Abstract

BackgroundBogijetong decoction (BGJTD) is a herbal drug formulation used in the traditional Asian medicine to treat neuropathic insults associated with diabetes and anticancer therapy. To understand the biological basis of BGJTD on protective effects against neuropathy, we investigated physiological and biochemical responses of the sciatic nerves deranged by taxol injection or crush injury in the rats.MethodsDissociated Schwann cells and neurons were prepared from the sciatic nerve and dorsal root ganglia (DRG) respectively and were treated with taxol and BGJTD. The sciatic nerve in the rat was injected with taxol or given crush injury. Animals were then administered orally with BGJTD. Effects of BGJTD treatment on cultured cells and in vivo sciatic nerves and DRG tissues were examined by immunofluorescence staining and western blot analysis. Sciatic nerve regeneration was assessed by histological observation using retrograde tracing technique and by behavioral hot plate test. Eighteen different herbal components of BGJTD were divided into 4 subgroups and were used to select herbal drugs that enhanced neurite outgrowth in cultured neurons.ResultsMorphological abnormalities in the sciatic nerve axons and DRG tissue caused by taxol injection were largely improved by BGJTD treatment. BGJTD treatment enhanced neurite outgrowth in cultured DRG neurons and improved Schwann cell survival. Phospho-Erk1/2 levels were elevated by BGJTD administration in the injured- or taxol-injected sciatic nerves. Vimentin phosphorylation catalyzed by cell division cycle 2 (Cdc2) kinase was induced from Schwann cells in the sciatic nerves after taxol injection and crush injury, and phospho-vimentin levels were further upregulated by BGJTD treatment. Retrograde tracing of DiI-labeled DRG sensory neurons revealed growth-promoting activity of BGJTD on axonal regeneration. A drug group (Be) composed of 4 active herbal components which were selected by neurite growth-enhancing activity was as effective as BGJDT for the recovery of thermal sensitivity of the hind paws which had been suppressed by taxol administration.ConclusionsThese data suggest that BGJTD and its active herbal components may protects the peripheral nerve from damage caused by taxol injection and nerve crush.

Highlights

  • Bogijetong decoction (BGJTD) is a herbal drug formulation used in the traditional Asian medicine to treat neuropathic insults associated with diabetes and anticancer therapy

  • Comparison among experimental groups showed that the mean length of individual axons in the longitudinal nerve sections were significantly decreased by taxol injection indicating their fragmentation and improved by BGJTD administration (Fig. 2a, b)

  • Staining pattern of the sciatic nerve axons, as seen by elongated fibers in DMSO vehicle control, was disintegrated by taxol injection, which was largely recovered in its integrity by BGJTD administration (Fig. 2c)

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Summary

Introduction

Bogijetong decoction (BGJTD) is a herbal drug formulation used in the traditional Asian medicine to treat neuropathic insults associated with diabetes and anticancer therapy. Peripheral neuropathy, referring to histological and physiological abnormalities caused by infections, nerve damages, diabetes, anticancer therapy and others [1], generates deficits of sensory and motor functions and affects the quality of life significantly. Structural alterations in peripheral axons and Schwann cells may be related with deficits in myelination and axonal transport that lead to abnormal conduction property of action potential through the axon [2]. Clinical studies reported that repeated administration of taxol can generate peripheral neuropathy by disrupting microtubule structure in axons [4,5,6]. Addition of taxol to cultured neurons resulted in decreased neurite outgrowth, and in vivo administration of taxol in rats generated morphological changes of myelinated fibers and degeneration of Schwann cells [7, 8]. In vivo application of taxol at low dose was shown to improve axonal regeneration after spinal cord injury, by stabilizing microtubule structure and reducing glial scarring around the injury cavity [10]

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