Combined Therapy of Yishen Zhuanggu Decoction and Caltrate D600 Alleviates Postmenopausal Osteoporosis by Targeting FoxO3a and Activating the Wnt/β-Catenin Pathway

Abstract

Background. Postmenopausal osteoporosis (PMO) is the most prevalent metabolic bone disease in women. Yishen Zhuanggu (YSZG) decoction and Caltrate D600 reportedly affects bone formation. This study aimed to investigate the efficacy and mechanism of YSZG decoction combined with Caltrate D600 in PMO treatment. Methods. Ovariectomy-induced PMO rat model was treated with YSZG or/and Caltrate D600 for 12 weeks. Femur bone mineral density (BMD), osteoporosis-related protein expression, and serum parameters were measured. Pathological features of femur bone tissues were observed using hematoxylin and eosin staining. Serum levels of oxidative stress parameters were measured using corresponding commercial kits. The mRNA and protein expression of FoxO3a, Wnt, and β-catenin was detected using qRT-PCR and western blotting. Results. The BMD and ultimate load of PMO rats were increased after treatment with YSZG. YSZG treatment promoted the bone trabeculae formation of PMO rats. YSZG treatment also induced bone differentiation and suppress oxidative stress in PMO rats, evidenced by the increased BALP, Runx2, OPG, SOD, and CAT levels, as well as the decreased TRACP 5b, RANKL, ROS, and MDA levels. Additionally, YSZG treatment downregulated the FoxO3a expression and upregulated the levels of Wnt and β-catenin in PMO rats. Caltrate D600 addition showed an auxiliary effect for YSZG. Conclusion. YSZG decoction exerts the antiosteoporotic effect on PMO by restraining the FoxO3a expression and activating the Wnt/β-catenin pathway, which has an impressive synergistic effect with Caltrate D600.

Anti-inflammatory and antioxidant traditional Chinese Medicine in treatment and prevention of osteoporosis

“…New Chinese medicine formulations including BuShenHuoXue capsules, Jianpi Qingchang Bushen decoction, Yishen Bugu Ye, Yunnan Baiyao, and Zhuanggu Zhitong capsules reduce inflammatory bone loss by directly regulating the level of pro-inflammatory factors or indirectly influencing the level of autophagy, thereby regulating the expression of inflammatory factors ( Yangyang L. et al, 2020 ; Jia-Cheng et al, 2020 ; Xiaobin et al, 2020 ; Ya-Li et al, 2022 ; Zhitao et al, 2022 ). Moreover, Gushudan, Fufang Lurong Jiangu capsules, and Yishen Zhuanggu decoction rely on their antioxidant effect to relieve cells suffering from oxidative stress and thus prevent the occurrence of osteoporosis ( Shuo et al, 2020 ; Wenqi et al, 2020 ; Bole et al, 2022 ).…”