Chemico-Biological Interactions最新文献

{"title":"Conformation and binding of 12 Microcystin (MC) congeners to PPP1 using molecular dynamics simulations: A potential approach in support of an improved MC risk assessment","authors":"Sabrina Jaeger-Honz ,&nbsp;Raymund Hackett ,&nbsp;Regina Fotler ,&nbsp;Daniel R. Dietrich ,&nbsp;Falk Schreiber","doi":"10.1016/j.cbi.2025.111372","DOIUrl":"10.1016/j.cbi.2025.111372","url":null,"abstract":"<div><div>Microcystins (MCs) occur frequently during cyanobacterial blooms worldwide, representing a group of currently about 300 known MC congeners, which are structurally highly similar. Human exposure to MCs via contaminated water, food or dietary supplements can lead to severe intoxications with ensuing high morbidity and in some cases mortality. Currently, one MC congener (MC-LR) is almost exclusively considered for risk assessment (RA) by the WHO. Many MC congeners co-occur during bloom events, of which MC-LR is not the most toxic. Indeed, MC congeners differ dramatically in their inherent toxicity, consequently raising question about the reliability of the WHO RA and the derived guidance values. Molecular dynamics (MD) simulation can aid in understanding differences in toxicity, as experimental validation for all known MC congeners is not feasible. Therefore, we present MD simulations of a total of twelve MC congeners, of which eight MC congeners were simulated for the first time. We show that depending on their structure and toxicity class, MCs adapt to different backbone conformations. These backbone conformations are specific to certain MC congeners and can change or shift to other conformations upon binding to PPP1, affecting the stability of the binding. Analysis of the interactions with PPP1 demonstrated that there are frequently occurring patterns for individual MC congeners, and that published PPP interactions could be reproduced. In addition, common but also unique patterns were found for individual MC congeners, suggesting differences in binding behaviour. The MD simulations presented here therefore enhance our understanding of MC congener-specific differences and demonstrated that congener-specific investigations are prerequisite for allowing characterisation of yet untested or even unknown MC congeners, thereby allowing for a novel potential approach in support of an improved RA of microcystins in humans.</div></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"407 ","pages":"Article 111372"},"PeriodicalIF":4.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142960259","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel approach to the prevention and management of chemotherapy-induced cardiotoxicity: PANoptosis","authors":"Chenchen Meng ,&nbsp;Yali Wang ,&nbsp;Tiantian Zheng ,&nbsp;Zheng Rong ,&nbsp;Zhengtian Lv ,&nbsp;Chenxia Wu ,&nbsp;Xinbin Zhou ,&nbsp;Wei Mao","doi":"10.1016/j.cbi.2025.111379","DOIUrl":"10.1016/j.cbi.2025.111379","url":null,"abstract":"<div><div>As a fundamental component of antitumor therapy, chemotherapy-induced cardiotoxicity (CIC) has emerged as a leading cause of long-term mortality in patients with malignant tumors. Unfortunately, there are currently no effective therapeutic preventive or treatment strategies, and the underlying pathophysiological mechanisms of CIC remain inadequately understood. A growing number of studies have shown that different mechanisms of cell death, such as apoptosis, pyroptosis, and necroptosis, are essential for facilitating the cardiotoxic effects of chemotherapy. The PANoptosis mode represents a highly synchronized and dynamically balanced programmed cell death (PCD) process that integrates the principal molecular characteristics of necroptosis, apoptosis, and pyroptosis. Recent research has revealed a significant correlation between PANoptosis and the apoptosis of tumor cells. Chemotherapy drugs can activate PANoptosis, which is involved in the development of cardiovascular diseases. These findings suggest that PANoptosis marks