中国临床药理学杂志

靶向代谢组学整合网络药理学研究栀子的“自解毒”效应及机制

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吕东霞 ^1a , 张帆 ^1a^,² , 高昕 ^1a , 张航星 ^1a , 王国旭 ² , 饶志 ² , 魏玉辉 ^1a^,^b^,²

中国临床药理学杂志 | 临床与基础桥接研究 2025,41(17): 2496-2502

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中国临床药理学杂志 |临床与基础桥接研究 2025 , 41 (17) : 2496 -2502

靶向代谢组学整合网络药理学研究栀子的“自解毒”效应及机制

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吕东霞^1a, 张帆^1a^,², 高昕^1a, 张航星^1a, 王国旭², 饶志², 魏玉辉^1a^,^b^,²

作者信息

^1a.兰州大学，第一临床医学院，甘肃兰州 730000

^1b.兰州大学，药学院，甘肃兰州 730000

^2.兰州大学第一医院，甘肃兰州 730000

通讯作者:

魏玉辉，教授，主任药师，博士生导师 Tel: （0931） 8356510 E-mail: yhwei@lzu.edu.cn

作者简介:

吕东霞（1999-），女，硕士研究生，主要从事中药肝损伤方面的临床工作和研究

Research of targeted metabolomics integrated network pharmacology on the "self-detoxification" effect and mechanism of Gardenia jasminoides Ellis

Dong-xia LÜ^1a, Fan ZHANG^1a^,², Xin GAO^1a, Hang-xing ZHANG^1a, Guo-xu WANG², Zhi RAO², Yu-hui WEI^1a^,^b^,²

Affiliations

^1a.The First School of Clinical Medicine, Lanzhou University, Lanzhou 730000, Gansu Province, China

^1b.School of Pharmacy, Lanzhou University, Lanzhou 730000, Gansu Province, China

^2.The First Hospital of Lanzhou University, Lanzhou 730000, Gansu Province, China

出版时间: 2025-09-17 doi: 10.13699/j.cnki.1001-6821.2025.17.017

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摘要

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目的

通过靶向代谢组学整合网络药理学研究栀子缓解其自身成分京尼平所致肝毒性的效应，即“自解毒”效应，并探讨其机制。

方法

将昆明种雄性小鼠随机分为3组（n=8），分别为空白组、对照组和实验组。空白组灌胃给予0.5%羧甲基纤维素钠（CMC-Na）空白溶剂，对照组灌胃给于100 mg·kg^-1·d^-1京尼平，实验组灌胃给于100 mg·kg^-1·d^-1的京尼平和520 mg·kg^-1·d^-1的栀子水提物粉末。连续给药28 d后，用全自动生化分析仪检测血清生化指标，用苏木精伊红（HE）染色法进行肝组织病理学检测，用超高效液相色谱-串联质谱系统（UPLC-MS/MS）法定量分析差异代谢物并进行靶向代谢组学分析，并分别预测栀子活性化合物、京尼平和肝损伤相关的靶点。最后，整合代谢组学和网络药理学的结果筛选出栀子自解毒效应相关的潜在靶点。

结果

实验组、对照组和空白组的谷丙转氨酶（ALT）分别为（35.75±8.50）、（53.00±14.43）和（37.38±3.11）U·L^-1；谷草转氨酶（AST）分别为（123.38±31.40）、（146.50±19.73）和（115.75±17.44）U·L^-1；实验组的ALT与对照组比较显著降低，在统计学上差异有统计学意义（P<0.05），试验组的AST与对照组比较，在统计学上差异无统计学意义（P>0.05）。靶向代谢组学共筛选出8种特征性内源性代谢物，分别是延胡索酸、异柠檬酸、马来酸、鸟氨酸、氨基己二酸、异石胆酸、哌啶酸和吡咯-2-羧酸，这8种差异代谢物诱导的代谢途径主要与精氨酸生物合成和三羧酸循环（TCA）代谢途径相关。

结论

栀子主要通过影响精氨酸生物合成和TCA代谢途径，改善京尼平所致肝脏内源性代谢物的代谢紊乱，并作用于相应靶点改善炎症和氧化应激，缓解京尼平导致的肝损伤，发挥自解毒效应。

关键词

栀子 / 京尼平 / 自解毒 / 肝毒性 / 靶向代谢组学

Abstract

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Objective

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.

Methods

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.

Results

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.

Conclusion

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.

Key words

Gardenia jasminoides Ellis / genipin / self-detoxification / hepatotoxicity / targeted metabolomics

引用本文

吕东霞, 张帆, 高昕, 张航星, 王国旭, 饶志, 魏玉辉. 靶向代谢组学整合网络药理学研究栀子的“自解毒”效应及机制. 中国临床药理学杂志, 2025 , 41 (17) : 2496 -2502 . DOI: 10.13699/j.cnki.1001-6821.2025.17.017

Dong-xia LÜ, Fan ZHANG, Xin GAO, Hang-xing ZHANG, Guo-xu WANG, Zhi RAO, Yu-hui WEI. Research of targeted metabolomics integrated network pharmacology on the "self-detoxification" effect and mechanism of Gardenia jasminoides Ellis[J]. Chinese Journal of Clinical Pharmacology, 2025 , 41 (17) : 2496 -2502 . DOI: 10.13699/j.cnki.1001-6821.2025.17.017

基金

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国家自然科学基金资助项目(82174067)
兰州大学2024年大学生创新创业推荐基金资助项目(202210730179)

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2025年第41卷第17期

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文章信息

doi: 10.13699/j.cnki.1001-6821.2025.17.017

接收时间：2025-07-15
首发时间：2026-08-05
出版时间：2025-09-17

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出版历史

收稿日期：2025-07-15

基金

国家自然科学基金资助项目(82174067)

兰州大学2024年大学生创新创业推荐基金资助项目(202210730179)

作者信息

^1a.兰州大学，第一临床医学院，甘肃兰州 730000

^1b.兰州大学，药学院，甘肃兰州 730000

^2.兰州大学第一医院，甘肃兰州 730000

通讯作者:

魏玉辉，教授，主任药师，博士生导师 Tel: （0931） 8356510 E-mail: yhwei@lzu.edu.cn

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https://castjournals.cast.org.cn/joweb/zglcylxzz/CN/10.13699/j.cnki.1001-6821.2025.17.017

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2种不同金属材料的力学参数

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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