Hubei University of Chinese Medicine

Yishen Qianggu Mixture (YSQGM) is a clinical empirical formula derived from Traditional Chinese Medicine (TCM) theory of "benefiting the kidney and strengthening bones," traditionally used to treat postmenopausal osteoporosis (PMOP) associated with kidney yang deficiency. Preliminary studies have shown that YSQGM improves bone mineral density (BMD), yet its integration of traditional efficacy with modern anti-inflammatory and bone metabolism-regulating mechanisms remains unclear.

To elucidate YSQGM's anti-inflammatory effects and mechanisms on PMOP, with emphasis on verifying its inflammation-regulating role via multi-omics analysis and experimental validation.

An ovariectomy (OVX)-induced PMOP model was established in 36 Sprague-Dawley (SD) rats randomly assigned to six groups. Rats received YSQGM or alendronate by gavage for 8 weeks. BMD and trabecular microarchitecture were assessed by micro-computed tomography (Micro-CT), while serum bone turnover markers and inflammatory cytokines were measured by ELISA. Untargeted metabolomics and network pharmacology were integrated to identify differential metabolites and construct protein-protein interaction networks. Key targets were further examined by molecular docking, molecular dynamics (MD) simulations, and in vivo/in vitro validation.

Medium and high doses of YSQGM significantly increased BMD, concomitantly decreased markers of bone formation and bone resorption, and ameliorated high-turnover PMOP. Untargeted metabolomics identified 46 differential metabolites and pinpointed ISL as a key anti-inflammatory constituent, with enriched pathways including triglyceride metabolism and the pentose phosphate pathway. Molecular docking and MD simulations predicted high affinity of ISL for PTGS2, MAPK14, GSK3B, and c-Fos. In vivo and in vitro experiments confirmed that YSQGM dose-dependently downregulated the expression of inflammation-related proteins (PTGS2, MAPK14, GSK3B, c-Fos, JNK, ERK, and NF-κB p65) and reduced osteoclast activity.

YSQGM ameliorates bone metabolic imbalance in PMOP by suppressing proinflammatory mediators in the IL-17/NF-κB/MAPK signaling axis, providing novel mechanistic evidence for the use of TCM in PMOP prevention and treatment.

Decabromodiphenyl ethane (DBDPE), a novel brominated flame retardant, has been widely detected in various environmental media and exhibits significant bioaccumulation potential. This study first analyzed the distribution characteristics of DBDPE in zebrafish tissues using a toxicokinetic model. The results revealed that DBDPE preferentially accumulated in the brain, with the concentration order being brain > liver > gonads, indicating a potential neurotoxic risk. Further research demonstrated that zebrafish chronically exposed to environmentally relevant concentrations of DBDPE exhibited abnormal social behaviors. Molecular analysis indicated that this neurobehavioral toxicity may be related to the disruption of neurotransmitter homeostasis and the upregulation of gene expression in the central nervous system induced by DBDPE. Notably, female zebrafish were found to be more sensitive to the neurotoxic effects of DBDPE. These findings not only clarify the tissue-specific accumulation characteristics of DBDPE but also reveal its sex-dependent neurotoxic differences, thereby providing important scientific evidence for the ecological risk assessment of this pollutant.