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基于中药组学结合超高效液相色谱-串联质谱法探讨栀子柏皮汤治疗湿热黄疸证的靶点及有效成分

Targets and Effective Constituents of ZhiziBaipi Decoction for Treating Damp-Heat Jaundice Syndrome Based on Chinmedomics Coupled with UPLC-MS/MS.

作者信息

Wei Wen-Feng, Sun Hui, Liu Shao-Bo, Lu Sheng-Wen, Zhang Ai-Hua, Wang Wan-Ying, Chai Wen-Jun, Wu Fang-Fang, Yan Guang-Li, Guan Yu, Wang Xi-Jun

机构信息

National TCM Key Laboratory of Serum Pharmacochemistry, Metabolomics Laboratory, Department of Pharmaceutical Analysis, National Chinmedomics Research Center, Heilongjiang University of Chinese Medicine, Harbin, China.

State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Taipa, Macau SAR, China.

出版信息

Front Pharmacol. 2022 Apr 5;13:857361. doi: 10.3389/fphar.2022.857361. eCollection 2022.

Abstract

Damp-heat jaundice syndrome (DHJS) is a diagnostic model of traditional Chinese medicine (TCM) that refers to jaundice caused by damp-heat pathogen invasion. DHJS is the most common clinical manifestation of TCM, with yellow skin, yellow eyes and anorexia. ZhiziBaipi Decoction (ZBD) is a classic TCM formula that is effective at treating DHJS and various liver diseases. However, the effective components of ZBD in the context of DHJS and the underlying mechanism are unclear. This study of ZBD using the DHJS rat model aimed to elucidate the pathobiology of DHJS and the metabolic targets of therapeutic ZBD, construct the network relationship between the components of ZBD and endogenous biomarkers, and clarify the underlying mechanism of ZBD in preventing and treating DHJS. Using chinmedomics as the core strategy, an animal model was generated, and the therapeutic effect of ZBD was evaluated based on behavioral, histopathological and biochemical indicators. Metabonomics tools were used to identify biomarkers of DHJS, TCM-based serum pharmacochemistry was used to analyze the effective constituents of ZBD, and chinmedomics technology was used to identify ZBD components highly related to DHJS biomarkers. A total of 42 biomarkers were preliminarily identified, and ZBD significantly affected the levels of 29 of these biomarkers. A total of 59 compounds in ZBD were characterized . According to chinmedomics analysis, the highly correlated components found in blood were isoformononetin, 3-O-feruloylquinic acid, glycyrrhizic acid, oxyberberine, obaculactone and five metabolites. Chinmedomics combined with UPLC-MS/MS was used to study the targets and effective constituents of ZBD for the treatment of DHJS.

摘要

湿热黄疸证(DHJS)是中医的一种诊断模型,指湿热之邪侵袭所致的黄疸。湿热黄疸证是中医最常见的临床表现,可见皮肤发黄、目黄及食欲不振。栀子柏皮汤(ZBD)是治疗湿热黄疸证及多种肝脏疾病有效的经典中药方剂。然而,栀子柏皮汤在湿热黄疸证背景下的有效成分及潜在机制尚不清楚。本研究采用湿热黄疸证大鼠模型对栀子柏皮汤进行研究,旨在阐明湿热黄疸证的病理生物学及栀子柏皮汤治疗的代谢靶点,构建栀子柏皮汤成分与内源性生物标志物之间的网络关系,并阐明栀子柏皮汤防治湿热黄疸证的潜在机制。以中药组学为核心策略,建立动物模型,并根据行为学、组织病理学和生化指标评估栀子柏皮汤的治疗效果。运用代谢组学工具鉴定湿热黄疸证的生物标志物,采用基于中药的血清药物化学分析栀子柏皮汤的有效成分,运用中药组学技术鉴定与湿热黄疸证生物标志物高度相关的栀子柏皮汤成分。初步鉴定出42个生物标志物,栀子柏皮汤显著影响其中29个生物标志物的水平。鉴定出栀子柏皮汤中的59种化合物。根据中药组学分析,血液中发现的高度相关成分有异鼠李素、3 - O - 阿魏酰奎尼酸、甘草酸、氧化小檗碱、奥巴内酯及5种代谢产物。运用中药组学结合超高效液相色谱 - 串联质谱技术研究栀子柏皮汤治疗湿热黄疸证的靶点及有效成分。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7fbf/9016223/c47a7ca3ef3b/fphar-13-857361-g001.jpg

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