Acute and subchronic in-vivo effects of Ferula hermonis L. and Sambucus nigra L. and their potential active isolates in a diabetic mouse model of neuropathic pain

BACKGROUND The prevalence of Diabetes mellitus (DM) is escalating rapidly worldwide, and associated with micro- and macrovascular complications. Diabetic neuropathy (DN) is a common complication of DM, and has a few approved therapies with limited efficacy and several side-effects. Herbal medicine is used worldwide as an effective alternative-medicine. The present study aims to investigate the activities of Ferula hermonis Boiss. EtAc (Ferula) and Sambucus nigra L. aqueous (Elder) extracts, and their potential active isolates; for acute (6 h) and subchronic (8 days) glucose homeostasis, in vivo antioxidant potential and DN amelioration in alloxan-induced DM mice model. METHODS DM was induced experimentally by injection of freshly prepared alloxan every 48-h for three times at a dose of 180 mg/kg. Utilizing tail-flick, hot-plate latencies (accessing thermal hyperalgesia) and von Frey filaments test (accessing tactile allodynia), DN was evaluated for longer period of time (8 weeks). RESULTS The most active isolates from Ferula was ferutinin, and Kaempferol from Elder utilizing bio-guided fractionation and RP-HPLC steeping methods. Compared to glibenclamide (GB) and tramadol (TRA), as positive controls, the highest doses of tested compounds exerted remarkable hypoglycemic and antinociceptive activities. The best acute hypoglycemic effect was observed with ferutinin (1.4 folds more effective than GB). Elder has shown the best subchronic hypoglycemic effect (2.6 folds more effective than GB) and the greatest efficacy against tactile allodynia following a single-administration, yet required repeated administration for improvement of thermal hyperalgesia. CONCLUSIONS Without the use-limiting-side-effects of existing therapies, Ferula, Elder and their active isolates have shown significant results in ameliorating DM and long standing diabetes-induced complications.