Current Pharmaceutical Design - Volume 25, Issue 12, 2019

Background: Immunity is the ultimate barrier between foreign stimuli and a host cell. Unwanted immune responses can threaten the host cells and may eventually damage a vital organ. Overproduction of inflammatory cytokines may also lead to autoimmune diseases. Inflammatory cells and pro-inflammatory cytokines can eventually progress to renal, cardiac, brain, hepatic, pancreatic and ocular inflammation that can result in severe damage in the long run. Evidence also suggests that inflammation may lead to atherosclerosis, Alzheimer’s, hypertension, stroke, cysts and cancers. Methods: This study was designed to correlate the possible molecular mechanisms for inflammatory diseases and prevent biochemical changes owing to inflammatory cytokines by using Resveratrol. Therefore, we searched and accumulated very recent literature on inflammatory disorders and Resveratrol. We scoured PubMed, Scopus, Science Direct, PLoS One and Google Scholar to gather papers and related information. Results: Reports show that inflammatory diseases are very complex, as multiple cascade systems are involved; therefore, they are quite difficult to cure. However, our literature search also correlates some possible molecular interactions by which inflammation can be prevented. We noticed that Resveratrol is a potent lead component and has multiple activities against harmful inflammatory cytokines and related microRNA. Our study also suggests that the anti-inflammatory properties of Resveratrol have been highly studied on animal models, cell lines and human subjects and proven to be very effective in reducing inflammatory cell production and pro-inflammatory cytokine accumulation. Our tables and figures also demonstrate recent findings and possible preventive activities to minimize inflammatory diseases. Conclusion: This study would outline the role of harmful inflammatory cytokines as well as how they accelerate pathophysiology and progress to an inflammatory disorder. Therefore, this study might show a potential therapeutic value of using Resveratrol by health professionals in preventing inflammatory disorders.

Background: This systematic review and meta-analysis of randomized controlled trials (RCTs) were performed to determine the effect of quercetin administration on blood pressures and endothelial function among patients with metabolic syndrome (MetS) and related disorders. Methods: We searched systematically online databases including Cochrane Library, EMBASE, MEDLINE, and Web of Science to identify the relevant RCTs until December 2018. Q-test and I2 statistics were applied to assess heterogeneity among the included studies. Data were pooled using a random-effects model and weighted mean difference (WMD) was considered as the overall effect size. Results: Out of 284 citations, 8 RCTs were included in the meta-analysis. We found a significant reduction in systolic blood pressure (SBP) (WMD: -1.69; 95% CI: -3.22, -0.17) following the intake of quercetin supplements. However, quercetin supplementation did not significantly affect diastolic blood pressure (DBP) (WMD: -3.14; 95% CI: -8.24, 1.95), vascular cell adhesion molecule 1 (VCAM-1) (WMD: -24.49; 95% CI: -53.74, 4.77) and intercellular adhesion molecule 1 (ICAM-1) (WMD: -5.78; 95% CI: -12.93, 1.38). Conclusion: In summary, the current meta-analysis demonstrated that quercetin supplementation significantly reduced SBP, yet did not affect DBP, VCAM-1 and ICAM-1 among patients with MetS and related disorders.

Background: As2O3 and resveratrol have been widely considered to be effective in anti-cancer therapies and the underlying mechanisms have been reported extensively. However, the combined treatment effect and potential target of As2O3 and resveratrol in the treatment of tumors remains elusive. The purpose of this study was to investigate the benefits and efficacy of As2O3 in combination with resveratrol in the treatment of colon cancer, as well as looking for new targets that could provide alternative explanation of the efficacy of drugs. Methods: The proliferation of cancer cells was measured by the MTT and EdU staining assay, while the apoptosis of cancer cells was determined by the flow cytometry. Western blot and immunoprecipitation were performed to measure the expression levels of proteins and the interaction between hERG and integrin β1, respectively. Results: In this study, we found that both As2O3 and resveratrol can effectively inhibit cell proliferation and promote cell apoptosis in colon cancer, and the combined effect of the two drugs on colon cancer cells is more preeminent. The combination of As2O3 with resveratrol, on the one hand reduced the expression of hERG channels on the membrane, and on the other hand weaken the binding between hERG and integrin β 1, which may be the main cause of downstream signaling pathways alterations, including the activation of the apoptotic pathway. Conclusion: Taken together, hERG, as a subunit of potassium ion channel on the cell membrane, is highly likely to be involved in the As2O3 and resveratrol induced intracellular signaling cascade disorder, and this novel signaling pathway that sustains the progression of colon cancer may be a promising therapeutic target for human colon cancer treatment in the future.

