Iranian Journal of Basic Medical Sciences最新文献

{"title":"Comprehensive and updated review on anti-oxidant effects of <i>Nigella sativa</i> and its constituent, thymoquinone, in various disorders.","authors":"Mohammad Reza Aslani, Saeideh Saadat, Mohammad Hossein Boskabady","doi":"10.22038/IJBMS.2024.75985.16453","DOIUrl":"10.22038/IJBMS.2024.75985.16453","url":null,"abstract":"<p><p>Several pharmacological effects were described for <i>Nigella sativa</i> (<i>N. sativa</i>) seed and it has been used traditionally to treat various diseases. In this review article, the updated and comprehensive anti-oxidant effects of <i>N. sativa</i> and its main constituent, thymoquinone (TQ), on various disorders are described. The relevant articles were retrieved through PubMed, Science Direct, and Scopus up to December 31, 2023. Various extracts and essential oils of <i>N. sativa</i> showed anti-oxidant effects on cardiovascular, endocrine, gastrointestinal and liver, neurologic, respiratory, and urogenital diseases by decreasing and increasing various oxidant and anti-oxidant marketers, respectively. The main constituent of the plant, TQ, also showed similar anti-oxidant effects as the plant itself. The anti-oxidant effects of different extracts and essential oils of <i>N. sativa</i> were demonstrated in various studies which were perhaps due to the main constituent of the plant, TQ. The findings of this review article suggest the possible therapeutic effect of <i>N. sativa</i> and TQ in oxidative stress disorders.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":"27 8","pages":"923-951"},"PeriodicalIF":2.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11193497/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141442639","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of lupeol and flutamide on experimentally-induced polycystic ovary syndrome in mice.","authors":"Ali Rezaei-Golmisheh, Rajabali Sadrkhanlou, Abbas Ahmadi, Hassan Malekinejad","doi":"10.22038/IJBMS.2024.77602.16783","DOIUrl":"10.22038/IJBMS.2024.77602.16783","url":null,"abstract":"<p><strong>Objectives: </strong>Polycystic ovary syndrome (PCOS) is one of the main causes of infertility in women. This study was conducted to uncover the effects of lupeol as an anti-androgenic triterpene on experimentally-induced PCOS in mice.</p><p><strong>Materials and methods: </strong>Eighty immature female mice were divided into 4 groups: Control (C), PCOS (P), Lupeol (L), and Flutamide (F). PCOS was induced in test groups by injection of Dehydroepiandrosterone (60 mg/kg/day, IP) for twenty days. Following the PCOS induction, the two groups of L and F were treated with lupeol (40 mg/kg/day) and/or flutamide (10 mg/kg/day) respectively and the two groups of C and P received sesame oil (0.1 ml/mouse/day) for 15 days. After the treatment period, ten animals in each group were selected for collecting blood and ovary samples. <i>In vitro</i> fertilization assessment was carried out on 10 remaining mice in each group. The hormonal assays and oxidative stress biomarker determination were performed on serum and tissue samples. Moreover, histopathological analyses were conducted on the ovaries.</p><p><strong>Results: </strong>PCOS-elevated concentration of LH and Testosterone was significantly (<i>P</i><0.05) lowered in lupeol and flutamide-received animals. Lupeol and flutamide both reduced PCOS-induced fibrosis and the number of atretic follicles. Both compounds declined the PCOS-increased lipid peroxidation and protein oxidation in serum and the ovaries. Lupeol increased the PCOS-reduced fertility rate and decreased the number of arrested embryos by 12%.</p><p><strong>Conclusion: </strong>These findings indicate that lupeol could be a novel compound in the treatment of PCOS as it reduced PCOS-induced structural and also functional disorders.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":"27 8","pages":"1067-1076"},"PeriodicalIF":2.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11193499/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141442642","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Renoprotective effect of <i>Limonium duriusculum</i> (de Girard) Kuntze via modulation of oxidative stress/ UPR markers and inflammation during cyclosporine-induced nephrotoxicity in rats.","authors":"Azzedine Redouane-Salah, Ameddah Souad, Wafa Kerkatou, Kamil Wojnicki, Adrian M Ramos, Alberto Ortiz, Bozena Kaminska, Ahmed Menad","doi":"10.22038/IJBMS.2024.77052.16661","DOIUrl":"10.22038/IJBMS.2024.77052.16661","url":null,"abstract":"<p><strong>Objectives: </strong>The present study aimed to explore the mechanisms underlying the potency of the renoprotective effect of the EtOAc fraction of <i>Limonium duriusculum</i> (EALD) (Plumbaginaceae) against cyclosporine A (CsA), in comparison to vitamin E (Vit. E).