Abstract
Background: Psoriasis is an inflammatory skin disease characterized by hyper-proliferating epidermal membrane and accumulation of dermal inflammatory cells. A profound understanding of mechanistic studies has revealed the potential role of TNF-α and IL-17a in disease pathogenesis. background: Psoriasis is an inflammatory skin disease labelled with hyper-proliferating epidermal membrane and accumulation of dermal inflammatory cells. Profound understanding of mechanistic studies revealed the potential role of TNF-α and IL-17a in the disease pathogenesis. Aim: The study aims to evaluate the inhibitory potential of octyl gallate on IL-17a through in silico analysis and validate its anti-inflammatory effects against oxidative stress and proinflammatory cytokines in vitro. Aim: The study aims to evaluate the inhibitory potential of octyl gallate on IL-17a through in silico analysis and validate its anti-inflammatory effects against oxidative stress and proinflammatory cytokines in vitro. Objective: The objective of the study is to evaluate the potential of octyl gallate for the treatment of psoriasis by targeting inflammatory mediators using in vitro and in silico approaches. Materials and Methods: The anti-oxidant potential of octyl gallate was evaluated through chemiluminescence and the Griess method. Cytotoxicity was evaluated via MTT assay. TNF-α levels were quantified through ELISA. Mechanistic studies were performed to recognize the inhibition of strong inflammatory mediators, such as TNF-α, IL-1β, IL-6, NCF-1, and NF-κB through gene expression analysis. Molecular docking was performed to study the underlying binding pattern of gallate inhibitor with IL-17a. result: Octyl gallate potently inhibited the TNF-α, reactive oxygen and nitrogen species while significantly reduces the expression of inflammatory genes. The docking analysis revealed that octyl gallate resides well in the binding pocket of IL17a. The physiochemical properties of gallate resulted good ADME profile. Results: Octyl gallate potently inhibited TNF-α, reactive oxygen, and nitrogen species while significantly reducing the expression of inflammatory genes. The docking analysis revealed that octyl gallate resides well in the binding pocket of IL17a. The physicochemical properties of gallate resulted in a good ADME profile. conclusion: Octyl gallate revealed significant antioxidant potential and downregulation of inflammatory genes principally involved in psoriasis. A new inhibitory target IL-17a of octyl gallate has been identified that together with TNF-α develops a feed forward state in disease pathogenesis. This study signifies the potential of octyl gallate to be a prospective lead molecule for treatment of psoriasis. Conclusion: Octyl gallate revealed a significant antioxidant potential and downregulation of inflammatory genes principally involved in psoriasis. A new inhibitory target IL-17a of octyl gallate has been identified that, together with TNF-α, develops a feed-forward state in disease pathogenesis. This study signifies the potential of octyl gallate to be a prospective lead molecule for the treatment of psoriasis. other: NA
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