CC BY 4.0 · Pharmaceutical Fronts 2020; 02(04): e179-e187
DOI: 10.1055/s-0041-1724032
Original Article

Determination of Tissue Distribution of Alisol G, a CB1R Antagonist, in Rats by Ultra-High-Performance Liquid Chromatography-Tandem Mass Spectrometry

Chen-Yu Gao*
1  Natural Products Pharm. Lab, National Pharmaceutical Engineering Research Center, China State Institute of Pharmaceutical Industry, Zhangjiang Hi-Tech Park, Pudong New District, Shanghai, People's Republic of China
,
Jian-Qiang Xi*
1  Natural Products Pharm. Lab, National Pharmaceutical Engineering Research Center, China State Institute of Pharmaceutical Industry, Zhangjiang Hi-Tech Park, Pudong New District, Shanghai, People's Republic of China
,
Ding-Zhong Song
1  Natural Products Pharm. Lab, National Pharmaceutical Engineering Research Center, China State Institute of Pharmaceutical Industry, Zhangjiang Hi-Tech Park, Pudong New District, Shanghai, People's Republic of China
,
Jie Yuan
1  Natural Products Pharm. Lab, National Pharmaceutical Engineering Research Center, China State Institute of Pharmaceutical Industry, Zhangjiang Hi-Tech Park, Pudong New District, Shanghai, People's Republic of China
,
Wu-Si Hao
1  Natural Products Pharm. Lab, National Pharmaceutical Engineering Research Center, China State Institute of Pharmaceutical Industry, Zhangjiang Hi-Tech Park, Pudong New District, Shanghai, People's Republic of China
,
Zhong-Bao Cui
1  Natural Products Pharm. Lab, National Pharmaceutical Engineering Research Center, China State Institute of Pharmaceutical Industry, Zhangjiang Hi-Tech Park, Pudong New District, Shanghai, People's Republic of China
,
Zhi-Hong Cheng*
1  Natural Products Pharm. Lab, National Pharmaceutical Engineering Research Center, China State Institute of Pharmaceutical Industry, Zhangjiang Hi-Tech Park, Pudong New District, Shanghai, People's Republic of China
› Author Affiliations
Funding This work was supported by China State Institute of Pharmaceutical Industry, National Pharmaceutical Engineering Research Center, Shanghai 201203, People's Republic of China.

Abstract

Peripheral CB1R blockers without crossing the blood–brain barrier (BBB) have demonstrated therapeutic benefits in metabolic syndromes, including obesity. Among them is Alisol G, a tetracyclic triterpene from Alismatis rhizoma (zexie), which can effectively reduce the weight of obese mice. Results from CP55940-induced [35S] GTPγS cannabinoid-type 1 receptor (CB1R) binding assay show an IC50 of 34.8 μmol/L for Alisol G, implicating its role as a CB1R antagonist. The purpose of our study is to assess whether Alisol G could serve as a peripheral CB1R antagonist for obesity treatment. In this study, we build a simple, reliable, and sensitive method to detect the concentration of Alisol G in rat tissue by ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). The results showed that Alisol G was mainly distributed in intestinal midgut, mucosa and small intestine, with little brain exposure. We suggested that intestine may be the main acting sites of Alisol G. Through comparison of brain and blood concentrations of Alisol G, our data showed that Alisol G cannot penetrate the BBB easily. In conclusion, Alisol G may represent a peripheral CB1R antagonist for the further treatment of obesity.

* Both authors contributed equally to this work.




Publication History

Received: 09 December 2020

Accepted: 12 January 2021

Publication Date:
19 March 2021 (online)

© 2021. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)

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