the point where the effectiveness of chemotherapy against tumors overlaps with the onset and development of cardiovascular diseases. Furthermore, previous studies have demonstrated that CIC can simultaneously induce pyrodeath, apoptosis, and necrotic apoptosis. Therefore, PANoptosis may represent a potential mechanism and target for the prevention of CIC. This study explored the interactions among the three main mechanisms of PCD, pyroptosis, apoptosis, and necroptosis in CICs and analyzed the relevant literature on PANoptosis and CICs. The purpose of this work is to serve as a reference for future investigations on the role of PANoptosis in the development and mitigation of cardiotoxicity associated with chemotherapy.</div></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"407 ","pages":"Article 111379"},"PeriodicalIF":4.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142960243","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alkaloids and nitrosamines in betel quid: A biochemical exploration of carcinogenicity","authors":"S.C. Rangani ,&nbsp;R.A.U.J. Marapana ,&nbsp;G.S.A. Senanayake ,&nbsp;P.R.D. Perera ,&nbsp;M.M. Pathmalal ,&nbsp;H.K. Amarasinghe","doi":"10.1016/j.cbi.2025.111383","DOIUrl":"10.1016/j.cbi.2025.111383","url":null,"abstract":"<div><div>Betel quid contains two major ingredients; <em>Areca catechu</em> and <em>Piper betel,</em> often consumed with slaked lime, tobacco, certain flavouring agents, colouring agents, herbs, and spices according to personal preferences. The areca nut alkaloids (arecoline, arecaidine, guvacine, and guvacoline), and tobacco alkaloids (nicotine, nornicotine) undergo nitrosation during chewing in the oral cavity with the presence of nitrite and thiocyanate and endogenously. Among the nitrosation products generated areca nut-derived nitrosamine (ADNA): 3-(methylnitrosamino) Propionitrile (MNPN) and the two tobacco-specific nitrosamines (TSNAs); <em>N</em>′-nitrosonornicotine (NNN) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone) (NNK) are considered Group 1 human carcinogens. The slaked lime increases pH, reactive oxygen species (ROS) generation, and inflammation further lead to oral potentially malignant disorders (OPMD). The juice swallowed results in carcinogenicity, mutagenicity, and toxicity in the gastrointestinal tract including hepatocytic carcinoma, stomach, and colon cancer. Areca nut pre-treatments (sun drying, roasting, boiling, and fermentation) increase the quid metabolism, and reduce the arecoline content and associated risks. We review biochemical carcinogenesis of betel quid ingredients and synergic adverse effects and possible mechanism of carcinogenesis of betel quid in the oral cavity and gastrointestinal tract to understand the implication of polyphenols and alkaloids of areca nut and betel quid on carcinogenic nitrosamine formation under oral, gastric, and intestinal conditions.</div></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"407 ","pages":"Article 111383"},"PeriodicalIF":4.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142981003","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Myriscagayanone C, a new compound from the fruit of myristica cagayanensis, inhibits fMLP-induced respiratory bursts by specifically preventing Akt translocation in human neutrophils","authors":"Hsiang-Ruei Liao ,&nbsp;Chen-Lung Chen ,&nbsp;Yu-Yao Kao ,&nbsp;Fu-Chao Liu ,&nbsp;Ching-Ping Tseng ,&nbsp;Jih-Jung Chen","doi":"10.1016/j.cbi.2024.111357","DOIUrl":"10.1016/j.cbi.2024.111357","url":null,"abstract":"<div><div>Neutrophils that are overactivated can cause inflammatory diseases. Neutrophils possess various surface receptors, including G-protein-coupled chemoattractant receptors, which assist in recognizing pathogen attacks and the inflammatory environment. Therefore, targeting G-protein-coupled chemoattractant receptors and their downstream molecules is important for preventing abnormal neutrophil activation. This study examines the effects and underlying