Deciphering the Skin Anti-Aging and Hair Growth Promoting Mechanisms of Opophytum forskahlii Seed Oil via Network Pharmacology

<i>Opophytum forskahlii</i> has a well-established ethnopharmacological significance. This study aimed to assess the skin anti-aging and hair growth-promoting activities of <i>O. forskahlii</i> seed oil (OFSO) and the underlying mechanism. GC-MS profiling revealed high levels of unsaturated fatty acids, linoleic acid (55.46%), and oleic acid (38.54%). The skin anti-aging activity of OFSO (3.125-100 µg/mL) was evaluated in normal human dermal fibroblasts (NHDFs) using MTT and enzyme inhibition assays. OFSO was non-cytotoxic and enhanced fibroblast proliferation in a dose-dependent manner, reaching 145.5% of control at 100 µg/mL (<i>p</i> < 0.05). OFSO significantly (<i>p</i> < 0.05) inhibited collagenase (48%), hyaluronidase (53%), elastase (57%), and tyrosinase (55%). The oil showed anti-inflammatory activity by inhibiting COX-1 and COX-2 (0.01-100 µg/mL) with IC₅₀ = 0.125 and 0.014 µg/mL, respectively. The hair growth promoting efficacy was assessed using adult male Wistar rats, randomly divided into control, OFSO-treated, and 2% minoxidil-treated groups (5 rats/group). Hair growth was assessed through visual scoring over 14 days of topical application and confirmed by histological examination and hair follicle counting. On day 14, the OFSO-treated group displayed almost complete hair coverage (score about 5.0), exceeding minoxidil (about 4.0), and significantly increased hair follicle number (14.0 ± 1 vs. 9.2 ± 0.8, <i>p</i> < 0.05). Histology confirmed that OFSO promoted hair follicle growth, differentiation, and transition from the telogen to the anagen phase. Network pharmacology analysis, integrating targets predicted via SwissTargetPrediction and disease-associated genes from GeneCards, identified PPARG, ESR1, and IL6 as key hub genes underlying OFSO's effects. PPARG enhances antioxidant defenses, anti-inflammatory responses, and sebaceous gland function; ESR1 supports collagen production, skin elasticity, and follicle vascularization; and IL6 modulates inflammation and triggers the anagen phase of hair growth. Functional enrichment revealed modulation of PPAR, estrogen, prolactin, and arachidonic acid metabolism pathways, suggesting that OFSO may regulate lipid metabolism, inflammation, hormonal signaling, and tissue regeneration. OFSO demonstrated promising anti-aging and hair growth activities, supporting further development and testing of cosmetic formulations.