Current Research in Pharmacology and Drug Discovery最新文献

{"title":"Three-dimensional spheroids of choroid-retinal vascular endothelial cells as an in-vitro model for diabetic retinopathy: Proof-of-concept investigation","authors":"Manish Gore ,&nbsp;Ankit Tiwari ,&nbsp;Devashree Jahagirdar ,&nbsp;Angayarkanni Narayanasamy ,&nbsp;Ratnesh Jain ,&nbsp;Prajakta Dandekar","doi":"10.1016/j.crphar.2022.100111","DOIUrl":"10.1016/j.crphar.2022.100111","url":null,"abstract":"<div><p>Diabetic retinopathy (DR) is a primary microvascular complication of <em>diabetes mellitus</em> and a vision-threatening condition. Vascular endothelial growth factor (VEGF) induces neovascularization and causes metabolic damage to the retinal and choroidal vasculature in diabetic patients. Existing drug screening models and treatment strategies for DR need to be refined through the establishment of relevant pre-clinical models, which may enable development of effective and safe therapies. The present study discusses the development of an <em>in-vitro</em> three-dimensional (3D) spheroid model, using RF/6A choroid-retinal vascular endothelial cells, to closely mimic the <em>in-vivo</em> disease condition. Compact, reproducibly-sized, viable and proliferating RF/6A spheroids were fabricated, as confirmed by microscopy, live/dead assay, cell proliferation assay and histological staining. <em>In-vitro</em> angiogenesis was studied by evaluating individual effects of VEGF and an anti-VEGF monoclonal antibody, Bevacizumab, and their combination on cellular proliferation and 3D endothelial sprout formation. VEGF stimulated angiogenic sprouting while Bevacizumab demonstrated a dose-dependent anti-angiogenic effect, as determined from the cellular proliferation observed and extent and length of sprouting. These investigations validated the potential of RF/6A spheroids in providing an alternative-to-animal, pathophysiologically-relevant model to facilitate pre-clinical and biomedical research related to DR.</p></div>","PeriodicalId":10877,"journal":{"name":"Current Research in Pharmacology and Drug Discovery","volume":"3 ","pages":"Article 100111"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590257122000311/pdfft?md5=8c1fc3b9bc02e5db442072529a4cb169&pid=1-s2.0-S2590257122000311-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42375327","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":"Anti-emetic effects of thalidomide: Evidence, mechanism of action, and future directions","authors":"Paul L.R. Andrews ,&nbsp;Robin S.B. Williams ,&nbsp;Gareth J. Sanger","doi":"10.1016/j.crphar.2022.100138","DOIUrl":"10.1016/j.crphar.2022.100138","url":null,"abstract":"<div><p>The rationale for using thalidomide (THD) as a treatment for nausea and vomiting during pregnancy in the late 1950s appears to have been based on its sedative or hypnotic properties. In contrast to contemporaneous studies on the anti-emetic activity of phenothiazines, we were unable to identify publications reporting preclinical or clinical evaluation of THD as an anti-emetic. Our survey of the literature revealed a clinical study in 1965 showing THD reduced vomiting in cancer chemotherapy which was substantiated by similar studies from 2000, particularly showing efficacy in the delayed phase of chemotherapy-induced nausea and vomiting. To identify the mechanism(s) potentially involved in thalidomide's anti-emetic activity we reviewed its pharmacology in the light of nausea and vomiting mechanisms and their pharmacology with a particular emphasis on chemotherapy and pregnancy. The process identified the following potential mechanisms: reduced secretion of Growth Differentiation Factor 15, suppression of inflammation/prostaglandin production, downregulation of cytotoxic drug induced upregulation of iNOS, and modulation of BK (K_Ca1.1) channels and GABA_A/glutamate transmission at critical points in the emetic pathways (nucleus tractus solitarius, area postrema). We propose ways to investigate these hypothesized mechanisms and discuss the associated challenges (e.g., objective quantification of nausea) in addition to some of the more general aspects of developing novel drugs to treat nausea and vomiting.</p></div>","PeriodicalId":10877,"journal":{"name":"Current Research in Pharmacology and Drug Discovery","volume":"3 ","pages":"Article 100138"},"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/8d/16/main.PMC9780081.