Liu Qi, Zhao Hong-Wei, Zhang Ai-Hua, Sun Hui, Zhao Xiao-Hang, Nan Yang, Kong Ling, Guan Yu, Zou Shi-Yu, Ma Zhong-Hua, Wang Xi-Jun
National Traditional Chinese Medicine Key Laboratory of Serum Pharmacochemistry, Research Center of Chinmedomics, Heilongjiang University of Chinese Medicine, Harbin 150040, China.
Infinitus(China)Company Ltd., Guangzhou 510623, China.
Zhongguo Zhong Yao Za Zhi. 2016 Aug;41(15):2901-2914. doi: 10.4268/cjcmm20161526.
The chinmedomics method was used to explore the effect of Nanshi capsule on endogenous metabolites of rats with kidney-yang deficiency syndrome, investigate the metabolites and metabolic pathways closely related to kidney-yang deficiency syndrome (KYDS)and identify the therapeutic basis of Nanshi capsule(NPC)as well as its action mechanism for KYDS. The routine biochemical indexes of serum were detected and histomorphology was observed. Based on the chinmedomics technology platform, discriminatory analysis in multivariate modes was conducted for rat blood and urine, thus to investigate the biomarkers of KYDS and the therapeutic effect of NPC against KYDS. Meanwhile, the main constituents of NPC in rat serum were also detected to analyze its correlation between the constituents in vivo and the biomarkers of KYDS, and determine the potential effective compounds for therapeutic effect. Eleven biomarkers of KYDS were identified in the rat models, involving steroid hormone biosynthesis, tryptophan metabolism and tyrosine metabolism. It was found that NPC could regulate steroid hormone biosynthesis, tryptophan metabolism and tyrosine metabolism; PCMS analysis showed that caffeic acid, 2-hydroxy-1-methoxy-anthraquinone, 1-hydroxy-2-methoxyanthraquinone, ferulic acid glucuronide conjugation, deacetylasperulosidic acid, cynaroside, betaine and umbelliferone were the main effective compounds of NPC for KYDS. In this study, cynaroside, betaine, umbelliferone and other compounds in NPC could integrally regulate the disturbance of metabolic profile in KYDS by improving the hormone synthesis, hormone synthesis pathway, hormone synthesis and release pathway in tyrosine metabolism and linoleic acid synthesis pathway in linoleic acid metabolism. These results indicated that the NPC had the characteristics of multi-pathway, multi-target and overall regulation in the treatment of KYDS. Chinmedomics approach can provide methodology support to discover innovative drug from traditional Chinese medicine.
采用中药血清药物化学方法探讨南氏胶囊对肾阳虚证大鼠内源性代谢产物的影响，研究与肾阳虚证密切相关的代谢产物及代谢途径，明确南氏胶囊治疗肾阳虚证的物质基础及其作用机制。检测血清常规生化指标并观察组织形态学。基于中药血清药物化学技术平台，对大鼠血液和尿液进行多变量模式判别分析，以研究肾阳虚证生物标志物及南氏胶囊对肾阳虚证的治疗作用。同时，检测大鼠血清中南氏胶囊的主要成分，分析其体内成分与肾阳虚证生物标志物的相关性，确定其治疗作用的潜在有效化合物。在大鼠模型中鉴定出11个肾阳虚证生物标志物，涉及甾体激素生物合成、色氨酸代谢和酪氨酸代谢。发现南氏胶囊可调节甾体激素生物合成、色氨酸代谢和酪氨酸代谢；主成分分析显示，咖啡酸、2-羟基-1-甲氧基蒽醌、1-羟基-2-甲氧基蒽醌、阿魏酸葡萄糖醛酸结合物、去乙酰车叶草苷酸、毛蕊花糖苷、甜菜碱和伞形花内酯是南氏胶囊治疗肾阳虚证的主要有效化合物。本研究中，南氏胶囊中的毛蕊花糖苷、甜菜碱、伞形花内酯等化合物可通过改善酪氨酸代谢中的激素合成、激素合成途径、激素合成与释放途径以及亚油酸代谢中的亚油酸合成途径，整体调节肾阳虚证代谢谱的紊乱。这些结果表明，南氏胶囊在治疗肾阳虚证方面具有多途径、多靶点和整体调节的特点。中药血清药物化学方法可为从中药中发现创新药物提供方法学支持。
