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

Network Pharmacology Study to Reveal the Potentiality of a Methanol Extract of <i>Caesalpinia sappan</i> L. Wood against Type-2 Diabetes Mellitus

Caesalpinia sappan L. (CS) is widely used to treat diabetic complications in south-east Asia, specifically in traditional Chinese medicine. This study intends to explain the molecular mechanism of how chemical constituents of CS interrelate with different signaling pathways and receptors involved in T2DM. GC-MS was employed to identify the chemical compounds from the methanol extract of CS wood (MECSW). Lipinski’s rule of five was applied, and 33 bioactive constituents have been screened from the CS extract. After that, 124 common targets and 26 compounds associated with T2DM were identified by mining several public databases. Protein–protein interactions and compound-target network were constructed using the STRING database and Cytoscape tool. Protein–protein interactions were identified in 121 interconnected nodes active in T2DM and peroxisome proliferator-activated receptor gamma (PPARG) as key target receptors. Furthermore, pathway compound target (PCT) analysis using the merger algorithm plugin of Cytoscape revealed 121 nodes from common T2DM targets, 33 nodes from MECSW compounds and 9 nodes of the KEGG pathway. Moreover, network topology analysis determined “Fisetin tetramethyl ether” as the key chemical compound. The DAVID online tool determined seven signaling receptors, among which PPARG was found most significant in T2DM progression. Gene ontology and KEGG pathway analysis implied the involvement of nine pathways, and the peroxisome proliferator-activated receptor (PPAR) pathway was selected as the hub signaling pathway. Finally, molecular docking and quantum chemistry analysis confirmed the strong binding affinity and reactive chemical nature of fisetin tetramethyl ether with target receptors exceeding that of the conventional drug (metformin), PPARs agonist (rosiglitazone) and co-crystallized ligands, indicating that fisetin could be a potential drug of choice in T2DM management. This study depicts the interrelationship of the bioactive compounds of MECSW with the T2DM-associated signaling pathways and target receptors. It also proposes a more pharmaceutically effective substance, fisetin tetramethyl ether, over the standard drug that activates PPARG protein in the PPAR signaling pathway of T2DM

In Vitro and In Vivo Biological Activities of Cissus adnata (Roxb.)

This study was conducted to evaluate the in vitro polyphenol content, antioxidant, cytotoxic, antibacterial, anthelmintic properties, and in vivo antinociceptive activity of the ethanol extract of Cissus adnata leaves (EECA) in different experimental models. Polyphenol contents were investigated using spectrophotometric techniques. Antioxidant activity was determined by 1,1-diphenyl-2-picrylhydrazyl radical (DPPH) radical-scavenging, ferric reducing power, and total antioxidant capacity assays. Cytotoxicity was determined by brine shrimp lethality bioassay and disc diffusion method was used for the antibacterial activity. Anthelmintic activity was studied using aquarium worm (Tubifex tubifex) whereas antinociceptive activity was evaluated in mice by acetic acid and formalin test. Phytochemical screening of EECA revealed the presence of alkaloids, carbohydrates, flavonoids, phenols, terpenoids, saponins, and tannins. EECA showed strong antioxidant activity with high polyphenol contents. It was observed that EECA possessed significant antibacterial activity with a low toxicity profile. EECA also demonstrated dose-dependent and statistically significant anthelmintic and antinociceptive activities. Our study shows that ethanol extract of C. adnata leaves possess strong antioxidant, antibacterial, anthelmintic and antinociceptive activities with lower toxicity. Further studies are needed to identify bioactive phytomolecules and to understand the mechanism of such actions better

Evaluation of anti-nociceptive and anti-inflammatory activities of the methanol extract of Holigarna caustica (Dennst.) Oken leaves

