Buqi-Tongluo Decoction inhibits osteoclastogenesis and alleviates bone loss in ovariectomized rats by attenuating NFATc1, MAPK, NF-κB signaling.

Yongxian LI; Jinbo YUAN; Wei DENG; Haishan LI; Yuewei LIN; Jiamin YANG; Kai CHEN; Heng QIU; Ziyi WANG; Vincent KUEK; Dongping WANG; Zhen ZHANG; Bin MAI; Yang SHAO; Pan KANG; Qiuli QIN; Jinglan LI; Huizhi GUO; Yanhuai MA; Danqing GUO; Guoye MO; Yijing FANG; Renxiang TAN; Chenguang ZHAN; Teng LIU; Guoning GU; Kai YUAN; Yongchao TANG; De LIANG; Liangliang XU; Jiake XU; Shuncong ZHANG

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Buqi-Tongluo Decoction inhibits osteoclastogenesis and alleviates bone loss in ovariectomized rats by attenuating NFATc1, MAPK, NF-κB signaling.

Author: Yongxian LI ¹ ; Jinbo YUAN ² ; Wei DENG ³ ; Haishan LI ³ ; Yuewei LIN ³ ; Jiamin YANG ³ ; Kai CHEN ² ; Heng QIU ² ; Ziyi WANG ² ; Vincent KUEK ⁴ ; Dongping WANG ³ ; Zhen ZHANG ³ ; Bin MAI ³ ; Yang SHAO ³ ; Pan KANG ³ ; Qiuli QIN ³ ; Jinglan LI ³ ; Huizhi GUO ³ ; Yanhuai MA ³ ; Danqing GUO ⁵ ; Guoye MO ⁶ ; Yijing FANG ⁷ ; Renxiang TAN ⁸ ; Chenguang ZHAN ³ ; Teng LIU ³ ; Guoning GU ³ ; Kai YUAN ⁶ ; Yongchao TANG ⁶ ; De LIANG ⁶ ; Liangliang XU ⁹ ; Jiake XU ¹⁰ ; Shuncong ZHANG ^{11
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Author Information

1. 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.
2. School of Biomedical Sciences, University of Western Australia, Western Australia 6102, Australia.
3. 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.
4. School of Biomedical Sciences, University of Western Australia, Western Australia 6102, Australia; Curtin Medical School, Curtin University, Western Australia 6102, Australia.
5. Foshan Hospital of Traditional Chinese Medicine, Foshan 528000, China.
6. 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.
7. The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510407, China; School of Public Health and Management, Guangzhou University of Chinese Medicine, Guangzhou 510405, China.
8. The State Key Laboratory of Pharmaceutical Biotechnology, Institute of Functional Biomolecules, Nanjing University, Nanjing 210008, China.
9. 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. Electronic address: xull-2016@gzucm.edu.cn.
10. School of Biomedical Sciences, University of Western Australia, Western Australia 6102, Australia. Electronic address: jiake.xu@uwa.edu.au.
11. 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. Electronic address: spinezsc@
12. com.
Publication Type:Journal Article
Keywords: Buqi-Tongluo; Estrogen deficiency; MAPK; NF-κB; NFATc1; Osteoclast; Osteoporosis
MeSH: Animals; NFATC Transcription Factors/genetics*; Drugs, Chinese Herbal/pharmacology*; Ovariectomy; Osteoclasts/metabolism*; Female; Osteogenesis/drug effects*; Rats, Sprague-Dawley; Rats; NF-kappa B/genetics*; Osteoporosis/genetics*; Signal Transduction/drug effects*; Bone Resorption/genetics*; Cell Differentiation/drug effects*; Humans; RANK Ligand/metabolism*; Mitogen-Activated Protein Kinases/genetics*; Transcription Factors
From: Chinese Journal of Natural Medicines (English Ed.) 2025;23(1):90-101
CountryChina
Language:English
Abstract: 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.