Vachellia gummifera (Willd.) Kyal. & Boatwr. mitigates UVA-induced oxidative stress in HaCaT keratinocytes

Vachellia gummifera (Willd.) Kyal. & Boatwr. (formerly known as Acacia gummifera) is a thorny, flowering plant endemic to Morocco. It was selected due to the limited research on its potential skin-protective properties, despite other species of the same genus being traditionally used to treat various skin ailments. In this study we annotated the phytochemical profile of its aqueous leaf extract using HPLC-MS/MS and evaluated its skin protective potential through in vitro assays, including antioxidant, anti-elastase, and anti-tyrosinase activities. Additionally, we assessed its protective potential against UVA-induced oxidative stress in immortalized human keratinocyte cell line (HaCaT), along with the underlying signaling pathways. LC-MS/MS analysis revealed 48 metabolites, mainly flavonoids and their glycosides. The extract exhibited in vitro antioxidant activities with IC50 values of 30.96 ± 2.10 and 232.33 ± 8.40 μg/mL for DPPH and ABTS, respectively, and a FRAP activity of 8.42 ± 0.52 mM FeSO₄/g extract. It also demonstrated moderate anti-tyrosinase properties with an IC50 value of 369.23 ± 12.01 μg/mL. In silico analyses of most of the identified compounds did not predict any skin sensitization. Accordingly, when tested on HaCaT cells up to 400 μg/mL, the extract showed no cytotoxic effects, suggesting its biocompatibility. Cells pre-treated with the extract effectively mitigated UVA-induced cellular damage, as it significantly inhibited reactive oxygen species production and glutathione depletion, measured by DCFDA and DTNB assays, respectively. Furthermore, the extract modulated the mitogen-activated protein kinase (MAPK) pathway by inhibiting UVA-induced phosphorylation of p38. Finally, a molecular docking analyses identified citric acid, hydroxycinnamic acid pentosyl hexoside and myricetin malonyl hexoside as the enzymes exhibiting the highest binding affinity towards tyrosinase. These findings suggest that V. gummifera possesses promising antioxidant and anti-aging properties, with potential applications in skin care and photoprotection.