Oxidative stress: Roles in skeletal muscle atrophy.

Oxidative stress, inflammation, mitochondrial dysfunction, reduced protein synthesis, and increased proteolysis are all critical factors in the process of muscle atrophy. In particular, oxidative stress is the key factor that triggers skeletal muscle atrophy. It is activated in the early stages of muscle atrophy and can be regulated by various factors. The mechanisms of oxidative stress in the development of muscle atrophy have not been completely elucidated. This review provides an overview of the sources of oxidative stress in skeletal muscle and the correlation of oxidative stress with inflammation, mitochondrial dysfunction, autophagy, protein synthesis, proteolysis, and muscle regeneration in muscle atrophy. Additionally, the role of oxidative stress in skeletal muscle atrophy caused by several pathological conditions, including denervation, unloading, chronic inflammatory diseases (diabetes mellitus, chronic kidney disease, chronic heart failure, and chronic obstructive pulmonary disease), sarcopenia, hereditary neuromuscular diseases (spinal muscular atrophy, amyotrophic lateral sclerosis, and Duchenne muscular dystrophy), and cancer cachexia, have been discussed. Finally, this review proposes the alleviation oxidative stress using antioxidants, Chinese herbal extracts, stem cell and extracellular vesicles as a promising therapeutic strategy for muscle atrophy. This review will aid in the development of novel therapeutic strategies and drugs for muscle atrophy.

An ultrasound-guided percutaneous electrical nerve stimulation regimen devised using finite element modeling promotes functional recovery after median nerve transection.

Percutaneous electrical nerve stimulation of an injured nerve can promote and accelerate peripheral nerve regeneration and improve function. When performing acupuncture and moxibustion, locating the injured nerve using ultrasound before percutaneous nerve stimulation can help prevent further injury to an already injured nerve. However, stimulation parameters have not been standardized. In this study, we constructed a multi-layer human forearm model using finite element modeling. Taking current density and activated function as optimization indicators, the optimal percutaneous nerve stimulation parameters were established. The optimal parameters were parallel placement located 3 cm apart with the injury site at the midpoint between the needles. To validate the efficacy of this regimen, we performed a randomized controlled trial in 23 patients with median nerve transection who underwent neurorrhaphy. Patients who received conventional rehabilitation combined with percutaneous electrical nerve stimulation experienced greater improvement in sensory function, motor function, and grip strength than those who received conventional rehabilitation combined with transcutaneous electrical nerve stimulation. These findings suggest that the percutaneous electrical nerve stimulation regimen established in this study can improve global median nerve function in patients with median nerve transection.

Case report: Ultrasound-guided multi-site electroacupuncture stimulation for a patient with spinal cord injury.

Introduction: Spinal cord injury causes permanent neurological deficits, which have devastating physical, social, and vocational consequences for patients and their families. Traditional Chinese medicine uses acupuncture to treat neuropathic pain and improve nerve conduction velocity. This treatment can also reduce peripheral nerve injury joint contracture and muscle atrophy in affected patients. And it's got a remarkable restoration when electrical stimulation therapy on impaired peripheral nerves in animal models and clinical trials. Case description: A 48-year-old woman was hit by a heavy object that injured her lower back. The patient had a T12-L1 vertebral flexion and stretch fracture with traumatic spinal stenosis. The patient was transferred to the rehabilitation department after posterior T12-L2-segment pedicle screw system distraction and reduction, internal fixation, decompression, and bone graft fusion. Ultrasound-guided electroacupuncture was used to stimulate the sacral nerve, the spinal nerve, and the head of the patient, accompanied by spinal joint loosening training, respiratory training, lumbar comprehensive sports training, paraplegic limbs comprehensive training, and other manipulative treatment. Outcomes: After the intervention, the patient showed significant improvements in sensory and motor scores, resulting in functional recovery according to ASIA and FIM. The patient gradually showed reasonable functional remission. Discussion: The sacral nerve, the spinal cord, and the head were electrically stimulated by ultrasound-guided electroacupuncture in terms of intervention, and various functions of the patient were alleviated to a certain extent. The efficacy of ultrasound-guided electroacupuncture stimulation in treating neurologic symptoms should be validated in future clinical trials.

Protective effects and molecular mechanisms of Achyranthes bidentata polypeptide k on Schwann cells.

