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.

Computational and Pharmacological Studies on the Antioxidant, Thrombolytic, Anti-Inflammatory, and Analgesic Activity of Molineria capitulata.

Molineria capitulata is an ornamental plant that has traditionally been used to treat several chronic diseases. The present study was designed to examine the antioxidant, cytotoxic, thrombolytic, anti-inflammatory, and analgesic activities of a methanolic extract of M. capitulata leaves (MEMC) using both experimental and computational models. Previously established protocols were used to perform qualitative and quantitative phytochemical screening in MEMC. A computational study, including molecular docking and ADME/T analyses, was performed. The quantitative phytochemical analysis revealed the total phenolic and flavonoid contents as 148.67 and 24 mg/g, respectively. Antioxidant activity was assessed by examining the reducing power of MEMC, resulting in absorbance of 1.87 at 400 µg/mL, demonstrating a strong reduction capacity. The extract exhibited significant protection against blood clotting and showed the highest protein denaturation inhibition at 500 µg/mL. In both the acetic acid-induced writhing and formalin-induced paw-licking models, MEMC resulted in significant potential pain inhibition in mice. In the computational analysis, 4-hydroxybenzaldehyde, orcinol glucoside, curcapital, crassifogenin C, and 2,6-dimethoxy-benzoic acid displayed a strong predictive binding affinity against the respective receptors. These findings indicated that M. capitulata possesses significant pharmacological activities to an extent supported by computational studies.

Appraisals of the Bangladeshi Medicinal Plant Calotropis gigantea Used by Folk Medicine Practitioners in the Management of COVID-19: A Biochemical and Computational Approach.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first recognized in Wuhan in late 2019 and, since then, had spread globally, eventually culminating in the ongoing pandemic. As there is a lack of targeted therapeutics, there is certain opportunity for the scientific community to develop new drugs or vaccines against COVID-19 and so many synthetic bioactive compounds are undergoing clinical trials. In most of the countries, due to the broad therapeutic spectrum and minimal side effects, medicinal plants have been used widely throughout history as traditional healing remedy. Because of the unavailability of synthetic bioactive antiviral drugs, hence all possible efforts have been focused on the search for new drugs and alternative medicines from different herbal formulations. In recent times, it has been assured that the Mpro, also called 3CLpro, is the SARS-CoV-2 main protease enzyme responsible for viral reproduction and thereby impeding the host's immune response. As such, Mpro represents a highly specified target for drugs capable of inhibitory action against coronavirus disease 2019 (COVID-19). As there continue to be no clear options for the treatment of COVID-19, the identification of potential candidates has become a necessity. The present investigation focuses on the in silico pharmacological activity of Calotropis gigantea, a large shrub, as a potential option for COVID-19 Mpro inhibition and includes an ADME/T profile analysis of that ligand. For this study, with the help of gas chromatography-mass spectrometry analysis of C. gigantea methanolic leaf extract, a total of 30 bioactive compounds were selected. Our analyses unveiled the top four options that might turn out to be prospective anti-SARS-CoV-2 lead molecules; these warrant further exploration as well as possible application in processes of drug development to combat COVID-19.

Chemical Profiles and Pharmacological Properties with in Silico Studies on Elatostema papillosum Wedd.

