Ameliorative Effect and Underlying Mechanisms of Total Triterpenoids from Psidium guajava Linn (Myrtaceae) Leaf on High-Fat Streptozotocin-induced Diabetic Peripheral Neuropathy in Rats

Purpose: To investigate whether the total triterpenoids extracted from Psidium Guajava leaves (TTPGL) attenuate the development of diabetic peripheral neuropathy in rats by regulating the NF-kappa B pathway of the inflammatory process and its signaling mediators. Methods: All the Sprague Dawley rats used were maintained in a clean environment on a 12 h light/12 h dark cycle. High-fat feeding and intraperitoneal injection of 40 mg/kg streptozotocin (STZ) were used to induce diabetes in the rats. The rats were randomly divided into 5 groups: diabetic mellitus (DM) group; TTPGL - 30 group, TTPGL - 60 group and TTPGL - 120 group treated by intragastric administration (i.g) with 30, 100 and 120 mg/kg/day TTPGL, respectively. The well-established drug, rosiglitazone (RSG, 3 mg/k/d, i.g.), was used as positive control. Normal rats served as control group. Nerve conduction velocity and sensitive tests were measured on weeks 1, 4 and 8. After 8 weeks administration, expression of pro-inflammatory molecules (TNF - alpha, IL - 6 and iNOS) and tissue proteins (Akt, IKK alpha, and NF - kappa B - p65) were evaluated to assess biochemical changes. Results: Compared to DM group, TTPGL (especially 120 mg/kg dose) treatment improved (p < 0.05) physical functions and provided neuronal protection in high - fat/streptozotocin - induced peripheral neuropathy rats. We found that the expressions of several pro - inflammatory factors such as tumor necrosis factor - alpha (TNF - alpha), IL - 6 and inducible nitric oxide synthase (iNOS) were highly suppressed (p < 0.05 or p < 0.01) by TTPGL in sciatic nerve. Mechanism analysis indicated that the ameliorative effect of TTPGL, in part, is through suppression of the expression of pro - inflammatory cytokines by NF - kappa B pathway mediation. Conclusion: TTPGL offers a potential therapeutic approach for the treatment of diabetic peripheral neuropathy.