Cytotoxicity evaluation and metabolism of hepatotoxicity components of Euodiae Fructus in L02 cells

Zhang, Wei; Ren, Kun; Wu, Shuangfeng; Guo, Jingyan; Ren, Shumeng; Pan, Yingni; Wang, Dongmei; Morikawa, Toshio; Hua, Hui‐Ming; Liu, Xiaoqiu

doi:10.1016/j.jchromb.2021.123040

Cited by 4 publications

(3 citation statements)

References 24 publications

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“…The Chinese Pharmacopoeia notes that Euodia rutaecarpa is a small toxic traditional Chinese medicine, and there have been reports of adverse reactions caused by improper use of Euodia rutaecarpa in clinical practice [24] . Although previous studies have investigated the chemical composition and pharmacological activity of Euodia rutaecarpa, there are still disagreements regarding its toxic components and target organs.…”

Section: Discussionmentioning

confidence: 99%

Elucidating the mechanism of hepatotoxicity in Euodia rutaecarpa: insights from QSAR toxicity prediction and metabolomics

Yang,

Lai,

et al. 2024

Acupuncture and Herbal Medicine

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Background: Euodia rutaecarpa, a Chinese medicine clinically used to treat gastrointestinal disorders, has been widely employed. However, Euodia rutaecarpa is regarded as a small toxic traditional Chinese medicine in the Chinese Pharmacopoeia and other herbal works. Using toxicity predictions combined with in vitro and in vivo studies, this study aimed to identify the toxic components and toxic target organs of Euodia rutaecarpa, and explore its toxic mechanism from a metabolic perspective. Method: The toxic target organs of Euodia rutaecarpa were identified through in vitro and in vivo studies. In vitro toxicity screening was performed by alkaloid enrichment and isolation. The potential toxicity of compounds was predicted by ADMET Predictor (Absorption, Distribution, Metabolism, Excretion, and Toxicity Predictor) based on QSAR (Quantitative Structure - Activity Relationship) construction. In addition, the study integrated the serum metabolomic analysis after the administration of potentially toxic components to clarify the effect of potentially toxic substances on metabolism in mice. Result: Comparing the acute toxicity in mice of different extraction methods and before and after processing, it was evident that Euodia rutaecarpa alcoholic extract had the highest toxicity, and the target organ of Euodia rutaecarpa toxicity was the liver. The alkaloid fraction of alcoholic extract of Euodia showed strong cytotoxicity. The potential toxicity of Euodia rutaecarpa was calculated and predicted by ADMET Predictor, and alkaloids are suspected to be responsible for the toxicity of Euodia rutaecarpa. Evodiamine significantly reduced the number of cells and increased the mitochondrial membrane potential in vitro. Different metabolites were significantly identified by serum metabolomics, of which bile acid metabolism and steroid hormone biosynthesis are the key pathways of hepatotoxicity. Conclusion: Clarify the scientific significance of clinical use of processed products by comparing the acute toxicity of different extraction methods before and after processing. Combining the toxicity prediction based on QSAR with the toxicity screening in vitro and in vivo, the potential toxic target organs and toxic components of Euodia rutaecarpa can be identified. Through metabolomics, we preliminarily revealed that the hepatotoxicity of Euodia rutaecarpa may be related to bile acid metabolism and steroid hormone biosynthesis. This study lays the foundation for elucidating the mechanism of Euodia rutaecarpa and evaluating its safety and quality.

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Section: Discussionmentioning

confidence: 99%

Elucidating the mechanism of hepatotoxicity in Euodia rutaecarpa: insights from QSAR toxicity prediction and metabolomics

Yang,

Lai,

et al. 2024

Acupuncture and Herbal Medicine

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“…After 1 h, β-EA was present in plasma, heart, liver, spleen, lung, kidney, jejunum, colon, and ileum, following a concentration trend: jejunum > ileum > colon > liver > kidney > lung > heart > spleen. The peak concentration was found in 4 h for most tissues, except in jejunum and colon wherein the concentration levels peaked at 1 h and 8 h respectively [113].…”

Section: Production Of No In Inflammation Inflammatory Markers and It...mentioning

confidence: 92%

“…The carrageenan-induced edema generated an increase in PGE2 levels, and β-EA significantly decreased PGE2 levels in a dose-dependent manner [112] (Table 1). Following these studies, a pharmacokinetic, and tissue distribution analysis measured β-EA in plasma and tissues in a rat model after oral administration of 85 mg/kg β-EA [113]. After 1 h, β-EA was present in plasma, heart, liver, spleen, lung, kidney, jejunum, colon, and ileum, following a concentration trend: jejunum > ileum > colon > liver > kidney > lung > heart > spleen.…”

Section: Production Of No In Inflammation Inflammatory Markers and It...mentioning

confidence: 99%

The Complexity of Sesquiterpene Chemistry Dictates Its Pleiotropic Biologic Effects on Inflammation

et al. 2022

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Sesquiterpenes (SQs) are volatile compounds made by plants, insects, and marine organisms. SQ have a large range of biological properties and are potent inhibitors and modulators of inflammation, targeting specific components of the nuclear factor-kappaB (NF-κB) signaling pathway and nitric oxide (NO) generation. Because SQs can be isolated from over 1600 genera and 2500 species grown worldwide, they are an attractive source of phytochemical therapeutics. The chemical structure and biosynthesis of SQs is complex, and the SQ scaffold represents extraordinary structural variety consisting of both acyclic and cyclic (mono, bi, tri, and tetracyclic) compounds. These structures can be decorated with a diverse range of functional groups and substituents, generating many stereospecific configurations. In this review, the effect of SQs on inflammation will be discussed in the context of their complex chemistry. Because inflammation is a multifactorial process, we focus on specific aspects of inflammation: the inhibition of NF-kB signaling, disruption of NO production and modulation of dendritic cells, mast cells, and monocytes. Although the molecular targets of SQs are varied, we discuss how these pathways may mediate the effects of SQs on inflammation.

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The attenuation effect of licorice on the hepatotoxicity of Euodiae Fructus by inhibiting the formation of protein conjugates and GSH depletion

Ren

Zhang

Liu

et al. 2023

Journal of Ethnopharmacology

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Cytotoxicity evaluation and metabolism of hepatotoxicity components of Euodiae Fructus in L02 cells

Cited by 4 publications

References 24 publications

Elucidating the mechanism of hepatotoxicity in Euodia rutaecarpa: insights from QSAR toxicity prediction and metabolomics

Elucidating the mechanism of hepatotoxicity in Euodia rutaecarpa: insights from QSAR toxicity prediction and metabolomics

The Complexity of Sesquiterpene Chemistry Dictates Its Pleiotropic Biologic Effects on Inflammation

The attenuation effect of licorice on the hepatotoxicity of Euodiae Fructus by inhibiting the formation of protein conjugates and GSH depletion

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