Therapeutic Potential of Beta Caryophyllene Combined with L Arginine in the Management of Diabetic Complications

Abstract

Diabetes mellitus presents a significant global health challenge, with increasing prevalence and substantial economic burdens. Chronic hyperglycaemia leads to severe complications, including nephropathy, neuropathy, cardiomyopathy, and retinopathy, often mediated by oxidative stress and inflammation. Advances in managing diabetic complications highlight the endocannabinoid system s role, particularly cannabinoid 2 receptor (CB2), in regulating metabolism, inflammation, and neuroprotection. Dysregulation of CB2 receptors is linked to diabetic nephropathy, neuropathy, retinopathy, and cardiomyopathy. CB2 activation shows promise in animal models, reducing kidney damage, neuropathic pain, retinal damage, and improving cardiac function. In diabetes, nitric oxide is disrupted, leading to various complications like impaired endothelial function, vasoconstriction, and increased oxidative stress, affecting organs such as the kidneys and eyes. Addressing underlying pathophysiological mechanisms such as dysregulated pathways involving the endocannabinoid system, oxidative stress, inflammation, and impaired nitric oxide bioavailability is crucial in managing diabetic complications. Targeted interventions aimed at these pathways have the potential to alleviate diabetes-related complications effectively. Beta-caryophyllene, a CB2 receptor agonist found in various plants, and L-arginine, a precursor to nitric oxide, possess individual therapeutic properties. While their combined effects remain understudied, preclinical evidence suggests potential synergies. This study investigates the efficacy of combining beta-caryophyllene and L-arginine in streptozotocin-induced diabetic complications, focusing on inflammatory markers, oxidative stress, and CB2 receptor modulation. In the in vitro studies, murine macrophage RAW 264.7 cells were treated with varying concentrations of Beta-caryophyllene, L-arginine and their combination, followed by lipopolysaccharide (LPS) induction to assess the anti-inflammatory potential.