Insightful Valorization of the Biological Activities of Pani Heloch Leaves through Experimental and Computer-Aided Mechanisms.

Pani heloch (Antidesma montanum) is traditionally used to treat innumerable diseases and is a source of wild vegetables for the management of different pathological conditions. The present study explored the qualitative phytochemicals; quantitative phenol and flavonoid contents; in vitro antioxidant, anti-inflammatory, and thrombolytic effects; and in vivo antipyretic and analgesic properties of the methanol extract of A. montanum leaves in different experimental models. The extract exhibited secondary metabolites including alkaloids, flavonoids, flavanols, phytosterols, cholesterols, phenols, terpenoids, glycosides, fixed oils, emodines, coumarins, resins, and tannins. Besides, Pani heloch showed strong antioxidant activity (IC50 = 99.00 µg/mL), while a moderate percentage of clot lysis (31.56%) in human blood and significant anti-inflammatory activity (p < 0.001) was achieved with the standard. Moreover, the analgesic and antipyretic properties appeared to trigger a significant response (p < 0.001) relative to in the control group. Besides, an in silico study of carpusin revealed favorable protein-binding affinities. Furthermore, the absorption, distribution, metabolism, excretion, and toxicity analysis and toxicological properties of all isolated compounds adopted Lipinski's rule of five for drug-like potential and level of toxicity. Our research unveiled that the methanol extract of A. montanum leaves exhibited secondary metabolites that are a good source for managing inflammation, pyrexia, pain, and cellular toxicity. Computational approaches and further studies are required to identify the possible mechanism which responsible for the biological effects.

Pharmacological and computer-aided studies provide new insights into Millettia peguensis Ali (Fabaceae).

Millettia peguensis, popular for its ethnopharmacological uses, was employed to evaluate its different pharmacological properties in this study. The analgesic studies of the plant have been performed by acetic acid-induced writhing and formalin-induced licking tests respectively, whereas the antidiarrheal experiment was done by castor oil-induced diarrheal test. Besides, antioxidant, cytotoxic, antimicrobial, thrombolytic evaluations were performed by DPPH scavenging with phenol content determination, brine shrimp lethality, disc diffusion and clot lysis methods respectively. Moreover, in silico study of the phytoconstituents was carried out by molecular docking and ADME/T analysis. The methanol extract of Millettia peguensis (MEMP) revealed significant biological activity in the analgesic and antidiarrheal test (p < 0.001) compared to the standards. Antioxidant assay displayed promising IC50 values (15.96 µg/mL) with the total phenol content (65.27 ± 1.24 mg GAE/g). In the cytotoxicity study, the LC50 value was found to be 1.094 µg/mL. Besides, MEMP was highly sensitive to the bacteria but less liable to clot lysis. Furthermore, phytoconstituents exposed potential binding affinity towards the selected receptors, whereas the ADME/T properties indicated the drug likeliness of the plant. The outcomes of these findings suggest the therapeutic potential of this plant against pain, diarrhea, inflammation, and tissue toxicity.

Pharmacological insights into Chukrasia velutina bark: Experimental and computer-aided approaches.

BACKGROUND: Chukrasia velutina is an enthnomedicinally used plant reported to have significant medicinal values. The present study aimed to explore the pharmacological activities of bark methanol extract using in vitro, in vivo and in silico models. METHODS: The study was designed to investigate the pharmacological effects of methanol extract of Chukrasia velutina bark (MECVB) through in vitro, in vivo and in silico assays. Analgesic activity was tested using formalin-induced nociception and acetic acid-induced writhing assays while the antipyretic effect was tested using yeast-induced hyperthermia in mice model. The antioxidant effect was tested using the DPPH and reducing power assay and the cytotoxic screening was tested using the brine shrimp lethality bioassay. In addition, in silico studies were conducted using computer aided methods. RESULTS: In the acetic acid-induced writhing assay, the extract showed 28.36% and 56.16% inhibition of writhing for doses of 200 and 400 mg/kg, respectively. Moreover, a dose-dependent formalin-induced licking response was observed in both early and late phase. In yeast-induced pyrexia, the MECVB exhibited (p < 0.05) antipyretic effect. The extract demonstrated an IC50 value of 78.86 µg/ml compared with ascorbic acid (IC50 23.53 µg/ml) in the DPPH scavenging assay. The compounds sitosterol, 5,7-dimethoxycoumarin and scopoletin were seen be effective in molecular docking scores against COX-I (2OYE), COX-II (6COX) and human peroxiredoxin 5 (1HD2). In ADME/T analysis, 5,7-dimethoxycoumarin and scopoletin satisfied Lipinski's rule of five and thus are potential drug candidates. CONCLUSION: The bark of Chukrasia velutina showed significant analgesic and antipyretic properties and is a potential source of natural anti-oxidative agents.

