
Drug Design Development and Therapy, Journal Year: 2024, Volume and Issue: Volume 18, P. 6359 - 6377
Published: Dec. 1, 2024
Modified Zuo Gui Wan (MZGW) was a combination of and red yeast rice used for treating osteoporosis (OP), but its mechanism remains unclear. We aimed to validate the anti-OP effect MZGW explore underlying mechanism. An ovariectomy (OVX) rat model in vivo RANKL-induced osteoclasts (OCs) vitro were established. Key active ingredients high dose (MZGW-H) group detected by UPLC-MS/MS. Micro-CT scans histomorphology analysis performed OVX rats. 16S rRNA gene sequencing investigate relationship between MZGW-H intestinal flora. CCK-8 assay applied examine optimal concentration drug serum (MZGW-DS) on osteoclasts. The qRT-PCR Western blotting utilized potential pathway MZGW, namely SCFA-GPR41-p38MAPK signaling pathway. GPR41 knocked down further reverse verify whether key MZGW-DS exert inhibitory three main blood components, Ferulic acid, L-Ascorbic acid Riboflavin, examined mainly showed that changed metabolism SCFAs. In studies verified ameliorated microstructure damage, improved histological changes reduced TRAP, BALP, BGP rats regulating revealed 5% most inhibit osteoclast differentiation. vitro, better than peripheral SCFAs inhibiting After knockout GPR41, could not expression osteoclast-related protein (CTSK NFATc1) via effectively ameliorates OVX-induced partially achieved increasing modulating
Language: Английский