中国科学院机构知识库网格
Chinese Academy of Sciences Institutional Repositories Grid
首页 机构 成果 学者
  
  1. CAS IR Grid
  2. 上海药物研究所
  3. 中国科学院上海药物研究所
Determination of the antidiabetic chemical basis of Phellodendri Chinensis Cortex by integrating hepatic disposition in vivo and hepatic gluconeogenese inhibition in vitro

文献类型：期刊论文

作者Tian, Xiaoting1,2; Xu, Zhou1,2; Hu, Pei1,2; Yu, Yanyan1,2; Li, Zhixiong1,2; Ma, Yuanjie1,2; Chen, Mingcang1,2; Sun, Zhaolin1,2; Liu, Fang1,2; Li, Jingya1,2
刊名JOURNAL OF ETHNOPHARMACOLOGY
出版日期2020-12-05
卷号263页码:10
关键词Phellodendri Chinensis cortex Hepatic disposition Pharmacokinetics Berberine Metabolites Hepatic gluconeogenesis
ISSN号0378-8741
DOI10.1016/j.jep.2020.113215
通讯作者Li, Jingya(jyli@simm.ac.cn) ; Huang, Chenggang(cghsimm@126.com)
英文摘要Ethnopharmacological relevance: Phellodendri Chinensis Cortex (PCC) has been an herb clinically used to treat diabetes, but the chemical basis of its antidiabetic effects has remained unclear. Aim of this study: Based on the efficacy of herbal medicine resulting from the cooperative response of the effective compounds in the target organs with sufficient exposure, the in vivo hepatic disposition and in vitro hepatic gluconeogenesis inhibition were integrated to elucidate the chemical basis for the antidiabetic effect of orally administered PCC from a target organ, liver, perspective. Materials and methods: With a developed and validated HPLC-MS/MS method, three alkaloids and five metabolites were determined in the portal vein plasma, liver, and systemic plasma of rats orally administered PCC. The inhibition of hepatic gluconeogenesis by the eight compounds was evaluated in primary hepatocytes. Results: The in vivo results showed that magnoflorine was present at the highest concentration among the target constituents in the plasma, where berberine showed a low concentration. In contrast, berberine showed the highest concentration in the liver, and its five metabolites exhibited substantial hepatic accumulation. This discrepancy was strongly associated with the hepatic disposition of the compounds. The hepatic disposition prevented the transfer of 96.1% of the phellodendrine, 71.1% of the berberine and 47.5% of the magnoflorine from the portal vein plasma to the systemic plasma, which corresponded to their hepatic distribution and hepatic metabolism. In vitro, berberine, M1, M4 and M5 significantly and dose-dependently inhibited hepatic glucose production. By integrating the hepatic exposure and inhibitory activity data, we estimated that berberine contributed the most (74%) to the total glucose production inhibition of the orally administered PCC decoction, followed by M4 (14%), M1 (11%) and M5 (1%). Conclusion: This study was the first to comprehensively describe the pharmacokinetic profiles and hepatic disposition of alkaloids in PCC, and concluded that berberine and its metabolites contributed the most to the total hepatic gluconeogenesis inhibition by orally administered PCC. These results reveal the chemical basis for the antidiabetic effect of orally administered PCC decoction, providing scientific evidence to support the clinical usage of PCC in diabetes treatment.
WOS关键词ALPHA-GLUCOSIDASE ; BERBERINE ; CHROMATOGRAPHY ; ALKALOIDS ; METABOLISM ; RATS ; EXTRACT ; IDENTIFICATION ; CONSTITUENTS ; AMURENSIS
资助项目National Natural Science Foundation of China[81973456] ; National Science and Technology Major Project of the Ministry of Science and Technology of China[2019ZX09201001-001-008] ; National Science and Technology Major Project of the Ministry of Science and Technology of China[2019ZX09201001-001-003] ; Shanghai Science and Technology Development Funds[18401931300] ; Innovated Youth Promotion Association of the Chinese Academy of Sciences[2019280]
WOS研究方向Plant Sciences ; Pharmacology & Pharmacy ; Integrative & Complementary Medicine
语种英语
WOS记录号WOS:000571666100002
出版者ELSEVIER IRELAND LTD
源URL[http://119.78.100.183/handle/2S10ELR8/291267]  
专题中国科学院上海药物研究所
通讯作者Li, Jingya; Huang, Chenggang
作者单位1.Chinese Acad Sci, Shanghai Inst Mat 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,Xu, Zhou,Hu, Pei,et al. Determination of the antidiabetic chemical basis of Phellodendri Chinensis Cortex by integrating hepatic disposition in vivo and hepatic gluconeogenese inhibition in vitro[J]. JOURNAL OF ETHNOPHARMACOLOGY,2020,263:10.
APA Tian, Xiaoting.,Xu, Zhou.,Hu, Pei.,Yu, Yanyan.,Li, Zhixiong.,...&Huang, Chenggang.(2020).Determination of the antidiabetic chemical basis of Phellodendri Chinensis Cortex by integrating hepatic disposition in vivo and hepatic gluconeogenese inhibition in vitro.JOURNAL OF ETHNOPHARMACOLOGY,263,10.
MLA Tian, Xiaoting,et al."Determination of the antidiabetic chemical basis of Phellodendri Chinensis Cortex by integrating hepatic disposition in vivo and hepatic gluconeogenese inhibition in vitro".JOURNAL OF ETHNOPHARMACOLOGY 263(2020):10.

入库方式： OAI收割

来源：上海药物研究所

浏览0
下载0
收藏0
其他版本

除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。