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10276779","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":"Antibacterial and antitumor activities of a lectin-rich preparation from Microgramma vacciniifolia rhizome","authors":"Gabriela Cavalcante da Silva ,&nbsp;Alisson Macário de Oliveira ,&nbsp;Wêndeo Kennedy Costa ,&nbsp;Antônio Felix da Silva Filho ,&nbsp;Maira Galdino da Rocha Pitta ,&nbsp;Moacyr Jesus Barreto de Melo Rêgo ,&nbsp;Ivone Antônia de Souza ,&nbsp;Patrícia Maria Guedes Paiva ,&nbsp;Thiago Henrique Napoleão","doi":"10.1016/j.crphar.2022.100093","DOIUrl":"10.1016/j.crphar.2022.100093","url":null,"abstract":"<div><p>The rhizome of <em>Microgramma vacciniifolia</em> contains a lectin (carbohydrate-binding protein) called MvRL. Studies demonstrated that a MvRL-rich fraction did not show <em>in vivo</em> genotoxicity and acute toxicity in mice. This study aimed to evaluate the MvRL-rich fraction from <em>M. vacciniifolia</em> rhizome for antibacterial activity <em>in vitro</em> and <em>in vivo</em> as well as antitumor effect <em>in vivo</em> using the Ehrlich carcinoma model in mice. The fraction showed antibacterial activity against <em>Acinetobacter baumannii</em>, <em>Escherichia coli</em>, <em>Klebsiella pneumoniae</em>, <em>Pseudomonas aeruginosa</em>, and <em>Staphylococcus aureus</em> with minimal inhibitory concentrations ranging from 31.2 to 125.0 ​μg/mL and minimal bactericidal concentrations from 62.5 to 200 ​μg/mL. The fraction was also effective <em>in vivo</em> against infection caused by these bacteria on <em>Tenebrio molitor</em> larvae considering the parameters evaluated. In regard to the antitumor activity, the treatments of Ehrlich carcinoma-bearing mice with the fraction at 100 and 200 ​mg/kg <em>per os</em> resulted in 62.58% and 75.43% of tumor inhibition, respectively. In conclusion, the MvRL-rich fraction showed <em>in vivo</em> antibacterial and antitumor activities and thus can be considered as an alternative of natural origin for the development of candidates for therapy.</p></div>","PeriodicalId":10877,"journal":{"name":"Current Research in Pharmacology and Drug Discovery","volume":"3 ","pages":"Article 100093"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S259025712200013X/pdfft?md5=b393f2d5693c4880f428baae24007eba&pid=1-s2.0-S259025712200013X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45344496","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":"Investigation of the cytotoxicity induced by didocosahexaenoin, an omega 3 derivative, in human prostate carcinoma cell lines","authors":"Glenn F. Robinson,&nbsp;Kartheek KY. Sooda,&nbsp;Roger M. Phillips,&nbsp;Simon J. Allison,&nbsp;Farideh A. Javid","doi":"10.1016/j.crphar.2022.100085","DOIUrl":"10.1016/j.crphar.2022.100085","url":null,"abstract":"<div><p>The aim of the present study was to investigate the cytotoxicity induced by an omega-3 derivative, didocosahexaenoin (Dido) on human prostate carcinoma cells and to compare the cytotoxicity to that of docosahexaenoic acid (DHA). Different carcinoma- and non-carcinoma cells were exposed to various concentrations of omega-3 compounds at varying exposure times and the cytotoxicity was measured by MTT assay. The mechanism of Dido-induced apoptosis was investigated in prostate carcinoma cells. Dido induced stronger cytotoxicity than DHA in human prostate carcinoma cells in a dose- and time-dependent manner. Dido was also more selective and potent in inducing cytotoxicity in prostate carcinoma cells than other carcinoma cell lines tested. Pre-treatment with Dido increased the level of reactive oxygen species (ROS) in prostate carcinoma cells. Pre-treatment with various antioxidants reduced the cytotoxicity induced by Dido. Pre-treatment with Dido ≥30 ​μM also induced apoptosis which was suggested to involve an externalisation of phosphatidyl serine, a significant increase in the mitochondrial membrane potential (p ​&lt; ​0.01) and the level of activated caspase 3/7 (p ​&lt; ​0.05) in prostate carcinoma cells. This study is the first to show that Dido induced cytotoxicity with high selectivity and higher potency than DHA in human prostate carcinoma cells. The mechanism of action is likely to involve an increase in the level of ROS, loss in the mitochondrial membrane potential as well as externalisation of phosphatidyl serine and increase in the caspase 3/7 activity. Dido may have potential to be used for the adjuvant therapy or combination therapy with conventional chemotherapeutic drugs.