Journal of Biochemical and Molecular Toxicology最新文献

{"title":"Correction to “Hypericin Regulates Inflammation Levels and Improves Depressive Symptoms in Rats With Post-Stroke Depression Through the MEK/ERK/CREB Pathway”","authors":"","doi":"10.1002/jbt.70357","DOIUrl":"https://doi.org/10.1002/jbt.70357","url":null,"abstract":"<p>Jia, K., Li, W., Li, Y. and Qian, L. (2025), Hypericin Regulates Inflammation Levels and Improves Depressive Symptoms in Rats With Post-Stroke Depression Through the MEK/ERK/CREB Pathway. Journal of Biochemical and Molecular Toxicology, 39: e70295.</p><p>The authors affiliation was published incorrectly as:</p><p><b>Kui Jia</b>^<b>1,2</b> <b>| Wenlong Li</b>^<b>1,2</b> <b>| Yifan Li</b>^<b>1,2</b> <b>| Lingling Qian</b>^<b>1,2</b></p><p>^<b>1</b> Department of Integrated Traditional Chinese and Western Medicine, The First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan province, 453100, China</p><p>^<b>2</b> Henan University of Chinese Medicine</p><p>This should have been read as:</p><p><b>Kui Jia</b>^<b>1,2</b> <b>| Wenlong Li</b>^<b>1</b> <b>| Yifan Li</b>^<b>1</b> <b>| Lingling Qian</b>^<b>1</b></p><p>¹ Department of Integrated Traditional Chinese and Western Medicine, The First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan province, 453100, China</p><p>² Henan University of Chinese Medicine</p>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 7","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jbt.70357","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144367354","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inorganic Arsenic-Induced Up-Regulation of MALAT1 Affects Cell Apoptosis via Disrupting the Binding Between IKBα and IKKβ, P65","authors":"Ruihuan Zhao,&nbsp;Yanhua Zhu,&nbsp;Xuefei Yang,&nbsp;Tingzhi Duan,&nbsp;Jingchao Yang,&nbsp;Bin Chen,&nbsp;Xinda Yang,&nbsp;Guanghui Ni,&nbsp;Shuting Li,&nbsp;Yuefeng He","doi":"10.1002/jbt.70374","DOIUrl":"https://doi.org/10.1002/jbt.70374","url":null,"abstract":"<div>\u0000 \u0000 <p>The toxicity and carcinogenicity of the environmental pollutant arsenic have been widely recognized. Dysregulation of apoptosis and proliferation, mediated by specific genes or signaling pathways, plays a pivotal role in arsenic-induced carcinogenesis. LncRNA <i>MALAT1</i> is an adverse prognostic marker in lung adenocarcinoma patients and is associated with metastasis. Here, we investigated the arsenic-induced upregulation of <i>MALAT1</i> and its impact on apoptosis. Our study combined epidemiological analyses of arsenic exposure with in vitro experiments. qRT-PCR assessed gene expression, while CCK-8, JC-1 staining, Hoechst 33342/PI assays, and Western blot analysis evaluated apoptosis, mitochondrial membrane potential, and apoptotic markers. RNA immunoprecipitation (RIP) and co-immunoprecipitation (Co-IP) assays elucidated interactions between <i>MALAT1</i> and key proteins. Our findings revealed that inorganic arsenic upregulates <i>MALAT1</i> expression in vivo and in vitro. We show that low expression of <i>MALAT1</i> diminishes survival and facilitates apoptosis in 16HBE cells, and knockdown of <i>MALAT1</i> inhibits the mRNA transcription of NF-κB pathway-related genes <i>BCL2</i>, <i>iap-1</i> and <i>IκBα</i> in 16HBE cells. Mechanistically, <i>MALAT1</i> knockdown attenuated IKBα phosphorylation and ubiquitination, impairing NF-κB pathway activation. <i>MALAT1</i> was proven to interact with IKBα, P65 and P50. Knockdown of <i>MALAT1</i> reduces the binding of IKBα to IKKβ and lowers IκBα protein phosphorylation. Meanwhlie, low expression of <i>MALAT1</i> enhances IKBα-P65 binding while weakening IKBα-IKKβ interactions, making it disadvantageous for IKBα to detach from the trimer formed by IKBα, P65 and P50. The repression of NF-κB signaling pathway target genes is responsible for cell apoptosis. Arsenic-promoted elevated expression of <i>MALAT1</i> impinges cell proliferation and apoptosis, providing a scientific rationale for arsenic toxicity and carcinogenicity.