</p><p><strong>Materials and methods: </strong>In the <i>in-vivo</i> experiment, a model of CsA-induced nephrotoxicity was established by dosing male Wistar rats with 25 mg/kg, for 14 days. The protective effect of EALD was investigated through pretreatment of rats with a dose of 200 mg/kg for 14 days, compared to the oral administration of Vit. E at 100 mg/kg. Renal function and markers of oxidative stress were then assessed. Furthermore, a complementary <i>in-vitro</i> study was carried out to evaluate CsA-induced endoplasmic reticulum stress (ERS) and inflammation on cell culture (3T3 cells and MCT cells) using western blot and quantitative RT-PCR..</p><p><strong>Results: </strong>Pretreatment of rats with EALD significantly attenuated the elevated levels of renal dysfunction markers (BUN, creatinine) and suppressed malondialdehyde (MDA) levels; It also significantly regulated the changes in superoxide dismutase (SOD), reduced glutathione (GSH), glutathione peroxydase (GPx), and glutathione S-transferase (GST) levels as compared to Vit. E, demonstrating a more effective recovery in renal tissues. Treatment of cells with CsA was linked to the expression of ERS and inflammatory markers activating transcription factor (ATF4), inositol-requiring enzyme 1α (IRE1α), binding immunoglobulin protein (BiP), and monocyte chemoattractant protein-1 (MCP1). In contrast, pretreatment of cells with EALD resulted in a significant decrease in both ERS and inflammatory markers.</p><p><strong>Conclusion: </strong>These findings indicate the renoprotective potential of <i>L. duriusculum</i>, as it demonstrated the ability to ameliorate CsA-induced renal dysfunction through its distinctive antioxidant properties.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":"27 8","pages":"1023-1032"},"PeriodicalIF":2.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11193500/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141442676","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Andrographolide demonstrates anti-proliferative activity in oral cancer by promoting apoptosis, the programmed cell death process.","authors":"Gauri Mansinh Kumbhar, Amol Dilip Jadhav, Supriya Kheur, Ladke Vaibhav Sunil","doi":"10.22038/ijbms.2024.76691.16599","DOIUrl":"10.22038/ijbms.2024.76691.16599","url":null,"abstract":"<p><strong>Objectives: </strong>Andrographolide has been studied on different types of human cancer cells, but very few studies have been conducted on oral cancer. The study aimed to evaluate the anticancer potential of Andrographolide on an oral cancer cell line (KB) through <i>in-silico</i> network analysis and <i>in vitro</i> assays.</p><p><strong>Materials and methods: </strong>The <i>in-silico</i> analysis involved the determination of drug-likeness prediction, prediction of common targets between oral cancer and andrographolide, Protein-Protein Interactions (PPI), hub genes, top 10 associated pathways by Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway, gene ontology (GO), and molecular docking experiments. <i>In vitro</i> assays comprised MTT assay, apoptosis assay, cell cycle analysis, intracellular reactive oxygen species (ROS) measurement, mitochondrial membrane potential (MMP), anti-migration activity, and gene expressions using polymerase chain reaction (PCR).</p><p><strong>Results: </strong>Fifteen common genes were obtained and were seen to be involved in cellular proliferation, regulation of apoptosis, migration of cells, regulation of MAPK cascade, and regulation of cell cycle. The most common genes involved in the top 10 pathways were MAPK1, MAPK8, MAPK14, and IL6 which were seen to be associated with the MAPK signaling pathway which may be the key pathway through which andrographolide may aid in treating oral cancer. <i>In vitro</i> assays showed anti-proliferative properties, late apoptosis, and anti-migratory properties.