</p></div>","PeriodicalId":10877,"journal":{"name":"Current Research in Pharmacology and Drug Discovery","volume":"3 ","pages":"Article 100085"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8790608/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39883747","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":"Ileal and colonic Crohn's disease: Does location makes a difference in therapy efficacy?","authors":"Raja Atreya ,&nbsp;Christian Bojarski ,&nbsp;Anja A. Kühl ,&nbsp;Zlatko Trajanoski ,&nbsp;Markus F. Neurath ,&nbsp;Britta Siegmund","doi":"10.1016/j.crphar.2022.100097","DOIUrl":"10.1016/j.crphar.2022.100097","url":null,"abstract":"<div><p>Within the IBD entity of Crohn's disease, there is currently no differentiation between ileal and colonic manifestation for recruitment of patients in clinical trials, well-powered analysis of study results or therapeutic decisions in daily clinical practice. However, there is accumulating evidence from epidemiological, genetic, microbial, immunological, and clinical characteristics that clearly indicate that ileal Crohn's disease represents a distinct disease entity, which differentiates itself from colonic Crohn's disease. This is also reflected by lower efficacy of targeted therapies in isolated ileal compared to colonic Crohn's disease. The distinct site-specific mechanisms that drive heightened non-response in ileal disease need to be analysed in-depth in the future, to enable optimized therapy in the individual Crohn's disease patient.</p></div>","PeriodicalId":10877,"journal":{"name":"Current Research in Pharmacology and Drug Discovery","volume":"3 ","pages":"Article 100097"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590257122000177/pdfft?md5=fc0aab03baba50b560c0c6a17e894e3a&pid=1-s2.0-S2590257122000177-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48766214","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":"Pretomanid for tuberculosis treatment: an update for clinical purposes","authors":"Sara Occhineri ,&nbsp;Tommaso Matucci ,&nbsp;Laura Rindi ,&nbsp;Giusy Tiseo ,&nbsp;Marco Falcone ,&nbsp;Niccolò Riccardi ,&nbsp;Giorgio Besozzi","doi":"10.1016/j.crphar.2022.100128","DOIUrl":"10.1016/j.crphar.2022.100128","url":null,"abstract":"<div><p>Coronavirus disease (COVID-19) pandemic determined a 10 years-set back in tuberculosis (TB) control programs. Recent advances in available therapies may help recover the time lost. While Linezolid (LZD) and Bedaquiline (BDQ), previously Group D second line drugs (SLDs) for TB, have been relocated to Group A, other drugs are currently being studied in regimens for drug resistant TB (DR-TB). Among these, Pretomanid (PA), a recently introduced antimycobacterial drug derived from nitroimidazole with both solid bactericidal and bacteriostatic effect, and with an excellent effectiveness and tolerability profile, is in the spotlight. Following promising data obtained from recently published and ongoing randomized controlled trials (RCTs), the World Health Organization (WHO) determined to include PA in its guidelines for the treatment of rifampicin-resistant (RR), multi drug resistant (MDR) and pre-extensively drug resistant TB (pre-XDR-TB) with BDQ, LZD and Moxifloxacine (MFX) in a 6-month regimen. Although further studies on the subject are needed, PA may also represent a treatment option for drug-susceptible TB (DS-TB), latent TB infection (LTBI) and non tuberculous mycobacteria (NTM). This narrative review aims to examine current implementation options and future possibilities for PA in the never-ending fight against TB.</p></div>","PeriodicalId":10877,"journal":{"name":"Current Research in Pharmacology and Drug Discovery","volume":"3 ","pages":"Article 100128"},"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/08/2c/main.PMC9461242.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10326730","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":"The safe use of inflammatory bowel disease therapies during the COVID-19 pandemic","authors":"Chethana Kamath MD,&nbsp;Erica J Brenner MD, MSCR","doi":"10.1016/j.crphar.2022.100101","DOIUrl":"10.1016/j.crphar.2022.100101","url":null,"abstract":"<div><h3>Background</h3><p>Patients with inflammatory bowel disease (IBD) often require the use of immunosuppressant medications that increase infection risk, leading to concerns over the safe use of IBD medications during the Coronavirus 19 (COVID-19) pandemic.