G protein-coupled amine receptor activity, neurotransmitter receptor activity, catecholamine binding (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003e). The main pathways were neuroactive ligand-receptor interaction, chemical carcinogenesis-receptor activation, serotonergic synapse, and Lipid and atherosclerosis (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e5\u003c/span\u003e). The enrichment results of the target pathway (Table\u0026nbsp;4) indicated that Gastrodiae Rhizoma, Lycii Fructus, and Ziziphi Spinosae Semen significantly acted on the neuroactive ligand-receptor interaction to exert sedation and tranquilizing mind effects.\u003c/p\u003e\n\u003cp\u003e\u003cimg src=\"https://myfiles.space/user_files/122228_c8a1650c59388082/122228_custom_files/img1688475131.png\"\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cp\u003e\u003cimg src=\"https://myfiles.space/user_files/122228_c8a1650c59388082/122228_custom_files/img1688475145.png\"\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n \u003cdiv align=\"left\" class=\"colspec\"\u003e\u003cbr\u003e\u003c/div\u003e\n \u003cdiv align=\"left\" class=\"colspec\"\u003e\u003cbr\u003e\u003c/div\u003e\n\u003c/div\u003e\n\u003cp\u003e2.5 Construction of component target network diagram\u003c/p\u003e\n\u003cp\u003eActive ingredient sedation and tranquilizing mind network were constructed using Cytoscape 3.9.1 (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e6\u003c/span\u003e). By analyzing the network Topology parameters that play a calming role through the built-in Network Analyzer of CytoScape 3.9.1, the core components and core action targets were obtained. Cytoscape network analysis showed that GQZ45 (Quercetin) had a connectivity degree of 34, betweenness centrality of 0.4017, and a closeness centrality of 0.4232. It was predicted that Quercetin was the main component of Gastrodiae Rhizoma, Lycii Fructus, and Ziziphi Spinosae Semen which played a calming role. Secondly, GQZ34 (Atropine) (connectivity: 27, betweenness: 0.1314, compactness: 0.4021), SZR2 (mydrine) in Ziziphi Spinosae Semen was the main component (connectivity: 14, betweenness: 0.0494, compactness: 0.3610), and TM12 (Dauricine) in Gastrodiae Rhizoma was the main component (connectivity: 8, betweenness: 0.0723, compactness: 0.3029) (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e5\u003c/span\u003e). The connectivity of PTGS2 in the network was 16, the mediation was 0.1250, and the tightness was 0.4232. It was predicted that PTGS2 was the main target for the calming effect of Gastrodiae Rhizoma, Lycii Fructus, and Ziziphi Spinosae Semen. PTGS1, MAOB, GABRA1, SLC6A2, ADRB2, CHRM1, HTR2A, and ADRA1A were also relatively important targets (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e6\u003c/span\u003e).\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n \u003cdiv align=\"left\" class=\"colspec\"\u003e\u003cbr\u003e\u003c/div\u003e\u0026nbsp;\u003ctable id=\"Tab5\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eMain active ingredient network node characteristic parameters\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eMark ID\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eCompound name\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eConnectivity\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eBetweenness\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eCompactness\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGQZ45\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003equercetin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.401702098\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.423220974\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGQZ34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAtropine\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.131435047\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.402135231\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGQZ7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ebeta-sitosterol\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.133755168\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.385665529\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTM12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003edauricine\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.072296565\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.302949062\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTM5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4-ethoxymethylphenyl-4\u0026apos;-hydroxybenzylether\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.042675336\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.372937294\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTM3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4-(4\u0026apos;-hydroxybenzyloxy)benzyl methyl ether\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.027101405\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.370491803\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSZR2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e(S)-Coclaurine\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.049455498\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.361022364\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSZR8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ezizyphusine\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.012606377\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.331378299\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSZR6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003esanjoinenine\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.003918413\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.325648415\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cdiv