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 7","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144367404","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Morin Attenuates Diclofenac-Induced Hepatocellular Death Injury via Nrf2/Ho-1/NQO1, Beclin-1/LC3A/LC3B and p53/Bax/Caspase Signalling Pathways","authors":"Nurhan Akaras,&nbsp;Hasan Şimşek,&nbsp;Cihan Gür,&nbsp;Sefa Küçükler,&nbsp;Mustafa İleritürk,&nbsp;Fatih Mehmet Kandemir","doi":"10.1002/jbt.70372","DOIUrl":"https://doi.org/10.1002/jbt.70372","url":null,"abstract":"<p>Diclofenac (DF), a nonsteroidal and anti-inflammatory drug, has limited use due to its adverse effects on the liver. On the other hand, morin, a bioflavonoid, has biological and pharmacological properties. This study aims to investigate whether morin may protect against diclofenac-induced liver toxicity. For this purpose, morin (50 or 100 mg/kg) treatment was given orally to the rats for 5 days, and DF (50 mg/kg) was administered intraperitoneally on the 4th and 5th days of the study. Molecular, biochemical, immunohistochemical and histological methods were used to investigate cyclooxygenase enzymes, oxidative stress, apoptosis and autophagy in liver tissue. According to the data obtained, it was observed that DF caused oxidative stress, autophagy and apoptosis damage in liver tissues. Morin showed antioxidant properties, causing a decrease in MDA in hepatic tissue, an increase in the activities of endogenous antioxidants (glutathione peroxidase, superoxide dismutase and catalase) and GSH, HO-1, Nrf2 and NQO1 mRNA levels. Moreover, morin reversed the changes in the levels of apoptotic and autophagic parameters such as bax, bcl-2, cytochrome c, p53, Apaf-1, caspase-3, caspase-6, caspase-9, beclin-1, LC3A, LC3B, MAPK14, MAP15, JNK. When the histopathological analysis results were examined, degenerative changes occurred in the livers of rats administered DF, while morin administration showed a morphological structure close to the control group. As a result, it was determined that oxidative stress, autophagy and apoptosis caused by DF were suppressed by morin, thus protecting the liver tissue from damage.</p>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 7","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jbt.70372","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144367482","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phthalate Exposure During Pregnancy and Lactation Transgenerationally Impairs the Epididymis in the Offspring of Rats","authors":"Ana Paula Franco Punhagui-Umbelino,&nbsp;Giovanna Fachetti Frigoli,&nbsp;Ariana Musa de Aquino,&nbsp;Barbara Campos Jorge,&nbsp;Luiz Guilherme Alonso-Costa,&nbsp;Rafaela Pires Erthal-Michelato,&nbsp;Arielle Cristina Arena,&nbsp;Wellerson Rodrigo Scarano,&nbsp;Glaura Scantamburlo Alves Fernandes","doi":"10.1002/jbt.70379","DOIUrl":"https://doi.org/10.1002/jbt.70379","url":null,"abstract":"<p>Phthalates are chemical compounds used as plasticizers in plastic products, for guaranteeing their flexibility. These compounds damage the epididymal morphophysiology. This study aimed to verify the changes in the epididymis of neonatal and adult rats over two generations. Pregnant Sprague–Dawley females were divided into four groups and gavaged daily from GD10 to PND21 with corn oil (Control:C) or the phthalate mixture at three doses (20, 200, and 200 mg/Kg). F1 animals were euthanized at 22PND and 120PND; unexposed females were mated with 90PND males to obtain the F2 generation. Male rats were euthanized at 22PND. Tissue remodeling of the compartments was observed at all doses in the 22PND animals of both generations. Treatment at 200 mg/Kg resulted in alterations, a decrease in the epithelium and a consequent increase in the lumen in the cauda in F1 PND22. The lumen in the caput and cauda increased, with a reduction in the interstitium at 200 mg/Kg in F2 PND22. The lumen diameter was reduced in the caput and increased in the interstitium at the two highest doses in adult animals. The expression of <i>GPR30</i>, <i>GPX3</i>, <i>GSR</i>, <i>IL10</i>, and <i>TNFa</i> was reduced in adult animals at the highest dose. <i>GPR30</i> expression increased at 200 mg/Kg dose in PND22. <i>TNFa</i> expression was reduced at all doses in F1 PND22 animals and significantly increased in F2 PND22 animals at 200 µg/Kg and 200 mg/Kg doses. In conclusion, phthalates modify the epididymal structure and impair gene expression, mainly in the late phase.