Li Yongxian, Yuan Jinbo, Deng Wei, Li Haishan, Lin Yuewei, Yang Jiamin, Chen Kai, Qiu Heng, Wang Ziyi, Kuek Vincent, Wang Dongping, Zhang Zhen, Mai Bin, Shao Yang, Kang Pan, Qin Qiuli, Li Jinglan, Guo Huizhi, Ma Yanhuai, Guo Danqing, Mo Guoye, Fang Yijing, Tan Renxiang, Zhan Chenguang, Liu Teng, Gu Guoning, Yuan Kai, Tang Yongchao, Liang De, Xu Liangliang, Xu Jiake, Zhang Shuncong
The First Clinical Academy, Guangzhou University of Chinese Medicine, Guangzhou 510405, China; The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510407, China; Lingnan Medical Research Center of Guangzhou University of Chinese Medicine, Guangzhou 510405, China; School of Biomedical Sciences, University of Western Australia, Western Australia 6102, Australia.
School of Biomedical Sciences, University of Western Australia, Western Australia 6102, Australia.
Chin J Nat Med. 2025 Jan;23(1):90-101. doi: 10.1016/S1875-5364(25)60810-7.
Osteoporosis is a prevalent skeletal condition characterized by reduced bone mass and strength, leading to increased fragility. Buqi-Tongluo (BQTL) decoction, a traditional Chinese medicine (TCM) prescription, has yet to be fully evaluated for its potential in treating bone diseases such as osteoporosis. To investigate the mechanism by which BQTL decoction inhibits osteoclast differentiation in vitro and validate these findings through in vivo experiments. We employed MTS assays to assess the potential proliferative or toxic effects of BQTL on bone marrow macrophages (BMMs) at various concentrations. TRAcP experiments were conducted to examine BQTL's impact on osteoclast differentiation. RT-PCR and Western blot analyses were utilized to evaluate the relative expression levels of osteoclast-specific genes and proteins under BQTL stimulation. Finally, in vivo experiments were performed using an osteoporosis model to further validate the in vitro findings. This study revealed that BQTL suppressed receptor activator of NF-κB ligand (RANKL)-induced osteoclastogenesis and osteoclast resorption activity in vitro in a dose-dependent manner without observable cytotoxicity. The inhibitory effects of BQTL on osteoclast formation and function were attributed to the downregulation of NFATc1 and c-fos activity, primarily through attenuation of the MAPK, NF-κB, and Calcineurin signaling pathways. BQTL's inhibitory capacity was further examined in vivo using an ovariectomized (OVX) rat model, demonstrating a strong protective effect against bone loss. BQTL may serve as an effective therapeutic TCM for the treatment of postmenopausal osteoporosis and the alleviation of bone loss induced by estrogen deficiency and related conditions.
骨质疏松症是一种常见的骨骼疾病，其特征是骨量和骨强度降低，导致骨骼脆性增加。补气血通络（BQTL）汤是一种中药方剂，其治疗骨质疏松症等骨骼疾病的潜力尚未得到充分评估。本研究旨在探讨BQTL汤在体外抑制破骨细胞分化的机制，并通过体内实验验证这些发现。我们采用MTS法评估不同浓度的BQTL对骨髓巨噬细胞（BMMs）的潜在增殖或毒性作用。通过抗酒石酸酸性磷酸酶（TRAcP）实验检测BQTL对破骨细胞分化的影响。利用逆转录-聚合酶链反应（RT-PCR）和蛋白质免疫印迹法（Western blot）分析BQTL刺激下破骨细胞特异性基因和蛋白质的相对表达水平。最后，使用骨质疏松症模型进行体内实验，进一步验证体外实验结果。本研究表明，BQTL在体外以剂量依赖的方式抑制核因子κB受体活化因子配体（RANKL）诱导的破骨细胞生成和破骨细胞吸收活性，且无明显细胞毒性。BQTL对破骨细胞形成和功能的抑制作用归因于活化T细胞核因子c1（NFATc1）和原癌基因c-fos活性的下调，主要是通过丝裂原活化蛋白激酶（MAPK）、核因子κB（NF-κB）和钙调神经磷酸酶信号通路的减弱。使用去卵巢（OVX）大鼠模型在体内进一步检测BQTL的抑制能力，结果表明其对骨质流失具有强大的保护作用。BQTL可能是一种有效的中药疗法，用于治疗绝经后骨质疏松症以及缓解雌激素缺乏和相关疾病引起的骨质流失。
