Integrated lipidomics and network pharmacology analysis to determine how Gu Fu Sheng Capsule improves lipid metabolism in rats with steroid-induced osteonecrosis of the femoral head.

BACKGROUND: Steroid-induced osteonecrosis of the femoral head (SONFH) is a prevalent refractory condition in orthopedics, often causing high disability rates. Gu Fu Sheng Capsule (GFSC) is commonly used to treat SONFH during the early and intermediate stages. However, the precise underlying mechanism of action of GFSC remains elusive. OBJECTIVE: To elucidate the mechanism through which GFSC improves lipid metabolism in rats with SONFH. METHODS: A rat model of SONFH was established by administering methylprednisolone and lipopolysaccharide. Micro-computed tomography assessed femoral head effects, while hematoxylin-eosin staining examined femoral head tissues. Pathological changes were evaluated using an automated biochemical analyzer to measure changes in serum lipid levels. Besides, quantitative lipidomics and network pharmacology were used to determine how GFSC impacts SONFH. qRT-PCR and Western blotting were performed to assess mRNA and protein expression levels of key targets. RESULTS: GFSC can enhance bone density and prevents surface collapse of the femoral head, improve hollow bone lacuna density, reduce adipocyte infiltration, minimize osteocyte cavities, regulate the serum lipid levels and enhance lipid metabolism in SONFH rats. Moreover, integrated lipidomics and network pharmacology suggested that GFSC affects lipid metabolism-related genes by regulating nine targets, thereby influencing four metabolites and two metabolic pathways, which may mainly be due to components in GFSC such as quercetin, tanshinone iia, berberine. Western blotting and qRT-PCR data highlighted that GFSC improves lipid metabolism by regulating TP53, HSP90AA1, and ESR1. CONCLUSION: GFSC effectively retards SONFH progression, potentially attributed to its ability to regulate lipid metabolism.