DECIPHERING THE PHARMACOLOGICAL INSIGHTS OF FRACTIONATED ELATOSTEMA PAPILLOSUM WED. AND HOLIGARNA LONGIFOLIA ROXB. THROUGH IN VITRO AND IN VIVO STUDIES

The present research intended to explore the biological activities, namely acute toxicity test and hypoglycemic as well as in vitro anti-arthritic along with the antibacterial activity of crude methanol extracts with its different soluble fractions like petroleum ether (PESF), carbon tetrachloride (CTCSF), chloroform (CSF) and aqueous soluble fraction (AQSF) of Holigarna longifolia and Elatostema papillosum. Phytochemical screening was performed by established protocols. Acute toxicity and hypoglycemic effects were performed in experimental and alloxan-induced diabetic rats. In vitro anti-arthritic and antibacterial activity were conducted by protein denaturation inhibitory and disc diffusion methods. It was observed that no rats exhibit any lethality types, which reveal the safety of plant fractionates. It was also seen that both plants' fractionates showed significant (p < 0.01) activity on hyperglycemia compared to standard. Upon investigation, it was observed that crude methanol and its CS fraction of E. papillosum and only CS fraction of H. longifolia significantly (p < 0.05) inhibited denaturation of bovine serum albumin protein compared to standard diclofenac sodium. Moreover, it was observed that crude methanol extract and its CS fraction of E. papillosum showed significant inhibitory action on all Gram-positive bacteria's growth. In contrast, the PES fraction highlighted an inhibitory zone of 26.7 and 24.7 mm, respectively, towards B. subtilis and S. aureus. This study provides some support to explain the traditional uses of H. longifolia and E. papillosum.&nbsp

Pharmacological studies on the antinociceptive, anxiolytic and antidepressant activity of Tinospora crispa

Pharmacological studies were performed in mice on the methanol extract of Tinospora crispa (TC), and of its hexane (HF) and chloroform (CF) fractions. Significant antinociceptive activity was observed for TC, HF, and CF in the acetic acid-induced writhing and formalin-induced paw licking tests. Anxiolytic and antidepressant activity were assessed using the open field, hole board, and elevated plus maze (EPM) tests. TC, HF, and CF demonstrated a significant decrease in spontaneous locomotor activity. They also showed an increase in the number of head-dippings in the hole board test, suggesting decreased fearfulness. TC, and most of its fractions, showed a significant increase of the time spent in the opened arm of the EPM, indicating reduced anxiety. A computational study (PASS prediction, molecular docking and ADME/T analyses) was performed to identify the phytochemicals responsible for activity. Syringin and secoisolariciresinol, displayed a strong predictive binding affinity towards the cyclooxygenase COX-1 and COX-2 enzymes and the KcsA potassium channel while rumphioside B showed the highest predicted binding affinity towards the human serotonin receptor. This provided some support to explain the observed in-vivo antinociceptive, anxiolytic and antidepressant effects and the traditional use of T. crispa as a remedy for pain

Biological Optimization of Polymer-Based Antiretroviral Drug Towards the Gut-Associated Lymphoid Tissue (GALT)

Background: Combination antiretroviral therapy (cART) has significantly decreased the disease mortality associated with HIV-1 but does not efficiently reach the HIV reservoir organs such as GALT. In this regard, the present study determined the efficacy of the polymer-based nanoformulations using F127 alone and in combination with L61 to encapsulate three clinically available cART drugs such as Emtricitabine (FTC), Tenofovir Disoproxil Fumarate (TDF), and Dolutegravir (DTG) in in vitro and in vivo system. Methods: The selected formulations were studied for their biological and chemical characterization towards human cell line viz. Caco-2 and Human peripheral blood mononuclear cells (PBMC) and in vivo mouse model. Results: The majority of the nanoformulations were observed to be in the size range of the nanoparticle. The safety study of all these formulations indicated that the combination of F127 + L61 formulations showed no significant toxicity, improved drug release properties in Caco 2, PBMC and in vitro Mcell model. The study has established a sustained release of the F127 + L61 nanoformulations for a period of 14 days in in vitro and in vivo models. Conclusions: The overall study proved that the combination of polymer-based formulations has potential applications in improving HIV-1 treatment with far fewer side effects compared to current therapy

GC-MS phytochemical profiling, pharmacological properties, and in silico studies of Chukrasia velutina leaves: a novel source for bioactive agents

