Abstract

NETWORK PHARMACOLOGY INTEGRATED WITH MOLECULAR DOCKING REVEALS A MULTI-TARGET ANTI-ACNE MECHANISM OF NEEM OIL (AZADIRACHTA INDICA) AND SHATADHAUTA GHRITA AGAINST ACNE VULGARIS

Jannat Diwate*, Shubham Kamdi, Pallavi Gondale, Tanmay Bante, Kalpesh Deshmukh, Vishal Akangire

ABSTRACT

Acne vulgaris is a common chronic inflammatory disorder of the pilosebaceous unit driven by androgen-dependent sebum overproduction, follicular hyperkeratinisation, colonisation by Cutibacterium acnes, and innate immune activation. Long-term use of conventional topical agents such as benzoyl peroxide is limited by skin irritation and antimicrobial resistance, renewing interest in multi-target herbal alternatives. This study combined network pharmacology and molecular docking to elucidate the mechanism underlying the traditional anti-acne use of Neem oil (Azadirachta indica) and Shatadhauta Ghrita, a classical Ayurvedic hundred-times-washed ghee formulation. Targets of the major phytoconstituents and acne-associated disease genes were intersected to identify sixteen common targets from a pool of 324 compound-associated and 113 disease-associated genes. Protein-protein interaction network and hub-gene analysis prioritised ten key targets, including tumour necrosis factor,peroxisome proliferator-activated receptor gamma, estrogen receptor 1, interleukin 1 beta and mechanistic target of rapamycin, with pathway enrichment implicating nucleotide-binding oligomerisation domain-like receptor, nuclear factor kappa B, toll-like receptor, mitogen-activated protein kinase and steroid hormone biosynthesis signalling. Molecular docking, benchmarked against benzoyl peroxide, identified nimbolide as the strongest and most consistent multi-target ligand, with palmitic acid and butyric acid showing favourable binding at interleukin 1 beta and mechanistic target of rapamycin, respectively. Most compounds satisfied drug-likeness criteria with acceptable predicted safety profiles. These integrated findings provide mechanistic support for the traditional anti-acne use of Neem oil and Shatadhauta Ghrita and identify nimbolide as a priority candidate for further experimental validation.

Keywords: Acne vulgaris, Network pharmacology, Molecular docking, Azadirachta indica, Shatadhauta Ghrita, Nimbolide.