</p>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 7","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jbt.70379","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144367405","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring Triptolide's Dual Role in Inflammation and Oxidative Stress: Responses of Organelles","authors":"Haoyue Xiao,&nbsp;Yuchen Liu,&nbsp;Dinglin Liu,&nbsp;Ying Xiang,&nbsp;Weijia Zhang","doi":"10.1002/jbt.70371","DOIUrl":"https://doi.org/10.1002/jbt.70371","url":null,"abstract":"<div>\u0000 \u0000 <p>Triptolide (TPL), isolated from the traditional Chinese herb Tripterygium wilfordii Hook. f., is a natural compound with complex pharmacological activities. TPL has significant therapeutic effects in rheumatoid arthritis, Alzheimer's disease, diabetic nephropathy, and other diseases through anti-inflammatory and antioxidant effects. However, its pro-inflammatory and antioxidant effects produce toxicity to multiple organs such as kidney, liver, and the reproductive organs. Thus, the effects of TPL on inflammation and oxidative stress broaden the therapeutic scope of TPL, but also limit its clinical application. In recent years, studies have shown that TPL can significantly affect the structure and function of multiple organelles such as endoplasmic reticulum, mitochondria and lysosomes. The presence of some special structures among these organelles, which are involved in the exchange of substances and information, may be an important reason for that TPL can cause alterations in multiple organelles. This review systematically summarizes the dual role and molecular mechanisms of TPL in inflammation and oxidative stress, and analyzes the cytological basis for the dual role of TPL from the aspects of organelles and their cross-talk, so as to provide a comprehensive and in-depth investigation for the fundamental research and clinic application of TPL.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 7","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144367480","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"miRNAs as Biomarkers and Therapeutic Targets in Celiac Disease: Current Advances and Future Directions","authors":"Reda M. Mansour,&nbsp;Ahmed S. Doghish,&nbsp;Ahmed Amr Raouf,&nbsp;Abdelrhman M. Mohamed,&nbsp;Aml Ghanem,&nbsp;Ahmed H. I. Faraag,&nbsp;Abanoub A. S. Shaker,&nbsp;Mohammed S. Elballal,&nbsp;Sherif S. Abdel Mageed,&nbsp;Yara A. Nassar,&nbsp;Ahmed I. Abulsoud,&nbsp;Nourhan M. Abdelmaksoud,&nbsp;Mohamed A. Ali,&nbsp;Mohamed Hemdan,&nbsp;Osama A. Mohammed,&nbsp;Mustafa Ahmed Abdel-Reheim,&nbsp;Mahmoud A. Elrebehy,&nbsp;Gharieb S. El-Sayyad","doi":"10.1002/jbt.70361","DOIUrl":"https://doi.org/10.1002/jbt.70361","url":null,"abstract":"<div>\u0000 \u0000 <p>This in-depth review examines the complex interactions between miRNAs and Celiac disease (CD) across various biological aspects. The discussion begins with an in-depth examination of miRNAs' biogenesis and functional pathways, highlighting their critical regulatory roles in cellular processes. The exploration extends to CD pathogenesis, elucidating how miRNAs contribute to the aberrant immune response against gluten in the small intestine. We navigate miRNAs' regulatory influence on intestinal development and innate and adaptive immunity, providing a panoramic view of their impact on CD etiology. Some miRNAs, such as miR-449a, miR-192-5p, miR-31-5p, miR-17, miR-30a, miR-638, miR-192, miR-194-5p, and miR-197, are dysregulated in CD and are involved in various pathways, including Notch1, tight junctions, and other pathogenetic pathways. The clinical importance of miRNAs takes center stage, unveiling their potential as diagnostic and prognostic markers and reshaping CD management. Investigating miRNA-based therapeutic interventions opens avenues for precision medicine in modulating CD's immune dysregulation. With clinical advancements such as locked nucleic acid-modified antimiRs that target miR-122 for the treatment of hepatitis C and miR-34a mimics for hepatocellular carcinoma, microRNAs are promising therapeutic targets. Additionally, novel delivery systems such as lipid nanoparticles and tissue-specific conjugates address the crucial challenges of targeted miRNA modulation. Extracellular vesicle miRNAs add a layer of complexity, acting as mediators in CD's systemic effects. Finally, we outline future perspectives, envisioning how the evolving landscape of miRNA research can propel advancements in understanding, diagnosis, and treatment, marking this review as a cornerstone for researchers and clinicians in the dynamic field of miRNAs and CD.