Isatidis Folium alleviates acetaminophen‐induced liver injury in mice by enhancing the endogenous antioxidant system

Ding, Chengyuan; Zhu, He

doi:10.1002/tox.22990

Cited by 11 publications

(6 citation statements)

References 39 publications

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“…Globally, acute APAP overdose is considered a major cause of drug‐induced hepatotoxicity and acute hepatic failure; however, the underlying pathophysiology remains poorly understood. The advantages of natural products, such as fewer side effects, low cytotoxicity, and substantial changes in bioactivity, have drawn considerable attention 22–24 . As one of the main active components of citrus fruits, naringin possesses several pharmacological effects, including antioxidant, antiinflammatory, and antiapoptotic properties 25,26 .…”

Section: Discussionmentioning

confidence: 99%

“…natural products, such as fewer side effects, low cytotoxicity, and substantial changes in bioactivity, have drawn considerable attention. [22][23][24] As one of the main active components of citrus fruits, naringin possesses several pharmacological effects, including antioxidant, antiinflammatory, and antiapoptotic properties. 25,26 Previous studies have shown that naringin can exert hepatoprotective effects.…”

Section: Naringin Increases Hepatic Nrf2 Expressionmentioning

confidence: 99%

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Naringin alleviates acetaminophen‐induced acute liver injury by activating Nrf2 via CHAC2 upregulation

Zhai

Dai

Chi

et al. 2022

Environmental Toxicology

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Severe acetaminophen (APAP)-induced hepatic damage is the second most common cause for hepatic transplantation. Clinically, hepatic damage caused by APAP is treated using N-acetyl-L-cysteine, which can induce numerous side effects. Naringin, a bioflavonoid abundant in grapefruit and other citrus fruits, displays marked antiinflammatory and antioxidant activities. Herein, we aimed to investigate the potential mechanism underlying naringin-mediated protection against APAP-induced acute hepatotoxicity. We observed that naringin afforded protection against APAPinduced acute liver failure in mice. Importantly, pretreatment with naringin before APAP administration further increased antioxidant enzyme expression, inhibited the production of proinflammatory cytokines, and activated apoptotic pathways. Furthermore, we observed that the protective effect was associated with the upregulation of cation transport regulator-like protein 2 (CHAC2) and nuclear factor erythroid derived-2-related factor 2 (Nrf2). Notably, CHAC2 knockdown inhibited Nrf2 activation and naringin-mediated antioxidant, antiinflammatory, and antiapoptotic effects in APAP-induced liver injury. Likewise, si-Nrf2 blocked the protective effect of naringin against APAP-induced liver injury. Collectively, our results indicate that naringin may be a potent CHAC2 activator, alleviating APAP-induced hepatitis via CHAC2-mediated activation of the Nrf2 pathway. These data provide new insights into mechanisms through which CHAC2 regulates APAP-induced liver injury by targeting Nrf2, which should be considered a novel therapeutic target.

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Section: Discussionmentioning

confidence: 99%

Section: Naringin Increases Hepatic Nrf2 Expressionmentioning

confidence: 99%

Naringin alleviates acetaminophen‐induced acute liver injury by activating Nrf2 via CHAC2 upregulation

Zhai

Dai

Chi

et al. 2022

Environmental Toxicology

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“…Paracetamol (acetaminophen) is a commonly used drug in clinic, which is mainly used for cold-induced fever, headache, joint pain, neuralgia, migraine, dysmenorrhea, and so on. Lycium Barbarum extract can significantly improve paracetamol-induced apoptosis to protect the liver from chemical damage ( Gündüz et al, 2015 ), and Isatidis Folium can enhance the endogenous antioxidant system and reduce paracetamol-induced liver damage in mice ( Ding and Zhu, 2020 ). Ahmed et al also found that Panax ginseng could be used as a hepatoprotective agent, which prevented cyclophosphamide (with immunosuppressive and anti-cancer potential)-induced liver injury by reducing the expression of TNF-α, IL-1β and Caspase3 genes, as well as increasing the BCL-2 gene expression, and its liver-protective effect is better than vitamin E ( Abdelfattah-Hassan et al, 2019 ).…”

Section: Characteristics Of Several Important Liver Diseasesmentioning

confidence: 99%

The Potential Application of Chinese Medicine in Liver Diseases: A New Opportunity

Wang

et al. 2021

Front. Pharmacol.

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Liver diseases have been a common challenge for people all over the world, which threatens the quality of life and safety of hundreds of millions of patients. China is a major country with liver diseases. Metabolic associated fatty liver disease, hepatitis B virus and alcoholic liver disease are the three most common liver diseases in our country, and the number of patients with liver cancer is increasing. Therefore, finding effective drugs to treat liver disease has become an urgent task. Chinese medicine (CM) has the advantages of low cost, high safety, and various biological activities, which is an important factor for the prevention and treatment of liver diseases. This review systematically summarizes the potential of CM in the treatment of liver diseases, showing that CM can alleviate liver diseases by regulating lipid metabolism, bile acid metabolism, immune function, and gut microbiota, as well as exerting anti-liver injury, anti-oxidation, and anti-hepatitis virus effects. Among them, Keap1/Nrf2, TGF-β/SMADS, p38 MAPK, NF-κB/IκBα, NF-κB-NLRP3, PI3K/Akt, TLR4-MyD88-NF-κB and IL-6/STAT3 signaling pathways are mainly involved. In conclusion, CM is very likely to be a potential candidate for liver disease treatment based on modern phytochemistry, pharmacology, and genomeproteomics, which needs more clinical trials to further clarify its importance in the treatment of liver diseases.

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“…Folium Isatidis is an Isatis indigotica Fort (Chen et al, 2022; Ding & Zhu, 2020). It belongs to Isatis of Cruciferae.…”

Section: Introductionmentioning

confidence: 99%

Determination of isoscoparin in mouse blood using UPLC–MS/MS and its pharmacokinetics

Huang

Jiang

Liang

et al. 2022

Biomedical Chromatography

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This study developed a UPLC-MS/MS method to detect isoscoparin in mouse blood, determined the pharmacokinetics of isoscoparin in mice after intravenous (5 mg/kg) and intragastric (20 mg/kg) administration, and calculated the absolute bioavailability.A HSS T3 column was used for separation, and the column temperature was set at 40 C. The mobile phases were acetonitrile and 0.1% formic acid, and the gradient elution procedure was used. The blood sample was treated with protein precipitant with acetonitrile-methanol (9:1, v/v). Multiple reaction monitoring mode was used for quantitative analysis in electrospray positive-ion mode. It showed a good linear relationship in the range of 1-4000 ng/mL (r > 0.998); the intra-day and inter-day precision was <12%, and the accuracy was 86-112%. The recovery was >68%, and the matrix effect was 86-90%. The half-life of isoscoparin was relatively short in mice, and the bioavailability was 2.6%. The developed UPLC-MS/MS method was rapid, sensitive, and suitable for the pharmacokinetics of isoscoparin in mice.

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Isatidis Folium alleviates acetaminophen‐induced liver injury in mice by enhancing the endogenous antioxidant system

Cited by 11 publications

References 39 publications

Naringin alleviates acetaminophen‐induced acute liver injury by activating Nrf2 via CHAC2 upregulation

Naringin alleviates acetaminophen‐induced acute liver injury by activating Nrf2 via CHAC2 upregulation

The Potential Application of Chinese Medicine in Liver Diseases: A New Opportunity

Determination of isoscoparin in mouse blood using UPLC–MS/MS and its pharmacokinetics

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