Current Research in Pharmacology and Drug Discovery最新文献

{"title":"Simvastatin ameliorates oxidative stress levels in HepG2 cells and hyperlipidemic rats","authors":"Kanika Verma ,&nbsp;Shikha Makwana ,&nbsp;Sarvesh Paliwal ,&nbsp;Vartika Paliwal ,&nbsp;Smita Jain ,&nbsp;Swati Paliwal ,&nbsp;Swapnil Sharma","doi":"10.1016/j.crphar.2022.100088","DOIUrl":"10.1016/j.crphar.2022.100088","url":null,"abstract":"<div><p>Simvastatin is an established anti-hyperlipidemic drug and few studies have indicated its role in the mitigation of oxidative stress. However, a systematic study considering molecular binding/interaction of simvastatin with anti-oxidant enzymes followed by confirmational <em>in vitro</em> and <em>in vivo</em> studies have never been done. We investigated the molecular binding of simvastatin with multiple anti-oxidant enzymes and assessed their levels after the treatment of simvastatin <em>in vitro</em> and <em>in vivo</em>. This study is the first to show the molecular binding of simvastatin to catalase through molecular docking analysis. Moreover, the anti-oxidative properties of simvastatin have not been studied in Lipopolysaccharide (LPS) induced oxidative stress in HepG2 cells. We found that simvastatin effectively attenuated oxidative stress in LPS induced HepG2 cells and high-fat diet (HFD) fed hyperlipidemic rats by increasing the levels of antioxidant enzymes. The activity of catalase and superoxide dismutase (SOD) both increased significantly in oxidatively stressed HepG2 cells after the treatment with simvastatin (10 ​μM, 24 ​h). In addition to this, he original cell morphology of oxidatively stressed cells was restored by simvastatin, and an increase in antioxidant enzymes, catalase (0.08 U/cells to 0.12 U/cells), and SOD (0.57 U/cells to 0.74 U/cells) was also noted in HepG2 cells. Furthermore, a significant increase in the antioxidant enzymes such as Catalase, SOD, and reduced glutathione (GSH) was noted after simvastatin treatment in the HFD model. Moreover, we also observed degradation of by-products of lipid peroxidation thiobarbituric acid reactive substances (TBARs), nitric oxide (NO), and protein carbonyl levels. This indicates that simvastatin enhances anti-oxidant enzyme activities and can be repurposed for the treatment of oxidative stress in liver diseases in humans after extensive clinical trials.</p></div>","PeriodicalId":10877,"journal":{"name":"Current Research in Pharmacology and Drug Discovery","volume":"3 ","pages":"Article 100088"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/5d/11/main.PMC8818901.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39908762","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacodynamic evaluation of the XOR inhibitor WN1703 in a model of chronic hyperuricemia in rats induced by yeast extract combined with potassium oxonate","authors":"Yuanyuan Li ,&nbsp;Xinying Zhu ,&nbsp;Fuyao Liu,&nbsp;Wen Peng,&nbsp;Lei Zhang,&nbsp;Jing Li","doi":"10.1016/j.crphar.2022.100098","DOIUrl":"10.1016/j.crphar.2022.100098","url":null,"abstract":"<div><p>Hyperuricemia is a common disease caused by a disorder of purine metabolism, which often causes hyperlipidemia and other metabolic diseases. WN1703 was demonstrated to be an effective xanthine oxidoreductase (XOR) inhibitor in our previous study. Here, we evaluated the pharmacodynamic effect of WN1703 on rats suffering from chronic hyperuricemia accompanied by disorders of lipid metabolism. We discovered that WN1703 was an efficacious uric acid (UA)-lowering compound. Simultaneously, it had effect on relieving renal injury, regulating lipid metabolism by reducing levels of triglycerides and low-density lipoprotein-cholesterol, increasing levels of high-density lipoprotein-cholesterol, and improving renal and liver lesions. WN1703 also exhibited anti-inflammatory and antioxidant activity by alleviating the increasing trend of levels of tumor necrosis factor-α, interleukin-1β, monocyte chemoattractant protein-1, and malondialdehyde, and improving the activity of superoxide dismutase and glutathione peroxidase. WN1703 appeared to be more effective than febuxostat in inhibiting XOR and had higher antioxidant activity. In general, the pharmacologic action of WN1703 showed a clear dose–effect relationship.