The current study attempted, for the first time, to qualitatively and quantitatively determine the phytochemical components of Elatostema papillosum methanol extract and their biological activities. The present study represents an effort to correlate our previously reported biological activities with a computational study, including molecular docking, and ADME/T (absorption, distribution, metabolism, and excretion/toxicity) analyses, to identify the phytochemicals that are potentially responsible for the antioxidant, antidepressant, anxiolytic, analgesic, and anti-inflammatory activities of this plant. In the gas chromatography-mass spectroscopy analysis, a total of 24 compounds were identified, seven of which were documented as being bioactive based on their binding affinities. These seven were subjected to molecular docking studies that were correlated with the pharmacological outcomes. Additionally, the ADME/T properties of these compounds were evaluated to determine their drug-like properties and toxicity levels. The seven selected, isolated compounds displayed favorable binding affinities to potassium channels, human serotonin receptor, cyclooxygenase-1 (COX-1), COX-2, nuclear factor (NF)-κB, and human peroxiredoxin 5 receptor proteins. Phytol acetate, and terpene compounds identified in E. papillosum displayed strong predictive binding affinities towards the human serotonin receptor. Furthermore, 3-trifluoroacetoxypentadecane showed a significant binding affinity for the KcsA potassium channel. Eicosanal showed the highest predicted binding affinity towards the human peroxiredoxin 5 receptor. All of these findings support the observed in vivo antidepressant and anxiolytic effects and the in vitro antioxidant effects observed for this extract. The identified compounds from E. papillosum showed the lowest binding affinities towards COX-1, COX-2, and NF-κB receptors, which indicated the inconsequential impacts of this extract against the activities of these three proteins. Overall, E. papillosum appears to be bioactive and could represent a potential source for the development of alternative medicines; however, further analytical experiments remain necessary.

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.

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.

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 activities 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. This study provides some support to explain the traditional use of T. crispa as a remedy for pain.

Pharmacological evidence for the use of Cissus assamica as a medicinal plant in the management of pain and pyrexia.

The existing therapeutic agents for the management of pain and pyrexia are not very efficient and accompanied by numerous side effects. Thus, new effective agents are the most needed. The present study investigates bioactivities and phytochemical screening of different parts of Cissus assamica (Vitaceae), a Bangladeshi tribal medicinal plant. Three plant parts stems, leaves and roots were collected, washed, dried, powdered and then prepared for cold extraction. The methanolic stems and leaves extracts were fractioned with four and two solvents respectively. Different plant extracts were then investigated for in vivo antinociceptive activity and only methanolic leaves extract was investigated for in vivo antipyretic activity. In Swiss-albino mice, 200 and 400 mg/kg body weight doses were used for all extracts. In the peripheral antinociceptive activity, the methanolic stem extract and its dichloromethane, chloroform, pet ether fractions and methanolic roots extract at their both doses showed significant antinociceptive responses when compared to standard diclofenac sodium (60.49% inhibition). In the central antinociceptive activity, the response was found significant for methanolic stem and methanolic roots extract in their both doses compared to standard morphine. In antipyretic activity, methanolic leaves extract significantly reduced pyrexia level at 400 and 200 mg/kg body weight doses after two, three and 4 h of administration when compared to standard. So our findings indicate that this plant possesses noteworthy pharmacological activities which may be a basis for further researches to establish a possible mode of action of its different parts.

Antibacterial, anthelmintic, and analgesic activities of Piper sylvaticum (Roxb.) leaves and in silico molecular docking and PASS prediction studies of its isolated compounds.

Background In the present study, we investigated the antibacterial, anthelmintic, and analgesic activities of methanol extract of P. sylvaticum leaves (MEPSL) in experimental models. Then, computational analysis (in silico molecular docking and PASS prediction) was performed to determine the potent phytoconstituents of total six isolated compounds of this plant for antibacterial and anthelmintic activities. Methods Qualitative and quantitative phytochemical studies were carried out by established methods. In vitro antibacterial activity was determined by disc diffusion technique and anthelmintic activity was tested against Tubifex tubifex worm whereas analgesic activity was determined by the acetic acid-induced writhing test in mice. Molecular docking study was performed using Schrödinger Maestro 10.1 and an online tool used for PASS prediction. Results Our phytochemical study revealed the presence of alkaloids, flavonoids, saponins, and also indicated a substantial amount of phenols (65.83 mg), flavonoids (102.56 mg), and condensed tannins (89.32 mg). MEPSL showed good antibacterial activity against both gram-positive and gram-negative bacteria. Our result exhibited that MEPSL has strong anthelmintic action compared to standard levamisole. In addition, the extract also showed a dose-dependent and statistically significant analgesic activity at the doses of 200 and 400 mg/kg, body weight. Docking studies showed that piperine and piperlonguminine have the best scores for the tested enzymes. PASS predicted the antibacterial and anthelmintic activity of both phytoconstituents. Conclusions This study suggests that MEPSL possess significant antibacterial, anthelmintic, and analgesic activities which could be related to the presence of several phytochemicals. The phytoconstituents, i.e. piperine and piperlonguminine were found to be most effective in computational studies.