</p><p><strong>Conclusion: </strong>According to the results obtained, andrographolide has shown anticancer properties and has the potential to be used as a chemotherapeutic drug. The <i>in-silico</i> approach used in the present study can aid as a model for future research in developing efficient cancer treatments.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":"27 10","pages":"1300-1308"},"PeriodicalIF":2.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11366947/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142125694","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MicroRNA miR-188-5p enhances SUMO2/3 conjugation by targeting SENP3 and alleviates focal cerebral ischemia/reperfusion injury in rats.","authors":"","doi":"10.22038/ijbms.2024.76165.16485","DOIUrl":"10.22038/ijbms.2024.76165.16485","url":null,"abstract":"<p><strong>Objectives: </strong>Expression of miR-188-5p changes upon experiencing cerebral I/R injury. SENP3 is a predicted target of miR-188-5p. The study aimed to examine the potential mechanism underlying the miR-188-5p mediated enhancement of SUMO2/3 conjugation via targeting SENP3 and alleviation against cerebral I/R injury.</p><p><strong>Materials and methods: </strong>Focal cerebral I/R was established in Sprague-Dawley rats using the MCAO model. The expression of miR-188-5p was modulated through intracerebroventricular (ICV) administration of its mimics or inhibitors. The expression of miR-188-5p, SENP3, and SUMO2/3 was detected using RT-qPCR or western blot analysis. Dual luciferase reporter assays were conducted to demonstrate the targeting effect of miR-188-5p on SENP3 in N2a cells. HE staining and TUNEL staining were performed to evaluate neurocellular morphological changes and detect neurocellular apoptosis, respectively. The extent of neurological deficits was evaluated using mNSS. TTC staining was used to evaluate the infarct area.</p><p><strong>Results: </strong>In the cerebral ischemic penumbra, the expression of miR-188-5p declined and SENP3 levels increased following I/R. Dual luciferase reporter assays confirmed that miR-188-5p directly acted on SENP3 in N2a cells. As a self-protective mechanism, SUMO2/3 conjugation increased after reperfusion. After ICV administration of miR-188-5p inhibitor, the expression of miR-188-5p was down-regulated, the expression of SENP3 was up-regulated, the SUMO2/3 conjugation decreased, and cerebral I/R injury was exacerbated. However, ICV administration of small hairpin RNA targeting SENP3 partially reversed the effects of the miR-188-5p inhibitor.</p><p><strong>Conclusion: </strong>MiR-188-5p mitigated cerebral I/R injury by down-regulating SENP3 expression and consequently enhancing SUMO2/3 conjugation in rats.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":"27 10","pages":"1260-1267"},"PeriodicalIF":2.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11366937/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142125703","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fucoidan alleviated autoimmune diabetes in NOD mice by regulating pancreatic autophagy through the AMPK/mTOR1/TFEB pathway.","authors":"Haiqi Gao, Yifan Zhou, Chundong Yu, Guifa Wang, Wenwei Song, Zixu Zhang, Lu Lu, Meilan Xue, Hui Liang","doi":"10.22038/IJBMS.2023.68739.14981","DOIUrl":"10.22038/IJBMS.2023.68739.14981","url":null,"abstract":"<p><strong>Objectives: </strong>The present study investigated the effect and its underlying mechanisms of fucoidan on Type 1 diabetes mellitus (T1DM) in non-obese diabetic (NOD) mice.</p><p><strong>Materials and methods: </strong>Twenty 7-week-old NOD mice were used in this study, and randomly divided into two groups (10 mice in each group): the control group and the fucoidan treatment group (600 mg/kg. body weight). The weight gain, glucose tolerance, and fasting blood glucose level in NOD mice were detected to assess the development of diabetes. The intervention lasted for 5 weeks. The proportions of Th1/Th2 cells from spleen tissues were tested to determine the anti-inflammatory effect of fucoidan. Western blot was performed to investigate the expression levels of apoptotic markers and autophagic markers. Apoptotic cell staining was visualized through TdT-mediated dUTP nick-end labeling (TUNEL).