Domesticated Argania spinosa in Eastern Morocco: HPLC-DAD/GC-MS Chemical Profiling, Antioxidant and Antidiabetic Activities, and Network Pharmacology-Guided Molecular Docking

Abstract

The argan tree (Argania spinosa) is an endemic Moroccan species known for its primary product, argan oil, which possesses exceptional nutritional and medicinal properties. The current study aimed to evaluate and compare the antidiabetic and antioxidant activities of argan oil obtained from the introduced and native argan tree in eastern Morocco, to analyze its chemical composition using HPLC-DAD and GC-MS, and to investigate the molecular mechanisms behind the obtained pharmacological activities through an in silico pharmacological networking and molecular docking study. The results revealed that argan oil from all three regions of Morocco (Oujda, Agadir, and Chouihya) is rich in oleic and linoleic acids as major constituents, along with the presence of significant tocopherols. Regarding the antioxidant assays, including DPPH radical scavenging and iron-reducing power tests, argan oil from Oujda exhibited the highest activity, with the lowest IC50 values of 15.25 ± 0.022 mg/mL and 28.5 ± 1.7 mg/mL, respectively. Concerning the antidiabetic activity, we found that oil from Chaouihya showed the strongest α-amylase inhibition, while Oujda oil had the highest antiglycation activity, indicating that even introduced argan trees retain potent bioactivity. The results of the in silico investigation suggested that tocopherols may contribute to the antioxidant and antidiabetic potential of argan oil, showing predicted antioxidant activity (Pa = 0.843–0.967) and favorable binding affinities toward iNOS (ΔG = −9.3 kcal mol−1) and α-glucosidase (ΔG = −8.2 kcal mol−1). The identified fatty acids also showed predicted insulin-promoting activity (Pa = 0.59–0.75) and moderate enzyme-binding potential. Pharmacological network analysis identified 51 shared genes associated with antioxidant, antidiabetic, and argan-related targets, with enrichment of the AGE–RAGE signaling pathway. These computational findings provide possible molecular associations that may help explain the observed biological activities, although they remain predictive and require experimental validation. Overall, the in silico analysis suggests that tocopherols could be among the contributors to the multi-target profile of Argania spinosa oil, while fatty acids may provide complementary effects related to glycemic regulation.