Hepatotoxicity induced by radix Sophorae tonkinensis in mice and increased serum cholinesterase as a potential supplemental biomarker for liver injury

Wang, Liping; Lu, Jinyao; Sun, Wei; Gu, Yingmin; Zhang, Chaochao; Ruo-min, Jin; Li, Lingyong; Zhang, Zean; Tian, Xue

doi:10.1016/j.etp.2017.01.003

Cited by 26 publications

(15 citation statements)

References 26 publications

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“…2D). These histopathological results are consistent with our previous study on radix S. tonkinensis -induced hepatotoxicity (5).…”

Section: Resultssupporting

confidence: 93%

“…A total of 44 male C57BL/6 mice used in this study were randomly divided into four experimental groups, with 11 mice/group. In a previous study by our group, moderate centrilobular hypertrophy was observed in the mice treated with 2.5 g/kg radix S. tonkinensis extracts, in which the calculated contents of OMT and MT were 40.5 and 69.1 mg/kg, respectively (5). Therefore, these were used as the working dosages in the current study.…”

Section: Methodsmentioning

confidence: 87%

“…However, it has been reported in clinical settings that liver function is abnormal, as evidenced by an increase in the levels of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bilirubin (TBil), after treatment with this herb (4). A recent study by our group revealed that single and repeated oral administration with extracts of radix S. tonkinensis may induce hepatotoxicity and even mortality in mice in a dose-dependent manner (5).…”

Section: Introductionmentioning

confidence: 99%

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Oxymatrine and its metabolite matrine contribute to the hepatotoxicity induced by radix Sophorae�tonkinensis in mice

Sun

et al. 2019

Exp Ther Med

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Previous studies by our group demonstrated that radix Sophorae tonkinensis could induce hepatotoxicity. However, it remains unclear which components of this herb may be responsible for its hepatotoxicity. The present study aimed to investigate the hepatic toxicity of treatment with matrine (MT) and oxymatrine (OMT) alone or simultaneously. Furthermore, the current study aimed to identify whether the hepatotoxicity induced by OMT is actually the toxic characterization of its metabolite MT. Hepatotoxicity was evaluated by biochemical and histopathological approaches in subchronic toxicity in mice, as well as via evaluation of cytotoxicity and enzyme leakage in AML12 liver cells. The results indicated that treatment of mice with OMT and MT individually or simultaneously resulted in centrilobular hypertrophy in the liver at doses equivalent to that contained in radix S. tonkinensis at a hepatotoxic dose, suggesting that MT and OMT are likely hepatotoxic components of this herb. OMT-induced hepatotoxicity may be primarily exerted via its metabolite MT in mice. Furthermore, OMT combined with MT was observed to be more toxic compared with OMT or MT alone. These results extend our understanding of the hepatotoxicity of radix S. tonkinensis and its active ingredients.

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“…2D). These histopathological results are consistent with our previous study on radix S. tonkinensis -induced hepatotoxicity (5).…”

Section: Resultssupporting

confidence: 93%

Section: Methodsmentioning

confidence: 87%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Oxymatrine and its metabolite matrine contribute to the hepatotoxicity induced by radix Sophorae�tonkinensis in mice

Sun

et al. 2019

Exp Ther Med

Self Cite

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“…Through in vivo experiments, the toxicity and target organs of Radix Sophorae tonkinensis extracts in ICR mice were studied, and the toxicities of its major bioactive components were compared. In these studies, administration of MT at doses of 118 and 154 mg/kg/day for 21 days produced major toxicity in the liver ( Wang L. et al., 2017 ). In human normal liver HL-7702 cells, MT at doses of 2.5-5 mg/mL for 24 h, increased the contents of ALT, AST, ALP, LDH, and MDA, promoted the induction of cell apoptosis, and decreased the level of GSH ( Zhang Q. et al., 2011 ).…”

Section: Toxicologymentioning

confidence: 99%

A Systematic Review of the Pharmacology, Toxicology and Pharmacokinetics of Matrine

You

Yang

et al. 2020

Front. Pharmacol.

