The Unripe Carob Extract (Ceratonia siliqua L.) as a Potential Therapeutic Strategy to Fight Oxaliplatin-Induced Neuropathy

Abstract

Background: Oxaliplatin-induced neuropathy (OIN) is a severe painful condition that strongly affects the patient’s quality of life and cannot be counteracted by the available drugs or adjuvants. Thus, several efforts are devoted to discovering substances that can revert or reduce OIN, including natural compounds. The carob tree, Ceratonia siliqua L., possesses several beneficial properties. However, its antalgic properties have not been substantially investigated and only a few investigations have been conducted on the unripe carob (up-CS) pods. Thus, the aims of this study were to evaluate for the first time the unripe variety of Apulian carob, chemically characterized and profiled as antioxidant potential of polyphenolic compounds as well as to investigate the ability of up-CS to reduce the neurotoxicity in a mouse model of oxaliplatin-induced neuropathic pain. Methods: By UHPLC-HRMS/MS analyses, 50 phenolic compounds, belonging mainly to n-galloylated glucoses and flavonoids were detected. Results: In a mouse model of oxaliplatin-induced neurotoxicity (2.4 mg/kg, 10 injections over two weeks), acute per os treatment with up-CS provoked a dose-dependent pain-relieving effect that completely counteracted oxaliplatin hypersensitivity at the dose of 200 mg/kg. Repeated oral administration of up-CS (100 mg/kg), concomitantly with oxaliplatin injection, exerted a protective effect against the development of thermal and mechanical allodynia. In addition, up-CS exerted a neuroprotective role against oxaliplatin-induced astrocytes activation in the spinal cord measured as GFAP-fluorescence intensity. Conclusions: Overall, our study contributes to the knowledge on up-CS properties by highlighting its protective activity in the painful condition related to the administration of oxaliplatin.