class=\"gridtable\"\u003e\n \u003cdiv align=\"left\" class=\"colspec\"\u003e\u003cbr\u003e\u003c/div\u003e\n \u003cdiv align=\"left\" class=\"colspec\"\u003e\u003cbr\u003e\u003c/div\u003e\u0026nbsp;\u003ctable id=\"Tab6\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 6\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eMain active ingredient target network node characteristic parameters\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eMark ID\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eCompound name\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eConnectivity\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eBetweenness\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eCompactness\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePTGS2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eProstaglandin G/H synthase 2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.12501423\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.423220974\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePTGS1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eProstaglandin G/H synthase 1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.086957031\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.410909091\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMAOB\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAmine oxidase\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.066102002\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.388316151\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGABRA1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGamma-aminobutyric acid receptor subunit alpha-1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.0491451\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.385665529\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSLC6A2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSodium-dependent noradrenaline transporter\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.020399725\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.331378299\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eADRB2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBeta-2 adrenergic receptor\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.041484238\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.383050847\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCHRM1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMuscarinic acetylcholine receptor M1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.00886712\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.320113314\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHTR2A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5-hydroxytryptamine receptor 2A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.018837197\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.345565749\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eADRA1A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAlpha-1A adrenergic receptor\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.028127314\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.352024922\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e2.6 Molecular docking verification\u003c/p\u003e\n\u003cp\u003eThe active ingredients (quercetin, dauricine, (S) - Coclaurine) ranking first in each main drug in Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e5\u003c/span\u003e were used as ligand compounds, and the core target (PTGS2) ranking first in Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e6\u003c/span\u003e was used as receptor protein for molecular docking. The Binding energy of PTGS2 with quercetin, dauricine, and (S) - Coclaurine was \u0026minus;\u0026thinsp;9.8 kcal/mol, -10.0 kcal/mol, and \u0026minus;\u0026thinsp;8.9 kcal/mol, respectively. The smaller the binding energy of ligand and receptor, the more stable the molecular binding conformation. It was generally believed that the ligand and receptor could bind at Binding energy\u0026lt;-5 kcal/mol. Among them, quercetin bound to PTGS2 through four hydrogen bonds formed by HIS-39, TYR-130, ARG-44, ASP-125, dauricine bound to PTGS2 through one hydrogen bond formed by APG-376, and (S) - Coclaurine bound to PTGS2 through two hydrogen bonds formed by GLY-45 and HIS-39. Therefore, it could be concluded that Gastrodiae Rhizoma, Lycii Fructus, and Ziziphi Spinosae Semen could effectively exert sedation and tranquilizing mind effects.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe study found that Quercetin and Luteolin, present in \u003cem\u003eHemerocallis citrina\u003c/em\u003e, were identified as the primary active compounds responsible for improving sleep in Drosophila melanogaster[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Furthermore, lower concentrations of Quercetin were observed to have positive effects on shoaling behavior and anxiety in Zebrafish[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Quercetin, known for its mitochondrial protective properties, shows potential in treating anxiety induced by methylamphetamine (MA) [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e18\u003c/span\u003e] and can also mitigate anxiety resulting from hypoxia-induced neonatal seizures (HINS) [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e19\u003c/span\u003e] by down-regulating the inflammatory response through the TLR4/NF kappa B pathway. Atropine, an anticholinergic drug, has the potential to serve as adjunctive therapy for Ketamine sedation[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. Dauricine, an alkaloid, exhibits promise as an Acetylcholinesterase inhibitor for the treatment of epilepsy, a nervous system disease [21]. Additionally, (S) - Coclaurine found in Ziziphi Spinosae Semen may have a significant impact on the treatment of insomnia induced by p-chlorophenylalanine (PCPA) in rats[\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. The aforementioned research findings indicate that quercetin, atropine, dauricine, and (S) - coclaurine demonstrate efficacy in addressing insomnia, anxiety, epilepsy, neurasthenia, and other neurological disorders.