Drug-induced liver injury caused acute hepatic failure and hepatitis frequently. In this investigation, kakuol and asarinin reduced the levels of serum alanine transaminase (ALT), aspartate transaminase (AST) and malondialdehyde (MDA) dramatically, and ameliorated the pathological damage of liver tissues in APAP-induced mice. Furthermore, both compounds increased the viabilities of APAP-induced L-O2 cells and extracellular glutathione (GSH) levels accompanied significantly by reducing the level of intracellular ROS in vitro. In addition, HSP90AA1/CDK2/mTOR signaling pathway and five target proteins (CDK2, HSP90AA1, HRAS, MMP1, mTOR) were proposed from network pharmacology and molecular docking prediction, and then the up-regulation of protein expression of CDK2, mTOR and down-regulation of HSP90AA1, HRAS, MMP1 by kakuol and asarinin in western blotting supported their mechanism.
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Kakuol and asarinin protecting liver injury via HSP90AA1/CDK2/mTOR signaling pathway.
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Yunnan Characteristic Plant Extraction Laboratory, Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education, Yunnan Key Laboratory of Research and Development for Natural Products, School of Pharmacy, School of Chemical Science and Technology, Yunnan University, Kunming 650091, PR China; State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, PR China. Electronic address:
Drug-induced liver injury caused acute hepatic failure and hepatitis frequently. In this investigation, kakuol and asarinin reduced the levels of serum alanine transaminase (ALT), aspartate transaminase (AST) and malondialdehyde (MDA) dramatically, and ameliorated the pathological damage of liver tissues in APAP-induced mice. Furthermore, both compounds increased the viabilities of APAP-induced L-O2 cells and extracellular glutathione (GSH) levels accompanied significantly by reducing the level of intracellular ROS in vitro.
View Article and Find Full Text PDF[Identification based on HPLC and anti-inflammatory targets as well as related constituents analysis of Asarum heterotropoides var. mandshuricum and A. sieboldii].
Zhongguo Zhong Yao Za Zhi
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State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University Beijing 100191, China.
The present work is to establish an HPLC characteristic chromatograms of Asarum heterotropoides var. mandshuricum(AH) and A. sieboldii(AS), combined with cluster analysis for the identification of the two species, and predict their potential anti-inflammatory related targets by network pharmacological method.
View Article and Find Full Text PDFSimultaneous determination of six constituents in Mahuang Fuzi Xixin by UPLC-PDA-MS/MS.
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a School of Pharmacy, Shenyang Pharmaceutical University, 110016 Shenyang , P.R. China.
Mahuang Fuzi Xixin (MFX), a classic recipe in traditional Chinese medicine, belongs to an exterior-relieving formula. For quality control of the MFX products, qualitative analysis using ultra-high performance liquid chromatography with diode-array detector-tandem mass spectrometry (UPLC-PDA-MS/MS) was undertaken. Six compounds from the MFX were simultaneously detected.
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Chem Biodivers
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BK21 Oriental Medical Science Center, College of Oriental Medicine, Kyung Hee University, 1 Hoeki-dong, Dongdaemun-gu, Seoul 130-701, Korea.
Bioassay-guided fractionation of the root extract of Asarum sieboldii led to the isolation of the four active compounds (-)-sesamin (1), (2E,4E,8Z,10E)-N-(2-methylpropyl)dodeca-2,4,8,10-tetraenamide (2), kakuol (3), and '3,4,5-trimethoxytoluene' (=1,2,3-trimethoxy-5-methylbenzene; 4), in terms of inhibition of lipopolysaccharide (LPS)-induced nitric oxide (NO) production. Compounds 1-4 showed potent inhibition of NO production, with IC(50) values in the low nanomolar-to-micromolar range. Also isolated were the known compounds methylkakuol (5), '3,5-dimethoxytoluene', safrole, asaricin, methyleugenol, and (-)-asarinin, which were found to be inactive in the above assay.
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