In vivo analgesic effect of different extracts of Hopea odorata leaves in mice and in silico molecular docking and ADME/T property analysis of some isolated compounds from this plant.

Background The current study evaluates the analgesic effect of different extracts of Hopea odorata leaves in mice followed by molecular docking and absorption, distribution, metabolism, excretion, and toxicity (ADME/T) analysis of isolated compounds derived from the plant with the COX-1 enzyme. Methods In the present study, the dried leaves of H. odorata were subjected to extraction using methanol, ethanol, and water. In vivo analgesic activity was evaluated by using the acetic acid-induced writhing test and formalin-induced paw licking test, and in silico molecular docking and ADME/T study were performed using Schrödinger Maestro (version 11.1) and online-based tools, respectively, on eight isolated compounds. Results The results showed that the methanolic extract of leaves has highest significant dose-dependent analgesic activity at both 200 and 400 mg/kg followed by ethanolic extract of leaves. Among all the compounds, ampelopsin showed the best docking score of -7.055, ensuring strong binding affinity between the ligand and the receptor, and ADME/T analysis using Web-based tools ensures the compound has not violated Lipinski's rule of five indicating its safety consumption. Conclusions The result confirms the analgesic activity of H. odorata leaves in both in vivo and in silico assays. The data support ampelopsin to be a potent analgesic compound worthy of future clinical trials and its "drug-likeliness".

Effects of Five Bangladeshi Plant Extracts on In vitro Thrombolysis and Cytotoxicity.

BACKGROUND: Piper Betle, Pterospermum acerifolium, Saraca indica, Argyreia speciosa, and Rhaphidophora glauca are medicinal plants commonly used as traditional medicine for the treatment of various diseases. To examine, whether organic extracts of these plants possess thrombolytic properties with minimal or no toxicity is our main aim of the study. MATERIALS AND METHODS: In vitro thrombolytic model was used to check the clot lysis effects using streptokinase (SK) as a positive control and water as a negative control. Cytotoxicity was screened by brine shrimp lethality bioassay using vincristine sulfate (VS) as positive control. RESULTS: Among herbal drugs, different organic extracts of P. betle, P. acerifolium, S. indica, A. speciosa, and R. glauca showed significant (P < 0.05 and P < 0.0001) clot lysis activity viz., 31.58% ±0.76%, 40.50% ±0.94%, 49.70% ±1.69%, 35.81% ±0.86%, and 43.80% ±0.91%, respectively, compared to reference drug SK (79.32% ±1.629%). In brine shrimp cytotoxic assay, mortality achieved by the extracts showed lethal concentration 50 (LC50) values 274.64 ± 3.46, 215.60 ± 4.59, 478.40 ± 6.98, 233.37 ± 2.56, and 209.32 ± 1.98 µg/ml, respectively, with reference to VS (LC50, 0.05 ± 0.34). CONCLUSION: In this study, S. indica, R. glauca, and P. acerifolium possessed effective thrombolytic activity. Further studies can be undertaken to identify certain structure of the ingredients in the extracts and to elucidate the precise mechanism of action. SUMMARY: Five Bangladesh medicinal plants, named Piper betle, Pterospermum acerifolium, Saraca indica, Argyreia speciosa, and Rhaphidophora glauca were subjected to comparative antithrombotic and toxicity based analysis. In comparative study, Saraca indica showed highest clot lysis (49.70 ± 1.69%) activity among the other plant with lowest toxicity (LC50: 478.40 ± 6.98) Abbreviations Used: h: Hour; min: Minutes; sec: Second; kg: Kilogram; g: Gram; µg: Microgram; L: Liter; mL: Millilitre; µL: Micro liter; µg/mL: Microgram per Milliliter; mg/kg: Milligram per kilogram; %: Percent; °C: Degree Celsius; et al.: et alliori (and others); w/w: Weight by Weight; v/v: Volume by Volume; SEM: Standard Error Mean; LC50: lethal concentration at 50.