mechanism of myriscagayanone C, a new compound obtained from the fruit of myristica cagayanensis, on neutrophil respiratory burst induced by fMLP. The immunoblotting assay was conducted to assess the mechanisms by which myriscagayanone C inhibits fMLP-induced respiratory burst by disrupting the translocation of Akt to the cellular membrane. Briefly, myriscagayanone C suppressed the production of superoxide anions induced by fMLP on human neutrophils in a concentration-dependent manner (IC₅₀: 4.73 ± 0.68 μM). Myriscagayanone C blocked fMLP-induced Akt translocation to the cell membrane, inhibiting Akt^T308 and Akt^S473 phosphorylation by PDK1^Y373/376 and mTOR^S2481, respectively. Myriscagayanone C inhibited fMLP-induced p47^phox phosphorylation and translocation. Myriscagayanone C did not inhibit the activity of PI3K, the amount of phosphatidylinositol (3, 4, 5)-trisphosphate, or the translocation of phosphorylated-PDK1^Y373/376 and -mTOR^S2481 to the membrane. Myriscagayanone C did not inhibit fMLP-induced PKC, Src, ERK1/2, p38 phosphorylation, and intracellular calcium mobilization. Myriscagayanone C did not inhibit the chemotaxis and CD11b expression induced by fMLP. Myriscagayanone C did not inhibit PMA-induced superoxide anion production and neutrophil extracellular trap formation. According to this data, myriscagayanone C inhibits fMLP-induced neutrophil superoxide anion production by interrupting the translocation of Akt to the plasma membrane, which affects the NADPH oxidase activity by preventing p47^phox phosphorylation and translocation.</div></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"407 ","pages":"Article 111357"},"PeriodicalIF":4.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142866678","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Equol promotes osteogenic differentiation of hPDLSCs by inhibiting oxidative stress via IL1B/NF-κB/CXCL1 signaling axis","authors":"Xiaoxi Jiang ,&nbsp;Xiao Chen ,&nbsp;Lingxiao He ,&nbsp;Dan Qin ,&nbsp;Minhai Nie ,&nbsp;Chunhui Li ,&nbsp;Xuqian Liu","doi":"10.1016/j.cbi.2024.111367","DOIUrl":"10.1016/j.cbi.2024.111367","url":null,"abstract":"<div><div>Oxidative stress (OS) inhibits the osteogenic differentiation of human periodontal ligament stem cells (hPDLSCs). Equol (Eq), a phytoestrogen, exhibits notable antioxidant properties and potential for preventing osteoporosis. However, the research on the regulatory effects of Eq on stem cell osteogenesis remains limited. This investigation aimed to identify whether Eq could protect the osteogenic potential of hPDLSCs under H₂O₂-induced oxidative microenvironment. We employed a series of assays, including CCK-8, DCFH-DA, ALP staining, ARS, RT-qPCR, and Western Blotting, to assess the changes in cell viability, antioxidant capacity, and osteogenic potential following H₂O₂ and Eq treatments. Our findings indicated that low concentrations of Eq had no cytotoxic effects on hPDLSCs and promoted their proliferation. Eq pre-treatment (0.5 μmol/L) partially counteracted the inhibitory effect of H₂O₂, reduced the generation of reactive oxygen species, and increased glutathione levels, thereby inhibiting oxidative damage. Eq suppressed the H₂O₂-induced inhibition of osteogenic differentiation, presenting as restoring the alkaline phosphatase levels and calcium nodule formation, as well as by upregulating the expression of BMP2 and RUNX2. Furthermore, bioinformatics analysis in this study suggested that the IL1B/NF-κB/CXCL1 signaling pathway might be a key pathway for Eq's enhancement of osteogenic differentiation potential of hPDLSCs under OS conditions. The activation of this axis by H₂O₂, which Eq can alleviate, was confirmed by validation experiments. This study provides new insights into the potential therapeutic application of Eq in alveolar bone resorption and bone regeneration research.</div></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"407 ","pages":"Article 111367"},"PeriodicalIF":4.