</p></div>","PeriodicalId":10877,"journal":{"name":"Current Research in Pharmacology and Drug Discovery","volume":"3 ","pages":"Article 100098"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590257122000189/pdfft?md5=7953d7503a72979fce77444ba6a602aa&pid=1-s2.0-S2590257122000189-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45609166","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhalation potential of N-Acetylcysteine loaded PLGA nanoparticles for the management of tuberculosis: In vitro lung deposition and efficacy studies","authors":"Vishal Puri ,&nbsp;Kabi Raj Chaudhary ,&nbsp;Arti Singh ,&nbsp;Charan Singh","doi":"10.1016/j.crphar.2022.100084","DOIUrl":"https://doi.org/10.1016/j.crphar.2022.100084","url":null,"abstract":"<div><p>Several studies have stated that mucus is a critical hurdle for drug delivery to the mucosal tissues. As a result, Polymeric nanoparticles that can overcome mucus barriers are gaining popularity for controlled drug delivery into intra-macrophages to attain high intracellular drug concentration. The present study was aimed to fabricate inhalable N-acetylcysteine (NAC) modified PLGA mucus penetrating particles using the double emulsion method (w/o/w) for target delivery to alveolar macrophages and minimize the dose-related adverse effects, efficiently encapsulate hydrophilic drug, sustain the release profile and prolong the retention time for the management of tuberculosis. Among the numerous formulations, the drug/polymer ratio of 1:10 with 0.50% PVA concentration and sonication time for 2 ​min ​s was chosen for further research. The formulated nanoparticles had a mean particle size of 307.50 ​± ​9.54 ​nm, PDI was 0.136 ​± ​0.02, zeta potential about −11.3 ​± ​0.4 ​mV, decent entrapment efficiency (55.46 ​± ​2.40%), drug loading (9.05 ​± ​0.22%), and excellent flowability. FTIR confirmed that NAC and PLGA were compatible with each other. SEM graphs elucidated that the nanoparticles were spherically shaped with a slightly rough surface whereas TEM analysis ensured the nanometer size nanoparticles and coating of lipid over NPs surface. PXRD spectrum concluded the transformation of the drug from crystalline to amorphous state in the formulation. <em>In vitro</em> release pattern was biphasic started with burst release (64.67 ​± ​1.53% within 12hrs) followed by sustained release over 48hrs thus enabling the prolonged replenishing of NAC. <em>In vitro</em> lung deposition study pronounced that coated NAC-PLGA-MPPs showed favorable results in terms of emitted dose (86.67 ​± ​2.52%), MMAD value (2.57 ​± ​0.12 ​μm), GSD value (1.55 ​± ​0.11 ​μm), and FPF of 62.67 ​± ​2.08% for the deposition and targeting the lungs. Finally, <em>in vitro</em> efficacy studies demonstrated that NAC-PLGA-MPPs presented more prominent antibacterial activity against <em>MTB</em> H37Rv strain as compared to NAC. Hence, PLGA based particles could be a better strategy to deliver the NAC for lung targeting.</p></div>","PeriodicalId":10877,"journal":{"name":"Current Research in Pharmacology and Drug Discovery","volume":"3 ","pages":"Article 100084"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590257122000049/pdfft?md5=9d6ce61748d75bd93ac5b28f8736af54&pid=1-s2.0-S2590257122000049-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91588968","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Down regulation of fatty acid synthase via inhibition of PI3K/AKT/mTOR in ovarian cancer cell line by novel organoselenium pseudopeptide","authors":"Abeer M. El-Saudi ,&nbsp;Miram A. Altouhamy ,&nbsp;Saad Shaaban ,&nbsp;Farid A. Badria ,&nbsp;Magdy M. Youssef ,&nbsp;Fardous F. El-Senduny","doi":"10.1016/j.crphar.2022.100134","DOIUrl":"10.1016/j.crphar.2022.100134","url":null,"abstract":"<div><p>Ovarian cancer (OC) is the 7th most common cancer in women world-wide and the 3rd most common female cancer. For the treatment of OC, there is no successful therapeutic. The medications that are currently available have significant side effects and a low therapeutic index. This work aimed to evaluate the anticancer activity of organoselenium pseudopeptide compound against OC cell lines. After treatment with 50 ​μM of compound <strong>4</strong> (CPD <strong>4</strong>), the viability was determined. The anticancer activity was further investigated by different methods including cell cycle and apoptosis analysis, colony formation assay, zymography, comet assay and Western blot. In comparison to a positive control, compound <strong>4</strong> showed cytotoxicity toward A2780CP cells rather than A2780 and SKOV-3 ​cells. Compound <strong>4</strong> was more selective to OC cells rather than HSF cells. Moreover, Compound <strong>4</strong> was able to inhibit cell migration and proliferation. The anticancer effect of compound <strong>4</strong> was found to be partially <em>via</em> cell cycle arrest, overexpression of p27 ​cell cycle inhibitor and induction of apoptosis through DNA fragmentation and activated production of ROS. Compound <strong>4</strong> had a differential effect on the modulation of PI3K/AKT/mTOR signaling pathway in the OC treated cell lines, also inhibited lipogenesis process <em>via</em> downregulation of FASN expression. <strong>Conclusion</strong>: This work highlights the unique role of Compound <strong>4</strong> against OC <em>via</em> modulation of oxidative stress, inhibition of survival PI3K/AKT/mTOR pathway. Compound <strong>4</strong> was found to be a promising alternative therapy for the treatment of OC in this investigation.