College of Pharmacy and International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Chinese Ministry of Education, Jinan University, Guangzhou 510632, PR China.
State Key Laboratory of Chinese Medicine and Molecular Pharmacology (Incubation), The Hong Kong Polytechnic University Shenzhen Research Institute, Shenzhen 518057, PR China.
J Chromatogr B Analyt Technol Biomed Life Sci. 2021 Jun 30;1176:122771. doi: 10.1016/j.jchromb.2021.122771. Epub 2021 May 18.
Xian-Ling-Gu-Bao capsule (XLGB) has been proven to prevent and treat osteoporosis. However, as a long-term oral formula, XLGB's effects on the metabolic capacity, structure and function of gut microbiota have yet to be elucidated in ovariectomized (OVX) rats. Our objectives were to evaluate the capacity of gut microbiota for metabolizing XLGB ingredients and to assess the effect of this prescription on gut microbiota. Herein, an integrated analysis that combined ultrahigh-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) and ultrahigh-performance liquid chromatography tandem triple quadrupole mass spectrometry (UPLC-TQD-MS) was conducted to determine the metabolic capacity of gut microbiota. The effects of XLGB on gut microbiota were explored by metagenomic sequencing in OVX rats. Fecal samples from each group were collected after intragastric administration for three months. In total, 64 biotransformation products were fully characterized with rat gut microbiota from the OVX group and the XLGB group. The deglycosylation reaction was the main biotransformation pathway in core structures in the group that was incubated with XLGB. Compared with the OVX group, different biotransformation products and pathways of the XLGB group after incubation for 2 h and 8 h were described. After three months of feeding with XLGB, the domesticated gut microbiota was conducive to the production of active absorbed components via deglycosylation, such as icaritin, psoralen and isopsoralen. Comparisons of the gut microbiota of the OVX and XLGB groups showed differences in the relative abundances of the two dominant bacterial divisions, namely, Firmicutes and Bacteroidetes. The proportion of Firmicutes was significantly lower and that of Bacteroidetes was significantly higher in the XLGB group. This result demonstrated that XLGB could provide a basis for the treatment of osteoporosis by regulating lipid and bile acid metabolism. In addition, the increase in Lactobacillus, Bacteroides and Prevotella could be an important factor that led to easier production of active absorbed aglycones in the XLGB group. Our observation provided further evidence of the importance of gut microbiota in the metabolism and potential activity of XLGB.
仙灵骨葆胶囊（XLGB）已被证明可预防和治疗骨质疏松症。然而，作为一种长期口服配方，其对去卵巢（OVX）大鼠肠道微生物群的代谢能力、结构和功能的影响尚未阐明。我们的目标是评估肠道微生物群代谢 XLGB 成分的能力，并评估该处方对肠道微生物群的影响。在此，我们采用超高效液相色谱与四级杆飞行时间质谱联用（UPLC-Q-TOF-MS）和超高效液相色谱串联三重四极杆质谱联用（UPLC-TQD-MS）的综合分析方法来确定肠道微生物群的代谢能力。通过 OVX 大鼠的宏基因组测序来研究 XLGB 对肠道微生物群的影响。每组大鼠经灌胃给药 3 个月后收集粪便样本。共对 OVX 组和 XLGB 组大鼠肠道微生物群的 64 种生物转化产物进行了全面表征。与 OVX 组相比，孵育 2 h 和 8 h 后，XLGB 组的不同生物转化产物和途径得到了描述。经过 3 个月的 XLGB 喂养，驯化的肠道微生物群有利于通过去糖基化产生具有活性的吸收成分，如淫羊藿苷、补骨脂素和异补骨脂素。OVX 组和 XLGB 组肠道微生物群的比较显示，两个主要细菌分区的相对丰度存在差异，即厚壁菌门和拟杆菌门。XLGB 组的厚壁菌门比例显著降低，拟杆菌门比例显著升高。这一结果表明，XLGB 可以通过调节脂质和胆汁酸代谢为骨质疏松症的治疗提供依据。此外，乳杆菌、拟杆菌和普雷沃氏菌的增加可能是 XLGB 组更容易产生具有活性的吸收苷元的重要因素。我们的观察结果进一步证明了肠道微生物群在 XLGB 代谢和潜在活性中的重要性。
