ArticleDrug design, development and therapy2024
Modified Zuo Gui Wan Ameliorates Ovariectomy-Induced Osteoporosis in Rats by Regulating the SCFA-GPR41-p38MAPK Signaling Pathway.
Article in Drug design, development and therapy, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed.
- Postbiotics as Emerging Therapeutics for Allergic Diseases: A Novel Approach Beyond Live Biologics.Probiotics and antimicrobial proteins · 2026Review
- Gut-bone axis crosstalk: Microbiota-driven immune-metabolic-neural networks in bone disorders and precision interventions.Journal of orthopaedic translation · 2026Review
- Targeting the gut‑bone axis through exercise: A novel approach to osteoporosis prevention and treatment (Review).International journal of molecular medicine · 2026Review
- The role of gut microbiota in osteoporosis: underlying mechanisms, clinical associations, and emerging biomaterials.Frontiers in immunology · 2026Review
- The Mediating Role of Bioactive Molecules in Gut Microbiota-Bone Metabolism Crosstalk.Nutrients · 2025Review
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Authors and funding
12 authors.
Funding
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Abstract
Objective: Modified Zuo Gui Wan (MZGW) was a combination of Zuo Gui Wan and red yeast rice used for treating osteoporosis (OP), but its mechanism remains unclear. We aimed to validate the anti-OP effect of MZGW and explore its underlying mechanism. Methods: An ovariectomy (OVX) rat model in vivo and a RANKL-induced osteoclasts (OCs) model in vitro were established. Key active ingredients in MZGW high dose (MZGW-H) group were detected by UPLC-MS/MS. Micro-CT scans and histomorphology analysis were performed in OVX rats. 16S rRNA gene sequencing was performed to investigate the relationship between the anti-OP effect of MZGW-H and intestinal flora. CCK-8 assay was applied to examine the optimal concentration of Modified Zuo Gui Wan drug serum (MZGW-DS) on osteoclasts. The qRT-PCR and Western blotting were utilized to explore the potential anti-OP pathway of MZGW, namely the SCFA-GPR41-p38MAPK signaling pathway. GPR41 was knocked down to further reverse to verify whether the pathway was the key pathway for MZGW-DS to exert its inhibitory effect on osteoclasts. Results: The three main blood components, Ferulic acid, L-Ascorbic acid and Riboflavin, were examined mainly by UPLC-MS/MS. 16S rRNA gene sequencing showed that MZGW-H changed the metabolism of SCFAs. In vivo studies verified that MZGW-H ameliorated microstructure damage, improved histological changes and reduced TRAP, BALP, and BGP in OVX rats by regulating the SCFA-GPR41-p38MAPK signaling pathway. CCK-8 revealed that 5% MZGW-DS group was the most optimal concentration of MZGW-DS to inhibit osteoclast differentiation. In vitro, MZGW-DS was better than peripheral blood concentration of SCFAs in inhibiting osteoclasts. After the knockout of GPR41, MZGW-DS could not inhibit the expression of osteoclast-related protein (CTSK and NFATc1) via SCFA-GPR41-p38MAPK signaling pathway. Conclusion: MZGW-H effectively ameliorates OVX-induced osteoporosis partially achieved by increasing SCFAs metabolism and modulating the SCFA-GPR41-p38MAPK signaling pathway.
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