Wei Qianyi, Zhou Yongrong, Hu Zhengtao, Shi Ye, Ning Qing, Ren Keyun, Guo Xinyu, Zhong Ronglin, Xia Zhi, Yin Yinghao, Hu Yongxin, Wei Yingjie, Shi Ziqi
Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210028, China; The Third Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, 210023, China.
Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210028, China; State Key Laboratory of Oral Drug Delivery Systems of Chinese Materia Medica, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, 210028, China; The Third Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, 210023, China.
J Ethnopharmacol. 2024 Jul 15;329:118130. doi: 10.1016/j.jep.2024.118130. Epub 2024 Mar 31.
Psoraleae Fructus (Bu Gu Zhi) is the fruit of Psoralea corylifolia L. (PCL) and has been used for centuries in traditional Chinese medicine formulas to treat osteoporosis (OP). A new drug called "BX" has been developed from PCL, but its mechanism for treating OP is not yet fully understood.
To explore the mechanism of action of BX in the treatment of ovariectomy-induced OP based function-oriented multi-omics analysis of gut microbiota (GM) and metabolites.
C57BL/6 mice were bilaterally ovariectomized to replicate the OP model. The therapeutic efficacy of BX was evaluated by bone parameters (BMD, BV/TV, Tb.N, Tb.Sp), hematoxylin and eosin (H&E) staining results, and determination of bone formation markers procollagen type Ⅰ amino-terminal peptide (PⅠNP) and bone-specific alkaline phosphatase (BALP). Serum and fecal metabolomics and high-throughput 16S rDNA sequencing were performed to evaluate effects on endogenous metabolites and GM. In addition, an enzyme-based functional correlation algorithm (EBFC) algorithm was used to investigate functional correlations between GM and metabolites.
BX improved OP in OVX mice by increasing BMD, BV/TV, serum PⅠNP, BALP, and improving Tb.N and Tb.Sp. A total of 59 differential metabolites were identified, and 9 metabolic pathways, including arachidonic acid metabolism, glycerophospholipid metabolism, purine metabolism, and tryptophan metabolism, were found to be involved in the progression of OP. EBFC analysis results revealed that the enzymes related to purine and tryptophan metabolism, which are from Lachnospiraceae_NK4A136_group, Blautia, Rs-E47_termite_group, UCG-009, and Clostridia_UCG-014, were identified as the intrinsic link between GM and metabolites.
The regulation of GM and restoration of metabolic disorders may be the mechanisms of action of BX in alleviating OP. This research provides insights into the function-oriented mechanism discovery of traditional Chinese medicine in the treatment of OP.
补骨脂是补骨脂（PCL）的果实，在中药配方中用于治疗骨质疏松症（OP）已有数百年历史。一种名为“BX”的新药已从补骨脂中研发出来，但其治疗OP的机制尚未完全明确。
基于肠道微生物群（GM）和代谢物的功能导向多组学分析，探索BX治疗去卵巢诱导的OP的作用机制。
对C57BL/6小鼠进行双侧卵巢切除以复制OP模型。通过骨参数（骨密度、骨体积分数、骨小梁数量、骨小梁间距）、苏木精-伊红（H&E）染色结果以及骨形成标志物Ⅰ型前胶原氨基端肽（PⅠNP）和骨特异性碱性磷酸酶（BALP）的测定来评估BX的治疗效果。进行血清和粪便代谢组学以及高通量16S rDNA测序以评估对内源性代谢物和GM的影响。此外，使用基于酶的功能相关算法（EBFC）算法研究GM与代谢物之间的功能相关性。
BX通过增加骨密度、骨体积分数、血清PⅠNP、BALP以及改善骨小梁数量和骨小梁间距改善了去卵巢小鼠的OP。共鉴定出59种差异代谢物，发现包括花生四烯酸代谢、甘油磷脂代谢、嘌呤代谢和色氨酸代谢在内的9条代谢途径与OP的进展有关。EBFC分析结果显示，来自毛螺菌科_NK4A136_组、布劳特氏菌属、Rs-E47_白蚁组、UCG-009和梭菌属_UCG-014的与嘌呤和色氨酸代谢相关的酶被确定为GM与代谢物之间的内在联系。
GM的调节和代谢紊乱的恢复可能是BX缓解OP的作用机制。本研究为中药治疗OP的功能导向机制发现提供了见解。
