Novel acetamide derivatives of 2-aminobenzimidazole prevent inflammatory arthritis in rats via suppression of pro-inflammatory mediators.

Benzimidazole ring system is an important pharmacophore with diverse pharmacological activities. In this study, we explored the anti-arthritic effects of newly synthesized acetamide derivatives of 2-aminobenzimidazole (N1 and N2) in rats. FTIR and NMR spectroscopies were used to characterize these compounds. Carrageenan (CRG) induced paw edema model was used to test the acute anti-inflammatory activity of various doses (10, 20 and 30 mg/kg) of N1 and N2 compounds. Based on acute anti-inflammatory effects, the most potent dose of each compound was selected and investigated in complete freund's adjuvant (CFA) induced inflammatory arthritis (RA) model (n = 4 in each group). Histopathological, hematological, radiographic, and RT-qPCR analyses were performed to assess the progression or resolution of inflammatory arthritis. The tested compounds produced a dose-dependent anti-inflammatory activity against CRG induced paw inflammation and similarly reduced edema in CFA induced inflammatory arthritis model. Histopathological and X-ray analyses of ankle joints revealed minimal inflammation and normal joint structures in N1 and N2 treated groups. The tested compounds also reduced the levels of autoantibodies and restored hematological parameters. Interestingly, the tested compounds did not elevate aspartate aminotransferase and alanine transaminase levels and displayed a better safety profile than methotrexate. N1 and N2 compounds also attenuated the transcript levels of IRAK1, NF-kB1, TNF-α, IL-1ß, IL17 and MMP1. In addition, N1 displayed a greater inhibition of mRNA levels of COX1, COX2, mPGES1 and PTGDS as compared to N2. Our findings demonstrate that N1 and N2 compounds possess strong anti-arthritic activity which can be attributed to the suppression of pro-inflammatory mediators.

Repurposing Drugs for COVID-19: An Approach for Treatment in the Pandemic.

CONTEXT: Drug repurposing is a relevant approach during the COVID-19 pandemic, because development of new drugs is time-consuming and costly, and the safety of new drugs is paramount. Drug repurposing focuses on researching new indications for existing drugs and can reduce the challenges faced in drug development. OBJECTIVE: The current review intended to examine the current status of drugs being repurposed for COVID-19 treatment. DESIGN: The research team performed a literature review, searching relevant literature databases to find abstracts of relevant articles in journals published from 2010 until May 16, 2020. The sources of data included Google Scholar, PubMed, and ScienceDirect. The search terms used included repositioning of drugs, repurposing of drugs and COVID-19 therapy, and SARS-CoV-2 therapy. SETTING: The research team conducted this study at the Department of Pharmacology, Punjab University College of Pharmacy, University of the Punjab, Lahore, Pakistan; Mangalbare Hospital, Morang, Nepal; and Dr Iwamura Memorial Hospital, Bhaktapur, Nepal. RESULTS: Repurposing of drugs from different pharmacological groups including antivirals like remdesivir, lopinavir, ritonavir, arbidol, oseltamivir, penciclovir, favipiravir, ganciclovir, and ribavirin; other antibiotics like azithromycin, ivermectin, eravacycline, valrubicin, streptomycin, nitazoxanide, teicoplanin, caspofungin, and colistin; and other agents like hydroxychloroquine, chloroquine, tocilizumab, camostat, nafamostat, carfilzomib, interferon, aprepitant, and dexamethasone can be considered for COVID-19 therapy. CONCLUSIONS: Although current results are promising, limitations to drug repurposing, such as a low success rate and the possibility of adverse events, can't be overlooked. With continuous research and technical advancements, repurposing will no doubt provide a notable scientific contribution to innovation in drug development and pharmacotherapy practice for the treatment of new diseases or existing diseases in a new way.

Chemical and pharmacological comparison of modern and traditional dosage forms of Joshanda.

Recently, a traditional remedy (Joshanda) has been replaced largely by modern ready-to-use dosage forms, which have not been compared to the original remedy. Therefore, the present study aimed to compare a number of modern dosage forms with traditional remedy. Seven brands, 3 batches each, were compared with a Lab-made formulation with reference to analytical (proximate analyses, spectroscopic and chromatographic metabolomes) and pharmacological profiles (anti-inflammatory and antibacterial activities). Chemical and pharmacological differences were found between Lab-made Joshanda and modern dosage forms. Such variations were also found within the brands and batches of modern formulations (p < 0.05). The Lab-made Joshanda showed significantly higher pharmacological activities as compared to modern brands (p ). The results of the present study indicate that modern dosage forms are unstandardised and less effective than the traditional remedy. Characteristic profiles obtained from Lab-made Joshanda may be used as reference to produce comparable dosage forms.

Antidiabetic activity of aqueous extract of Sigesbeckia orientalis (St. Paul's Wort) in alloxan-induced diabetes model

The current study evaluated antidiabetic and antihyperlipidemic activities of aqueous extract of Sigesbeckia orientalis L. (St. Paul's Wort) (AESO) in an alloxan-induced diabetic rat model. Following OECD guidelines safe doses of AESO were assessed in rats for the main study. Serum/bood glucose, α-amylase, and lipids levels and histopathological evaluations were conducted to assess antidiabetic and associated antihyperlipidemic efficacies of AESO. AESO was found to be safe up to the dose of 2000 mg/kg. Significant (p < 0.05) reduction in glucose and lipids (total cholesterol, triglycerides, low-density lipoproteins) levels was observed in AESO treatment groups. Serum α-amylase, high-density lipoproteins, and total body weight was increased significantly (p < 0.05) in diabetic rats treated with AESO. Histopathological data showed improvement in hepatocyte and pancreatic β-cells islets architecture. HPLC analysis identified quercetin, gallic acid, vanillic acid, p-coumaric acid, m-coumaric acid and cinnamic acid in AESO which are suggested to be responsible for observed antihyperglycemic and antihyperlipidemic attributes. Further studies to standardise the extract and evaluation of safety profile in long-term toxicity studies are recommended for safe and effective antidiabetic nutraceuticals development.