\u003c/p\u003e \u003cp\u003eSleep disorders have been found to potentially occur in the central pain inhibition pathway, Cyclooxygenase (COX) pathway, and endogenous Cannabinoid (eCB) pathway[\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. A case study reported the development of symptoms such as anxiety, irritability, lethargy, insomnia, aggression, impulsivity, and hypomania in a patient with depression and Spondylolisthesis after taking Celecoxib, a cyclooxygenase-2 inhibitor [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. Prostaglandin peroxylactone synthase (PTGS), also known as cyclonenenebb oxygenase (COX), is a crucial enzyme involved in the biosynthesis of Prostaglandin, serving as both a double Oxygenase and peroxidase [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. PTGS encompasses two distinct isozymes, namely constitutive PTGS1 and inducible PTGS2, both of which serve as targets for Nonsteroidal anti-inflammatory drugs (NSAIDs) [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. Based on our molecular docking findings, it is postulated that quercetin, dauricine, and (S) - Coclaurine present in Gastrodiae Rhizoma, Lycii Fructus, and Ziziphi Spinosae Semen possess the potential to effectively interact with PTGS2, thereby mitigating the adverse effects of NSAIDs such as insomnia, anxiety, and irritability. Hence, we present a potential schematic representation (Fig.\u0026nbsp;\u003cspan refid=\"Fig8\" class=\"InternalRef\"\u003e8\u003c/span\u003e) elucidating the plausible mechanism underlying the sedative and anxiolytic effects of Gastrodiae Rhizoma, Lycii Fructus, and Ziziphi Spinosae Semen. Through functional analysis of the convergence between constituents and disease targets, it was observed that the neuroactive ligand-receptor interaction pathway may also facilitate the sedative and anxiolytic properties of other constituents. This finding has been substantiated by numerous research reports [\u003cspan additionalcitationids=\"CR28\" citationid=\"CR28\" class=\"CitationRef\"\u003e27\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e29\u003c/span\u003e], such as the neuroactive ligand-receptor interaction and the upregulation of Oxytocin signal transduction, which have emerged as the foremost regulatory processes in the efficacy of Mongolian medical warm acupuncture for insomnia treatment [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e30\u003c/span\u003e].\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eIn contrast to synthetic pharmaceuticals, traditional Chinese medicine possesses the attributes of \"multi-component\", \"multi-target\", and \"multi-pathway\" [\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. The field of network pharmacology, an emerging discipline in systematic drug investigation, endeavors to comprehend the mechanisms and interactions of drugs with multiple targets. This novel approach has revolutionized the conventional paradigm of one-drug-one-target, ushering in a new era of highly efficacious multi-target drugs [\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e32\u003c/span\u003e]. However, this prediction holds a prominent position in the field, although it relies on several assumptions that need to be verified. Consequently, it is susceptible to potential false positive outcomes and necessitates rigorous experimental validation. Moreover, it may not provide a comprehensive and reliable understanding of the treatment mechanism. Given the limitations and challenges, this approach additionally provides scientific researchers with guidance in designing and investigating pharmaceuticals from a prospective and analytical standpoint. This has significantly contributed to the reduction of drug consumption rates [\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e33\u003c/span\u003e] and has further enhanced the composition and effectiveness of medications. In the future, it is imperative to integrate machine learning, experimental validation, and clinical application to enhance the rationality of drug design.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThe core active ingredients of Gastrodiae Rhizoma, Lycii Fructus, and Ziziphi Spinosae Semen were quercetin, atropine, dauricine, and (S) - coclaurine, etc. The core targets were PTGS2, PTGS1, MAOB, GABRA1, SLC6A2, ADRB2, CHRM1, HTR2A, etc. Molecular docking verification showed that quercetin, dauricine, and (S) - coclaurine can work well with PTGS2. The biological pathways of sedation and tranquilizing mind mainly include neuroactive ligand-receptor interaction, chemical carcinogenesis receptor activation, serotonin synapse, lipid, and atherosclerosis, etc. This study preliminarily revealed the multi-component, multi-target, and multi-pathway mechanism of the sedation and tranquilizing mind effect of Gastrodiae Rhizoma, Lycii Fructus, and Ziziphi Spinosae Semen, which can provide a basis for the development and utilization of Gastrodiae Rhizoma, Lycii Fructus, and Ziziphi Spinosae Semen.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAuthor Contributions:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eData analysis: CHZ, ZRZ; Draft the first draft: CHZ; Literature research: CHZ; Review final draft: ZRS.