Chukrasia velutina is a local medicinal plant commonly known as chikrassy in Bangladesh, India, China, and other South Asian countries. The leaves, bark, and seeds are vastly used as herbal medicine for fever and diarrhea, and its leaves essential oils are used for antimicrobial purposes. In this study, we discuss the neuropsychiatric properties of C. velutina leaves through several animal models, quantitative and qualitative phytochemical analysis, and computational approaches. Neuropsychiatric effects were performed in rodents on the methanolic extract of C. velutina leaves (MECVL). Antidepressant, anxiolytic, and sedative effects experimented through these rodent models were used such as the force swimming test (FST), tail suspension test (TST), hole board test (HBT), elevated plus maze test (EPMT), light/dark box test (LDBT), open field test (OFT), and hole cross test (HCT). In these rodent models, 200 and 400 mg/kg doses were used which exhibited a significant result in the force swimming and tail suspension test (p < 0.001) for the antidepressant effect. In the anxiolytic study, the results were significant in the hole board, elevated plus maze, and light/dark box test (p < 0.001) for doses of 200 and 400 mg/kg. The result was also significant in the open field and hole cross test (p < 0.001) for sedative action in the sake of similar doses. Moreover, qualitative and quantitative studies were also performed through phytochemical screening and GC-MS analysis, and fifty-seven phytochemical compounds were found. These compounds were analyzed for pharmacokinetics properties using the SwissADME tool and from them, thirty-five compounds were considered for the molecular docking analysis. These phytoconstituents were docking against the human serotonin receptor, potassium channel receptor, and crystal structure of human beta-receptor, where eight of the compounds showed a good binding affinity towards the respective receptors considered to the reference standard drugs. After all of these analyses, it can be said that the secondary metabolite of C. velutina leaves (MECVL) could be a good source for inhibiting the neuropsychiatric disorders which were found on animal models as well as in computational studies

Unravelling the biological activities of the Byttneria pilosa leaves using experimental and computational approaches

Byttneria pilosa is locally known as Harijora, and used by the native hill-tract people of Bangladesh for the treatment of rheumatalgia, snake bite, syphilis, fractured bones, elephantiasis and an antidote for poisoning. The present study was carried out to determine the possible anti-inflammatory, analgesic, neuropharmacological and anti-diarrhoeal activity of the methanol extract of B. pilosa leaves (MEBPL) through in vitro, in vivo and in silico approaches. In the anti-inflammatory study, evaluated by membrane stabilizing and protein denaturation methods, MEBPL showed a significant and dose dependent inhibition. The analgesic effect of MEBPL tested by inducing acetic acid and formalin revealed significant inhibition of pain in both tests. During the anxiolytic evaluation, the extract exhibited a significant and dose-dependent reduction of anxiety-like behaviour in mice. Similarly, mice treated with MEBPL demonstrated dose-dependent reduction in locomotion effect in the open field test and increased sedative effect in the thiopental sodium induced sleeping test. MEBPL also showed good anti-diarrheal activity in both castor oil induced diarrheal and intestinal motility tests. Besides, a previously isolated compound (beta-sitosterol) exhibited good binding affinity in docking and drug-likeliness properties in ADME/T studies. Overall, B. pilosa is a biologically active plant and could be a potential source of drug leads, which warrants further advanced study

Acoplamiento molecular para actividad trombólitica de algunos compuestos aislados de Clausena lansium.