</p></div>","PeriodicalId":10877,"journal":{"name":"Current Research in Pharmacology and Drug Discovery","volume":"3 ","pages":"Article 100134"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/d8/3b/main.PMC9780069.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10438049","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Amelioration of experimentally induced inflammatory arthritis by intra-articular injection of visnagin","authors":"Sowmyasree Gurram,&nbsp;Pratibha Anchi,&nbsp;Biswajit Panda,&nbsp;Sayali Santosh Tekalkar,&nbsp;Ravindra Bapu Mahajan,&nbsp;Chandraiah Godugu","doi":"10.1016/j.crphar.2022.100114","DOIUrl":"10.1016/j.crphar.2022.100114","url":null,"abstract":"<div><h3>Background</h3><p>Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease characterized by synovial hyperplasia, cartilage destruction and bone erosion. Visnagin (VIS) is a proven anti-inflammatory agent and in this study, we aimed to evaluate the anti-arthritic activity of VIS when administered via intra-articular (I.A.) route of administration.</p></div><div><h3>Materials and methods</h3><p>RAW 264.7 ​cells were stimulated with lipopolysaccharide (LPS) (1 ​μg/mL) and treated with VIS at concentrations of 12.5 and 25 ​μM. Arthritis was induced in Sprague Dawley rats by administering Complete Freund's Adjuvant (CFA) (1 ​mg/mL) through (I.A.) route and treated with VIS via (I.A.) route at doses of 3 and 10 ​mg/kg twice a week for 3 weeks. Protective effects were assessed by arthritic score, behavioral studies for pain evaluation, radiological assessment, histopathological examination and molecular studies.</p></div><div><h3>Results</h3><p>Our results indicated that VIS significantly reduced LPS induced inflammation in RAW 264.7 ​cells. While in arthritic rats, VIS reduced the disease scorings with improvement towards pain. Pathological examination demonstrated that VIS reduced knee joint inflammation and cartilage destruction. Radiographic analysis and molecular studies also supported the protective effects of VIS.</p></div><div><h3>Conclusion</h3><p>The results of the study imply that VIS exerted potential anti-inflammatory and anti-arthritic activity in <em>in vitro</em> and <em>in vivo</em> models of RA.</p></div>","PeriodicalId":10877,"journal":{"name":"Current Research in Pharmacology and Drug Discovery","volume":"3 ","pages":"Article 100114"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/23/ef/main.PMC9389203.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40433140","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A review of fenfluramine for the treatment of Dravet syndrome patients","authors":"Kayla Simon ,&nbsp;Hunter Sheckley ,&nbsp;Christopher L. Anderson ,&nbsp;Zhao Liu ,&nbsp;Paul R. Carney","doi":"10.1016/j.crphar.2021.100078","DOIUrl":"10.1016/j.crphar.2021.100078","url":null,"abstract":"<div><h3>Introduction</h3><p>Dravet Syndrome (DS) is a rare epileptiform disorder typically presenting within the first year of life of a normally developing infant. It is characterized by several prolonged seizures that are often resistant to current anti-epileptic drug (AED) regimens. This paper outlines the history and clinical trials of the drug fenfluramine, a drug that when used in addition to AED regimens may provide hope to children affected by DS.</p></div><div><h3>Body</h3><p>Fenfluramine (3-trifulormethyl-N-ethylamphetamine) is an amphetamine derivative that primarily affects serotonin neurotransmitter levels. It was initially prescribed in the 1960s as an appetite suppressant marketed as a weight loss drug. However, it was removed from the markets due to its association with cardiac valvopathies. It continued to by studied in epilepsy by Gastaut in the 1980s in children with self-induced syncope and irretractable epilepsy. In 2012, Ceulemans et al. studied the use of fenfluramine in patients with DS. Following the success of that retrospective case study, Nabbout et al. and Legae et al. conducted two randomized control trials leading to the FDA approval of fenfluramine under its trade name Fintepla in 2020.</p></div><div><h3>Discussion</h3><p>The success of the randomized control trials suggests the addition of fenfluramine to current AED regimens may lead to better control of seizures in patients with DS. The side effects of fenfluramine prove to be manageable and the concern for valvopathies has not been reproducible with low dose fenfluramine.