Profiling metabolites of Ficus natalensis hochst. fruit by UPLC-MS/MS and evaluation of anti-inflammatory activity

Ficus natalensis (Natal fig), an evergreen tree of the family Moraceae, is widely distributed across tropical and temperate regions and cultivated in Egypt. Members of the Moraceae family are traditionally employed as expectorants, hypoglycemic agents, and mild laxatives, with reported neuroprotective, analgesic, anti-inflammatory, and antihypertensive effects. The present study aimed to profile the secondary metabolites of F. natalensis fruit using ultra-performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS) and test its anti-inflammatory potential. A total of 160 metabolites were annotated in both positive and negative ionization modes, belonging to diverse phytochemical classes such as phenolics (41), flavonoids (21), acids (26), glycosides (11), terpenoids, coumarins (4), iridoids (3), fatty acids/ester (22), sterols (8), sugar derivatives (6), and terpenoids (18). The anti-inflammatory activity of F. natalensis fruit methanolic extract was investigated using nitric acid (NO) inhibition assay, revealing an IC₅₀ of 28.54 ± 1.66 µg/mL, compared to resveratrol as a standard anti-inflammatory with an IC₅₀ value of 10.21 ± 0.68 µg/mL. Major bioactive constituents, including ellagic acid, gallic acid, betulinic acid, and quercetin derivatives, were identified and may underline the observed anti-inflammatory effect. The current findings highlight F. natalensis fruit as a rich source of bioactive metabolites with potential anti-inflammatory effect.