Exploring the material basis of genipin-induced hepatotoxicity in vitro
10.16438/j.0513-4870.2023-0131
- VernacularTitle:京尼平所致肝细胞毒性的物质基础研究
- Author:
Fan ZHANG
1
;
Dong-xia LV
2
;
Yu-song DONG
2
;
Jia-qi QIN
3
;
Guo-xu WANG
3
;
Yang LUO
2
;
Zhi RAO
1
;
Yu-hui WEI
1
Author Information
1. The First Hospital of Lanzhou University, Lanzhou 730000, China
2. The 1st School of Clinical Medicine, Lanzhou University, Lanzhou 730000, China
3. School of Pharmacy, Lanzhou University, Lanzhou 730000, China
- Publication Type:Research Article
- Keywords:
genipin;
open-ring tautomer;
gardenia blue;
hepatotoxicity;
material basis
- From:
Acta Pharmaceutica Sinica
2023;58(10):3032-3039
- CountryChina
- Language:Chinese
-
Abstract:
The current study explored the hepatotoxicity among closed-ring genipin, open-ring tautomer of genipin and gardenia blue that generated from genipin and amino acid reaction using HepaRG cells to identify the material basis of genipin-induced hepatotoxicity in vitro. The effects of temperature, pH value and different kinds of amino acids on the chemical structure tautomerism between closed-ring and open-ring tautomer of genipin and the production of gardenia blue were investigated firstly, which aimed to explicit the conditions that could distinguish the closed-ring genipin and its open-ring tautomer, and the conditions generating gardenia blue, which were applied to prepare different kinds of gardenia blue; the CCK-8 kit was employed to analyze the hepatotoxicity of closed-ring genipin, open-ring tautomer of genipin and gardenia blue. From the results, it was found that, the structure transformation from close-ring to open-ring of genipin could be inhibited under the condition with acid environment; being essential groups to generate gardenia blue, the primary amino group and the open-ring tautomer of genipin reacting to generate the dihydropyridine ring was probably the key structure of gardenia blue; the structure characteristics existed apparent distinction at the reactive temperature of 37 ℃ and 80 ℃; compared to the culture condition with pH = 7.4, the concentration of genipin with close-ring in culture medium was significantly increased at pH = 5, but the cell viability did not decreased; the cell toxicity of gardenia blue was apparently lower than open-ring tautomer of genipin, and even some kinds of gardenia blue showed growth promoting effect on HepaRG cells. Here, it was suggested potentially that open-ring tautomer of genipin be the important material basis to induce hepatotoxicity, which could provide a cue and lay a foundation for the elucidation of the underlying mechanism of genipin-induced hepatotoxicity.
