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

Xiaokang Wang,Yanqing Lv,Xiucun Li,Jinjin Ma,Chunling Ye,Xiaoqi Zhang,Kaihe Ye,Songcheng Wei

doi:10.4314/tjpr.v15i2.15

Abstract

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-κB 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/12h 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 - α, IL - 6 and iNOS) and tissue proteins (Akt, IKKα, and NF – κB - 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 - α (TNF - α), 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 - κB pathway mediation.Conclusion: TTPGL offers a potential therapeutic approach for the treatment of diabetic peripheral neuropathy.Keywords: Triterpenoids, Psidium Guajava, Diabetic peripheral neuropathy, Pro inflammatory cytokines, NF-κB pathway

Highlights

Psidium guajava Linn., commonly known as guava, has been naturalized in South - East Asia [1]
Many of the pathophysiological pathways of diabetic neuropathy focused on inflammation and its mechanisms appear to converge upon the activation of NF - κB in diabetic neuropathy [5,6]
In addition to modulating of pro - inflammatory responses, NF - κB causes the transcription of pro - inflammatory mediators such as interleukin - 6 (IL - 6), tumor necrosis factor - α (TNF - α) and inducible nitric oxide synthase [7]

Summary

INTRODUCTION

Psidium guajava Linn., commonly known as guava, has been naturalized in South - East Asia [1] In oriental regions, such as Taiwan, guava leaves is boiled and the extract is used in folk medicine for the treatment of diabetes [2] but few of the extract has been investigated for their preclinical or clinical efficacy. Blood samples obtained from the tail vein of rats were monitored for glucose once a week using reagent strips with a glucometer (Onetouch Ultra 2, Johnson & Johnson, Milpitas, CA, USA). Membranes were incubated with anti - rabbit IgG conjugated to HRP (1:1000 dilution) at room temperature for 1 h. The slices were incubated with fluorescein conjugated secondary antibody at room temperature for 1.5 h [14].

RESULTS

DISCUSSION

CONCLUSION