La Clausena lansium (Familia- Rutaceae), comúnmente conocida como wampi o vampi, se encuentra en las tierras de barbecho o en terrenos baldíos en Bangladesh. Este estudio pretende hacer acoplamientos moleculares para identificar posibles afinidades de enlace de los fitocompuestos de Clausena lansium, específicamente Clausemarin B, Clausenaline C, Clausenaline E, Murrayanine, vanillic acid y Xanthotoxol en busca de la molecula principal de actividad trombolitica. El acoplamiento molecular realizado por Schrodinger ofreció un amplio rango de cocientes de acoplamiento que fueron para Clausemarin B , Clausenaline C , Clausenaline E, Murrayanine , vanillic acid and Xanthotoxol -6.926, -4.041, -4.889 , -4.356, -3.007 and -5.816 respectivamente. Entre todos los compuestos fue Clausemarin B el que mostró el mejor coeficiente de acoplamiento. Por tanto Clausemarin B es el más eficaz para actividad trombolitica. En el futuro serán necesarias investigaciones in vivo para identificar la actividad trombolitica de los compuestos aisladosde Clausena lansium.Clausena lansium (Family- Rutaceae) is commonly known as wampee, is found in fallow lands throughout Bangladesh. Our aim of the study to performed molecular docking studies to identify potential binding affinities of the phytocompounds from Clausena lansium, namely Clausemarin B, Clausenaline C, Clausenaline E, Murrayanine, vanillic acid and Xanthotoxol for searching of lead molecule for thrombolytic activity. A wide range of docking score found during molecular docking by Schrodinger. Clausemarin B , Clausenaline C , Clausenaline E, Murrayanine , vanillic acid and Xanthotoxol showed the docking score -6.926, -4.041, -4.889 , -4.356, -3.007 and - 5.816 respectively. Among all the compounds Clausemarin B showed the best docking score. So, Clausemarin B is the best compounds for thrombolytic activity, as it possessed the best value in Molecular docking. Further in vivo investigation need to identify the thrombolytic activity of isolated compounds from Clausena lansium

Antinociceptive Activity of Macaranga denticulata Muell. Arg. (Family: Euphorbiaceae): In Vivo and In Silico Studies

Background: The present study was conducted to investigate the antinociceptive activity of methanol extract of Macaranga denticulata (Met.MD) in an animal model, followed by molecular docking analysis. Methods: Antinociceptive activity was determined by acetic acid-induced writhing and formalin-induced licking test in mice. Then, molecular docking study was performed to identify compounds having maximum activity against the COX-1 enzyme using Schrödinger Maestro (version 10.1) to determine docking fitness. Results: A preliminary phytochemical analysis of Met.MD revealed that it contained alkaloids, carbohydrates, phenols, flavonoids, tannins, and terpenoids. Met.MD exhibited a dose-dependent and statistically significant antinociceptive activity in the acetic acid and formalin test at the doses of 200 and 400 mg/kg. In addition, our docking study showed that macarangin had the best fitness score of −5.81 with COX-1 enzyme among six major compounds of M. denticulata. Conclusions: Results of the present study confirmed the potential antinociceptive activity of M. denticulata leaf extract in both in vivo and in silico models

Biochemical and computational approach of selected phytocompounds from Tinospora crispa in the management of COVID-19

A pandemic caused by the novel coronavirus (SARS-CoV-2 or COVID-19) began in December 2019 in Wuhan, China, and the number of newly reported cases continues to increase. More than 19.7 million cases have been reported globally and about 728,000 have died as of this writing (10 August 2020). Recently, it has been confirmed that the SARS-CoV-2 main protease (Mpro) enzyme is responsible not only for viral reproduction but also impedes host immune responses. The Mpro provides a highly favorable pharmacological target for the discovery and design of inhibitors. Currently, no specific therapies are available, and investigations into the treatment of COVID-19 are lacking. Therefore, herein, we analyzed the bioactive phytocompounds isolated by gas chromatography–mass spectroscopy (GC-MS) from Tinospora crispa as potential COVID-19 Mpro inhibitors, using molecular docking study. Our analyses unveiled that the top nine hits might serve as potential anti-SARS-CoV-2 lead molecules, with three of them exerting biological activity and warranting further optimization and drug development to combat COVID-19

Molecular docking for thrombolytic activity of some isolated compounds from Clausena lansium.

Clausena lansium (Family- Rutaceae) is commonly known as wampee, is found in fallow lands throughout Bangladesh. Our aim of the study to performed molecular docking studies to identify potential binding affinities of the phytocompounds from Clausena lansium, namely Clausemarin B, Clausenaline C, Clausenaline E, Murrayanine, vanillic acid and Xanthotoxol for searching of lead molecule for thrombolytic activity. A wide range of docking score found during molecular docking by Schrodinger. Clausemarin B , Clausenaline C , Clausenaline E, Murrayanine , vanillic acid and Xanthotoxol showed the docking score -6.926, -4.041, -4.889 , -4.356, -3.007 and -5.816 respectively. Among all the compounds Clausemarin B showed the best docking score. So, Clausemarin B is the best compounds for thrombolytic activity, as it possessed the best value in Molecular docking. Further in vivo investigation need to identify the thrombolytic activity of isolated compounds from Clausena lansium