Exploration of In Vivo and In Vitro Biological Effects of Sonneratia caseolaris (L.) Fruits Supported by Molecular Docking and ADMET Study.

Sonneratia caseolaris (L.) is a common mangrove plant which has significant medicinal value in traditional medicine. Ethanol extract from the fruits of S. caseolaris (SCE) was used in this project to explore its different pharmacological effects considering its traditional usage. In the castor oil-induced diarrheal method, SCE significantly lengthened the latency of the first defecation period up to 95.8 and 119.4 min as well as lowering stool count by 43.3% and 64.4% at the doses of 250 and 500 mg/kg, respectively. In evaluating the neuropharmacological effect using the open-field model, a significant central nervous system (CNS) depressant nature was observed after a reduction in the no. of squares crossed by mice at various time intervals. In evaluating the blood coagulation effect, SCE significantly reduced blood clotting time at 5.86, 5.52, and 5.01 min at 25, 50, and 100 mg/ml doses, respectively. In the assessment of the anthelmintic effect, SCE significantly killed Paramphistomum cervi (P. cervi) where the death times of the nematodes were 40.3, 36.8, and 29.9 min at 12.5, 25, and 50 mg/ml doses, respectively. The extract showed a very poor cytotoxic effect in brine shrimp lethality bioassay. In molecular docking analysis, maslinic acid, oleanolic acid, luteolin, luteolin 7-O-ß-glucoside, myricetin, ellagic acid, and R-nyasol showed the best binding affinities with the selected proteins which might be the credible reasons for eliciting pharmacological responses. Among these seven compounds, only luteolin 7-O-ß-glucoside had two violations in Lipinski's rule of five.

Comparative antihyperglycemic, analgesic and anti-inflammatory potential of ethanolic aerial root extracts of Ceriops decandra and Ceriops tagal: Supported by molecular docking and ADMET analysis.

Ceriops decandra (Griff.) (CD) and Ceriops tagal (Perr.) (CT) are two mangrove plants of the Sundarbans distributed along the coastal areas of South Asia and South Pacific Africa. Traditionally, these plants are used to treat diabetes, pain, angina, hemorrhage, and ulcer. In this study, we investigated the antioxidative, antihyperglycemic, analgesic, and anti-inflammatory potential of the aerial roots of CD and CT. At first, the antioxidative potential of CD and CT ethanolic extracts were investigated qualitatively and quantitatively by 2,2-diphenyl-1-picryl hydrazyl (DPPH) radical and hydrogen peroxide scavenging assays and by determining total antioxidant capacity. The total phenolic, flavonoid, tannin, and terpenoid contents of CD and CT were also estimated. The extracts' antihyperglycemic, analgesic, and anti-inflammatory potential were evaluated by oral glucose tolerance test, acetic acid-induced writhing test, and formaldehyde-induced paw-edema test, respectively. In vitro α-glucosidase and α-amylase enzyme inhibitory activities were also assessed. The CD and CT extracts were also analyzed using GCMS for the presence of phytochemicals. Then, molecular docking was carried out with α-glucosidase, α-amylase, cyclooxygenase-II (COX-II), 3-lipoxygenase (3-LOX) enzymes using the compounds found in GCMS analysis as well as the previously reported compounds from CD and CT. Finally, the pharmacokinetic and toxicological profiles of eight selected compounds were assessed with SwissADME and admetSAR server. In the antioxidative, antihyperglycemic, analgesic, and anti-inflammatory activity tests, CT extract showed a greater potential than CD extract. In addition, CT extract demonstrated higher α-glucosidase enzyme inhibitory activity in comparison to CD extract although CD extract exhibited better α-amylase enzyme inhibitory activity. Molecular docking studies revealed the presence of potentially bioactive compounds in both CD and CT. 2-(2-methylphenyl)-1-phenyl-(z)-1-propene of CD demonstrated good binding affinities for α-glucosidase, COX-II, and 3-LOX. In addition, 5S*,8S*,9S*,10R*,13S*)-18-hydroxy-16-nor-3-oxodolabr-4(18)-en-15-oic acid had high binding interactions for both α-glucosidase and α-amylase while 2',5,5'-tetramethyl-1,1'-biphenyl, 2-methyl-4-(3'-phenylpropyl)piperidine and decandrin C had high binding interactions for both COX-II and 3-LOX. Finally, 5S*,8S*,9S*,10R*,13S*)-18-hydroxy-16-nor-3-oxodolabr-4(18)-en-15-oic acid, decandrin C, 2-(2-methylphenyl)-1-phenyl-(z)-1-propene and 2-methyl-4-(3'-phenylpropyl)piperidine demonstrated better pharmacokinetic and toxicological properties in the ADMET analysis compared to the others. Hence it can be concluded that the present study supports the traditional usage of CD and CT for diabetes and pain and reveals the presence of bioactive phytochemicals in both.

