Andrographolide attenuates oxidative stress and apoptosis in osteoporosis rats via MEK/ERK and Beclin-1/ATG-5-mediated autophagy pathway.

Abstract

Objectives: To explore how andrographolide (AG) activates autophagy and reduces oxidative stress in osteoporosis.

Methods: An ovariectomized rat (OVX) model was created in vivo. Osteoblasts were obtained from rat skulls in vitro, and an oxidative stress model was induced by H2O2. Masson staining and micro-CT were utilized to assess pathological damage to bone tissue following treatment with AG, 3-MA, or silencing the ATG-5 gene. The kit detected changes in oxidative stress-related indices, flow cytometry detected apoptosis, alkaline phosphatase and Alizarin Red S staining assessed osteogenic differentiation ability, and Western blot detected changes in osteogenic differentiation-related indices and autophagy-related indices.

Key findings: AG therapy clearly reduced pathological damage and inhibited oxidative stress in OVX rats. AG also significantly boosted osteoblast viability, reduced apoptosis, and facilitated osteoblast differentiation. Furthermore, AG treatment substantially elevated the expression of Runx, OPG, BMP-2, as well as autophagy-related proteins MEK, ERK, ATG-5, Beclin-1, and LC3.

Conclusions: These findings indicate that AG possesses antioxidant and anti-osteoporosis properties, and that its mechanism may be linked to the MEK/ERK and Beclin-1/ATG-5-mediated autophagy pathways. These results establish the groundwork for the development of AG as an osteoporosis treatment, as well as new directions and therapeutic targets for the intervention of oxidative stress and autophagy-related disorders.