Polygonati Rhizoma reduces inflammation and improves muscle atrophy and fibrosis in sarcopenia through the EGFR/MAPK pathway

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This preprint investigated Polygonati Rhizoma extract (PRE) as a potential treatment for sarcopenia, using ultra-high-performance liquid chromatography–tandem mass spectrometry to profile compounds, network pharmacology and molecular docking to prioritize targets/pathways, and a D-galactose-induced sarcopenia mouse model to test functional and tissue outcomes. The authors report that PRE (60 and 120 mg/kg for 8 weeks) improved exercise capacity and reduced muscle atrophy and fibrosis, alongside suppression of inflammatory markers. Mechanistically, PRE was associated with enhanced EGFR phosphorylation, activation of MAPK signaling, and inhibition of TNF and CTNNB1-mediated fibrotic pathways, with pathway analysis implicating MAPK, IL-17, and TNF signaling cascades. A major caveat stated is that the work is a preprint and not peer reviewed, and the abstract does not describe limitations such as sample size or translational validation beyond mice. The paper does not explicitly discuss endometriosis or adenomyosis; it was included in the corpus via a keyword match in the upstream search index.

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Abstract

Polygonati Rhizoma, a traditional Chinese medicine, demonstrates therapeutic potential for sarcopenia, though its bioactive components and mechanisms remain unclear. Ultra-high-performance liquid chromatography-tandem mass spectrometry identified 826 compounds in Polygonati Rhizoma extract(PRE), with Genistein, Camptothecin, and Chrysoeriol highlighted as key bioactive constituents. Network pharmacology analysis revealed critical targets including EGFR, TNF, and CTNNB1, along with associated pathways such as MAPK, IL-17, and TNF signaling. Molecular docking confirmed strong binding affinities between these compounds and targets, with binding energies below -5 kcal/mol. In a D-galactose-induced sarcopenia mouse model, PRE administered at 60 and 120 mg/kg for 8 weeks improved exercise capacity, reduced muscle atrophy and fibrosis through histopathological assessments, and suppressed inflammatory markers. Mechanistic studies demonstrated that the extract enhanced EGFR phosphorylation, activated MAPK signaling, and inhibited TNF and CTNNB1-mediated fibrotic pathways. Pathway analysis further linked these effects to MAPK, IL-17, and TNF signaling cascades, underscoring their roles in mitigating inflammation and fibrosis. This study identifies Genistein, Camptothecin, and Chrysoeriol as pivotal components of Polygonati Rhizoma, acting through multi-target and multi-pathway mechanisms to alleviate sarcopenia. The findings provide a scientific foundation for its clinical application in treating muscle atrophy disorders.
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Polygonati Rhizoma reduces inflammation and improves muscle atrophy and fibrosis in sarcopenia through the EGFR/MAPK pathway | Authorea try { document.documentElement.classList.add('js'); } catch (e) { } var _gaq = _gaq || []; _gaq.push(['_setAccount', 'G-8VDV14Y67G']); _gaq.push(['_trackPageview']); (function() { var ga = document.createElement('script'); ga.type = 'text/javascript'; ga.async = true; ga.src = ('https:' == document.location.protocol ? 'https://ssl' : 'http://www') + '.google-analytics.com/ga.js'; var s = document.getElementsByTagName('script')[0]; s.parentNode.insertBefore(ga, s); })(); Skip to main content Preprints Collections Wiley Open Research IET Open Research Ecological Society of Japan All Collections About About Authorea FAQs Contact Us Quick Search anywhere Search for preprint articles, keywords, etc. Search Search ADVANCED SEARCH SCROLL This is a preprint and has not been peer reviewed. Data may be preliminary. 