Herbs’ Disease-matched Pharmacological Mechanisms of HuanglianJiedu Decoction in Behavioral and Psychological Symptoms of Dementia in Alzheimer's Disease

Abstract Along with cognitive deficit, behavioral and psychological symptoms in dementia (BPSD) is another characteration of Alzheimer's disease that hamper clinical management and exacerbate burden for caregivers. However, therapeutic management of BPSD remains challenging. HuanglianJiedu decoction (HLJDD), a traditional Chinese prescription which contains Coptidis rhizome(Huang lian), Scutellariae radix (Huang-qin), Phellodendri chinrnsis cortex (Huang-bai) and Gardeniae fructus (Zhi-zi), is applied to treat BPSD. So elucidating the herbs’ disease-matched pharmacological mechanisms underlying HLJDD, further put forward each herbs’ disease-matched combination are critical to the application of HLJDD. In this study, network pharmacology was used to determine the targets and biological processes regulated by HLJDD in the treatment of BPSD. Moreover, molecular docking was utilized to evaluate the binding activity between the herbs' main active ingredients and neurotransmitter receptors. The results showed that the KEGG signaling pathway of HLJDD in treating BPSD mainly lies in TNF signaling pathway and AGE-RAGE signaling pathway in diabetic complications. Scutellariae radix and Phellodendri chinrnsis cortex exhibited better anti-BPSD effects when compared to Coptidis rhizoma and Gardeniae fructus. Scutellariae radix exhibited superior anti-neuroinflammation functions, with better blood vessel regulation effects. Phellodendri chinrnsis cortex showed a higher binding affinity to the dopamine D2 receptor (DRD2) and 5-hydroxytryptamine receptor 2A (HTR2A). Coptidis rhizoma and Gardeniae fructus were better in neuronal signaling. In conclusion, for treating BPSD, Scutellariae radix and Phellodendri chinrnsis cortex are the principal herbs while Coptidis rhizoma and Gardeniae fructus are the ancillary herbs. Beta-sitosterol, stigmasterol, chelerythrine, campesterol and berberine are the potential effective ingredients in treating BPSD.