</p></div><div><h3>Objectives</h3><p>To summarize available evidence on the safety and appropriate use of IBD medications during the COVID-19 pandemic, particularly in regard to risk of severe COVID-19 outcomes such as hospitalization, respiratory failure, or death for patients on IBD therapeutics.</p></div><div><h3>Conclusions</h3><p>The majority of IBD medications are safe to continue during the COVID-19 pandemic, with a few notable exceptions. Patients with IBD who do not have COVID-19 should continue their prescribed IBD therapies, although steroids are associated with severe COVID-19 outcomes and should be weaned when possible. Corticosteroids should be tapered and discontinued when possible in patients with IBD who test positive for COVID-19 as well. Patients with IBD who test positive for COVID-19 should hold biologics, thiopurines, methotrexate, and tofacitinib for at least 2 weeks, and those who have symptoms should not restart these medications until symptom resolution. During the COVID-19 pandemic, all patients with IBD should continue to follow public health guidance including social distancing, masking, and COVID-19 vaccination recommendations.</p></div>","PeriodicalId":10877,"journal":{"name":"Current Research in Pharmacology and Drug Discovery","volume":"3 ","pages":"Article 100101"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590257122000219/pdfft?md5=9778853321ade305c57b923f44f0ddbe&pid=1-s2.0-S2590257122000219-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46704838","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":"Cellular and molecular mechanisms, genetic predisposition and treatment of diabetes-induced cardiomyopathy","authors":"Urvashi Sharma,&nbsp;Manodeep Chakraborty,&nbsp;Devid Chutia,&nbsp;Nihar Ranjan Bhuyan","doi":"10.1016/j.crphar.2022.100126","DOIUrl":"10.1016/j.crphar.2022.100126","url":null,"abstract":"<div><p>Diabetes mellitus is a common disease affecting millions of people worldwide. This disease is not limited to metabolic disorders but also affects several vital organs in the body and can lead to major complications. People with diabetes mellitus are subjected to cardiovascular complications, such as cardiac myopathy, which can further result in major complications such as diabetes-induced cardiac failure. The mechanism underlying diabetes-induced cardiac failure requires further research; however, several contributing factors have been identified to function in tandem, such as reactive oxygen species production, inflammation, formation of advanced glycation end-products, altered substrate utilisation by mitochondria, activation of the renin–angiotensin–aldosterone system and lipotoxicity. Genetic factors such as microRNAs, long noncoding RNAs and circular RNAs, as well as epigenetic processes such as DNA methylation and histone modifications, also contribute to complications. These factors are potential targets for developing effective new therapies. This review article aims to facilitate in depth understanding of these contributing factors and provide insights into the correlation between diabetes mellitus and cardiovascular complications. Some alternative targets with therapeutic potential are discussed to indicate favourable targets for the management of diabetic cardiomyopathy.</p></div>","PeriodicalId":10877,"journal":{"name":"Current Research in Pharmacology and Drug Discovery","volume":"3 ","pages":"Article 100126"},"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/dc/d2/main.PMC9780063.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10437353","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":"Fabrication and evaluation of mannose decorated curcumin loaded nanostructured lipid carriers for hepatocyte targeting: In vivo hepatoprotective activity in Wistar rats","authors":"Manish Kumar Gupta ,&nbsp;Vipul Sansare ,&nbsp;Birendra Shrivastava ,&nbsp;Santosh Jadhav ,&nbsp;Prashant Gurav","doi":"10.1016/j.crphar.2022.100083","DOIUrl":"https://doi.org/10.1016/j.crphar.2022.100083","url":null,"abstract":"<div><p>Curcumin is a well-recognized antioxidant phytoactive isolated from the rhizomes of <em>Curcuma longa</em>. Numerous landmark investigations have proved the antioxidant and hepatoprotective potential of curcumin. The aim of present study was to target curcumin loaded nanocarriers to hepatocytes using asialoglycoprotein receptors targeting strategy. Mannose, a water-soluble carbohydrate, was hydrophobized by anchoring stearylamine with an objective to conjugate mannose on the surface of curcumin loaded nanostructured lipid carriers