Metabolic Profiling Analysis of the Effect and Mechanism of Gushiling Capsule in Rabbits With Glucocorticoid-Induced Osteonecrosis of the Femoral Head

Abstract

Gushiling capsule (GSLC) is an effective traditional Chinese medicine for the treatment of glucocorticoid-induced osteonecrosis of the femoral head (GIONFH). This study established the serum metabolite profiles of GSLC in rabbits and explored the metabolic mechanism and effect of GSLC on GIONFH. Seventy-five Japanese white rabbits were randomly divided into the control, model, and GSLC groups. The rabbits in the model group and the GSLC group received injection of prednisolone acetate. Meanwhile, rabbits in the GSLC group were treated by gavage at a therapeutic dose of GSLC once a day. The control group and the model group received the same volume of normal saline gavage. Three groups of serum samples were collected at different time points, and the changes in the metabolic spectrum were analyzed by ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The resulting data set was analyzed using multivariate statistical analysis to identify potential biomarkers related to GSLC treatment. The metabolic pathway was analyzed by MetaboAnalyst 4.0 and a heatmap was constructed using the HEML1.0.3.7 software package. In addition, histopathological and radiography studies were carried out to verify the anti-GIONFH effects of GSLC. Principal component analysis (PCA) and partial least squares-discriminant analysis (PLS-DA) score plots revealed a significant separation trend between the control group and the model group and the GSLC group (1–3 weeks), but there were no significant differences in the GSLC group (4–6 weeks). Orthogonal PLS-DA (OPLS-DA) score plots also revealed an obvious difference between the model and the GSLC groups (4–6 weeks). Ten potential metabolite biomarkers, mainly phospholipids, were identified in rabbit serum samples and demonstrated to be associated with GIONFH. Hematoxylin and eosin staining and magnetic resonance imaging indicated that the pathological changes in femoral head necrosis in the GSLC group were less than in the model group, which was consistent with the improved serum metabolite spectrum. GSLC regulated the metabolic disorder of endogenous lipid components in GIONFH rabbits. GSLC may prevent and treat GIONFH mainly by regulating phospholipid metabolism in vivo.

Altered gut microbe metabolites in patients with alcohol‑induced osteonecrosis of the femoral head: An integrated omics analysis

“…In addition, it was reported that glycerophospholipids were distinguished in the bone trabecula and plasma of patients with ONFH compared with those in healthy controls, most glycerophospholipids were upregulated in patients with ONFH ( 59 , 60 ). Mei et al ( 61 ) previously reported that glycerophospholipid metabolism was the metabolic pathway that was the most significantly altered in rabbits with SONFH, suggesting it to be a potential pathway for the targeted intervention against SONFH. In the future, the detailed mechanism of how glycerophospholipid metabolism impacts AONFH requires further study.…”

Network-Based Pharmacological Study on the Mechanism of Guishao-Liujun Decoction in the Treatment of Gastric Cancer

“…Its effect could be the overall effect of a set of effective components comprising numerous chemical components or the effect of its metabolites once they enter the body. As a result, it is unscientific to equate effective components, targets, and pathways with diseases, and it is vital to evaluate the holistic view of traditional Chinese medicine and the metabolic process in vivo from a clinical standpoint ( Chen et al, 2022 ; Mei et al, 2022 ). 4) When existing network pharmacology analyzes the action targets of pharmaceutical ingredients, it can only predict using energy matching and compound geometric characteristics matching, but not the combined action type of the two, such as the target’s activation or inactivation state, the drug’s agonist or antagonist, and so on.…”

Screening and identification of potential key biomarkers for glucocorticoid-induced osteonecrosis of the femoral head

“…In the fight against Severe Acute Respiratory Syndrome (SARS) in 2003, glucocorticoids were used at high doses to save a large number of critically ill patients. Unfortunately, these steroid hormones also had side effects—the incidence of GIONFH was as high as 24–30% [ 9 – 11 ]. As for the novel coronavirus disease 2019 (COVID-19) epidemic, which is similar to SARS, steroid hormone is still an important medication for the treatment of infections to rescue lives, who will also be at risk of developing GIONFH in the future[ 12 – 14 ].…”