18 March 2025 V1 Latest version Share on Polygonati Rhizoma reduces inflammation and improves muscle atrophy and fibrosis in sarcopenia through the EGFR/MAPK pathway Authors : Zhongyuan Liu , Zining Huang , Yang Li , and Zhiwen Zhang 0000-0002-3303-9046 [email protected] Authors Info & Affiliations https://doi.org/10.22541/au.174229427.73222692/v1 186 views 126 downloads Contents Abstract Supplementary Material Information & Authors Metrics & Citations View Options References Figures Tables Media Share Abstract Polygonati Rhizoma, a traditional Chinese medicine, demonstrates therapeutic potential for sarcopenia, though its bioactive components and mechanisms remain unclear. Ultra-high-performance liquid chromatography-tandem mass spectrometry identified 826 compounds in Polygonati Rhizoma extract(PRE), with Genistein, Camptothecin, and Chrysoeriol highlighted as key bioactive constituents. Network pharmacology analysis revealed critical targets including EGFR, TNF, and CTNNB1, along with associated pathways such as MAPK, IL-17, and TNF signaling. Molecular docking confirmed strong binding affinities between these compounds and targets, with binding energies below -5 kcal/mol. In a D-galactose-induced sarcopenia mouse model, PRE administered at 60 and 120 mg/kg for 8 weeks improved exercise capacity, reduced muscle atrophy and fibrosis through histopathological assessments, and suppressed inflammatory markers. Mechanistic studies demonstrated that the extract enhanced EGFR phosphorylation, activated MAPK signaling, and inhibited TNF and CTNNB1-mediated fibrotic pathways. Pathway analysis further linked these effects to MAPK, IL-17, and TNF signaling cascades, underscoring their roles in mitigating inflammation and fibrosis. This study identifies Genistein, Camptothecin, and Chrysoeriol as pivotal components of Polygonati Rhizoma, acting through multi-target and multi-pathway mechanisms to alleviate sarcopenia. The findings provide a scientific foundation for its clinical application in treating muscle atrophy disorders. Supplementary Material File (figure 1.tif) Download 6.68 MB File (figure 2.tif) Download 17.70 MB File (figure 3.tif) Download 6.49 MB File (figure 4.tif) Download 14.76 MB File (figure 5.tif) Download 2.07 MB File (figure 6.tif) Download 34.58 MB File (figure legends.docx) Download 11.62 KB File (manuscript.docx) Download 148.75 KB File (table 1.docx) Download 96.39 KB File (table s1.docx) Download 11.80 KB File (table2.docx) Download 16.50 KB File (table3.docx) Download 22.50 KB Information & Authors Information Version history V1 Version 1 18 March 2025 Copyright This work is licensed under a Non Exclusive No Reuse License. Keywords atrophy inflammation molecular docking network pharmacology polygonati rhizoma sarcopenia Authors Affiliations Zhongyuan Liu Hubei University of Traditional Chinese Medicine View all articles by this author Zining Huang Hubei University School of Life Sciences View all articles by this author Yang Li Affiliated Hospital of Hubei University of Traditional Chinese Medicine View all articles by this author Zhiwen Zhang 0000-0002-3303-9046 [email protected] Affiliated Hospital of Hubei University of Traditional Chinese Medicine View all articles by this author Metrics & Citations Metrics Article Usage 186 views 126 downloads .FvxKWukQNSOunydq8rnd { width: 100px; } Citations Download citation Zhongyuan Liu, Zining Huang, Yang Li, et al. Polygonati Rhizoma reduces inflammation and improves muscle atrophy and fibrosis in sarcopenia through the EGFR/MAPK pathway. Authorea . 18 March 2025. DOI: https://doi.org/10.22541/au.174229427.73222692/v1 If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. Simply select your manager software from the list below and click Download. For more information or tips please see 'Downloading to a citation manager' in the Help menu . Format Please select one from the list RIS (ProCite, Reference Manager) EndNote BibTex Medlars RefWorks Direct import Tips for downloading citations document.getElementById('citMgrHelpLink').addEventListener('click', function() { popupHelp(this.href); return false; }); $(".js__slcInclude").on("change", function(e){ if ($(this).val() == 'refworks') $('#direct').prop("checked", false); $('#direct').prop("disabled", ($(this).val() == 'refworks')); }); View Options View options PDF View PDF Figures Tables Media Share Share Share article link Copy Link Copied! Copying failed. 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