Background: The recent Nipah virus (NiV) outbreak in India has caused a state of chaos, with potential to become the next international pandemic. There is still a great deal to learn about NiV for the development of a potent treatment against it. The NiV non-structural proteins play important roles in the lifecycle of the virus, with the RNA-dependent RNA-polymerase (RdRp) being a vital component in viral replication. In this study, we not only provide a comprehensive overview of all the literature concerning NiV, we also propose a model of the NiV RdRp and screen for potential inhibitors of the viral enzyme. Methods: In this study, computational tools were utilized in the design of a NiV RdRp homology model. The active site of RdRp was then identified and potential inhibitors of the protein were discovered with the use of pharmacophore-based screening. Results: Ramachandran plot analysis revealed a favourable model. Upon binding of nucleoside analog, 4’- Azidocytidine, active site residues Trp1714 and Ser1713 took part in stabilizing hydrogen bonds, while Thr1716, Ser1478, Ser1476 and Glu1465 contributed to hydrophobic interactions. Pharmacophore based screening yielded 18 hits, of which ZINC00085930 demonstrated the most optimal binding energy (-8.1 kcal/mol), validating its use for further analysis as an inhibitor of NiV. Conclusion: In this study we provide a critical guide, elucidating on the in silico requirements of the drug design and discovery process against NiV. This material lays a foundation for future research into the design and development of drugs that inhibit NiV.

Background: The promising eventual fate of blockchain in healthcare has a lot more extensive prospect. Blockchain is a novel structure that gives another design to storage and trade of data among different members of a particular network. In case of a hospital, blockchain takes into consideration the creation of a better treatment structure by the expert doctor in order to arrange the meeting based on the symptoms of patients throughout the world by the electronic system. Blockchain technology is crucial for biomedical and human services applications as social insurance has turned out to be a standout among the most essential rising application areas of the blockchain distributed ledger technology. Result: By and large, blockchain is treated as a conveyed record to store social insurance related information for allocation, trading, dissecting, footage, and affirming purposes among accomplices. The advantage of blockchain databases versus traditional dispersed databases is that they are decentralized, permanent, and perfected with advanced digital payment frameworks and hash chain occasion structure. The blockchain code is an unlocked resource and can be utilized, altered, and customized by its clients. Conclusion: Nowadays, blockchain is expected to be almost universally adopted across medical organizations around the world. The purpose of this review article is to comprehend the current explored subjects, difficulties, and future headings in regards to blockchain innovation from the specialized perspective in the health care system.

Urinary Tract Infections (UTIs); second-ranking infectious diseases are regarded as a significant global health care problem. The UTIs annually cost tens of millions of dollars for governments worldwide. The main reason behind these costs is incorrect or indefinite treatment. There are a wide range of gram-negative and grampositive bacteria which may cause UTIs in males and females, children and adults. Among gram-negative bacteria, some members of Enterobacteriaceae such as Escherichia coli (E.coli) strains have significant contribution in UTIs. Uropathogenic E.coli (UPEC) strains are recognized as typical bacterial agents for UTIs. Thus, sharp and accurate diagnostic tools are needed for detection and identification of the microbial causative agents of UTIs. In parallel with the utilization of suitable diagnostic methods-to reduce the number of UTIs, effective and definite treatment procedures are needed. Therefore, the prescription of accurate, specific and effective antibiotics and drugs may lead to a definite treatment. However, there are many cases related to UTIs which can be relapsed. Due to a diversity of opportunistic and pathogenic causative microbial agents of UTIs, the treatment procedures should be achieved by the related antimicrobial agents. In this review, common and effective antimicrobial agents which are often prescribed for UTIs caused by UPEC will be discussed. Moreover, we will have a sharp look at their (antimicrobials) molecular treatment mechanisms.

