Investigating the molecular mechanisms of Jiangu Decoction in treating type 2 diabetic osteoporosis

Type 2 diabetic osteoporosis (T2DOP) is a metabolic bone disease characterized by impaired bone structure and decreased bone strength in diabetic patients. Jiangu Decoction (JGD), a traditional Chinese poly-herbal formulation, has shown efficacy in mitigating osteoporosis (OP) and fractures caused by osteoporosis in diabetic patients in clinical trials. In addition, JGD has been proven to promote the proliferation of osteoblasts. However, the specific mechanisms underlying these effects remain unclear.

This study aimed to elucidate the molecular mechanisms underlying the therapeutic effects of JGD in treating T2DOP.

Liquid chromatography-mass spectrometry (LC-MS) was utilized to elucidate the chemical profile of JGD. A T2DOP mouse model (C57BL/6) was established by combining a high-fat diet with streptozotocin (STZ). Micro-computed tomography (micro-CT) imaging, three-point bending tests, and histological staining were utilized to assess alterations in bone mass, bone quality, and bone strength in mice. Mouse Calvaria 3T3-E1 (MC3T3-E1) cells were treated with 33 mmol/L D-glucose (HG), and the protective effect of JGD on the high glucose injury model was observed. Western blotting and qRT-PCR were employed to analyze alterations in biomarkers associated with the Keap1/Nrf2/HO-1 signaling pathway, both in vivo and in vitro.

A total of 909 compounds were identified in JGD using LC-MS. Subsequently, the function of JGD was evaluated both in vitro and in vivo. The findings indicated that JGD promoted bone formation, enhanced bone microstructure, and ameliorated diabetic symptoms in T2DOP mice. Additionally, JGD increased alkaline phosphatase (ALP) activity, facilitated bone mineralization, and upregulated the expression levels of osteogenic marker genes such as runt-related transcription factor 2 (Runx2), osteocalcin (Ocn), and collagen type 1 alpha (Col1a1). Importantly, JGD reduced oxidative stress levels and decreased the accumulation of reactive oxygen species by modulating the Keap1/Nrf2/HO-1 axis both in vivo and in vitro.

Our study suggests that JGD could alleviate T2DOP impairment, closely linked to the Keap1/Nrf2/HO-1 signaling pathway.