Ethnopharmacological relevance: Holigarna caustica (Dennst.) is commonly used in traditional medicine to treat a variety of painful conditions such as eye irritation, inflammation, arthritis, skin diseases, cuts and wounds.Aim of the study: The present study was undertaken to investigate the anti-nociceptive and anti-inflammatory activities of the methanol extract of H. caustica leaves and to elucidate its possible mechanism(s) of action.Materials and methods: Fresh leaves of H. caustica were collected, dried, and extracted with methanol (MEHC). MEHC was subjected to activity testing, using chemical-induced (acetic acid and formalin test) and heat-induced (hot plate and tail immersion test) pain models. To determine the possible mechanism behind the anti-nociceptive activity of MEHC, the opioid antagonist naltrexone was used to evaluate the involvement of opioid receptors in the case of formalin, hot plate and tail immersion tests, while the involvement of the cGMP and ATP-sensitive K+ channel pathways were assessed using methylene blue and glibenclamide respectively, in the acetic acid-induced writhing test. In parallel, the carrageenan-induced paw oedema model was used to determine the anti-inflammatory potential of the extract. Exploratory and motor behaviours were evaluated by the open-field test. Various bioactive compounds potentially responsible for the anti-nociceptive and anti-inflammatory activities were ascertained using GC-MS analysis.Results: MEHC showed strong, significant and dose-dependent anti-nociceptive activity in all chemical-induced and heat-induced pain models at all experimental doses. The association of opioid receptors with the observed anti-nociceptive effects was confirmed by using naltrexone. The cGMP and ATP-sensitive K+ channel pathway was also shown to be involved in the anti-nociceptive activity of MEHC. In addition, MEHC exhibited a dose-dependent inhibition of inflammatory oedema induced by carrageenan. MEHC was not connected with changes in either the locomotor activity or motor responses of mice. In a GC-MS analysis, 40 compounds were identified, among which twelve are documented bioactive compounds with potent analgesic and anti-inflammatory properties.Conclusions: Our current study revealed that MEHC possesses strong central and peripheral anti-nociceptive as well as anti-inflammatory activity. It may also be concluded that both opioid receptors as well as the cGMP and ATP-sensitive K+ channel pathway are involved in the anti-nociceptive mechanism of MEHC. This study rationalizes the ethnomedicinal use of H. caustica leaves in various painful conditions.</p

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

Investigation of the Biological Activities and Characterization of Bioactive Constituents of <i>Ophiorrhiza rugosa</i> var. <i>prostrata</i> (D.Don) &amp; Mondal Leaves through In Vivo, In Vitro, and In Silico Approaches

Ophiorrhiza rugosa var. prostrata is one of the most frequently used ethnomedicinal plants by the indigenous communities of Bangladesh. This study was designed to investigate the antidiarrheal, anti-inflammatory, anthelmintic and antibacterial activities of the ethanol extract of O. rugosa leaves (EEOR). The leaves were extracted with ethanol and subjected to in vivo antidiarrheal screening using the castor oil-induced diarrhea, enteropooling, and gastrointestinal transit models. Anti-inflammatory efficacy was evaluated using the histamine-induced paw edema test. In parallel, in vitro anthelmintic and antibacterial activities were evaluated using the aquatic worm and disc diffusion assays respectively. In all three diarrheal models, EEOR (100, 200 and 400 mg/kg) showed obvious inhibition of diarrheal stool frequency, reduction of the volume and weight of the intestinal contents, and significant inhibition of intestinal motility. Also, EEOR manifested dose-dependent anti-inflammatory activity. Anthelmintic action was deemed significant (P &lt; 0.001) with respect to the onset of paralysis and helminth death. EEOR also resulted in strong zones of inhibition when tested against both Gram-positive and Gram-negative bacteria. GC-MS analysis identified 30 compounds within EEOR, and of these, 13 compounds documented as bioactive showed good binding affinities to M3 muscarinic acetylcholine, 5-HT3, tubulin and GlcN-6-P synthase protein targets in molecular docking experiments. Additionally, ADME/T and PASS analyses revealed their drug-likeness, likely safety upon consumption and possible pharmacological activities. In conclusion, our findings scientifically support the ethnomedicinal use and value of this plant, which may provide a potential source for future development of medicines

Anxiolytic, antidepressant and antioxidant activity of the methanol extract of Canarium resiniferum leaves

Background and aim This study evaluated the anxiolytic, antidepressant, and antioxidant activity of the methanol extract of Canarium resiniferum (MECR) leaves, and determined the total phenolic and flavonoid contents in this extract. Experimental procedure The anxiolytic effect of MECR (100, 200, 400 mg/kg, p.o.) was tested in mice using the elevated plus-maze (EPM) test, the hole-board test (HBT), and the light-dark box (LDB) test. Its antidepressant effect was evaluated in the tail suspension (TST) and the forced swim (FST) tests. The total phenolic (TPC) and flavonoid (TFC) content was measured using standard colorimetric assays. Antioxidant activity was determined using the DPPH radical scavenging and ferric reducing antioxidant power (FRAP) assays. Results and conclusion MECR, at all doses, showed dose-dependent anxiolytic activity. At 400 mg/kg, it significantly increased the time spent and number of entries in the open arms (EPM test), the number of head-dips (HBT), and the time spent into the light compartment (LDB) test compared to the control. In the TST and FST, MECR dose-dependently reduced the duration of immobility compared to untreated animals. This was significant for all doses except for 100 mg/kg in the FST model. MECR showed high TPC and TFC (90.94 ± 0.75 mg GAE/g and 51.54 ± 0.78 mg QE/g of dried extract, respectively) and displayed potent activity in the DPPH radical scavenging (IC50 = 177.82 μg/mL) and FRAP assays. These findings indicate that C. resiniferum has the potential to alleviate anxiety and depression disorders, which merits further exploration

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

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