Background: In the progression of atherosclerosis, platelet activation and the interaction of platelets with leukocytes play a crucial role in arterial thrombus formation and are associated with the pathophysiology of carotid and cerebrovascular disease (CVD), including ischemic stroke. With aged participants, we evaluated and followed up the change in circulating factor and platelet-leukocyte aggregate levels in participants with or without CVD history. This study investigated whether circulating factor changes and ultrasonographic characteristics link to CVD risk and other relating long-term outcomes. Materials and Methods: Two hundred fifteen participants who enrolled in the study were divided into two groups with CVD and without CVD history. We evaluated and analyzed the correlation between ultrasonography-based morphological characteristics and circulating factor-based functional changes in both groups. Results: There was no difference in p-selectin level between both groups. However, activated monocyte and platelet-monocyte aggregate levels were higher in patients with previous CVD than without previous CVD. Circulating factor and ultrasonographical characteristics were correlated in the group with CVD, whereas these factors were not correlated in the group without CVD. Conclusion: We found that circulating blood factor levels showed a different tendency in participants with and without CVD history. The results depict that atherosclerotic severity might depend on the history of CVD and progression of atherosclerosis. We suggest that the circulating factor levels, atherosclerotic severity, and history of CVD are considered in the observation of pathologic progression to manage the development of CVD risks and CVD relating outcomes.

Ethnopharmacological Relevance: Mucuna pruriens (Mp) belongs to Leguminosae family, it is native of tropical regions and used to treat several maladies such as urinary, neurological, and menstruation disorders, constipation, edema, fever, tuberculosis, ulcers, diabetes, arthritis, dysentery, and cardiovascular diseases. Mp seeds are rich in bioactive compounds, for instance, lectins, a heterogeneous group of proteins and glycoproteins with a potential role as therapeutic tools for several conditions, including gastric disorders. This study investigated the acute toxicity, gastroprotective, and antioxidant activities of a lectin from Mucuna pruriens seeds (MpLec) on ethanol-induced gastropathy model in mice. Material and Methods: Mice received MpLec (5 or 10 mg/kg; i.v.) and were observed for acute toxicity signs; in another experimental series, mice were pre-treated with MpLec (0.001; 0.01 or 0.1 mg/kg, i.v.), ranitidine (80 mg/kg, p.o.), or saline (0.3 mL/30g, i.v.) before ethanol 99.9% (0.2 mL/animal, p.o.), and euthanized 30 min after ethanol challenge. Macroscopic and microscopic gastric aspects, biochemical parameters (tissue hemoglobin levels, iron-induced lipid peroxidation, GSH content, SOD activity, and gastric mucosal PGE2) were measured. Additionally, pharmacological tools (yohimbine, indomethacin, naloxone, L-NAME) were opportunely used to clarify MpLec gastroprotective mechanisms of action. Results: No toxicity signs nor death were observed at acute toxicity tests. MpLec reduced ethanol-induced gastric damage, edema, and hemorrhagic patches formation, as well as decreased lipid peroxidation, SOD activity, and increased GSH content. Yohimbine and indomethacin prevented MpLec effects, suggesting the involvement of alpha-2 adrenoceptors and prostaglandins in the MpLec-mediated effects. Conclusion: MpLec does not present toxicity signs and shows gastroprotective and antioxidant activities via alpha-2 adrenoceptors and prostaglandins in the ethanol-induced gastropathy model.