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Context The anthelminthic effect of Ocimum species (Lamiaceae) has been reported, however, its anti-filarial effect has not been explored to date. Objective This study evaluates the effect of Ocimum sanctum L. (OS) against lymphatic filarial parasites. Material and methods The ethanol extract of OS (EOS) leaves was tested for anti-filarial activity against Setaria cervi . Equal size and number ( n = 10) of adult female S. cervi worms were incubated in 125, 250 or 375 μg/mL EOS extract for 6 h at 37 °C. The OS bioactive components were identified by UPLC-ESI-MS/MS and subjected to docking and molecular dynamics (MD) simulation against filarial antioxidant proteins. Results The EOS significantly inhibited the motility of adult female S. cervi after 6 h of incubation. The motility was found to be reduced by 53.7% in 375 µg/mL and 43.8% in 250 µg/mL EOS after 6 h of treatment. The UPLC-ESI-MS/MS analysis of ethanol extract of O. sanctum revealed the presence of 13 bioactive compounds. The docking analysis showed eight OS bioactive compounds to have high binding affinity (> 4.8 kcal/mol) towards antioxidant proteins of filarial parasites. Additionally, MD simulation studies showed significant impact of (RMSD ≤ 10 Å) chlorogenic acid, luteolin and ursolic acid on filarial antioxidant enzymes/proteins. To our knowledge, this is the first report of the anti-filarial activity of Ocimum sanctum . Discussion and conclusions The effect of EOS and OS bioactive components on human filarial parasites can be further evaluated for the development of new anti-filarial formulations.

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Background: Tat protein is considered essential for substantial HIV-1 replication, and is also required to break HIV-1 latency, resulting in productive HIV replication. The multifaceted regulatory role of HIV Tat and the fact that it is expressed in the early stages of HIV infection justifies its potential as an anti-HIV drug target. Objective: The present study was undertaken with the aim to target HIV-1 Tat protein with natural compounds which could help in identifying potential inhibitors against HIV-1 Tat. Methods: In this study, we compared the binding of Tat protein and Human P-TEFb Tat protein complex (TPC) with phyto-steroids and terpenes to evaluate their potential for HIV-1 treatment. The docking ability of plant products with HIV-1 Tat and TPC was studied with respect to Dissociation constant, Geometric shape complementary score, approximate interface area and binding energy using Patch dock and YASARA. Molecular dynamics simulation was set up to investigate the interactions of the natural compounds with Tat protein and human tat protein complex (TPC). Results: The binding energy and dissociation constant of Diosgenin, Catharanthine and Ginkgolide A with Tat and TPC was comparable to antiretroviral drugs Maraviroc and Emtricitabine. The natural products Diosgenin, Ginkgolide A and Catharanthine showed highest binding energy and were stable with Tat protein and TPC in the entire MD simulation run. Conclusion: The natural products Diosgenin, Ginkgolide A and Catharanthine showed highest binding energy and were stable with Tat protein and TPC in the entire MD simulation run. The binding energy and dissociation constant of Diosgenin, Catharanthine and Ginkgolide A with Tat and TPC was comparable to antiretroviral drugs Maraviroc and Emtricitabine.

Here in drug docking analysis, molecular dynamics simulations and ex vivo approaches were used to demonstrate the anti-filarial effects of nutraceuticals against immune modulatory proteins of lymphatic filarial parasites.

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This article describes studies on the design, synthesis, and biological evaluation of pyrazole‐containing β‐amino carbonyl compounds (5a–5q) as DPP‐4 inhibitors and anti‐diabetic agents. In contrast, mannich reactions went smoothly with bismuth nitrate (Bi (NO3)3) catalyst in the presence of ethanol and produced pyrazole‐containing β‐amino carbonyl compounds in good yield. Molecular docking studies of designed derivatives with DPP‐4 enzyme (PDB: 2OLE), compounds 5d, 5h, 5j, and 5k showed excellent interaction. 3D QSAR and pharmacophoric model studies were also carried out. ADMET parameters, pharmacokinetic properties, and in vivo toxicity studies further confirmed that all the designed compounds were found to have good bioavailability and were less toxic. Further, these compounds were evaluated as enzyme‐based in vitro DPP‐4 inhibitory activity, and 5d, 5h, 5i, 5j, and 5k exhibited IC50 toward DPP‐4 enzyme of 10.52, 10.41, 5.55, 4.16, and 7.5 nM, respectively. The most potent compound, 5j, was further selected for in vivo anti‐diabetic activity using an STZ‐induced diabetic mice model, and 5j showed a significant diabetic control effect.

Lymphatic Filariasis (LF) affects more than 863 million people in tropical and subtropical areas of the world, causing high morbidity and long illnesses leading to social exclusion and loss of wages. A combination of drugs Ivermectin, Diethylcarbamazine citrate and Albendazole is recommended by WHO to accelerate the Global Programme to Eliminate Lymphatic Filariasis (GPELF). To assess the outcome of GPELF, to re-evaluate and to formulate further strategies there is an imperative need for high quality diagnostic markers. This study was undertaken to identify Lymphatic Filarial biomarkers which can detect LF infections in asymptomatic cases and would also serve as indicators for differentiating among different clinical stages of the disease. A combination of Fourier-transform infrared spectroscopy (FT-IR), MMP zymography, SDS-PAGE, classical 2DE along with MALDI-TOF/MS was done to identify LF biomarkers from serum samples of different stages of LF patients. FT-IR spectroscopy coupled with univariate and multivariate analysis of LF serum samples, revealed significant differences in peak intensity at 3300, 2950, 1645, 1540 and 1448 cm-1 (p<0.05). The proteomics analysis results showed that various proteins were differentially expressed (p<0.05), including C-reactive protein, α-1-antitrypsin, heterogeneous nuclear ribonucleoprotein D like, apolipoproteins A-I and A-IV in different LF clinical stages. Functional pathway analysis suggested the involvement of differentially expressed proteins in vital physiological pathways like acute phase response, hemostasis, complement and coagulation cascades. Furthermore, the differentiation between different stages of LF cases and biomarkers identified in this study clearly demonstrates the potential of the human serum profiling approach for LF detection. To our knowledge, this is the first report of comparative human serum profiling in different categories of LF patients.