Identification of potential phytochemicals from Citrus Limon against main protease of SARS-CoV-2: molecular docking, molecular dynamic simulations and quantum computations.

The outbreak of coronavirus disease (COVID-19) caused by a novel RNA virus emerged at the end of 2019. Most of the patient's symptoms are mild to moderate, and influenza, acute respiratory distress syndrome (ARDS) and multi-organ failure are common. The disease is mild to moderate in most patients and is reported in many cases such as pneumonia, ARDS and multi-organ dysfunction. This study's objective is to evaluate 25 natural compounds from Citrus limon (CL) used by comprehensive molecular docking, density functional theory (DFT) and molecular dynamics analysis against SARS-CoV-2 main protease (Mpro). Among all the experimental compounds, diosmetin has shown the best docking values against the Mpro of SARS-CoV-2 compared to the standard antiviral drug. In DFT calculations, the order associated with biochemical reactivity is as follows: eriodictoyl > quercetin > spinacetin > diosmetin > luteolin > apigenin, whereas the regions of oxygen and hydrogen atoms from the selected isolated compounds are appropriate for electrophilic and nucleophilic attacks, respectively. Also, HOMO-LUMO and global descriptors values indicated a promising result of these compounds. Moreover, a molecular dynamics simulation study revealed the stable conformation and binding pattern in a stimulating environment of natural compounds CL. Considering molecular docking, simulation, and DFT analysis of the selected compounds, notably eriodictoyl, quercetin, and diosmetin showed good potential against SARS-CoV-2 Mpro. Our in silico study revealed promising antiviral activity, which may be considered a potential key factor or a therapeutic target for COVID-19.Communicated by Ramaswamy H. Sarma.

Unveiling pharmacological studies provide new insights on Mangifera longipes and Quercus gomeziana.

Mangifera longipes and Quercus gomeziana both is an ethnomedicinally important Asian herb that has been known for numerous healing activity of tribal people. The present research aims to investigate the phytochemical analysis with in vitro, in vivo possibilities of the soluble ethanol extract of M. longipes root (EEMLR) and Q. gomeziana leaves (EEQGL) by an experimental approach. The plant extract of EEMLR and EEQGL was found secondary metabolites, notably steroids, glycosides, tannins, flavonoids, saponins, gums, and alkaloids. Additionally, the extract showed significant activity in antioxidant, antipyretic, anti-inflammatory, membrane stabilization, cytotoxic, thrombolytic, and analgesic activities while no response in antibacterial activity. Our findings reveal that soluble ethanol extract of EEMLR and EEQGL is safe, which can be an effective source for exploring new medicinal products. This research's outcomes may provide potentials for mitigating pyrexia, inflammation, pain, cellular toxicity, and coagulation.

Anti-Inflammatory, Thrombolytic and Hair-Growth Promoting Activity of the n-Hexane Fraction of the Methanol Extract of Leea indica Leaves.

