Molecular Docking, Metabolite Profile, In Vitro Antioxidant, Anticholinergic, Antidiabetic, and Antiglaucoma Properties of Royal Jelly
Ebubekir İzol, Ülkü Yerebasan, Esma Kayaoğlu, Münire Turhan, Mustafa Abdullah Yılmaz, Adem Necip, Rüya Sağlamtaş, Hülya Akıncıoğlu, İlhami GülçinBackground/Objectives: Royal jelly is a biologically active bee product with a complex chemical composition and diverse biological properties. This study aimed to comprehensively characterize the phytochemical composition of royal jelly and evaluate its antioxidant capacity, enzyme-inhibitory abilities, and potential molecular interactions with target enzymes. Methods: The phytochemical profile of royal jelly was characterized using liquid chromatography–tandem mass spectrometry (LC–MS/MS). Total phenolic and flavonoid contents were determined spectrophotometrically. Antioxidant activity was evaluated using DPPH•, ABTS•+, and DMPD•+ scavenging assays, together with Fe3+, CUPRAC, and FRAP reducing methods. Enzyme-inhibitory abilities were assessed against human carbonic anhydrase I and II (hCA I and hCA II), acetylcholinesterase (AChE), butyrylcholinesterase (BChE), α-glucosidase, and α-amylase. Molecular docking analyses were subsequently performed to investigate the interactions of major identified compounds with enzyme active sites. Results: LC–MS/MS analysis revealed a diverse profile of phenolic and flavonoids, including quinic acid, caffeic acid, chlorogenic acid, p-coumaric acid, apigenin, luteolin, kaempferol, and amentoflavone. Royal jelly exhibited considerable antioxidant activity, with IC50 values of 29.33, 29.20, and 21.65 μg/mL in the DPPH•, ABTS•+, and DMPD•+ scavenging assays, respectively. It also demonstrated notable reducing capacity in Fe3+ reduction (0.702 μg/mL), CUPRAC (1.444 μg/mL), and FRAP (0.964 μg/mL) assays. Significant inhibitory ability was observed against hCA I (1.12 μg/mL), hCA II (1.33 μg/mL), AChE (1.44 μg/mL), BChE (1.52 μg/mL), α-glucosidase (2.04 μg/mL), and α-amylase (2.11 μg/mL). Docking analyses indicated that major constituents, particularly quinic acid, could interact with key catalytic residues through hydrogen bonding and electrostatic interactions. Conclusions: Royal jelly possesses a rich polyphenolic profile accompanied by substantial antioxidant and multi-target enzyme-inhibitory abilities. These findings provide biochemical and molecular evidence supporting the potential of royal jelly as a functional food and nutraceutical ingredient and highlight its value as a source of bioactive compounds for further pharmacological investigation.