Targeting psoriatic inflammation with natural compounds: mechanistic insights and therapeutic promise

Abstract

Psoriasis is a chronic immune-mediated skin disorder characterized by aberrant keratinocyte proliferation, immune cell dysregulation, and sustained inflammation driven by cytokines, such as TNF-α, IL-17, and IL-23. Despite advancements in biologic therapies, limitations related to cost, safety, and resistance have prompted interest in alternative strategies. This review explores the pharmacological basis of natural products as promising anti-psoriatic agents, focusing on compounds with multi-targeted mechanisms including anti-inflammatory, anti-oxidant, anti-proliferative, and immunomodulatory activities. Key phytochemicals, such as curcumin, thymoquinone, glycyrrhizin, and boswellic acids, are examined for their roles in modulating psoriatic pathways like NF-κB, IL-23/Th17 axis, and oxidative stress. Evidence from preclinical and clinical studies highlights their potential in reducing psoriasis area and severity index (PASI) scores, mitigating immune hyperactivity, and enhancing the safety and efficacy of standard therapies. Despite promising outcomes, translational hurdles persist, including extract standardization, pharmacokinetic limitations, and regulatory barriers. The integration of omics-based research and advanced formulation technologies is essential to support the clinical application of these agents. This review underscores the therapeutic potential of natural compounds as viable complements or alternatives in modern psoriasis management.