Exploration of the hepatoprotective chemical base of an orally administered herbal formulation (YCHT) in normal and CCl4-intoxicated liver injury rats. Part 2: Hepatic disposition in vivo and hepatoprotective activity in vitro

doi:10.1016/j.jep.2019.02.022

	Exploration of the hepatoprotective chemical base of an orally administered herbal formulation (YCHT) in normal and CCl4-intoxicated liver injury rats. Part 2: Hepatic disposition in vivo and hepatoprotective activity in vitro
	Tian, Xiaoting 1,2; Liu, Huan 1,2; Qiao, Shida 1,2; Yin, Hao 1,2; Chen, Mingcang 1,2; Hu, Pei 1,2; Wang, Yangyang 1,2; Peng, Huige 1,2; Liu, Fang 1,2; Pan, Guoyu 1,2
刊名	JOURNAL OF ETHNOPHARMACOLOGY
	2019-05-23
卷号	236 页码:161-172
关键词	Yin-Chen-Hao Tang Hepatic disposition Pharmacokinetics Hepatoprotection HepG2 Carbon tetrachloride
ISSN号	0378-8741
DOI	10.1016/j.jep.2019.02.022
通讯作者	Pan, Guoyu(gypan@simm.ac.cn) ; Huang, Chenggang(cghsimm@126.com)
英文摘要	Ethnopharmacological relevance: Yin-Chen-Hao Tang (YCHT) has been a very popular, hepatoprotective three-herb formula with an unclear chemical base. Aim of this study: To reveal the hepatoprotective chemical base of oral-dosed YCHT, we bridged the hepatic disposition of six compounds in vivo and their hepatoprotection in vitro. Materials and methods: In vivo, following the oral administration of YCHT in normal and CCl4-induced liver injury rats, the determinations of chlorogenic acid, 4-hydroxyacetophenone, geniposide, genipin, rhein and emodin were conducted in the portal vein plasma, the liver, and the systemic plasma. In vitro, the hepatoprotective activities of these compounds were determined in the CCl4-induced HepG2 cells. Results: Consistent with the highest content in YCHT, geniposide had the highest exposure in vivo. Inconsistent with the negligible content, rhein, 4-hydroxyacetophenone, emodin and genipin showed substantial hepatic accumulations. In contrast, chlorogenic acid, an ingredient that has a high content in YCHT, elicited no hepatic exposure. In normal rats, the hepatic disposition prevented the compounds entering into the systemic plasma from the portal vein plasma by 44.9-100%, except for rhein. CCl4-induced liver injury caused a decreased hepatic exposure of 4-hydroxyacetophenone, rhein and emodin by 50%. In vitro, all six compounds exerted the hepatoprotection by increasing cell viability, decreasing hepatic marker enzymes and inhibiting lipid peroxidation at varying levels. Conclusion Geniposide, rhein, emodin, 4-hydroxyacetophenone and genipin directly resisted liver injury in oral-dosed YCHT, while chlorogenic acid likely played an indirect role. This study proved that YCHT exerted hepatoprotection through multiple components and multiple actions. However, close attention should be paid to the possible side effects and oral dosage of YCHT in clinics.
资助项目	National Science and Technology Major Project of the Ministry of Science and Technology of China[2018ZX09731016-003] ; National Science and Technology Major Project of the Ministry of Science and Technology of China[2018ZX09201001-001-008] ; Shanghai Science and Technology Development Fund[18401931300] ; National Natural Science Foundation for Young Scientists of China[81603280]
WOS关键词	CHLOROGENIC ACID PROTECTS ; GENIPIN PROTECTS ; ALPHA-NAPHTHYLISOTHIOCYANATE ; ISCHEMIA/REPERFUSION INJURY ; RHUBARB ANTHRAQUINONES ; D-GALACTOSAMINE ; GENIPOSIDE ; ANTIOXIDANT ; HEPATOTOXICITY ; INFLAMMATION
WOS研究方向	Plant Sciences ; Pharmacology & Pharmacy ; Integrative & Complementary Medicine
语种	英语
出版者	ELSEVIER IRELAND LTD
WOS记录号	WOS:000465049300019
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/290002]
专题	中国科学院上海药物研究所
通讯作者	Pan, Guoyu; Huang, Chenggang
作者单位	1.Chinese Acad Sci, Shanghai Inst Materia Med, 501 Hai Ke Rd Zhangjiang, Shanghai 201203, Peoples R China 2.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
推荐引用方式 GB/T 7714	Tian, Xiaoting,Liu, Huan,Qiao, Shida,et al. Exploration of the hepatoprotective chemical base of an orally administered herbal formulation (YCHT) in normal and CCl4-intoxicated liver injury rats. Part 2: Hepatic disposition in vivo and hepatoprotective activity in vitro[J]. JOURNAL OF ETHNOPHARMACOLOGY,2019,236:161-172.
APA	Tian, Xiaoting.,Liu, Huan.,Qiao, Shida.,Yin, Hao.,Chen, Mingcang.,...&Huang, Chenggang.(2019).Exploration of the hepatoprotective chemical base of an orally administered herbal formulation (YCHT) in normal and CCl4-intoxicated liver injury rats. Part 2: Hepatic disposition in vivo and hepatoprotective activity in vitro.JOURNAL OF ETHNOPHARMACOLOGY,236,161-172.
MLA	Tian, Xiaoting,et al."Exploration of the hepatoprotective chemical base of an orally administered herbal formulation (YCHT) in normal and CCl4-intoxicated liver injury rats. Part 2: Hepatic disposition in vivo and hepatoprotective activity in vitro".JOURNAL OF ETHNOPHARMACOLOGY 236(2019):161-172.