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To investigate the effect of Gardenia jasminoides Ellis (Zhi-zi) in alleviating the hepatotoxicity induced by its constituent, genipin, which is called the "self-detoxification" effect, and to explore its mechanism through targeted metabolomics and integrated network pharmacology.
Male mice of the Kunming breed were randomly divided into three groups (n=8) including blank group, control group and experimental group. Blank group was administered a blank solvent 0.5% carboxymethyl cellulose (CMC-Na) by gavage; control group was administered genipin by gavage at a dose of 100 mg·kg-1·d-1, and experimental group was administered 100 mg·kg-1·d-1 genipin and 520 mg·kg-1·d-1 Zhi-zi aqueous extract powder by gavage. After 28 days of continuous administration, serum biochemical indicators were measured using an automated biochemical analyzer, liver tissue pathology was examined using hematoxylin and eosin (HE) staining, and differential metabolites were quantified and analyzed using ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) for targeted metabolomics analysis. The targets associated with active compounds in Zhi-zi, genipin, and liver damage were predicted separately. Finally, the results of metabolomics and network pharmacology were integrated to screen the potential targets related to the self-detoxification effect of Zhi-zi.
The alanine transaminase (ALT) levels in experimental group, control group and blank group were (35.75±8.50), (53.00±14.43) and (37.38±3.11) U·L-1, respectively; the aspartate transaminase (AST) levels were (123.38±31.40), (146.50±19.73) and (115.75±17.44) U·L-1, respectively. Compared with control group, experimental group showed significant decrease in ALT levels, with statistically significant difference (P<0.05). Compared with control group, the AST levels in experimental group showed no statistically significant difference (P>0.05). Targeted metabolomics identified 8 characteristic endogenous metabolites including fumaric acid, isocitric acid, maleic acid, ornithine, aminocaproic acid, isoLCA, pipecolic acid and pyrrole-2-carboxylic acid, and the metabolic pathways induced by these 8 differentially expressed metabolites were primarily associated with arginine biosynthesis and the tricarboxylic acidcycle (TCA) metabolic pathways.
Zhi-zi can improve the metabolic disorders of endogenous metabolites in the liver caused by genipin by affecting the arginine biosynthesis and the TCA metabolic pathway, and improve inflammation and oxidative stress by acting on the corresponding targets to alleviate the hepatic injuries caused by genipin and exerting the self-detoxification effect.
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| 科 Family | 属数 Number of genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) | 属 Genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) |
|---|---|---|---|---|---|---|
| 鹅膏菌科Amanitaceae | 2 | 11 | 5.26 | 鹅膏菌属 Amanita | 10 | 4.78 |
| 小菇科 Mycenaceae | 2 | 12 | 5.74 | 丝盖伞属 Inocybe | 5 | 2.39 |
| 多孔菌科 Polyporaceae | 8 | 14 | 6.70 | 蜡蘑属 Laccaria | 5 | 2.39 |
| 红菇科 Russulaceae | 3 | 23 | 11.00 | 小皮伞属 Marasmius | 6 | 2.87 |
| 小菇属 Mycena | 11 | 5.26 | ||||
| 光柄菇属 Pluteus | 5 | 2.39 | ||||
| 红菇属 Russula | 17 | 8.13 | ||||
| 栓菌属 Trametes | 5 | 2.39 |
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