</p><p><strong>Results: </strong>The results suggested that fucoidan ameliorated T1DM, as evidenced by increased body weight and improved glycemic control of NOD mice. Fucoidan down-regulated the Th1/Th2 cells ratio and decreased Th1 type pro-inflammatory cytokines' level. Fucoidan enhanced the mitochondrial autophagy level of pancreatic cells and increased the expressions of Beclin-1 and LC3B II/LC3B I. The expression of p-AMPK was up-regulated and p-mTOR1 was inhibited, which promoted the nucleation of transcription factor EB (TFEB), leading to autophagy. Moreover, fucoidan induced apoptosis of pancreatic tissue cells. The levels of cleaved caspase-9, cleaved caspase-3, and Bax were up-regulated after fucoidan treatment.</p><p><strong>Conclusion: </strong>Fucoidan could maintain pancreatic homeostasis and restore immune disorder through enhancing autophagy via the AMPK/mTOR1/TFEB pathway in pancreatic cells.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":"27 1","pages":"31-38"},"PeriodicalIF":2.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10722478/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139074070","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Joining COPE: Opportunities and benefits for the Iranian Journal of Basic Medical Sciences.","authors":"Leila Arabi, Ali Roohbakhsh, Bizhan Malaekeh-Nikouei, Bibi Sedigheh Fazly Bazzaz","doi":"10.22038/ijbms.2023.76381.16530","DOIUrl":"10.22038/ijbms.2023.76381.16530","url":null,"abstract":"","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":"27 1","pages":"1-2"},"PeriodicalIF":2.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10722480/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139074073","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Voluntary exercise improves pulmonary inflammation through NF-κB and Nrf2 in type 2 diabetic male rats.","authors":"Seyed Zanyar Athari, Fariba Mirzaei Bavil, Rana Keyhanmanesh, Hajie Lotfi, Yousef Sajed, Aref Delkhosh, Fariba Ghiasi","doi":"10.22038/IJBMS.2023.70416.15307","DOIUrl":"10.22038/IJBMS.2023.70416.15307","url":null,"abstract":"<p><strong>Objectives: </strong>This study aimed to evaluate the effects of voluntary exercise as an anti-inflammatory intervention on the pulmonary levels of inflammatory cytokines in type 2 diabetic male rats.</p><p><strong>Materials and methods: </strong>Twenty-eight male Wistar rats were divided into four groups (n=7), including control (Col), diabetic (Dia), voluntary exercise (Exe), and diabetic with voluntary exercise (Dia+Exe). Diabetes was induced by a high-fat diet (4 weeks) and intraperitoneal injection of streptozotocin (35 mg/kg), and animals did training on the running wheel for 10 weeks as voluntary exercise. Finally, the rats were euthanized and the lung tissues were sampled for the evaluation of the levels of pulmonary interleukin (IL)-10, IL-11, and TNF-α using ELISA, and the protein levels of Nrf-2 and NF-κB using western blotting and tissue histopathological analysis.</p><p><strong>Results: </strong>Diabetes reduced the IL-10, IL-11, and Nrf2 levels (<i>P</i><0.001 to P<0.01) and increased the levels of TNF-α and NF-κB compared to the Col group (<i>P</i><0.001). Lung tissue levels of IL-10, IL-11, and Nrf2 in the Dia+Exe group enhanced compared to the Dia group (<i>P</i><0.001 to <i>P</i><0.05), however; the TNF-α and NF-κB levels decreased (<i>P</i><0.001). The level of pulmonary Nrf2 in the Dia+Exe group was lower than that of the Exe group while the NF-κB level increased (<i>P</i><0.001). Moreover, diabetes caused histopathological changes in lung tissue which improved with exercise in the Dia+Exe group.</p><p><strong>Conclusion: </strong>These findings showed that voluntary exercise could improve diabetes-induced pulmonary complications by ameliorating inflammatory conditions.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":"27 1","pages":"74-80"},"PeriodicalIF":2.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10722479/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139074076","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthesis and evaluation of gene delivery vectors based on PEI-modified metal-organic framework (MOF) nanoparticles.","authors":"Somayeh Khosrojerdi, Leila Gholami, Majid Khazaei, Alireza Hashemzadeh, Majid Darroudi, Reza Kazemi Oskuee","doi":"10.22038/IJBMS.2023.71892.15644","DOIUrl":"10.22038/IJBMS.2023.71892.15644","url":null,"abstract":"<p><strong>Objectives: </strong>Zirconium-based metal-organic frameworks (MOFs) nanostructures, due to their capability of easy surface modification, are considered interesting structures for delivery. In the present study, the surfaces of UIO-66 and NH2-UIO-66 MOFs were modified by polyethyleneimine (PEI) 10000 Da, and their efficiency for plasmid delivery was evaluated.