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142916598","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Platinum as both a drug and its modulator – Do platinum nanoparticles influence cisplatin activity?","authors":"Patrycja Bełdzińska ,&nbsp;Barbara Galikowska-Bogut ,&nbsp;Marcin Zakrzewski ,&nbsp;Katarzyna Bury ,&nbsp;Marzena Jamrógiewicz ,&nbsp;Dariusz Wyrzykowski ,&nbsp;Grzegorz Gołuński ,&nbsp;Rafał Sądej ,&nbsp;Jacek Piosik","doi":"10.1016/j.cbi.2024.111365","DOIUrl":"10.1016/j.cbi.2024.111365","url":null,"abstract":"<div><div>Breast cancer was the most frequent cause of cancer death in females in 2022. Despite the development of personalized therapies, chemotherapy frequently remains the only available treatment method. However, the administration of classic antineoplastic drugs, like cisplatin (CDDP), often causes severe side effects and may lead to drug resistance making the therapy inefficient. Therefore, there is a great need for new, effective treatment regimens development. For this reason, we applied platinum nanoparticles (PtNPs) to verify if they can influence the CDDP activity with particular emphasis on the differences due to nanoparticles’ sizes.</div><div>We employed a broad spectrum of physicochemical methods, including Dynamic Light Scattering, Atomic Force Microscopy, Isothermal Titration Calorimetry, Fourier Transform Infrared Spectroscopy, and Near Infrared Spectroscopy and also Differential Scanning Calorimetry, to characterize the possible interactions between nanoparticles and CDDP. Moreover, the impact of PtNPs on CDDP biological activity was investigated using the Ames mutagenicity test on <em>Salmonella enterica</em> serovar Typhimurium TA102 and MTT assay on two breast cancer cell lines MDA-MB-231 and SKBR3.</div><div>The obtained results revealed PtNPs direct interactions with CDDP dependent on the nanoparticles’ size. Despite the lack of explicit confirmation of PtNPs aggregation by AFM imaging and DLS, further physicochemical methods indicated structural changes between nanoparticles alone and PtNPs-CDDP mixtures. Moreover, the biological assays confirmed that PtNPs decrease CDDP mutagenicity and also slightly increase its cytotoxicity on the chosen cell lines. The latter effects are ambiguous, nevertheless, provide a valuable basis for further research.</div></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"407 ","pages":"Article 111365"},"PeriodicalIF":4.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142916599","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Copper exposure induces neurotoxicity through ferroptosis in C. elegans","authors":"Jianglan Wei ,&nbsp;Ying Zhang ,&nbsp;Wei Shi,&nbsp;Lu Lu,&nbsp;Qian Zhou,&nbsp;Yuepu Pu,&nbsp;Lihong Yin","doi":"10.1016/j.cbi.2024.111369","DOIUrl":"10.1016/j.cbi.2024.111369","url":null,"abstract":"<div><div>Copper, as a vital trace element and ubiquitous environmental pollutant, exhibits a positive correlation with the neurodegenerative diseases. Recent studies have highlighted ferroptosis's significance in heavy metal-induced neurodegenerative diseases, yet its role in copper-related neurotoxicity remains unclear. This study aimed to investigate the role of ferroptosis in copper-induced neurotoxicity. Previously, we established that copper induced motor behaviors inhibition and neuronal degeneration through oxidative stress in <em>Caenorhabditis elegans</em> (<em>C</em>. <em>elegans</em>). This study revealed that the behavior inhibition (head thrash, body bends, pumping frequency and defecation interval) and neuronal degeneration (GABAergic neurons and dopaminergic neurons) in copper-treated nematodes were reversed by the ferroptosis inhibitor Fer-1. Additionally, copper treatment increased the Fe²⁺ level and MDA content, and decreased GSH content, suggesting copper activated the ferroptosis in <em>C. elegans</em>. Furthermore, studies found that copper exposure altered the expression of ferroptosis-related genes <em>gpx-1</em>, <em>ftn-1</em>, and <em>acs-17</em> in <em>C. elegans</em>. The results showed RNAi of <em>gpx-1</em> and RNAi of <em>ftn-1</em> significantly promoted Cu-induced neurotoxicity, while the RNAi of <em>acs-17</em> appeared to rescue the Cu-induced ferroptosis and neurotoxicity. In conclusion, Cu might induce behavior inhibition and neuronal degeneration through ferroptosis in <em>C. elegans</em>. The findings of this study provided new insights in the mechanisms underlying Cu-induced neurotoxicity.