Analgesic, Anti-inflammatory, Antipyretic, and In Silico Measurements of Sonneratia caseolaris (L.) Fruits from Sundarbans, Bangladesh.

Sonneratia caseolaris is a widely distributed mangrove plant having much therapeutic importance in traditional medicine. This plant is reported for possessing numerous compounds that are already used for many therapeutic purposes. After finding the presence of antioxidant components in the qualitative antioxidative assay, we went to conduct quantitative tests where the total contents of phenolics, flavonoids, and tannins were estimated as 122 mg GAE/gm, 613 mg QE/gm, and 30 mg GAE/gm, respectively. In DPPH free radical, H2O2, and superoxide radical scavenging assay, the SC50 values were found to be 87, 66, and 192 µg/ml, respectively. In FeCl3 reducing power assay, the RC50 of SC extract and ascorbic acid were 80 and 28 µg/ml, respectively. This extract revealed a significant peripheral analgesic effect in the acetic acid-induced writhing model in mice by reducing the writhing impulse by about 21% and 39% at 250 and 500 mg/kg doses, respectively, and a central analgesic effect in the tail immersion method by elongating the time up to about 22% and 37% at the same doses. In the anti-inflammatory test in mice, this extract reduced the paw edema size over the observed period in a dose-dependent manner. It also showed a significant reduction in the elevated rectal temperature of mice in the observing period in Brewer's yeast-induced pyrexia model. In silico analysis revealed better binding characteristics of ellagic acid and luteolin among other compounds with various receptors that might be responsible for antioxidative and anti-inflammatory properties. From our observation, we suppose that SC fruits might be a potential source of drug leads for various inflammatory disorders.

In silico profiling of analgesic and antihyperglycemic effects of ethanolic leaves extract of Amischotolype mollissima: Evidence from in vivo studies.

The aim of this study is to assess the antioxidative profile and related pharmacological potentialities of the ethanolic extract of Amischotolype mollissima leaves, traditionally used in treating pain, injury, malarial fever, epilepsy and hyperacidity, followed by a computational approach for the analysis of bioactive compounds identified by GC-MS. In GC-MS analysis, the extract yielded ten compounds, with 4,6-di-t-butyl-2-alpha-methyl benzyl phenol having the highest amount. In vitro investigation of the antioxidative properties of the plant was conducted with 2,2-diphenyl-1-picryl hydrazyl (DPPH) radical and hydrogen peroxide scavenging assays. The amounts of secondary metabolites phenolics, flavonoids, and tannins were measured at 142 mg GAE/g, 534 mg QE/g, and 110 mg GAE/g, respectively. An acute toxicity study was carried out on mice, which revealed no toxicity up to the dosage of 4000 mg/kg bw. For the dosages of extract at 250 and 500 mg/kg bw, the writhing response test induced by acetic acid exhibited a statistically significant (p < 0.05) analgesic effect in mice. The oral glucose tolerance test (OGTT) and alpha-glucosidase enzyme inhibitory activity assay were used to examine the antihyperglycemic potential, in which the extract reduced the blood glucose level to 6.22 mmol/l and 3.82 mmol/l, at dosages of 250 and 500 mg/kg bw, respectively at 60 min in OGTT even though no activity was observed in the α-glucosidase enzyme inhibitory assay. In an antibacterial assay, the extract's minimum inhibitory concentration (MIC) against E. coli, P. aeruginosa, and S. aureus was determined to be 8, 16, and 8 µg/ml, respectively. This study shows that the usage of A. mollissima leaves in folklore medication is justified.