1. Oryza coarctata (Roxb.), a mangrove plant of Bangladesh, revealed antidiarrheal potential in vivo and in silico.
- Author
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Islam, Md. Monirul, Nisha, Jerin Alam, Parvez, Md. Raihan, Zilani, Md. Nazmul Hasan, Faruque, Muaz, Biswas, Rajesh, and Anisuzzman, Md.
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ACUTE toxicity testing , *MOLECULAR dynamics , *METABOLITES , *PHYTOCHEMICALS , *ANTIOXIDANT testing , *EPICATECHIN , *CATECHIN - Abstract
• Oryza coarctata (Roxb.), a mangrove plant in Bangladesh, was screened to identify active chemicals in the plant. • The phytochemical investigation, GC-MS, and HPLC analysis detected distinct phytochemicals. • The ethanol extract of O. coarctata showed marked antidiarrheal activities in vivo through a novel intestinal antisecretory mechanism. • Molecular docking and dynamics simulation revealed the structural stability of the complexes of selected phytochemicals, suggesting antidiarrheal activity through neprilysin inhibition. Plants are a rich source of medicinal compounds. The Sundarbans in Bangladesh, the largest deltaic swamp forest in the world, are home to many plant species, but research on the bioactivities of many of these plants is still lacking. The current study aims to explore the antioxidative and antidiarrheal effects of Oryza coarctata (common name: wild rice) and the responsible pharmacophores through in silico approaches. Ethanol extract of the experimental plant was subject to preliminary phytochemical screening, GC-MS, and HPLC analysis to identify secondary metabolites. In vitro antioxidant test and in vivo antidiarrheal assay was done. Moreover, molecular docking and dynamics simulation were performed on neprilysin protein to corroborate in vivo observational results. In the phytochemical tests, different secondary metabolites were found to be present. The result of the GC-MS ascertained 21 compounds having the highest yield of bicyclo[4.1.0]heptane-7-carboxylic acid-4-acetylphenyl ester (22.38%), and HPLC identified seven polyphenols with the most significant amount of (-) epicatechin (39.48 mg/100 g of dry extract). The quantitative measurement of total polyphenol, flavonoid, and terpenoid contents resulted in 158 mg GAE/g, 257 mg QE/g, and 19.85 mg UAE/g of dry extract. The SC 50 (50% scavenging capacity) of the extract in the DPPH and hydrogen peroxide scavenging assay was 56 µg/mL and 63.52 µg/mL as compared to 4 µg/mL and 11.07 µg/mL of ascorbic acid, respectively. The extract also posed ferric-reducing antioxidant capacity, which varied with concentration. In the acute toxicity study on mice, the extract produced no toxicity up to 3,000 mg/kg. The extract significantly (p<0.001) attenuated 72.59% and 79.04% diarrhea in castor oil- and 67.83% and 78.27% in magnesium sulfate-induced diarrheal models at 200 and 400 mg/kg oral doses in comparison to 83.88% reduction in castor oil- and 86.09% reduction in magnesium sulfate-induced model by the standard racecadotril at 20 mg/kg dose. In silico studies confirmed the structural stability of the docked complexes, and (-) epicatechin of all compounds revealed the best binding poses with the neprilysin (an enkephalinase) throughout a molecular dynamics simulation of 100 ns. Therefore, our findings provide a solid pharmacological basis for the antioxidant and antidiarrheal properties of O. coarctata and suggest that (-) epicatechin, 2,4-difluorobenzoic acid-2-propylphenyl ester (DE), bicyclo[4.1.0]heptane-7-carboxylic acid-4-acetylphenyl ester (BE), and 3-benzylsulfanyl-3-fluoro-2-trifluoromethyl-acrylonitrile (BA) could be the potential leads against neprilysin for antidiarrheal drug development. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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