Preclinical Evaluation of Anti-Acne Topical Creams Containing Psorospermum Febrifugum Stem Bark Extract: Lipase Inhibition, Sebum Regulation, and Dermal Safety

Abstract

Background: Acne vulgaris is a multifactorial inflammatory disorder of the pilosebaceous unit characterised by excessive sebum production, follicular hyperkeratinisation, microbial dysbiosis, and inflammatory activation. Limitations of conventional therapies, including irritation and antimicrobial resistance, have increased interest in plant-derived topical agents offering multi-target efficacy with improved tolerability. Psorospermum febrifugum Spach is traditionally used for dermatological conditions; however, its standardised formulation and mechanistic anti-acne evaluation remain limited. Notably, no previous study has integrated phytochemical characterisation, topical formulation development, mechanistic lipase enzyme evaluation, in vivo sebum suppression, and dermal safety assessment for this species within a single preclinical framework. Aim: To formulate standardised topical creams containing Psorospermum febrifugum stem bark extract and evaluate their lipase inhibitory activity, sebum-regulating effects, dermal safety, and phytochemical basis in preclinical models. Methods: Botanically authenticated stem bark was extracted by cold maceration using 70% ethanol. A dichloromethane (DCM) fraction was prepared and analysed by TLC-GC-MS. Oil-in-water creams (1– 5% w/w extract) were developed and evaluated for stability. In vitro anti-acne activity was assessed using a fluorometric lipase inhibition assay employing porcine pancreatic lipase as a validated surrogate model for acne-associated lipolytic activity. Sebum-regulating efficacy was evaluated in an oleic acid–induced seborrhoea rat model following topical application for 14 days. Dermal tolerability was assessed per OECD Guideline 404. Results: Extraction yield was 15.1 ± 0.1% w/w. Phytochemical analysis revealed substantial phenolics (162.3 ± 5.1 mg GAE/g), flavonoids (124.5 ± 3.8 mg QE/g), and terpenoids (211.9 ± 6.2 mg/g). TLC-GC-MS identified 42 compounds across three bands, predominantly fatty acids and derivatives. Extract-loaded creams demonstrated significant, concentration-dependent lipase inhibition (p < 0.001), with the highest concentration achieving 57% inhibition. The formulations significantly reduced oleic acid–induced sebum production in a dose- and time-dependent manner (p < 0.001), with a strong positive correlation between lipase inhibition and sebum reduction (r = 0.88, p < 0.01). All formulations were classified as non-irritant. Conclusion: Standardised Psorospermum febrifugum extract formulated as a topical cream exhibited significant lipase inhibition, sebum suppression, and favourable dermal tolerability. These findings support further preclinical and clinical investigation of its potential as a multi-target botanical candidate for acne management. Keywords: Psorospermum febrifugum , acne vulgaris, herbal medicine, topical cream, lipase inhibition, sebum regulation, dermal safety, fatty acids, phytochemical characterisation