Evaluation of irritation and delayed hypersensitivity potential of a Clinacanthus nutans cream: a phase 1 clinical trial

Clinacanthus nutans (CN), commonly known as Sabah snake grass, is traditionally used in Malaysia for burns, bites, viral lesions (e.g., Varicella Zoster), diabetes, gout, and other inflammatory skin conditions. Recent studies have demonstrated CN’s anti-inflammatory, antiviral, antioxidant, anticancer, antidiabetic, and immunomodulatory effects. Despite promising preclinical data, human safety data on topical CN formulations remain limited. A single-centre clinical trial was conducted at Hospital Al-Sultan Abdullah (HASA), Universiti Teknologi MARA (UiTM), from July to December 2024 to evaluate the safety and tolerability of a topical CN cream in healthy adults (≥18 years). Exclusion criteria included pregnancy, active skin disease, recent topical/systemic therapy, or known allergy to CN or chlorophyll. Following ISO 10993-10:2002 standards, participants underwent patch testing at 48, 96 hours, and Day 7 for irritation and allergy, followed by a 21-day occlusive application for sensitisation and tolerability, and photoallergic/phototoxicity evaluation comparing ultra violet A (UVA)- irradiated (5 J/cm²) and non-irradiated sites, with readings at 48, 72 hours, and one week. Ninety-two participants were enrolled (66.3 % female). Three (3.3 %) developed mild allergic contact dermatitis, and one (1.1 %) showed intolerance during prolonged exposure. No photoallergic or phototoxic responses were observed. All adverse events were mild, reversible, and occurred only in female participants; three were obese and one was overweight. Topical CN cream demonstrated good tolerability, with no photo-related reactions, fulfilling international safety benchmarks for botanical topical preparations. These findings justify further clinical investigation and development for potential therapeutic use.