Naringenin ameliorates postmenopausal osteoporosis by inhibiting BMSC oxidative stress via the PI3K/AKT/NRF2 pathway.

Authors

Yalong Zhang, Shuyan Cao, Dailuo Li, Xinxin Jing, Jialuo Zheng, Zhiyu Xu, Yanlong Wang, Wenzhe Yin

Published in

Naunyn-Schmiedeberg's archives of pharmacology. Jun 19, 2026. Epub Jun 19, 2026.

Abstract

Oxidative stress plays a critical role in the pathogenesis of various bone diseases, particularly osteoporosis. Naringenin, a small molecule compound confirmed to possess antioxidative stress properties, exerts anti-inflammatory effects in multiple diseases and can ameliorate osteoporotic symptoms. However, the precise mechanism by which Naringenin treats osteoporosis remains unclear. This study investigates the mechanism by which Naringenin inhibits oxidative stress in Bone Marrow Mesenchymal Stem Cells (BMSCs) to treat postmenopausal osteoporosis (PMOP). A mouse model of postmenopausal osteoporosis (PMOP) was established by ovariectomy (OVX). Micro-computed tomography (micro-CT) and histological staining were used to evaluate the therapeutic efficacy of naringenin against PMOP. Network pharmacology and molecular docking were applied to explore the underlying mechanism of naringenin in the treatment of PMOP. Cell counting kit-8 (CCK-8) assay, alkaline phosphatase (ALP) staining, Alizarin Red S (ARS) staining, Western blot and immunofluorescence staining were performed to investigate the effects and mechanisms of naringenin on relieving oxidative stress in bone marrow mesenchymal stem cells (BMSCs) and ameliorating PMOP. Naringenin alleviated bone loss caused by postmenopausal osteoporosis and upregulated the expression of BCL-2, RUNX2 and NRF2 in BMSCs within bone tissues. In the hydrogen peroxide (H₂O₂)-induced BMSC injury model, naringenin activated the PI3K/AKT/NRF2 signaling pathway, thereby inhibiting oxidative stress-mediated cell apoptosis and the decline in osteogenic differentiation capacity. Treatment with a PI3K/AKT inhibitor reversed these beneficial effects, confirming the specificity of this signaling pathway. Naringenin treats postmenopausal osteoporosis by inhibiting BMSC oxidative stress via the PI3K/AKT/NRF2 pathway, presenting a potential new target for osteoporosis therapy.

PMID:
42319419
Bibliographic data and abstract were imported from PubMed on 19 Jun 2026.

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