Majoon Ushba alleviated IL-17A sensitized keratinocyte ferroptosis via JAK-2-STAT-3 signaling axis and reversed imiquimod induced psoriasiform inflammation

  • Pharm Biol. 2026 Dec;64(1):575-598. doi: 10.1080/13880209.2026.2654904.
Arulkumaran Rithvik  1 ,  Shangomitra Bhattacharjee  1 ,  Gouri H Illanad  1 ,  Pawan Kumar  2 ,  Ghazala Javed  2 ,  Ritu Karwasra  2 ,  Zaheer Ahmed  2 ,  Mahaboobkhan Rasool  1
Affiliations
  • 1. Immunopathology Lab, School of Biosciences and Technology, Vellore Institute of Technology (VIT), Vellore, Tamil Nadu, India.
  • 2. Central Council for Research in Unani Medicine, Ministry of Ayush, Government of India, New Delhi, India.
PMID: 41973793 DOI: 10.1080/13880209.2026.2654904
Abstract

Context: Psoriasis is a relapsing autoimmune disease exacerbated by aberrant interleukin (IL)-17 A activity. Majoon Ushba, a unani polyherbal formulation implicated in clinical cases of psoriasis lacks immunopharmacological validation.

Objective: The study aims to investigate the pre-clinical efficacy of Majoon Ushba and its therapeutic role in mitigating IL-17A-induced keratinocytes Ferroptosis via ablation of JAK-2/STAT-3 pathway.

Materials and methods: HaCaT cells were stimulated with IL-17A to assess the activation of the JAK-2-STAT-3 pathway. The STAT-3 inhibitor, S3I-201, was used to confirm the role of the STAT-3 axis in keratinocyte Ferroptosis. Majoon Ushba pretreatment was assessed to determine its efficacy in alleviating keratinocyte Ferroptosis. An imiquimod (IMQ)-induced psoriasis mouse model was used to evaluate the pre-clinical efficacy of Majoon Ushba. Furthermore, prior high-performance liquid chromatography (HPLC) profiling was leveraged for in-silico docking analysis to identify the binding affinities of key phytoconstituents with IL-17RA and STAT-3.

Results: Majoon Ushba alleviated the IL-17A/JAK-2-STAT-3 axis, improved GPX4 expression, and regulated lipid peroxidation. Subsequently, Majoon Ushba also reversed the expression of pathogenic mediators and led to a reduction in serum cytokine levels of IL-17A, IL-23, and IFN-γ. An in-silico docking analysis suggested favorable binding affinities for key phytoconstituents of Majoon Ushba against IL-17RA and STAT-3. Aligned with pre-clinical and in vitro results, the computational findings offer initial evidence that the polyherbal formulation may influence the IL-17A/JAK-2-STAT-3 signaling pathway.

Discussion and conclusion: In conclusion, our preliminary findings reveal a plausible mechanistic basis for the anti-psoriatic efficacy of Majoon Ushba, warranting larger clinical trials in psoriasis patient cohorts.

Keywords
IL-17A cytokine; Majoon Ushba; Psoriasis; ferroptosis.
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