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      Sophorae tonkinensis radix polysaccharide attenuates acetaminophen-induced liver injury by regulating the miR-140-5p-related antioxidant mechanism

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          Abstract

          STRP1, a polysaccharide active ingredient isolated from the traditional Chinese medicine Sophorae tonkinensis radix, has demonstrated a protective effect against acetaminophen (APAP)-induced liver injury (AILI). The underlying molecular mechanism was investigated in this study. Here, an acute liver damage mouse model was generated by APAP (400 mg/kg) and used to identify the protective effect of STRP1 (200 mg/kg) on mouse livers. In vitro cell experiments were used to further verify the related signaling pathways. Initially, in our study, STRP1 treatment reduced APAP-induced liver injury by decreasing aminotransferase activity and cell apoptosis and increasing cell proliferation. Furthermore, STRP1 treatment significantly increased Nrf2 expression and alleviated oxidative stress caused by reactive oxygen species in AILI. Based on bioinformatics and experimental studies, miR-140-5p was identified and found to be reduced by STRP1, increasing Nrf2 expression. Additionally, Nrf2 played an important role in the protective impact of STRP1-suppressed miR-140-5p expression. Generally, these results showed that STRP1-mediated suppression of miR-140-5p expression mitigates AILI by activating the Nrf2-mediated Nrf2-Keap1 pathway. This study revealed that STRP1 might be a potential treatment agent for AILI.

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          Most cited references39

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          MicroRNAs as regulators, biomarkers and therapeutic targets in liver diseases

          MicroRNAs (miRNAs) are small, non-coding RNAs that post-transcriptionally regulate gene expression by binding to specific mRNA targets and promoting their degradation and/or translational inhibition. miRNAs regulate both physiological and pathological liver functions. Altered expression of miRNAs is associated with liver metabolism dysregulation, liver injury, liver fibrosis and tumour development, making miRNAs attractive therapeutic strategies for the diagnosis and treatment of liver diseases. Here, we review recent advances regarding the regulation and function of miRNAs in liver diseases with a major focus on miRNAs that are specifically expressed or enriched in hepatocytes (miR-122, miR-194/192), neutrophils (miR-223), hepatic stellate cells (miR-29), immune cells (miR-155) and in circulation (miR-21). The functions and target genes of these miRNAs are emphasised in alcohol-associated liver disease, non-alcoholic fatty liver disease, drug-induced liver injury, viral hepatitis and hepatocellular carcinoma, as well liver fibrosis and liver failure. We touch on the roles of miRNAs in intercellular communication between hepatocytes and other types of cells via extracellular vesicles in the pathogenesis of liver diseases. We provide perspective on the application of miRNAs as biomarkers for early diagnosis, prognosis and assessment of liver diseases and discuss the challenges in miRNA-based therapy for liver diseases. Further investigation of miRNAs in the liver will help us better understand the pathogeneses of liver diseases and may identify biomarkers and therapeutic targets for liver diseases in the future.
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            Oxidative Stress as a Critical Factor in Nonalcoholic Fatty Liver Disease Pathogenesis.

            Nonalcoholic fatty liver disease (NAFLD), characterized by liver triacylglycerol build-up, has been growing in the global world in concert with the raised prevalence of cardiometabolic disorders, including obesity, diabetes, and hyperlipemia. Redox imbalance has been suggested to be highly relevant to NAFLD pathogenesis. Recent Advances: As a major health problem, NAFLD progresses to the more severe nonalcoholic steatohepatitis (NASH) condition and predisposes susceptible individuals to liver and cardiovascular disease. Although NAFLD represents the predominant cause of chronic liver disorders, the mechanisms of its development and progression remain incompletely understood, even if various scientific groups ascribed them to the occurrence of insulin resistance, dyslipidemia, inflammation, and apoptosis. Nevertheless, oxidative stress (OxS) more and more appears as the most important pathological event during NAFLD development and the hallmark between simple steatosis and NASH manifestation.
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              Oxidative stress in the pathophysiology of type 2 diabetes and related complications: Current therapeutics strategies and future perspectives

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                Author and article information

                Contributors
                Journal
                J Tradit Complement Med
                J Tradit Complement Med
                Journal of Traditional and Complementary Medicine
                Elsevier
                2225-4110
                16 January 2024
                July 2024
                16 January 2024
                : 14
                : 4
                : 467-476
                Affiliations
                [a ]Department of Pharmacy, Affiliated Hospital of Nantong University, Nantong, 226001, PR China
                [b ]School of Pharmacy, Jiangsu Key Laboratory of Inflammation and Molecular Drug Targets, Nantong University, Nantong, 226001, PR China
                Author notes
                []Corresponding author. maxiaofei1113@ 123456163.com
                [∗∗ ]Corresponding author. xiner_nt@ 123456163.com
                [1]

                These authors contributed equally to this work.

                Article
                S2225-4110(24)00006-3
                10.1016/j.jtcme.2024.01.006
                11259709
                39035693
                eb3a5bc2-5ace-4436-95c7-45b684cac06b
                © 2024 Center for Food and Biomolecules, National Taiwan University. Production and hosting by Elsevier Taiwan LLC.

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 15 June 2023
                : 14 December 2023
                : 16 January 2024
                Categories
                Article

                sophorae tonkinensis radix,polysaccharide,liver injury,mir-140-5p,antioxidant

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