Fuzi Attenuates Diabetic Neuropathy in Rats and Protects Schwann Cells from Apoptosis Induced by High Glucose

Han, Jing; Tan, Peng; Li, Zhiyong; Wu, Yan; Li, Chun; Wang, Yong; Wang, Beibei; Zhao, Shuang; Liu, Yonggang

doi:10.1371/journal.pone.0086539

Cited by 38 publications

(29 citation statements)

References 19 publications

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“…Exposure of Schwann cells to high glucose levels in vitro causes oxidative stress that is accompanied by over activation of caspase-9 and apoptosis regulator BAX, and decreased levels of apoptosis regulator Bcl-2 (REF. 80), changes that indicate mitochondrial internal stress. In an important study published in 2011, targeted disruption of Schwann cell mitochondria in a transgenic mouse model critically affected neuronal survival and produced a peripheral neuropathy resembling that caused by diabetes 81 .…”

Section: Oxidative Stress and Mitochondrial Dysfunctionmentioning

confidence: 99%

Schwann cell interactions with axons and microvessels in diabetic neuropathy

et al. 2017

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The incidence of diabetes mellitus has increased dramatically over the past two to three decades. According to the International Diabetes Federation Diabetes Atlas, 415 million people worldwide had diabetes in 2015, and this number is expected to grow by 5% annually, predominantly as a result of increasing prevalence of type 2 diabetes. Furthermore, an estimated 100 million Europeans and 80 million Americans have impaired glucose tolerance or prediabetes. Few people die from acute diabetes in countries with comprehensive health care systems, but the disease is inflicting a huge medical, social and economic burden on society owing to the need for lifelong treatment of its systemic consequences and the insidious development of multi-organ damage.Peripheral neuropathy (BOXES 1,2) is a common but often neglected complication of long-term diabetes, and the lack of treatment options reflects an incomplete understanding of the pathogenic mechanisms. Hyperglycaemia is generally accepted as the primary pathogenic insult in type 1 and type 2 diabetic neuropathy, although roles are emerging for other factors, such as impaired insulin signalling, hypertension and dyslipidaemia (particularly for type 2 diabetes), which might precede overt hyperglycaemia 1 . Many preclinical studies, and occasional clinical studies, have indicated that diabetic neuropathy -like diabetic nephropathy and retinopathy -results from microvascular disease, with a focus on axonal degeneration as a consequence of ischaemia and/or hypoxia. This mechanism, however, is likely to be only one aspect of a more complex pathogenesis.The earliest descriptions of pathology in diabetic neuropathy indicated that Schwannopathy accompanied axonal degeneration. The majority of clinical and basic research in diabetic neuropathy since then has focused on the effects on neurons. However, accumulating data from research into the development and regeneration of the PNS has identified Schwann cells as equally indispensable components that maintain neuronal structure and function, nourish axons, and promote survival and growth upon injury. The early reports from 1979 that demonstrated morphological changes in Schwann cells in human diabetic neuropathy 2 are now supported by an increased awareness of molecular alterations in Schwann cells during diabetes 3 . Schwann cells express a wide range of receptors and, when they sense insults or danger signals, they upregulate synthesis and secretion of factors that stimulate neuroprotection, regrowth and remyelination, or factors that aggravate disease phenotypes 4 . The most recent studies have demonstrated that Schwann cells regulate many aspects of axonal function, so that disruption of their metabolism by diabetes results in the accumulation of neurotoxic intermediates and compromises production of neuronal support factors, contributing to axonal degeneration, endothelial dysfunction and diabetic neuropathy. Abstract | The prevalence of diabetes worldwide is at pandemic levels, with the number of patients increasing by 5% annu...

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Section: Oxidative Stress and Mitochondrial Dysfunctionmentioning

confidence: 99%

Schwann cell interactions with axons and microvessels in diabetic neuropathy

et al. 2017

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“…Fuzi extract (in a hydrochloric acid solution) protected Schwann cells from high glucose injury and apoptosis, mainly due to the alkaloids. Also, the mitochondria pathway mediates the protective effect . These studies indicate that active ingredients of Fuzi possess effects of anti‐inflammatory, anti‐anxiety, and protect nerve cells.…”