The anti-inflammatory, thrombolytic, and hair growth-promoting activity of the n-hexane fraction from the methanol extract of Leea indica (NFLI) leaves was investigated. NFLI showed significant inhibition of hemolysis and protein denaturation, and exhibited a concentration-dependent thrombolytic activity. When applied topically to mice at concentrations of 10, 1, 0.1%, NFLI demonstrated a significant increase in average hair length (p < 0.001) compared with untreated animals. NFLI (1% concentration) exhibited the highest percentage of hair regrowth on day 7, 14 and 21 (81.24, 65.60, and 62.5%, respectively). An in silico study was further conducted to predict the binding affinity of phytochemicals previously reported in L. indica towards PGD2 synthase (PDB ID: 2VD1), an enzyme that catalyses the isomerisation of prostaglandin H2 to PGD2 which is involved in hair loss. Phthalic acid, farnesol, n-tricosane, n-tetracosane, and n-heptacosane showed the best ligand efficiencies towards PGD2 synthase and their intermolecular interactions were visualised using BIOVIA Discovery Studio Visualizer. Our results indicate that L. indica could represent a promising natural alternative to tackle alopecia.

Potential of Plant Bioactive Compounds as SARS-CoV-2 Main Protease (Mpro) and Spike (S) Glycoprotein Inhibitors: A Molecular Docking Study.

Since the outbreak of the COVID-19 (coronavirus disease 19) pandemic, researchers have been trying to investigate several active compounds found in plants that have the potential to inhibit the proliferation of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2). The present study aimed to evaluate bioactive compounds found in plants using a molecular docking approach to inhibit the main protease (Mpro) and spike (S) glycoprotein of SARS-CoV-2. The evaluation was performed on the docking scores calculated using AutoDock Vina (AV) as a docking engine. A rule of five (Ro5) was calculated to determine whether a compound meets the criteria as an active drug orally in humans. The determination of the docking score was performed by selecting the best conformation of the protein-ligand complex that had the highest affinity (most negative Gibbs' free energy of binding/ΔG). As a comparison, nelfinavir (an antiretroviral drug), chloroquine, and hydroxychloroquine sulfate (antimalarial drugs recommended by the FDA as emergency drugs) were used. The results showed that hesperidin, nabiximols, pectolinarin, epigallocatechin gallate, and rhoifolin had better poses than nelfinavir, chloroquine, and hydroxychloroquine sulfate as spike glycoprotein inhibitors. Hesperidin, rhoifolin, pectolinarin, and nabiximols had about the same pose as nelfinavir but were better than chloroquine and hydroxychloroquine sulfate as Mpro inhibitors. This finding implied that several natural compounds of plants evaluated in this study showed better binding free energy compared to nelfinavir, chloroquine, and hydroxychloroquine sulfate, which so far are recommended in the treatment of COVID-19. From quantum chemical DFT calculations, the ascending order of chemical reactivity of selected compounds was pectolinarin > hesperidin > rhoifolin > morin > epigallocatechin gallate. All isolated compounds' C=O regions are preferable for an electrophilic attack, and O-H regions are suitable for a nucleophilic attack. Furthermore, Homo-Lumo and global descriptor values indicated a satisfactory remarkable profile for the selected compounds. As judged by the RO5 and previous study by others, the compounds kaempferol, herbacetin, eugenol, and 6-shogaol have good oral bioavailability, so they are also seen as promising candidates for the development of drugs to treat infections caused by SARS-CoV-2. The present study identified plant-based compounds that can be further investigated in vitro and in vivo as lead compounds against SARS-CoV-2.

Pharmacological insights and prediction of lead bioactive isolates of Dita bark through experimental and computer-aided mechanism.