</p><p><strong>Materials and methods: </strong>Two different approaches, were employed to prepare surface-modified nanoparticles. The physicochemical characteristics of the resulting nanoparticles, as well as their transfection efficiency and cytotoxicity, were investigated on the A549 cell line.</p><p><strong>Results: </strong>The sizes of DNA/nanocarriers for PEI-modified UIO-66 (PEI-UIO-66) were between 212-291 nm and 267-321 nm for PEI 6-bromohexanoic acid linked UIO-66 (PEI-HEX-UIO-66). The zeta potential of all was positive with the ranges of +16 to +20 mV and +23 to +26 mV for PEI-UIO-66 and PEI-HEX-UIO-66, respectively. Cellular assay results showed that the PEI linking method had a higher rate of gene transfection efficiency with minimal cytotoxicity than the wet impregnation method. The difference between transfection of modified nanoparticles compared to the PEI 10 kDa was not significant but the PEI-HEX-UIO-66 showed less cytotoxicity.</p><p><strong>Conclusion: </strong>The present study suggested that the post-synthetic modification of MOFs with PEI 10000 Da through EDC/NHS+6-bromohexanoic acid reaction can be considered as an effective approach for modifying MOFs' structure in order to obtain nanoparticles with better biological function in the gene delivery process.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":"27 2","pages":"203-213"},"PeriodicalIF":2.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10790290/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139485552","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Polyherbal extract improves glycometabolic control in alloxan-induced diabetic rats <i>via</i> down-regulating the MAPK/JNK pathway, modulating Nrf-2/Keap-1 expression, and stimulating insulin signaling.","authors":"Bilal Aslam, Asif Hussain, Muhammad Naeem Faisal, Shaneel Kousar, Alishbah Roobi, Muhammad Rehan Sajid, Aneela Gul","doi":"10.22038/IJBMS.2023.72553.15780","DOIUrl":"10.22038/IJBMS.2023.72553.15780","url":null,"abstract":"<p><strong>Objectives: </strong>This study focused on the evaluation of antioxidant and antidiabetic activities of polyherbal extract (PHE), containing <i>Cassia absus</i> (L.), <i>Gymnema sylvestre</i> (R. Br.), <i>Nigella sativa</i> (L.), and <i>Piper nigrum</i> (L.), in alloxan-induced diabetes model.</p><p><strong>Materials and methods: </strong><i>In vitro</i>, HPLC characterization, DPPH scavenging assay, and α-amylase inhibition test were conducted. <i>In vivo</i>, acute oral toxicity of PHE was assessed. Alloxan-induced diabetic Wistar rats (n=6) were orally treated with PHE (200, 400, and 600 mg/kg/day) and glibenclamide (GLB; 10 mg/kg/day) for six consecutive weeks. Then, biochemical biomarkers, oxidative stress parameters, histopathological examination, and mRNA expression levels (RT-qPCR) were determined.</p><p><strong>Results: </strong>The presence of polyphenols in PHE was confirmed in correlation to marked DPPH scavenging (IC₅₀: 1.60 mg/ml) and α-amylase inhibition (IC₅₀: 0.82 mg/ml). PHE demonstrated no toxicity in rats up to a dose of 2000 mg/kg. In diabetic rats, PHE dose-dependently ameliorated the serum levels of glucose, insulin, glycated hemoglobin A1c (HbA1c), leptin, and glucokinase (GCK). Also, PHE substantially alleviated serum inflammatory markers (TNF-α and CRP) and oxidative stress indicators (MDA, SOD, and CAT) in pancreatic tissues. PHE, particularly at 600 mg/kg, attenuated cellular oxidative stress <i>via</i> modulating the mRNA expression levels of genes regulating MAPK/JNK (Mapk-8, Traf-4, and Traf-6) and Nrf-2/Keap-1 pathways and promoted insulin signaling through up-regulating insulin signaling cascade (Pdx-1, Ins-1, and Ins-2), as compared to GLB. Furthermore, histopathological findings supported the aforementioned results.</p><p><strong>Conclusion: </strong>Our study suggests that polyherbal extract has promising antioxidant and antidiabetic activities by modulating the MAPK/JNK, Nrf-2/Keap-1, and insulin signaling pathways.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":"27 2","pages":"170-179"},"PeriodicalIF":2.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10790299/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139485611","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}