Carob leaves: Phytochemistry, antioxidant properties, vasorelaxant effect and mechanism of action

Ceratonia siliqua L., is a species of significant nutritional and industrial interest with extensive traditional uses. This fabaceae is renowned for its medicinal properties, including the treatment of high blood pressure. Due to its chemical composition, carob exhibits several valuable therapeutic functions such as antioxidant, antidiarrheal, antidiabetic, and antibacterial actions. This study investigates the chemical composition of Ceratonia siliqua L. leaves aqueous extract (CsAE) and explores the vasorelaxant effect and its underlying mechanisms. Acute toxicity and antioxidant activity of CsAE were also examined. The phytochemical profile was elucidated using TLC and UHPLC-MS. The vasorelaxant effect and mechanisms were studied on thoracic aortic rings from normotensive rats, using various antagonists. Acute toxicity was assessed by orally administering the extract to mice. Antioxidant activity was evaluated using β-carotene bleaching and DPPH. TLC analysis of CsAE reveals flavonoids and hydrolysable tannins. Gallic acid, myricitrin, quercitrin as well as galloylglucopyranoside derivatives were identified by UHPLC-MS. CsAE relaxed phenylephrine-precontracted aorta in a concentration-dependent manner. This response was reduced when the aorta was denuded or pretreated with L-NAME, hydroxocobalamin, ODQ, 4-AP, TEA, calmidazolium chloride, and thapsigargin. CsAE showed significant antioxidant activity with no observed toxicity in the experimental animals. CsAE has a significant vasodilatory effect, mediated through the CaM/eNOS/sGC pathway, activation of Kca and Kv, and intracellular calcium mobilization into SERCA. It also exhibits strong antioxidant activity, with no observed toxicity in the experimental animals. These findings represent the first evidence of the vasorelaxant effect of Ceratonia siliqua L. leaves from Eastern Morocco. [Display omitted] •Aqueous extract of Ceratonia siliqua leaves is very rich in phenolic compounds, notably flavonoids and hydrolyzable tannins.•The extract induces an important vasorelaxation, in a dose-dependent manner.•The primary mechanism mainly involves the production of nitric oxide by the endothelium via the Ca2+-calmodulin-NOS complex.•Carob leaves demonstrate significant antioxidant activity without observed toxicity.