Antioxidant, Anti-Inflammatory, and Anxiolytic-Like Effects of Urena sinuata L.: In Vitro, In Vivo, and In Silico Studies

Background: Urena sinuata L. is a shrubby wild plant used for centuries in folk medicine to treat bronchitis, rheumatism, fever, and waist pain. It is evident that it possesses antioxidant, anti-diarrheal, anti-atherothrombotic, sedative, anxiolytic, and analgesic effects in various test systems. Objectives: The goal of this research was to evaluate the anti-inflammatory, antioxidant, and anxiolytic activity along with the preliminary phytochemical investigation of the ethanolic leaf extract of U. sinuata (ELEUS). Additionally, we also performed an in silico study to see the possible anxiolytic effects of its previously reported phytochemicals. Methods: Scavenging methods for nitric oxide (NO center dot), 2,2-diphenyl-1-picrylhydrazyl (DPPH), and hydroxyl radical ((OH)-O-center dot) were used to determine antioxidant activity. The egg albumin model was used to assess anti-inflammatory action, while the elevated plus maze tested anxiolytic activity in adult male Swiss albino mice. For the latter case, the control group received vehicle (10 mL/kg), the standard group received diazepam (DZP: 2 mg/kg), and the test groups received ELEUS at 200 and 400 mg/kg. Additionally, both the test groups were combined with DZP 2 mg/kg. All these treatments were given via oral gavage. Finally, we performed an in silico study to check the possible interactions of its literature-claimed compounds with gamma-aminobutyric acid (GABA)(A) receptor subunits. Results: Findings suggest that the ELEUS exhibited significant (p < 0.05) concentration-dependent antioxidant and antiinflammatory effects. The highest activity was observed at 100 mu g/mL. In mice, the extract had an anxiolytic effect that was significant (p < 0.05) and was dose-dependent. ELEUS 200 and 400 mg/kg were seen to potentiate the anxiolytic activity of the standard drug DZP (2 mg/kg) significantly (p < 0.05). Quercetagetin-6,7-O-dimethylether-3'-beta-D-gluco-pyranoside, quercetagetin-6,7-O-dimethylether-4'-beta-D glucopyranoside, and quercetagetin-6,7-O-dimethylether-3-beta-D-glucopyranosid of U. sinuata showed better interaction capacity with the GABAA receptor protein (alpha(1), alpha(2), alpha(3), alpha(4), alpha(5), and alpha(6)) than the standard drug (diazepam). Conclusions: ELEUS possesses many important phytochemical groups and exhibits concentration-dependent antioxidant and anti-inflammatory effects as well as dose-dependent anxiolytic effects. U. sinuata may be a good source of plant-based therapeutically active lead compounds for inflammation, oxidative stress, neurological diseases, and disorders like anxiety.