</p></div>","PeriodicalId":10877,"journal":{"name":"Current Research in Pharmacology and Drug Discovery","volume":"3 ","pages":"Article 100078"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/3b/61/main.PMC8695265.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39789123","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Medical management of chronic pouch inflammation","authors":"Maia Kayal,&nbsp;Marla C. Dubinsky","doi":"10.1016/j.crphar.2022.100095","DOIUrl":"10.1016/j.crphar.2022.100095","url":null,"abstract":"","PeriodicalId":10877,"journal":{"name":"Current Research in Pharmacology and Drug Discovery","volume":"3 ","pages":"Article 100095"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590257122000153/pdfft?md5=f1eacd36b010cbf839d0e193ca6a39a8&pid=1-s2.0-S2590257122000153-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41652691","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Galantamine tethered hydrogel as a novel therapeutic target for streptozotocin-induced Alzheimer's disease in Wistar rats","authors":"Manickam Rajkumar ,&nbsp;Murugesan Sakthivel ,&nbsp;Kottaisamy Senthilkumar ,&nbsp;Ramasundaram Thangaraj ,&nbsp;Soundarapandian Kannan","doi":"10.1016/j.crphar.2022.100100","DOIUrl":"10.1016/j.crphar.2022.100100","url":null,"abstract":"<div><p>Amyloid-β (Aβ) plaque formation, neuronal cell death, and cognitive impairment are the unique symptoms of Alzheimer's disease (AD). No single step remedy is available to treat AD, so the present study aimed to improve the drugability and minimize the abnormal behavioral and biochemical activities in streptozotocin (STZ) induced AD experimental Wistar rats. In particular, we explored the utilization of methacrylated gelatin (GelMA), which is a biopolymeric hydrogel that mimics the natural tissue environment. The synthesized biopolymeric gel contained the drug galantamine (Gal). Investigations were conducted to evaluate the behavioral activities of STZ-induced AD experimental rats under STZ ​+ ​GelMA ​+ ​Gal treatment. The experimental groups comprised the control and STZ, STZ ​+ ​GelMA, STZ ​+ ​Gal, and STZ ​+ ​GelMA ​+ ​Gal (10 ​mg/kg) treated rats. Intracerebroventricular STZ ensures cognitive decline in terms of an increase in the escape latency period, with a decrease in the spontaneous alteration of behavioral activities. Our results indicated decrease Aβ aggregation in the hydrogel-based drug treatment group and significant decreases in the levels of acetylcholinesterase and lipid peroxidation (<em>p</em> ​&lt; ​0.001). In addition, the glutathione and superoxide dismutase activities appeared to be improved in the STZ ​+ ​GelMA ​+ ​Gal group compared with the other treatment groups. Furthermore, histopathological and immunohistochemical experiments showed that the GelMA ​+ ​Gal treated AD rats exhibited significantly improved behavioral and biochemical activities compared with the STZ treated AD rats. Therefore, STZ ​+ ​GelMA ​+ ​Gal administration from the pre-plaque stage may have a potential clinical application in the prevention of AD. Thus, we conclude that hydrogel-based Gal drugs are efficient at decreasing Aβ aggregation and improving the neuroinflammatory process, antioxidant activity, and neuronal growth.</p></div>","PeriodicalId":10877,"journal":{"name":"Current Research in Pharmacology and Drug Discovery","volume":"3 ","pages":"Article 100100"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590257122000207/pdfft?md5=df1ec666f8a8dc260e899bccd6ff055a&pid=1-s2.0-S2590257122000207-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45652675","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Indole: A promising scaffold for the discovery and development of potential anti-tubercular agents","authors":"Nilesh Gajanan Bajad ,&nbsp;Sudhir Kumar Singh ,&nbsp;Sushil Kumar Singh ,&nbsp;Tryambak Deo Singh ,&nbsp;Meenakshi Singh","doi":"10.1016/j.crphar.2022.100119","DOIUrl":"10.1016/j.crphar.2022.100119","url":null,"abstract":"<div><p>Indole-containing small molecules have been reported to have diverse pharmacological activities. The aromatic heterocyclic scaffold, which resembles various protein structures, has received attention from organic and medicinal chemists. Exploration of indole derivatives in drug discovery has rapidly yielded a vast array of biologically active compounds with broad therapeutic potential. Nature is the major source of indole scaffolds, but various classical and advanced synthesis methods for indoles have also been reported. One-pot synthesis is widely considered an efficient approach in synthetic organic chemistry and has been used to synthesize some indole compounds. The rapid emergence of drug-resistant tuberculosis is a major challenge to be addressed. Identifying novel targets