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 7","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144367357","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fargesin Exerts Neuroprotective Effect Against Cerebral Ischemia/Reperfusion Injury in Rats via Alteration of NF-κB Signaling Pathway","authors":"Ming Qiao,&nbsp;Yan Peng,&nbsp;Ting Yan,&nbsp;Jie Liu,&nbsp;JingFang Yue,&nbsp;Qing Zhu,&nbsp;XueGang Peng,&nbsp;ShuangXia Xiong,&nbsp;Gang Wen","doi":"10.1002/jbt.70354","DOIUrl":"https://doi.org/10.1002/jbt.70354","url":null,"abstract":"<div>\u0000 \u0000 <p>Neuro-inflammation is an important contributor in neurological disorders. Increased levels of cytokines and inflammatory markers are observed during brain damage. Fargesin is a naturally occurring compound classified as a lignan, a type of polyphenol frequently found in plants. It is particularly notable for its abundance in certain medicinal plants, such as Magnolia species, which are extensively used in traditional Asian medicine. Fargesis possess the potent antioxidant and anti-inflammatory effect. We aim to investigate the inflammatory pathway-mediated neuroprotective effect of fargesin against cerebral ischemia/reperfusion (I/R) injury in rats. Different doses of fargesin were administered to the rats before they performed 2 h of right middle cerebral artery occlusion (MCAO) using the intraluminal filament technique, followed by 22 h of reperfusion. Neurological score, brain edema, brain water content, evans blue leakage, sodium (Na⁺)/calcium (Ca²⁺)/potassium (K⁺) ATPase, antioxidant, cytokines, matrix metalloproteinases (MMP) and inflammatory parameters were estimated. Treatment with fargesin significantly (<i>p</i> &lt; 0.001) suppressed the neurological parameters alongwith reduction of brain water content, brain edema, evans blue leakage and infract volume. Fargesin treatment remarkably (<i>p</i> &lt; 0.001) suppressed the level of malonaldehyde (MDA) and boosted the level of superoxide dismutase (SOD), glutathione reductase (GR), catalase (CAT), glutathione (GSH), glutathione peroxidase (GPx) along with alteration of inflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6 and IL-10. Fargesin treatment significantly (<i>p</i> &lt; 0.001) suppressed the level of inflammatory parameters inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), prostaglandin (PGE₂), Nuclear factor kappa factor (NF-κB), transforming growth factor-β (TGF-β) and MMP level such as MMP-2, MMP-3 and MMP-9 level. Fargesin treatment remarkably suppressed the mRNA expression of Toll-like receptor 4 (TLR4), syndecan, colony-stimulating factor (CSF), aquaporin-1, REX1 and organic cation transporter 3 (OCT3). Fargesin demonstrated a brain protective effect against cerebral ischemia reperfusion through a lowering of inflammatory markers.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 7","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144367352","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anti-Inflammatory Effect of Dopamine D2 Receptor Agonist Cabergoline Against L-Arginine-Induced Acute Pancreatitis in Rats","authors":"Randa A. Zaghloul,&nbsp;Dalia H. El-Kashef,&nbsp;Medhat Taha,&nbsp;Noha Abdel-Rahman","doi":"10.1002/jbt.70370","DOIUrl":"https://doi.org/10.1002/jbt.70370","url":null,"abstract":"<div>\u0000 \u0000 <p>Severe acute pancreatitis (SAP) is an inflammatory disorder of the pancreas that may extend to other organs resulting in systemic injury. Unfortunately, there is no specific treatment beyond supportive management. Therefore, the current study explores the role of cabergoline (CAB) against <span>l</span>-arginine (<span>l</span>-arg)-induced SAP and systemic injury. Thirty male, adult, Sprague−Dawley rats were arbitrarily allocated into five groups; Normal, CAB (rats received CAB [0.5 mg/kg, orally], SAP [rats were intraperitoneally injected with 50% <span>l</span>-arg at 250 mg/100 g, 50% w/v, pH 7.4, twice with 1 h interval]), SAP + CAB-L, and SAP + CAB-H (rats received CAB [0.1 and 0.5 mg/kg, orally, respectively, for 7 days then were injected with <span>l</span>-arg twice with 1 h interval]). The results indicated that CAB significantly mitigated <span>l</span>-arg-induced damage to the pancreas, lung, liver, and kidney as observed through histopathological examination. Oral administration of CAB (0.5 mg/kg) significantly reduced the serum activities of amylase, lipase, ALT, AST, and the level of creatinine (<i>p</i> &lt; 0.001), and ameliorated pancreatic oxidative stress marked by pancreatic levels of MDA and GSH (<i>p</i> &lt; 0.001), compared to the SAP group. Moreover, CAB (0.5 mg/kg) significantly reduced inflammation as indicated by reduced levels of TNF-α, IL-6, -1β, and NLRP3 (<i>p</i> &lt; 0.001, 0.001, 0.01, and 0.001, respectively). Additionally, CAB reduced the levels of TLR4, NF-κB, NLRP3, and caspase-1 in the pancreatic tissues upon comparison with the SAP group. In conclusion, CAB could offer a new avenue for the prevention of SAP and systemic inflammation mitigation.