</div></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"407 ","pages":"Article 111369"},"PeriodicalIF":4.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142928874","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bisphenol S induced endothelial dysfunction via mitochondrial pathway in the vascular endothelial cells, and detoxification effect of albumin binding","authors":"Rong Tian,&nbsp;Jia-Xin Li,&nbsp;Naihao Lu","doi":"10.1016/j.cbi.2025.111382","DOIUrl":"10.1016/j.cbi.2025.111382","url":null,"abstract":"<div><div>As a replacement of bisphenol A, bisphenol S (BPS) is commonly used in the wrappers and food containers of daily life. Epidemiological studies demonstrate a close link between BPS exposure and vascular diseases, where the biological activities of BPS remain scarcely known. Herein, the effects of BPS on endothelial function as well as the underlying mechanism were investigated in human umbilical vein endothelial cells (HUVECs) and mouse arteries. It was found that exposure of BPS dose-dependently induced endothelial dysfunction (i.e., decline of nitric oxide (NO) formation) in HUVECs, accompanied by the increase of reactive oxygen species (ROS) production and loss of mitochondria membrane potential. Mitochondria-specific antioxidant (Mito-Tempol) or superoxide scavenger (tiron) abolished the harmful effects of BPS, while superoxide dismutase (SOD)-specific siRNA exhibited negative influence, suggesting that mitochondrial ROS was responsible for BPS-induced endothelial dysfunction and SOD was a sensitive target of BPS. Consistently, plasma NO formation and endothelium-dependent vasodilation was significantly impaired in mice exposed to dietary BPS. In addition, the binding of bovine serum albumin (BSA, the most abundant protein in blood) to BPS considerably alleviated ROS formation and endothelial dysfunction in HUVECs. BPS primarily interacted with Sudlow site I of albumin to generate BSA-BPS complex through static mechanism, in which the hydrogen bonds and electrostatic forces played important roles. Altogether, dietary exposure to emerging BPS would disrupt vascular homeostasis via the induction of mitochondrial ROS formation and consequent endothelial dysfunction, highlighting the detoxification impact of albumin protein on the hazardous effects of environmental pollutants.</div></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"407 ","pages":"Article 111382"},"PeriodicalIF":4.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142967591","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fluorescent probes for detecting and imaging mitochondrial hydrogen sulfide","authors":"Yi-Wen Zhu ,&nbsp;Ebenezeri Erasto Ngowi ,&nbsp;Ao-Qi Tang ,&nbsp;Ti Chu ,&nbsp;Yan Wang ,&nbsp;Zulfa Ismail Shabani ,&nbsp;Lucas Paul ,&nbsp;Tong Jiang ,&nbsp;Xin-Ying Ji ,&nbsp;Dong-Dong Wu","doi":"10.1016/j.cbi.2024.111328","DOIUrl":"10.1016/j.cbi.2024.111328","url":null,"abstract":"<div><div>Hydrogen sulfide (H₂S) is a potent redox-active signaling molecule commonly dysregulated in disease states. The production of H₂S and its involvement in various pathological conditions associated with mitochondrial dysfunction have extensively documented. During stress, cystathionine gamma-lyase and cystathionine beta-synthase in cytosol are copiously translocated into the mitochondria to boost H₂S production, confirming its pivotal role in mitochondrial activities. However, little study has been done on H₂S levels in tissues, cells and organelles, mainly due to the absence of precise and