Polyphenols and extracts from Zingiber roseum (Roxb.) Roscoe leaf mitigate pain, inflammation and pyrexia by inhibiting cyclooxygenase-2: an in vivo and in silico studies.

Zingiber roseum (Roxb.) Roscoe, a perennial herb from the Zingiberaceae family, has a long history of traditional use in the treatment of several ailments including pain, inflammation, fever, cough, arthritis, skin diseases, and liver infections. This study sought to confirm the efficacy of Zingiber roseum (Roxb.) Roscoe leaves methanol extract (ZrlME) as reported in traditional usage by evaluating its analgesic, anti-inflammatory, and antipyretic capabilities. In addition, in silico molecular docking of the metabolites identified in ZrlME was studied to verify the experimental outcomes. ZrlME demonstrated strong dose-dependent analgesic efficacy against all analgesic tests. ZrlME (400 mg/kg) showed higher anti-inflammatory activity than the standard in the carrageenan-induced paw edema test model. A significant reduction of rectal temperature (3.97°F↓) was also recorded at the same dose of ZrLME after 24 h of treatment. Seven polyphenolic metabolites were identified and quantified by HPLC-DAD analysis, including 3, 4- dihydroxy benzoic acid, (-) epicatechin, rutin hydrate, p-coumaric acid, trans-ferulic acid, rosmarinic acid, and myricetin. Strong binding affinities (ranges from -5.8 to -8.5 Kcal/mol) between the aforesaid polyphenols and cyclooxygenase-2 were discovered. Moreover, molecular dynamics simulations (MDS) demonstrated that these polyphenols exhibit significant COX-2 inhibitory activity due to their high stability in the COX-2 active site. In computational prediction, the polyphenols were also found to be nontoxic, and a variety of biological activities, such as antioxidant, analgesic, anti-inflammatory, antipyretic, and hepatoprotective, were observed. The results of this study revealed that ZrlME possesses notable analgesic, anti-inflammatory, and antipyretic properties.

Integrating in vivo and in silico approaches to investigate the potential of Zingiber roseum rhizome extract against pyrexia, inflammation and pain.

Zingiber roseum is a perennial herb in the Zingiberaceae family. The plant is native to Bangladesh, and rhizomes are frequently used in traditional medicine to cure gastric ulcers, asthma, wounds, and rheumatic disorders. Therefore, the present study aimed to analyse the antipyretic, anti-inflammatory, and analgesic properties of Z. roseum rhizome to confirm its efficacy in traditional applications. After 24 h of treatment, ZrrME (400 mg/kg) showed a considerable drop in rectal temperature (3.42°F) compared to standard paracetamol (5.26°F). At both doses (200 and 400 mg/kg), ZrrME showed a substantial dose-dependent decrease in paw oedema. However, after 2, 3 and 4 h of testing, the extract (200 mg/kg) had a lower anti-inflammatory response than standard indomethacin, whereas the higher dose (400 mg/kg) of rhizome extract had a more robust response compared to standard. ZrrME also showed substantial analgesic activity against all in vivo analgesic test models. The in vivo findings were further evaluated by in silico study of our previously identified compounds of ZrrME with the cyclooxygenase-2 enzyme (3LN1). The substantial binding energy (ranges from-6.2 to-7.7 Kcal/mol) of the polyphenols (excluding catechin hydrate) to the COX-2 enzyme affirm the in vivo test results of the present studies. In addition, the compounds were found effective as antipyretic, anti-inflammatory, and analgesic agents, according to the biological activity prediction software. Both in vivo and in silico results demonstrated promising antipyretic, anti-inflammatory, and pain-relieving effects of Z. roseum rhizome extract, which corroborate the claim of its traditional uses.