Phytochemical and anti-neuropathic investigations of Crocus sativus via alleviating inflammation, oxidative stress and pancreatic beta-cells regeneration

OBJECTIVE: The aim of this study is to investigate the phytochemical and the long-term anti-neuropathic potentials of Crocus sativus cultivated in the University botanical garden, and explore its most bioactive compounds and their underlying mechanisms of action. METHODS: Phytochemical analysis and bio-guided isolation-procedures including RP-HPLC and (1)H and (13)C NMR utilizing biological models of diabetes, inflammation, and diabetic-neuropathy were used. Cultivated saffron (S-RCED) and Spanish-saffron stigma (S-SP) alone or in combination with Camellia sinus (CS) were investigated. RESULTS: The RP-HPLC analyses showed the presence of picrocrocin, crocin I, crocin II, crocin I’, crocin II’, and safranal (SAF) in both S-SP and S-RCED extracts with higher-concentrations. It had been shown that SAF was the most bioactive-compound in Crocus sativus. Both S-SP and S-RCED possessed significant (P < 0.05) anti-diabetic activities in acute (6 h), subchronic (8 d) and chronic (8 weeks) models. S-RCED had been proven with more hypoglycemic potentials when compared to S-SP and SAF. S-SP, S-RCED, and SAF produced significant anti-inflammatory and anti-nociceptive activities against carrageenan-induced inflammatory, hyperalgesic and tactile diabetic-neuropathy models, respectively. S-SP, S-RCED, and SAF elevated serum catalase, reduced glutathione, and insulin serum levels, ameliorated lipid peroxidation and HbA1c levels, and histopathologically regenerated the pancreatic beta-cells. Combinations with CS showed more significant efficacy than the single component. CONCLUSION: The oxidative stress reduction, insulin secretagogue, and pancreatic beta-cells regeneration potentials might be responsible for the mechanism underlying the anti-diabetic, anti-inflammatory and anti-diabetic neuropathy activities. Thus, the cultivated Crocus sativus might be clinically useful for protecting against many serious-disorders.