High-Fat Diet-Induced Neuropathy of Prediabetes and Obesity: Effect of PMI-5011, an Ethanolic Extract ofArtemisia dracunculusL.

Pierre Watcho,Roman Stavniichuk,Irina G Obrosova,David M Ribnicky,Ilya Raskin

doi:10.1155/2010/268547

Abstract

Artemisia species are a rich source of herbal remedies with antioxidant and anti-inflammatory properties. We evaluated PMI-5011, an ethanolic extract of Artemisia dracunculus L., on neuropathy in high-sfat diet-fed mice, a model of prediabetes and obesity developing oxidative stress and proinflammatory changes in peripheral nervous system. C57Bl6/J mice fed high-fat diet for 16 weeks developed obesity, moderate nonfasting hyperglycemia, nerve conduction deficit, thermal and mechanical hypoalgesia, and tactile allodynia. They displayed 12/15-lipoxygenase overexpression, 12(S)-hydroxyeicosatetraenoic acid accumulation, and nitrosative stress in peripheral nerve and spinal cord. PMI-5011 (500 mgkg−1d−1, 7 weeks) normalized glycemia, alleviated nerve conduction slowing and sensory neuropathy, and reduced 12/15-lipoxygenase upregulation and nitrated protein expression in peripheral nervous system. PMI-5011, a safe and nontoxic botanical extract, may find use in treatment of neuropathic changes at the earliest stage of disease.

Highlights

Diabetic distal symmetric sensorimotor polyneuropathy affects ∼50% of patients with diabetes mellitus and is a leading cause of foot amputation [1]
We evaluated PMI5011, an ethanolic extract of Artemisia dracunculus L., on neuropathy in high-sfat diet-fed mice, a model of prediabetes and obesity developing oxidative stress and proinflammatory changes in peripheral nervous system
We previously demonstrated that a high-fat diet (HFD)fed mouse with alimentary obesity, hyperinsulinemia, and impaired glucose tolerance develops nerve conduction velocity deficit and small sensory fiber neuropathy and displays increased sorbitol pathway activity, oxidative-nitrosative stress, and pro-inflammatory changes in peripheral nervous system (PNS)

Summary

Introduction

Diabetic distal symmetric sensorimotor polyneuropathy affects ∼50% of patients with diabetes mellitus and is a leading cause of foot amputation [1]. Evidence for the development of neuropathic changes at the prediabetic stage, prior to development of overt hyperglycemia and diabetes mellitus, is emerging from both clinical [2,3,4] and experimental [5,6,7] studies. Except the aldose reductase inhibitor epalrestat in Japan and α-lipoic acid in several countries, no pathogenetic treatment for diabetic or prediabetic neuropathy is currently available. PMI-5011 [16, 17], an ethanolic extract of Artemisia dracunculus L. with a good safety profile [16], has been found to inhibit activity of aldose reductase [18], the first enzyme of the sorbitol pathway, known to play an important role in the pathogenesis of both diabetic and prediabetic neuropathy [6, 19,20,21,22,23]

Methods

Results

Conclusion