for targeting asialoglycoprotein receptors on hepatocytes. Mannose conjugated stearylamine was synthesized and characterized using various analytical techniques. The synthesized targeting ligand was incorporated curcumin loaded nanostructured lipid carriers and characterized by photon correlation spectroscopy. Zeta potential measurement was used to confirm the conjugation of the synthesized ligand to the surface of drug-loaded nanostructured lipid carriers. CCl₄ induced hepatotoxicity in male Wistar rats was used as an experimental animal model to evaluate the hepatoprotective potential of formulated drug encapsulated nanostructured lipid carriers. The hepatoprotective potential was assessed by measuring serum liver injury markers and oxidative stress parameters in the liver post–mitochondrial supernatant. Mannose conjugated nanostructured lipid carriers showed acceptable particle size which revealed its suitability for hepatocyte targeting. In addition to this, mannose conjugated nanocarriers revealed significantly better (p ​&lt; ​0.05) reduction of serum liver injury markers and proinflammatory cytokines compared to the unconjugated one which confirmed hepatocytes targeting potential of the synthesized ligand. Asialoglycoprotein receptors targeting could be a landmark strategy for hepatocyte targeting. Thus, the synthesized mannose anchored stearylamine could be a promising novel targeting ligand having hepatocyte targeting potential.</p></div>","PeriodicalId":10877,"journal":{"name":"Current Research in Pharmacology and Drug Discovery","volume":"3 ","pages":"Article 100083"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590257122000037/pdfft?md5=ddc5d43d3768c827e41700e0dfeafb39&pid=1-s2.0-S2590257122000037-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89988136","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":"Blood pressure-lowering and cardiovascular effects of plumbagin in rats: An insight into the underlying mechanisms","authors":"Maira Ahmad,&nbsp;Taseer Ahmad,&nbsp;Hafiz Muhammad Irfan,&nbsp;Nabeela Noor","doi":"10.1016/j.crphar.2022.100139","DOIUrl":"10.1016/j.crphar.2022.100139","url":null,"abstract":"<div><h3>Background</h3><p>Plumbagin, a natural phenolic compound is investigated for response against blood pressure and vascular reactivity.</p></div><div><h3>Methodology</h3><p>Blood pressure lowering effects were observed by <em>in-vivo</em> invasive evaluation in normotensive rats, and <em>in-vitro</em> experimentation to measure changes of tension in isolated rat aorta and contractility in atria.</p></div><div><h3>Results</h3><p>The percentage decrease in mean arterial pressure (MAP) observed with plumbagin intravenously at doses of 0.1, 0.5, 1, 5, 10 ​μg/kg in normotensive rats was 7.16 ​± ​2.35, 15.5 ​± ​5.62, 19.5 ​± ​5.27, 26 ​± ​6.67, 34.33 ​± ​8.80, respectively. Plumbagin exerted vasorelaxant effects in rat aorta, unaffected by the removal of vascular endothelium, and _L-NAME and methylene blue pretreatment. Plumbagin completely inhibited phenylephrine (1 ​μM) and High K⁺ (80 ​mM) induced contractions. Similar to a Ca⁺² channel antagonist, plumbagin caused a rightward shift in the Ca⁺² concentration-response-curves (CRCs), resembling nifedipine. Pre-incubation with plumbagin, significantly suppressed contractions induced by phenylephrine in Ca⁺²-free medium via disrupting Ca⁺² release from intracellular stores. No change in vasorelaxant response was observed with the addition of potassium channel blockers, TEA and BaCl₂. In rat atrial strips, plumbagin exerted significant negative inotropic and chronotropic effects. No significant change was observed with atropine and atenolol pretreatment, so the effect appeared independent of muscarinic and beta-adrenergic receptors.</p></div><div><h3>Conclusion</h3><p>This study suggests the blood pressure lowering effects of plumbagin. That could be contributed by a decrease in vascular resistance via calcium antagonism, interferences in calcium efflux, and depressive effects on the rate and force of cardiac contraction. Further studies would be necessary to probe deeper into the underlying mechanisms.</p></div>","PeriodicalId":10877,"journal":{"name":"Current Research in Pharmacology and Drug Discovery","volume":"3 ","pages":"Article 100139"},"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/76/82/main.PMC9780077.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10438051","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}