and drug candidates for tuberculosis is therefore crucial. Researchers have extensively explored indole derivatives as potential anti-tubercular agents or drugs. Indole scaffolds containing the novel non-covalent (decaprenylphosphoryl-β-D-ribose2′-epimerase) DprE1 inhibitor 1,4-azaindole is currently in clinical trials to treat <em>Mycobacterium tuberculosis</em>. In addition, DG167 indazole sulfonamide with potent anti-tubercular activity is undergoing early-stage development in preclinical studies. Indole bearing cationic amphiphiles with high chemical diversity have been reported to depolarize and disrupt the mycobacterial membrane. Some indole-based compounds have potential inhibitory activities against distinct anti-tubercular targets, including the inhibition of cell wall synthesis, replication, transcription, and translation, as summarized in the graphical abstract. The success of computer-aided drug design in the fields of cancer and anti-viral drugs has accelerated <em>in silico</em> studies in antibacterial drug development. This review describes the sources of indole scaffolds, the potential for novel indole derivatives to serve as anti-tubercular agents, <em>in silico</em> findings, and proposed actions to facilitate the design of novel compounds with anti-tubercular activity.</p></div>","PeriodicalId":10877,"journal":{"name":"Current Research in Pharmacology and Drug Discovery","volume":"3 ","pages":"Article 100119"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/61/c3/main.PMC9389259.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40433137","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inonotus obliquus aqueous extract prevents histopathological alterations in liver induced by environmental toxicant Microcystin","authors":"Pir Mohammad Ishfaq ,&nbsp;Shivani Mishra ,&nbsp;Anjali Mishra ,&nbsp;Zaved Ahmad ,&nbsp;Shovanlal Gayen ,&nbsp;Subodh Kumar Jain ,&nbsp;Swati Tripathi ,&nbsp;Siddhartha Kumar Mishra","doi":"10.1016/j.crphar.2022.100118","DOIUrl":"10.1016/j.crphar.2022.100118","url":null,"abstract":"<div><p>Environmental toxicants like microcystins are known to adversely impact liver physiology and lead to the increased risk for abnormal liver function and even liver carcinoma. Chaga mushroom (<em>Inonotus obliquus</em>) is reported for various properties mainly antibacterial, antiallergic, anti-inflammatory, antioxidant, and anticancer properties. This study was aimed to assess the effect microcystin (MC-LR) on histopathology of liver in mice and a preventive measure by using aqueous extract of <em>Inonotus obliquus</em> (IOAE). Adult Balb/c mice were administered with MC-LR at 20 ​μg/kg body weight, per day, intraperitoneal (i.p.) for 4 weeks. IOAE was treated to one group of MC-LR mice at 200 ​mg/kg body weight, per oral, for 4 weeks. Histological staining for liver structural details and biochemical assays for functions were assessed. The results of the study showed that MC-LR drastically reduced the body weight of mice which were restored close to the range of control by IOAE treatment. MC-LR exposed mice showed 1.9, 1.7 and 2.2-fold increase in the levels of SGOT, SGPT and LDH which were restored by IOAE treatment as compared to control (one-fold). MC-LR exposed mice showed reduced level of GSH (19.83 ​± ​3.3 ​μM) which were regained by IOAE treatment (50.83 ​± ​3.0 ​μM). Similar observations were noted for catalase activity. Histological examinations show that MC-LR exposed degenerative changes in the liver sections which were restored by IOAE supplementation. The immunofluorescence analysis of caspase-3 counterstained with DAPI showed that MC-LR led to the increased expression of caspase-3 which were comparatively reduced by IOAE treatment. The cell viability decreased on increasing the concentration of MC-LR with 5% cell viability at concentration of 10 ​μg MC-LR/mL as that of control 100% Cell viability. The IC₅₀ was calculated to be 3.6 ​μg/ml, indicating that MC-LR is chronic toxic to AML12 mouse hepatocytes. The molecular docking interaction of NF-κB-NIK with ergosterol peroxidase showed binding interaction between the two and showed the plausible molecular basis for the effects of IOAE in MC-LR induced liver injury. Collectively, this study revealed the deleterious effects of MC-LR on liver through generation of oxidative stress and activation of caspase-3, which were prevented by treatment with IOAE.</p></div>","PeriodicalId":10877,"journal":{"name":"Current Research in Pharmacology and Drug Discovery","volume":"3 ","pages":"Article 100118"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/c7/6c/main.PMC9389225.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40433139","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}