Antioxidant-Rich Woodfordia fruticosa Leaf Extract Alleviates Depressive-Like Behaviors and Impede Hyperglycemia.

Dhaiphul (Woodfordia fruticosa) is a frequently demanded plant in South-East Asian regions for its diverse medicinal values. This study was proposed to examine antioxidant, antidiabetic, and antidepressant potentials of methanol extract of W. fruticosa leaves (MEWF) and its derived n-hexane (NHFMEWF) and ethyl acetate (EAFMEWF) fractions through in vitro, in vivo, and computational models. Among test samples, MEWF and EAFMEWF contained the highest phenolic content and showed maximal antioxidant activity in DPPH radical scavenging and ferric reducing power assays. In comparison, NHFMEWF possessed maximum flavonoid content and a significantly potent α-amylase inhibitory profile comparable with positive control acarbose. In animal models of depression (forced swimming and tail suspension test), EAFMEWF and NHFMEWF demonstrated a dose-dependent antidepressant-like effect; explicitly, the depressive-like behaviors significantly declined in EAFMEWF-treated dosing groups in contrast to the control group. In the computational analysis, previously isolated flavonoid compounds from Dhaiphul leaves manifested potent binding affinity against several key therapeutic target proteins of diabetes and depressive disorders including α-amylase, serotonin transporter, dopamine transporter, and neuronal nitric oxide synthase with varying pharmacokinetics and toxicity profiles. This research's outcomes may provide potential dietary supplements for mitigating hyperglycemia, cellular toxicity, and depressive disorder.

Central and peripheral pain intervention by Ophiorrhizarugosa leaves: Potential underlying mechanisms and insight into the role of pain modulators.

ETHNOPHARMACOLOGICAL RELEVANCE: Ophiorrhiza rugosa var. prostrata is a traditional medicinal plant used by the indigenous and local tribes (Chakma, Marma and Tanchangya) of Bangladesh for the management of chest pain, body ache, and earache. However, the knowledge of anti-nociceptive and anti-inflammatory potentials of this plant is scarce. AIM OF THE STUDY: Therefore, we scrutinized the anti-nociceptive and anti-inflammatory properties of O. rugosa leaves along with its possible mechanism(s) of action using chemical and heat-induced pain models. METHODS AND MATERIALS: O. rugosa was extracted using 100% ethanol (EEOR) followed by exploring phytochemicals and assessing acute toxicity. To determine anti-nociceptive potentials, chemical-induced (acetic acid and formalin) and heat-induced (hot plate and tail immersion) nociceptive models were followed. To investigate the possible involvement of opioid receptors during formalin, hot plate, and tail immersion tests, naltrexone was administered whereas methylene blue and glibenclamide were used to explore cGMP involvement and ATP-sensitive K+ channel pathways, respectively. Moreover, the anti-inflammatory potential was assessed using the carrageenan-induced paw edema test model. Motor behaviours of EEOR were assessed by the open-field test. Finally, bioactive constituents (identified by GC-MS) from O. rugosa were subjected to molecular docking and ADME/t analysis to evaluate its potency and safety. RESULTS: During chemical-induced and heat-induced pain models, EEOR exhibited significant and effective nociception suppression at all experimental doses (200 and 400 mg/kg). Also, the administration of naltrexone corroborated the association of opioid receptors with the anti-nociceptive activity by EEOR. Similarly, cGMP and ATP-sensitive K+ channel pathways were also found to be involved in the anti-nociceptive mechanism. Furthermore, significant and dose-dependent inhibition of inflammation induced by carrageenan was recorded for EEOR. Both doses of EEOR did not affect the animal's locomotor capacity in the open-field test. Besides, in silico test identified the key compounds (loliolide, harman, squalene, vitamin E, and gamma-sitosterol) that inhibited some particular receptors regarding pain and inflammation. CONCLUSION: This research exposes central and peripheral pain intervention as well as anti-inflammatory activity of O. rugosa. Also, the identified compounds from this plant support its activities by effectively inhibiting anti-nociceptive and anti-inflammatory receptors. Overall, these outcomes valorize the ethnomedicinal efficacy of O. rugosa in managing various painful conditions.

