Computational identification of polyphenols from medicinal plant extracts with biological activity against oxidative stress-related diseases: An in silico anti-inflammatory study

Oxidative stress-induced inflammation plays a pivotal role in the progression of numerous chronic diseases, necessitating the exploration of plant-derived polyphenols for their therapeutic potential. This study investigated acetone leaf extracts of C. peragua, E. croceum, M. arborescens, R. caffra, and T. tomentosa. In vitro assays assessed total polyphenol content, antioxidant, anti-inflammatory, and antidiabetic properties using standard techniques, while in silico molecular docking explored the interactions of selected polyphenols against 5-lipoxygenase (5-LOX) proteins (1RRL and 2IUJ), a key inflammatory enzyme. T. tomentosa exhibited the highest polyphenol content (511.33 ± 0.8 mg GAE/g dry extract), while C. peragua demonstrated superior antioxidant activity (IC₅₀ = 13.3 ± 2.5 µg/mL). M. arborescens displayed the strongest 5-LOX inhibition (IC₅₀ = 15.50 ± 1.8 µg/mL), while R. caffra and T. tomentosa exhibited the highest inhibition of α-amylase (49.39 ± 0.5%) and α-glucosidase (42.07 ± 0.3%), respectively. In silico docking identified procyanidins B1 and B2 as the most potent inhibitors of 5-LOX (-10.1 kcal/mol), followed by rutin (-9.9 kcal/mol). Although no direct correlation was observed between total polyphenol content and biological activity, a relationship emerged between in vitro 5-LOX inhibition and both antioxidant (r = 0.668, p = 0.017) and α-glucosidase inhibitory activities (r = 0.602, p = 0.033). The results indicate that specific polyphenolic compounds, rather than total polyphenol content, contribute to the demonstrated activities. The study's approach of combining experimental assays with computational docking highlights the potential of these extracts. These findings contribute to the search for plant-based therapeutic agents that targets inflammation and metabolic disorders.