New sesquiterpenoids from Bontia daphnoides: antioxidant and antidiabetic evaluation

Bontia daphnoides, commonly known as "olive brush", is a medicinal plant traditionally used in the management of diabetes mellitus. The current study evaluated the phytochemical composition along with the antioxidant and antidiabetic activities of the hydroethanolic extract of B. daphnoides aerial parts. The plant extract was found to be rich in phenolics (85.67 ± 0.018 mg GAE per g) and flavonoids (13.109 ± 0.007 mg QE per g). Phytochemical investigation yielded several metabolites from the n-hexane fraction including dehydromyoporone (1), β-sitosterol (2), α-amyrin (3), and β-sitosterol glucoside (4). The dichloromethane fraction afforded two new γ-lactone-containing sesquiterpenes (5) and (6), while the n-butanol fraction provided 8-acetylharpagide (7), verbascoside (acteoside) (8), crenatoside (9), and apigenin-7-O-glucuronide (10). The hydroethanolic extract of the plant exhibited antioxidant capacity, with 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity of 109.239 ± 0.429 mg AAE per g and phosphomolybdenum reducing power of 152.20 ± 0.053 mg AAE per g. Furthermore, it demonstrated potent inhibition of α-glucosidase (IC₅₀ = 0.047 ± 0.001 mg mL^-1) and α-amylase (IC₅₀ = 0.088 ± 0.003 mg mL^-1) enzymes, with activities comparable to or surpassing acarbose activities (IC₅₀ = 0.072 ± 0.002 mg mL^-1 and 0.092 ± 0.003 mg mL^-1, respectively). In alloxan-induced diabetic rats, oral administration of the plant extract (200 and 400 mg kg^-1, 21 days) reduced blood glucose levels and alleviated oxidative stress by increasing reduced glutathione (GSH) levels, decreasing malondialdehyde (MDA) levels, and improving liver histology. Collectively, these findings highlight B. daphnoides as a rich source of antioxidant and antidiabetic metabolites, supporting its traditional use and suggesting its potential for development of novel therapeutic agents against diabetes and its complications.