accurate detection tools. Thus, there is an urgent need to determine and monitor the levels of H₂S in these important organelles. Fluorescent probes are efficient tools for detecting and monitoring various important biomolecules including biological thiols. The development of fluorescent probes is a multi-pronged approach which involves coupling fluorophores with responsive sites. The use of fluorescent probes for monitoring mitochondrial H₂S levels has recently received widespread attention, resulting in numerous publications depicting their synthesis, mechanism of action, application, and potential challenges. Fluorescent probes offer precise and timely results, high sensitivity and selectivity, low biotoxicity, and minimal background interference. In this review, we aim to report designs of such probes, reaction mechanisms and their application in detecting mitochondrial H₂S levels. Fluorescent probes can help uncover physio/pathological levels of H₂S in essential organelles, its interactions with various biomarkers and associated consequences in biological systems.</div></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"407 ","pages":"Article 111328"},"PeriodicalIF":4.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142788099","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oxymatrine reduces hepatic lipid synthesis in rat model of nonalcoholic steatohepatitis by regulating Sirt1/AMPK and LXR/Plin2/SREBP-1c pathways","authors":"Jingfang Xiong ,&nbsp;Gaofeng Chen ,&nbsp;Ying He ,&nbsp;Changqing Zhao ,&nbsp;Dongya Chen ,&nbsp;Yihui Liu ,&nbsp;Zhaolin Zhang ,&nbsp;Yijun Wu ,&nbsp;Hong Xu","doi":"10.1016/j.cbi.2024.111370","DOIUrl":"10.1016/j.cbi.2024.111370","url":null,"abstract":"<div><div>Nonalcoholic Steatohepatitis (NASH) is a common liver disease with limited treatment options. Oxymatrine (OMT) has been reported to treat liver diseases effectively. This study aims to explore the mechanisms of OMT in NASH. Male Sprague-Dawley rats were fed a high-fat and high-sucrose diet and hepatocytes were stimulated with oleic acid (OA) to establish NASH models, then, NASH models were intervened with OMT. <em>In vivo</em>, liver injury and lipid accumulation extents were evaluated by serum and liver biochemical indexes, and histological analysis. <em>In vitro</em>, cell viability and lipid accumulation degrees were measured. Additionally, the relationships between perilipin 2 (Plin2) and liver X-activated receptor alpha (LXRα) as well as Plin2 and sterol regulatory element binding protein-1c (SREBP-1c), sirtuin 1 (Sirt1)/adenosine 5‘-monophosphate-activated protein kinase (AMPK) pathway-, liver X-activated receptor (LXR)/Plin2/SREBP-1c pathway- and lipid synthesis-related proteins were detected both <em>in vivo</em> and <em>in vitro.</em> Finally, Sirt1 was knocked down in hepatocytes. OMT not only reduced serum alanine aminotransferase activity and triglyceride content, liver triglyceride and free fatty acid levels in NASH rats, but also improved hepatic injury and lipid accumulation. <em>In vitro</em>, OMT enhanced viability, and downregulated lipid accumulation in OA-induced hepatocytes. Both <em>in vivo</em> and <em>in vitro</em> results revealed Plin2 directly interacted with LXRα and SREBP-1c, and OMT activated Sirt1/AMPK pathway but inhibited the expressions of LXR/Plin2/SREBP-1c pathway and lipid synthesis (acetyl-CoA carboxylase, fatty acid synthase, stearoyl-Coenzyme A desaturase 1) related proteins in NASH models. Importantly, Sirt1 knockdown reversed the protective effects of OMT in OA-stimulated hepatocytes. OMT may reduce hepatic lipid synthesis in NASH by activating the Sirt1/AMPK pathway and inhibiting the LXR/Plin2/SREBP-1c pathway, suggesting that OMT may be a promising strategy for treating NASH.</div></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"407 ","pages":"Article 111370"},"PeriodicalIF":4.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142924213","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}