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

Abstract

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.