An integrated exploration of pharmacological potencies of Bischofia javanica (Blume) leaves through experimental and computational modeling.

Bischofia javanica (Blume), an edible wild plant, has both prospective nutraceutical and therapeutic properties. Here, we intended to explore the pharmacological potentials of the methanol extract of B. javanica (MEBJ) through integrated approaches. Phytochemical screening revealed the presence of important phytoconstituents which were found to be safe during cytotoxicity analysis. The sedative potential of MEBJ (200 and 400 mg/kg) was determined by employing open field, hole cross, and thiopental sodium-induced sleeping time tests, where a significant reduction of the locomotor performance and an enhancement in the duration of sleeping have been observed, respectively. In addition, mice treated with MEBJ exhibited superior exploration during both elevated plus maze and hole board tests. In parallel, anti-diabetic potency was investigated via alpha-amylase inhibitory assay, where a dose-response increase in the percentage of inhibition has been marked. A similar response, such as an increased percentage of clot lysis, was observed during the thrombolytic test. Furthermore, molecular docking was performed with the identified compounds, demonstrated strong binding affinities to the target receptors of the experiments as mentioned above. Also, ADME/T and toxicological parameters verified the drug-like properties of the identified compounds. Collectively, these results indicate bioactivity of Bischofia javanica, which can be a potential candidate in the food and pharmaceutical industries.

Unveiling Pharmacological Responses and Potential Targets Insights of Identified Bioactive Constituents of Cuscuta reflexa Roxb. Leaves through In Vivo and In Silico Approaches.

Cuscuta reflexa Roxb. is traditionally used by the indigenous communities of Bangladesh to treat different diseases, such as pain, edema, tumor, jaundice, and skin infections. This study tested neuro-pharmacological, anti-nociceptive, and antidiarrheal activities by in vivo and in silico experiments for the metabolites extracted (methanol) from the leaves of Cuscuta reflexa (MECR). During the anxiolytic evaluation analyzed by elevated plus maze and hole board tests, MECR (200 and 400 mg/kg) exhibited a significant dose-dependent reduction of anxiety-like behavior in mice. Similarly, mice treated with MECR demonstrated a dose-dependent decrease in the time of immobility in both forced swimming and tail suspension tests. In addition, anti-nociceptive activity was assessed by the chemical-induced (acetic acid and formalin) pain models. In both cases, 400 mg/kg was found to be most effective and significantly (p < 0.001) inhibited acetic acid stimulated writhing and formalin-induced licking (pain response) in mice. Furthermore, antidiarrheal efficacy determined by the castor-oil induced diarrheal model manifested an evident inhibition of diarrheal stool frequency. In parallel, previously isolated bioactive compounds were documented based on the biological activities and subjected to in silico studies to correlate with the current pharmacological outcomes. The selected isolated compounds (15) displayed favorable binding affinities to potassium channels, human serotonin receptor, COX-1, COX-2, M3 muscarinic acetylcholine receptor, and 5-HT3 receptor proteins. Additionally, the ADME/T and toxicological properties were justified to unveil their drug-like properties and toxicity level. Overall, Cuscuta reflexa is bioactive and could be a potential source for the development of alternative medicine.

Intervention in Neuropsychiatric Disorders by Suppressing Inflammatory and Oxidative Stress Signal and Exploration of In Silico Studies for Potential Lead Compounds from Holigarna caustica (Dennst.) Oken leaves.