Section: Neuropharmacological Effect Of Aconiti Lateralis Radix Praepmentioning

confidence: 77%

Neuropharmacological effects of Aconiti Lateralis Radix Praeparata

Zhao

Sun

Yang

et al. 2020

Clin Exp Pharma Physio

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Aconiti Lateralis Radix Praeparata (Fuzi in Chinese), which are the lateral roots of Aconitum Carmichaelii Debx, is widely used in China to treat many neurological diseases. Fuzi, in its various forms, has many neuropharmacological effects. It can act as an analgesic and help with depression, epilepsy, and dementia. However, the neuropharmacological effects of Aconiti Lateralis Radix Praeparata are seldom comprehensively reviewed. In this review, the neuropharmacological activities of some components contained in Aconiti Lateralis Radix Praeparata are considered. These include aconitine, mesaconitine, hypaconitine, total alkaloid, polysaccharide‐1, benzoylmesaconine, fuziline, songorine, and napelline. We also specifically discuss the antidepressant effects of total alkaloids and polysaccharide‐1. This review may provide a theoretical basis for further utilization of Aconiti Lateralis Radix Praeparata for diseases that affect the central nervous system.

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“…However, in clinical trials, no great improvement was reported in nerve conduction velocities and despite the initial promise of gene therapy, there is still currently no treatment available that can effectively repair the damage induced by DPN [25-27]. Several traditional natural medicines have been found to relieve the symptoms of DPN through antioxidant properties and by inhibiting the apoptotic nature of SCs in hyperglycemic conditions [28, 29]. For instance, Radix aconite lateralis preparata, a traditional Chinese medicine that has long been used to treat diabetes and paralysis, is thought to inhibit the apoptotic nature of SCs in hyperglycemic conditions through mitigated glucose-induced mitochondrial dysfunction [28].…”

Section: Discussionmentioning

confidence: 99%

“…Several traditional natural medicines have been found to relieve the symptoms of DPN through antioxidant properties and by inhibiting the apoptotic nature of SCs in hyperglycemic conditions [28, 29]. For instance, Radix aconite lateralis preparata, a traditional Chinese medicine that has long been used to treat diabetes and paralysis, is thought to inhibit the apoptotic nature of SCs in hyperglycemic conditions through mitigated glucose-induced mitochondrial dysfunction [28]. Similarly, Yang et al found by measuring MDA, SOD, and GSH-Px in the sciatic nerve tissue of STZ-induced DPN rats that Tang Bi Kang another traditional Chinese medicine, could treat DPN through antioxidative and anti-inflammatory responses [29].…”

Section: Discussionmentioning

confidence: 99%

Expression of Nrf2 Promotes Schwann Cell-Mediated Sciatic Nerve Recovery in Diabetic Peripheral Neuropathy

Tang

Chen

Liu

et al. 2018

Cell Physiol Biochem

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Background/Aims: High glucose-induced oxidative stress and inflammatory responses play an important role in painful diabetic neuropathy by activating the TLR4/NFκB signal pathway. Schwann cells (SCs) are integral to peripheral nerve biology, contributing to saltatory conduction along axons, nerve and axon development, and axonal regeneration. SCs provide a microenvironment favoring vascular regeneration but their low survival ratio in hyperglycemic conditions suppress the function to promote nerve growth. Nuclear factor erythroid 2-related factor 2 (Nrf2) promotes remyelination after peripheral nerve injury. The aim of this study was to identify the role of Nrf2 in SC-mediated functional recovery after sciatic nerve injury. Methods: We compared plasma inflammatory factors in diabetic patients (DN) with/without diabetic peripheral neuropathy (DPN) and assessed whether Nrf2 expression in SCs could repair peripheral nerve injury in a rat model. Nrf2, TLR4/NFκB signal pathway and apoptosis relative protein expression were detected by western blot. Apoptosis and angiogenesis were determined by immunofluorescence and tubule formation assay, respectively. Regenerated nerves were determined by transmission electron microscope. Results: Higher levels of inflammatory factors and VEGF expression were found in DPN patients. Cellular experiments indicate that Nrf2 expression inhibits hyperglycemia-induced apoptosis and promotes angiogenesis by regulating the TLR4/NFκB signal pathway. Animal experiments show that nerve conduction velocity, myelin sheath thickness, and sciatic vasa nervorum are restored with transplantation of SCs overexpressing Nrf2. Conclusions: Taken together, the high survival ratio of SCs in a DPN rat model indicates that overexpression of Nrf2 restores nerve injury.

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Fuzi Attenuates Diabetic Neuropathy in Rats and Protects Schwann Cells from Apoptosis Induced by High Glucose

Cited by 38 publications

References 19 publications

Schwann cell interactions with axons and microvessels in diabetic neuropathy

Schwann cell interactions with axons and microvessels in diabetic neuropathy

Neuropharmacological effects of Aconiti Lateralis Radix Praeparata

Expression of Nrf2 Promotes Schwann Cell-Mediated Sciatic Nerve Recovery in Diabetic Peripheral Neuropathy

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