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 7","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144367355","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring Astragaloside IV in Ischemic Heart Disease: A Comprehensive Systematic Review and Meta-Analysis of Preclinical Cardiotoxicity Models","authors":"Alosh Greeny,&nbsp;Gollapalle Lakshminarayanashastry Viswanatha,&nbsp;Rekha Raghuveer Shenoy,&nbsp;Shylaja Hanumanthappa,&nbsp;Dinesh Kumar Chellappan,&nbsp;Jagnoor Singh Sandhu,&nbsp;Saumya Khanna,&nbsp;Nandakumar Krishnadas","doi":"10.1002/jbt.70365","DOIUrl":"https://doi.org/10.1002/jbt.70365","url":null,"abstract":"<p>This systematic review and meta-analysis were conducted to evaluate the therapeutic efficacy of Astragaloside IV (As-IV) in ischemic heart disease based on the preclinical evidence and to correlate the cardioprotective effect with various available mechanisms. This systematic review and meta-analysis were conducted based on the results of a thorough literature search in databases of published papers, such as PubMed, Embase, and Google Scholar. A total of 18 studies that met the inclusion/exclusion criteria were included. The meta-analysis has shown the significant therapeutic efficacy of As-IV on ischemic heart disease. As-IV has decreased the myocardial infarction size, the left ventricular weight indices, the left ventricular internal diameter in systole, and the left ventricular internal diameter in diastole. As-IV has decreased the level of the third type of collagen and the decreased activity of creatine kinase and lactate dehydrogenase. Also, As-IV has markedly decreased the rate of apoptosis and the expression of the proapoptotic markers such as caspase-3 and Bax. The left ventricular systolic pressure, as well as the arterial shortening edge and the ejection fraction, has increased. The levels of the antiapoptotic protein Bcl-2 increased. In addition, As-IV has a powerful anti-inflammatory influence by inhibiting the main markers of inflammation, such as TLR4, IL-1, TNF-α, and TGF-β. As-IV has also caused an effect on angiogenesis by increasing the VEGF level. The results have revealed the As-IV, as a decent universal medicine for ischemic heart disease because of its variety of actions and effectiveness.</p>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 7","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jbt.70365","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144367356","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protective Effects of Chrysin Against Diclofenac-Induced Nephrotoxicity in Rats via Attenuation of Oxidative Stress, Apoptosis and Endoplasmic Reticulum Stress","authors":"Cuneyt Caglayan,&nbsp;İzzettin Ekinci,&nbsp;Cihan Gur,&nbsp;Adnan Ayna,&nbsp;İbrahim Bayav,&nbsp;Fatih Mehmet Kandemir","doi":"10.1002/jbt.70373","DOIUrl":"https://doi.org/10.1002/jbt.70373","url":null,"abstract":"<p>Diclofenac (DCL) is a broadly prescribed non-steroidal anti-inflammatory drug (NSAID) for pain management and has been linked to nephrotoxicity despite its therapeutic benefits. This study provides new insights into the palliative impacts of chrysin (CH) against DCL-induced kidney damage by modulating oxidative injury, endoplasmic reticulum (ER) stress and apoptosis. The rats were divided into five groups: the control group (Group 1), CH-only group (50 mg/kg, Group 2), DCL-only group (50 mg/kg, Group 3), DCL + CH (25 mg/kg, Group 4), and DCL + CH (50 mg/kg, Group 5). DCL injection led to significant renal damage marked by elevated serum urea, creatinine and malondialdehyde (MDA) levels, reduced glutathione (GSH) concentration, and decreased activities of antioxidant enzymes (glutathione peroxidase, superoxide dismutase and catalase). The mRNA expression levels of <i>Ho-1</i> and <i>Nrf2</i> were also suppressed. Additionally, DCL treatment triggered apoptosis as evidenced by increased expression of <i>Bax</i> and <i>caspase-3</i> alongside decreased <i>Bcl-2</i> expression. Furthermore, DCL induced ER stress was confirmed by upregulation of <i>Perk</i>, <i>Ire1</i>, <i>Atf-6</i>, and <i>Grp78</i> transcription levels. Also, it was demonstrated that DCL treatment upregulated <i>Mmp2</i> and <i>Mmp9</i> levels. Treatment with CH significantly mitigated these adverse effects suggesting that CH effectively protects DCL-induced kidney toxicity by targeting multiple pathways. In summary, this study highlights the importance of CH as a promising therapeutic agent for alleviating kidney damage associated with DCL toxicity.</p>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 6","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jbt.70373","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144314965","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}