International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Ministry of Education (MOE) of China, Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, Institute of Traditional Chinese Medicine & Natural Products, College of Pharmacy, Jinan University, Guangzhou, 510632, China; Guangzhou Key Laboratory of Formula-Pattern of Traditional Chinese Medicine, School of Traditional Chinese Medicine, Jinan University, Guangzhou, 510632, China.
International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Ministry of Education (MOE) of China, Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, Institute of Traditional Chinese Medicine & Natural Products, College of Pharmacy, Jinan University, Guangzhou, 510632, China.
J Ethnopharmacol. 2023 Oct 5;314:116605. doi: 10.1016/j.jep.2023.116605. Epub 2023 May 11.
Bu-Zhong-Yi-Qi-Tang is a famous traditional Chinese medicine formula that has been prevalent in China for over 700 years to treat spleen-qi deficiency related diseases, such as gastrointestinal and respiratory disorders. However, the bioactive components responsible for regulating spleen-qi deficiency remain unclear and have puzzled many researchers.
The current study focuses on efficacy evaluation of regulating spleen-qi deficiency and screening the bioactive components of Bu-Zhong-Yi-Qi-Tang.
The effects of Bu-Zhong-Yi-Qi-Tang were evaluated through blood routine examination, immune organ index, and biochemical analysis. Metabolomics was utilized to analyze the potential endogenous biomarkers (endobiotics) in the plasma, and the prototypes (xenobiotics) of Bu-Zhong-Yi-Qi-Tang in the bio-samples were characterized using ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry. Then, these endobiotics were used as "bait" to predict targets based on network pharmacology and to screen potential bioactive components from the absorbed prototypes in the plasma by constructing an "endobiotics-targets-xenobiotics" association network. Further, the anti-inflammatory activities of representative compounds (calycosin and nobiletin) were validated through poly(I:C)-induced pulmonary inflammation mice model.
Bu-Zhong-Yi-Qi-Tang exhibited immunomodulatory and anti-inflammatory activities in spleen-qi deficiency rat, as supported by the observation of increased levels of D-xylose and gastrin in serum, an increase in the thymus index and number of lymphocytes in blood, as well as a reduction in the level of IL-6 in bronchoalveolar lavage fluid. Furthermore, plasma metabolomic analysis revealed a total of 36 Bu-Zhong-Yi-Qi-Tang related endobiotics, which were mainly enriched in primary bile acids biosynthesis, the metabolism of linoleic acid, and the metabolism of phenylalanine pathways. Meanwhile, 95 xenobiotics were characterized in plasma, urine, small intestinal contents, and tissues of spleen-qi deficiency rat after Bu-Zhong-Yi-Qi-Tang treatment. Using an integrated association network, six potential bioactive components of Bu-Zhong-Yi-Qi-Tang were screened. Among them, calycosin was found to significantly reduce the levels of IL-6 and TNF-α in the bronchoalveolar lavage fluid, increase the number of lymphocytes, while nobiletin dramatically decreased the levels of CXCL10, TNF-α, GM-CSF, and IL-6.
Our study proposed an available strategy for screening bioactive components of BYZQT regulating spleen-qi deficiency based on "endobiotics-targets-xenobiotics" association network.
补中益气汤是一种著名的中药方剂，在中国已有 700 多年的历史，用于治疗脾胃气虚相关疾病，如胃肠道和呼吸道疾病。然而，负责调节脾胃气虚的生物活性成分仍不清楚，这让许多研究人员感到困惑。
本研究旨在评估补中益气汤调节脾胃气虚的功效，并筛选其生物活性成分。
通过血常规检查、免疫器官指数和生化分析评估补中益气汤的作用。利用代谢组学分析血浆中的潜在内源性生物标志物（内源性生物），并采用超高效液相色谱-四极杆飞行时间串联质谱法对生物样品中的补中益气汤原型（外源性生物）进行特征分析。然后，将这些内源性生物作为“诱饵”，基于网络药理学预测靶点，并通过构建“内源性生物-靶点-外源性生物”关联网络，筛选血浆中吸收原型的潜在生物活性成分。此外，通过聚（I：C）诱导的肺炎症小鼠模型验证代表性化合物（毛蕊异黄酮和川陈皮素）的抗炎活性。
补中益气汤在脾气虚大鼠中表现出免疫调节和抗炎活性，这一点得到了血清中 D-木糖和胃泌素水平升高、胸腺指数和血液中淋巴细胞数量增加以及支气管肺泡灌洗液中 IL-6 水平降低的支持。此外，血浆代谢组学分析共发现 36 种与补中益气汤相关的内源性生物，主要富集在初级胆汁酸生物合成、亚油酸代谢和苯丙氨酸代谢途径中。同时，在给予补中益气汤治疗后，脾气虚大鼠的血浆、尿液、小肠内容物和组织中鉴定出 95 种外源性生物。通过整合关联网络，筛选出 6 种补中益气汤的潜在生物活性成分。其中，毛蕊异黄酮可显著降低支气管肺泡灌洗液中 IL-6 和 TNF-α的水平，增加淋巴细胞数量，而川陈皮素则显著降低 CXCL10、TNF-α、GM-CSF 和 IL-6 的水平。
本研究提出了一种基于“内源性生物-靶点-外源性生物”关联网络筛选补中益气汤调节脾胃气虚的生物活性成分的有效策略。