Holigarna caustica (Dennst.), a popular plant used in folk medicine in Bangladesh, is often used by the local folk practitioner to treat a variety of chronic diseases. The present research is an attempt to find out an innovative therapeutic prospect for the management of neuropsychiatric disorders. The methanol extract of H. caustica leaves (MEHC) were utilized on various behavioral tests for assessing anxiolytic, anti-depressant, and anti-inflammatory activities. The antioxidant potentials and quantitative phytochemicals were evaluated through spectrophotometric methods. Results revealed that treatment of MEHC (200 and 400 mg/kg) significantly reduced anxiety like behaviors in mice, particularly, 400 mg/kg efficiently improved % of entries and time spent (p < 0.05) in the open arms in elevated plus maze test, whereas, superior head dipping tendency (p < 0.05) was observed in hole-board test. In contrast, mice treated with 200 mg/kg revealed better anxiolytic effect in both open field and hole-cross tests. During antidepressant evaluation, mice administrated with MEHC exhibited active behaviors (swimming and struggling) in forced swimming and tail suspension tests. In parallel, MEHC manifested a noteworthy (p < 0.001) suppression of inflammatory response induced by histamine. The MEHC also showed strong antioxidant activities in 1,1-diphenyl-2-picrylhydrazyl radical (DPPH) (IC50: 57.64 µg/mL) scavenging, H2O2 (IC50: 51.60 µg/mL) scavenging, and ferric reducing power assay. The levels of total phenol, flavonoid, flavonol, condensed tannin, and antioxidant were estimated as higher in MEHC. Moreover, 11 compounds were documented as bioactive, displayed good binding affinities to potassium channel receptor, human serotonin receptor, cyclooxygenase (COX-1 and 2), and xanthine oxidoreductase enzyme targets in molecular docking experiments. Furthermore, ADME/T and Prediction of Activity Spectra for Substances (PASS) analyses exposed their drug-likeness, nontoxic upon consumption, and likely pharmacological actions. Overall, the H. caustica is potentially bioactive as evident by in vivo, in vitro, and computational analysis. Our findings support the folkloric value of this plant, which may provide a potential source towards developing drug leads.

Ficus cunia Buch.-Ham. ex Roxb. (leaves): An experimental evaluation of the cytotoxicity, thrombolytic, analgesic and neuropharmacological activities of its methanol extract.

Background The aim of this experiment was to evaluate the cytotoxic, thrombolytic, analgesic, sedative-hypnotic and anxiolytic activities of the methanolic extract of Ficus cunia leaves. Methods Primary phytochemical screening was accomplished by using established methods. Cytotoxicity was studied by brine shrimp lethality test, and the thrombolytic assay was conducted through clot lysis method with human blood. The in vivo action was done using mice of both sexes. The analgesic activity was evaluated by acetic acid-induced writhing test and formalin-induced paw licking test. Open field, hole cross and thiopental Na-induced sleeping time test were used to examine the sedative-hypnotic activity, and elevated plus maze (EPM) and hole board test were used to identify the anxiolytic activity. Results The results elicited that the extract contained several phytochemicals such as alkaloid, flavonoid, and tannin. The extract was found to have a median lethal concentration (LC50) value of 55.48 µg/mL in the brine shrimp lethality bioassay. It was also assessed for antithrombotic activity when compared with streptokinase; it has significant (p < 0.001) thrombolytic effect (34.72 ± 1.74%) contrasted with standard streptokinase (67 ± 1.56%). The extract at doses of 200 and 400 mg/kg produced inhibition of 32.58% and 46.63% in acetic acid-induced pain and 45.88 and 61.18% in formalin-induced pain. The sedative and hypnotic activities on the central nervous system of the methanol extract of F. cunia (MEFC) leaves were evaluated. The extract delivered critical sedative impact at the doses of 200 and 400 mg/kg (by oral route) treated with reference to the substance diazepam, and the hypnotic impact was also observed in the case of mice. MEFC at its maximum dose (400 mg/kg) significantly (p < 0.01) increased the time spent in the open arms of the EPM. In the hole board test, there was a dose-dependent (at 200 and 400 mg/kg) and a significant (p < 0.05 and p < 0.01) increase in the number of head pokes in comparison to control. Conclusions The results of the present study gave a helpful baseline in progression for the possible use of MEFC as a cytotoxic, thrombolytic, analgesic, sedative-hypnotic and anxiolytic drug.