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Matrine (MT) is a naturally occurring alkaloid and an bioactive component of Chinese herbs, such as Sophora flavescens and Radix Sophorae tonkinensis. Emerging evidence suggests that MT possesses anti-cancer, anti-inflammatory, anti-oxidant, antiviral, antimicrobial, anti-fibrotic, anti-allergic, antinociceptive, hepatoprotective, cardioprotective, and neuroprotective properties. These pharmacological properties form the foundation for its application in the treatment of various diseases, such as multiple types of cancers, hepatitis, skin diseases, allergic asthma, diabetic cardiomyopathy, pain, Alzheimer's disease (AD), Parkinson's disease (PD), and central nervous system (CNS) inflammation. However, an increasing number of published studies indicate that MT has serious adverse effects, the most obvious being liver toxicity and neurotoxicity, which are major factors limiting its clinical use. Pharmacokinetic studies have shown that MT has low oral bioavailability and short half-life in vivo. This review summarizes the latest advances in research on the pharmacology, toxicology, and pharmacokinetics of MT, with a focus on its biological properties and mechanism of action. The review provides insight into the future of research on traditional Chinese medicine.

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“…Separation was performed on a C8 column with a mobile phase containing acetonitrile, water, and formic acid. Cytisine, matrine, and oxymatrine in radix Sophorae tonkinensis extracts were determined simultaneously on a C18 column with a mobile phase containing acetonitrile, water, and phosphoric acid [ 15 ]. Thirteen plant alkaloids including cytisine in a human specimen such as serum or urine were determined on a C18 column with a mobile phase containing acetonitrile and phosphate buffer at pH 6.5 [ 16 ].…”

Section: Introductionmentioning

confidence: 99%

Determination of Cytisine and N-Methylcytisine from Selected Plant Extracts by High-Performance Liquid Chromatography and Comparison of Their Cytotoxic Activity

Petruczynik

Wróblewski

Misiurek

et al. 2020

Toxins

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Quinolizidine alkaloids exhibit various forms of biological activity. A lot of them were found in the Leguminosae family, including Laburnum and Genista. The aim of the study was the optimization of a chromatographic system for the analysis of cytisine and N-methylcytisine in various plant extracts as well as an investigation of the cytotoxic activities of selected alkaloids and plant extracts obtained from Laburnum anagyroides, Laburnum anagyroides L. quercifolium, Laburnum alpinum, Laburnum watereri, Genista germanica, and Genista tinctoria against various cancer cell lines. The determination of investigated compounds was performed by High Performance Liquid Chromatography with Diode Array Detection (HPLC-DAD), while High Performance Liquid Chromatography coupled with Quadrupole Time-of-Flight–Mass Spectrometry (HPLC-QTOF-MS) was applied for the qualitative analysis of plant extracts. The retention, separation selectivity, peaks shape, and systems efficiency obtained for cytisine and N-methylcytisine in different chromatographic systems were compared. The application of columns with alkylbonded and phenyl stationary phases led to a very weak retention of cytisine and N-methylcytisine, even when the mobile phases containing only 5% of organic modifiers were used. The strongest retention was observed when hydrophilic interaction chromatography (HILIC) or especially when ion exchange chromatography (IEC) were applied. The most optimal system in terms of alkaloid retention, peak shape, and system efficiency containing an strong cation exchange (SCX) stationary phase and a mobile phase consisted of 25% acetonitrile and formic buffer at pH 4.0 was applied for investigating alkaloids analysis in plant extracts. Cytotoxic properties of the investigated plant extracts as well as cytisine and N-methylcytisine were examined using human tongue squamous carcinoma cells (SCC-25), human pharyngeal squamous carcinoma cells (FaDu), human triple-negative breast adenocarcinoma cell line (MDA-MB-231), and human breast adenocarcinoma cell line (MCF-7). The highest cytotoxic activity against FaDu, MCF-7, and MDA-MB cancer cell lines was observed after applying the Genista germanica leaves extract. In contrast, the highest cytotoxic activity against SCC-25 cell line was obtained after treating with the seed extract of Laburnum watereri. The investigated plant extracts exhibit significant cytotoxicity against the tested human cancer cell lines and seem to be promising for further research on its anticancer activity.

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Hepatotoxicity induced by radix Sophorae tonkinensis in mice and increased serum cholinesterase as a potential supplemental biomarker for liver injury

Cited by 26 publications

References 26 publications

Oxymatrine and its metabolite matrine contribute to the hepatotoxicity induced by radix Sophorae�tonkinensis in mice

Oxymatrine and its metabolite matrine contribute to the hepatotoxicity induced by radix Sophorae�tonkinensis in mice

A Systematic Review of the Pharmacology, Toxicology and Pharmacokinetics of Matrine

Determination of Cytisine and N-Methylcytisine from Selected Plant Extracts by High-Performance Liquid Chromatography and Comparison of Their Cytotoxic Activity

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