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Artabotrys odoratissimus Bark Extract Restores Ethanol Induced Redox Imbalance and Toxicity in Hepatocytes and In Vivo Model

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Abstract

Alcohol-induced oxidative stress is a key player in the development of liver diseases, and herbal alternatives are important means of ameliorating the hepatotoxic effects. The study aimed to evaluate the hepatoprotective potentiality of Artabotrys odoratissimus, an important medicinal shrub from the family Annonaceae. The phenolic compounds from bark ethanol extract (BEE) were detected using RP-HPLC. The in vitro hepatoprotective activity against ethanol-induced damage was studied in HepG2 cells with cell viability assays, mitochondrial membrane potential (MMP) assay, reactive oxygen species (ROS) assay, double staining assay and western blotting. The in vivo mice model was used to evaluate the alcohol-induced stress with liver function enzymes, lipid profile and histopathology. All the thirteen phenolic compounds detected with HPLC were docked onto protein targets such as aspartate amino transferase (AST), alkaline phosphatase (ALP) and inducible nitric oxide synthase (NO). The RP-HPLC detected the presence of various phenolics including rutin, chlorogenic acid and catechin, amongst others. Co-administration of BEE with ethanol alleviated cell death, ROS and MMP in HepG2 cells compared to the negative control. The extract also modulated the MAP kinase/caspase-3 pathway, thereby showing protective effects in HepG2 cells. Also, pre-treatment for 14 days with the extract in the mice model before a single toxic dose (5 g/kg body weight) reduced the liver injury by bringing the levels of liver function enzymes, lipid profile and bilirubin to near normal. In silico analysis revealed that rutin showed the best binding affinity with all the target proteins in the study. These results provide evidence that BEE possesses significant hepatoprotective effects against ethanol-induced oxidative stress in hepatic cells and in vivo models, which is further validated with in silico analysis.

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The data that support the findings of this study will be made available on request from the corresponding author.

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Authors and Affiliations

  1. Laboratory of Experimental Medicine, Department of PG Studies and Research in Biotechnology, Kuvempu University, Shankarghatta, 577451, Karnataka, India

    Meghana P, Sandeep Kumar Jain R, Prashanth N, Inchara Moodbagil C & Kumaraswamy H M

  2. Research Unit of DNA Barcoding of Thai Medicinal Plants, Department of Pharmacognosy and Pharmaceutical Botany, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, 10330, Thailand

    Santhosh Kumar J U

  3. Department of Food Technology, Davangere University, Davangere, 577007, Karnataka, India

    Sharath R

  4. Department of Pharmaceutical Chemistry, Post Graduate Centre, Kadur, Kuvempu University, Chikkamagaluru, Karnataka, 577548, India

    Satyanarayan N D

  5. Liveon Biolabs Private Limited, Tumkur, 572106, Karnataka, India

    Rajesh R

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Meghana P: methodology, investigation, formal analysis, writing – original draft, review and editing. Sandeep Kumar Jain R: methodology, investigation, writing – review and editing. Prashanth N: investigation, formal analysis, writing – review and editing. Santhosh J U: formal analysis, writing – original draft, review and editing. Sharath R: formal analysis, writing – original draft, review and editing. Satyanarayan N D: methodology, supervision, formal analysis. Rajesh R: conceptualization, methodology, supervision. Inchara Moodbagil C: writing – original draft, review and editing. Kumaraswamy H M: conceptualization, methodology, supervision, formal analysis, writing – review and editing.

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P, M., R, S.K.J., N, P. et al. Artabotrys odoratissimus Bark Extract Restores Ethanol Induced Redox Imbalance and Toxicity in Hepatocytes and In Vivo Model. Appl Biochem Biotechnol 195, 3366–3383 (2023). https://doi.org/10.1007/s12010-022-04275-y

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