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eFunding\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work was supported by the Ministry of Finance and Ministry of Agriculture and Rural Areas: special subsidy of national modern agricultural industrial technology system (CARS-21) and Shaanxi Ningqiang Gastrodia elata Product Development (KJ2022\u0026mdash;001)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eConflict of interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eOjemann LM, Nelson WL, Shin DS, Rowe AO and Buchanan RA (2006) Tian ma, an ancient Chinese herb, offers new options for the treatment of epilepsy and other conditions. 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Drug Dev Res 75:299-312. doi: 10.1002/ddr.21214\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"molecular-diversity","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"modi","sideBox":"Learn more about [Molecular Diversity](http://link.springer.com/journal/11030)","snPcode":"11030","submissionUrl":"https://submission.nature.com/new-submission/11030/3","title":"Molecular Diversity","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Gastrodiae Rhizoma, Lycii Fructus, and Ziziphi Spinosae Semen, insomnia, network pharmacology, sedation and tranquilizing mind","lastPublishedDoi":"10.21203/rs.3.rs-3133115/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3133115/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eMethod\u003c/h2\u003e \u003cp\u003eThe chemical constituents and therapeutic targets of Gastrodiae Rhizoma, Lycii Fructus, and Ziziphi Spinosae Semen were acquired from TCMSP, HERB, and ETCM databases. Active components were identified using ADME criteria, while the primary targets associated with sedation and mental tranquility were obtained from GENECARDS, OMIM, and DRUGBANK databases. To investigate potential functional protein modules within the network, a protein-protein interaction (PPI) network analysis was conducted using the STRING platform. The METASCAPE platform was employed for the analysis of the \"component-target\" and its associated biological processes and pathways. Subsequently, the construction of the \"component-target\" network was accomplished using Cytoscape 3.9.1 software. Finally, the validation of molecular docking was conducted through AUTODOCK. Results: The findings revealed that Quercetin, Atropine, dauricine, (S)-Coclaurine, and other active ingredients were identified as the core constituents of Gastrodiae Rhizoma, Lycii Fructus, and Ziziphi Spinosae Semen. Additionally, PTGS2, PTGS1, MAOB, GABRA1, SLC6A2, ADRB2, CHRM1, HTR2A, and other targets were identified as the core targets. The results of the molecular docking analysis demonstrated that Quercetin, dauricine, and (S)-Coclaurine exhibited strong binding affinity towards PTGS2. The predominant biological pathways associated with sedation and tranquilization primarily involved neuroactive ligand-receptor interaction and activation of receptors involved in chemical carcinogenesis. This study provides initial findings on the multi-component, multi-target, and multi-pathway mechanism underlying the sedative and tranquilizing effects of Gastrodiae Rhizoma, Lycii Fructus, and Ziziphi Spinosae Semen. These findings have the potential to serve as a foundation for the future development and utilization of Gastrodiae Rhizoma, Lycii Fructus, and Ziziphi Spinosae Semen.\u003c/p\u003e","manuscriptTitle":"Study on the Mechanism of Gastrodiae Rhizoma, Lycii Fructus, and Ziziphi Spinosae Semen in Sedation and tranquilizing mind","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2023-07-05 15:15:21","doi":"10.21203/rs.3.rs-3133115/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Major revision","date":"2023-10-07T06:18:18+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2023-10-06T04:13:10+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2023-07-17T03:55:10+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"917b8c21-9f0b-4a44-a2cd-a102df70ae9b","date":"2023-07-16T15:23:35+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"1be04436-6b6a-4a33-8ac8-1bf1b9a10b03","date":"2023-07-16T09:10:10+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2023-07-15T05:06:08+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2023-07-03T20:55:46+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2023-07-03T08:12:41+00:00","index":"","fulltext":""},{"type":"submitted","content":"Molecular Diversity","date":"2023-07-02T15:17:48+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"molecular-diversity","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"modi","sideBox":"Learn more about [Molecular Diversity](http://link.springer.com/journal/11030)","snPcode":"11030","submissionUrl":"https://submission.nature.com/new-submission/11030/3","title":"Molecular Diversity","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"ed5d4235-9d47-4706-9763-c30e3c40e622","owner":[],"postedDate":"July 5th, 2023","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2023-11-06T15:05:42+00:00","versionOfRecord":{"articleIdentity":"rs-3133115","link":"https://doi.org/10.1007/s11030-023-10756-x","journal":{"identity":"molecular-diversity","isVorOnly":false,"title":"Molecular Diversity"},"publishedOn":"2023-11-02 15:00:56","publishedOnDateReadable":"November 2nd, 2023"},"versionCreatedAt":"2023-07-05 15:15:21","video":"","vorDoi":"10.1007/s11030-023-10756-x","vorDoiUrl":"https://doi.org/10.1007/s11030-023-10756-x","workflowStages":[]},"version":"v1","identity":"rs-3133115","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3133115","identity":"rs-3133115","version":["v1"]},"buildId":"-D5TCW68w8eVRRLyjaTIo","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}