Dita bark (Alstonia scholaris (L.) R. Br.) is an ethnomedicine used for the management of various ailments. This study aimed to investigate the biological properties of methanol extract of A. scholaris bark (MEAS), through in vivo, in vitro and in silico approaches alongside its phytochemical profiling. Identification and nature of the bioactive secondary metabolites were studied by the established qualitative tests and GC-MS analysis. The antidepressant activity was determined by forced swimming test (FST) and tail suspension test (TST) in mice. The anti-inflammatory and thrombolytic effect was evaluated using inhibition of protein denaturation technique and clot lysis technique, respectively. Besides, computational studies of the isolated compounds and ADME/T analysis were performed by Schrödinger-Maestro (v11.1) software, and PASS prediction was conducted through PASS online tools. The GC-MS analysis revealed the presence of several secondary metabolites in MEAS. Treatment with MEAS revealed a significant reduction of immobility time in a dose-dependent manner in FST and TST. Besides, MEAS showed substantial anti-inflammatory effects at the higher dose (400 µg/mL) as well as revealed notable clot lysis effect as compared to control. In the case of computer-aided investigation, all compounds meet the condition of Lipinski's rule of five. PASS study also predicted for all compounds, and among these safe compound furazan-3-amine showed the most spontaneous binding energy for both antidepressant and thrombolytic activities, as well as 5-dimethylamino-6 azauracil, found promising for anti-inflammatory activity. Taken together, the investigation concludes that MEAS can be a potent source of antidepressant, anti-inflammatory, and thrombolytic agents.

Biological Evaluation, DFT Calculations and Molecular Docking Studies on the Antidepressant and Cytotoxicity Activities of Cycas pectinata Buch.-Ham. Compounds.

Cycas pectinata Buch.-Ham. is commonly used in folk medicine against various disorders. The present study investigated the antidepressant and cytotoxicity activity of methanol extract of C. pectinata (MECP) along with quantitative phytochemical analysis by GC-MS method. Here, the GC-MS study of MECP presented 41 compounds, among which most were fatty acids, esters, terpenoids and oximes. The antidepressant activity was assessed by the forced swimming test (FST) and tail suspension test (TST) models. In contrast, MECP (200 and 400 mg/kg) exhibited a significant and dose-dependent manner reduction in immobility comparable with fluoxetine (10 mg/kg) and phenelzine (20 mg/kg). MECP showed a weak toxicity level in the brine shrimp lethality bioassay (ED50: 358.65 µg/mL) comparable to the standard drug vincristine sulfate (ED50: 2.39 µg/mL). Three compounds from the GC-MS study were subjected to density functional theory (DFT) calculations, where only cyclopentadecanone oxime showed positive and negative active binding sites. Cyclopentadecanone oxime also showed a good binding interaction in suppressing depression disorders by blocking monoamine oxidase and serotonin receptors with better pharmacokinetic and toxicological properties. Overall, the MECP exhibited a significant antidepressant activity with moderate toxicity, which required further advance studies to identify the mechanism.

Deciphering the Pharmacological Properties of Methanol Extract of Psychotria calocarpa Leaves by In Vivo, In Vitro and In Silico Approaches.

The present study explores the neuropharmacological, antinociceptive, antidiarrheal, antioxidant, thrombolytic and cytotoxic activity of methanol extract of Psychotria calocarpa leaves (MEPC). In anxiolytic activity testing of MEPC by elevated plus maze test, hole-board test and light-dark test, the extract exhibited a dose-dependent reduction of anxiety while the open field test observed a decreased locomotion. The administration of MEPC revealed a significant dose-dependent reduction of depressant behavior in forced swimming and tail suspension test. Additionally, the antinociceptive and antidiarrheal activity exposed a significant reduction of nociception and diarrheal behavior at the highest dose. In addition, a strong antioxidant activity was observed in DPPH-free radical-scavenging assay (IC50 = 461.05 µg/mL), total phenol content (118.31 ± 1.12 mg) and total flavonoid content (100.85 ± 0.97 mg). The significant clot-lysis activity was also observed with moderate toxicity (LC50 = 247.92 µg/mL) level in the lethality assay of brine shrimp. Moreover, in silico molecular docking study showed that the compound Psychotriasine could offer promising active site interactions for binding proteins. Furthermore, ADME/T and toxicological properties of the compound satisfied the Lipinski's rule of five and Veber rules for drug-like potential and toxicity level. Overall, MEPC had a potential neuropharmacological, antinociceptive, antidiarrheal and antioxidant activity that warranted further investigation.