BACKGROUND: Achyranthes bidentata polypeptide k (ABPPk) is an active ingredient used in traditional Chinese medicine separated from Achyranthes bidentata polypeptides. So far, the role of ABPPk in peripheral nerve protection has not been comprehensively studied. METHODS: In this study, primary Schwann cells exposed to serum deprivation were treated with ABPPk or nerve growth factor (NGF) in vitro. Cell viability, cell apoptosis, apoptosis-related protein expression, and antioxidant enzyme activity were analyzed. To further explore the underlying molecular mechanisms and key regulatory molecules involved in the effects of ABPPk, integrative and dynamic bioinformatics analysis at different time points was carried out following RNA-seq of Schwann cells subjected to serum deprivation. RESULTS: We found that ABPPk could effectively reduce Schwann cell apoptosis caused by serum deprivation, which was comparable to NGF's anti-apoptotic effects. ABPPk had the largest number of upregulated and downregulated differential expression genes at the earliest 0.5 h time, while NGF had fewer differential expression genes at this early stage. The significant difference at this time point between the two groups was also displayed in heatmaps. The molecular regulation of diseases and functions and canonical pathways revealed that ABPPk had more participation and advantages in the vasculature and immune system areas, especially angiogenesis regulation. Also, ABPPk demonstrated an earlier start in these molecular regulations than NGF. Furthermore, the analysis of transcription factors also illustrated that ABPPk not only had more key initial regulatory factors participating in vascular-related processes, but these also remained for a longer period. There was no significant difference in neural-related molecular regulation between the two groups. CONCLUSIONS: Using high-throughput sequencing technology, our work unveiled the protective effects of ABPPk on Schwann cells after serum deprivation in a more comprehensive manner. These results further enrich the positive functions and molecular mechanisms of ABPPk and traditional Chinese medicine and benefit the discovery of novel therapeutic targets for peripheral nerve regeneration.

Cortical Activations and BCI Performances at Different Speeds of Visual and Proprioceptive Stimulation.

Motor imagery based brain-computer interface (MI-BCI) is one of the most common paradigms utilized in neurofeedback training (NFT) for rehabilitation engineering. Specifically, finding an appropriate feedback protocol is significantly important to improve the effectiveness of the motor training system. To this end, we investigated the electroencephalography(EEG) oscillatory patterns measured by event-related desynchronization (ERD) when sixteen participants accepted the visual and proprioceptive stimulation achieving the kinematic hand grasping movements at three different speeds (i.e. 1/3 Hz, 2/3 Hz and 1 Hz). The EEG results indicated that the ERD patterns showed no significant difference in sensorimotor cortex (i.e. C3 and FC3 channels) by comparing the three conditions. Nevertheless, the 2/3 Hz stimulation speed could achieve a significantly better classification performance than the other two conditions across all participants. Therefore, the visual and proprioceptive electrical stimulation achieving the kinematic hand grasping at 2/3 Hz speed might provide an available approach for the online MI-BCI system based NFT system in the future.

Achyranthes bidentata Polypeptide Protects Schwann Cells From Apoptosis in Hydrogen Peroxide-Induced Oxidative Stress.

ABPPk, the active ingredient separated from Achyranthes bidentata polypeptides, is a traditional Chinese medicine with multiple pharmaceutical properties. In this study, we investigated the molecular mechanisms of ABPPk in protecting Schwann cells (SCs) from H2O2-induced cell apoptosis. The viability of SCs pretreated with ABPPk was elevated significantly by MTT assay estimation. Meanwhile, the apoptosis of SCs was reduced which was showed in flow cytometry and transferase-mediated dUTP nick end labeling analysis. Furthermore, the addition of ABPPk also increased the activities of SOD and GSH accompanied with a decrease in MDA and LDH activities. According to Western blot analysis, the upregulation of Bcl-2, also downregulation of Bax and cleaved caspase-3 were demonstrated in SCs which was ABPPk pretreated. Further research showed that PI3K/AKT and ERK1/2 pathways in SCs have been activated after pretreatment of ABPPk. Collectively, results in our study suggested that ABPPk protected SCs from H2O2-induced oxidative damage by reducing the expression of apoptotic molecules and enhancing the activities of antioxidant enzymes, which inhibited the apoptosis of SCs modulated by PI3K/AKT and ERK1/2 signaling pathways. In our perspectives, ABPPk as an active factor with its antioxidative activities has potential and promising therapeutic effects in the prevention of neurologic disorders.

Achyranthes bidentata polypeptide protects dopaminergic neurons from apoptosis in Parkinson's disease models both in vitro and in vivo.

BACKGROUND AND PURPOSE: Parkinson's disease (PD) is a neurodegenerative disorder closely associated with dopaminergic neuron loss. It is well documented that Achyranthes bidentata polypeptides (ABPP) are potent neuroprotective agents in several kinds of neurons. Therefore, we proposed that ABPP might play a beneficial role against PD by protecting dopaminergic neurons from apoptosis. EXPERIMENTAL APPROACH: SH-SY5Y cells and primary rat dopaminergic neurons were pretreated with ABPP fraction k (ABPPk), a purified fraction of ABPP, and then the cells were exposed to 1-methyl-4-phenylpyridinium iodide (MPP+ ) to induce apoptosis. Cell viability, LDH activity, a Tunel assay and protein levels of Bcl-2 and Bax were analysed. In an in vivo PD model induced by MPTP, ABPPk was intranasally delivered to mice. Behavioural tests, immunohistochemistry, immunostaining, Nissl staining, qRT-PCR and Western blot were employed to evaluate the potential effects of ABPPk on PD in mice. KEY RESULTS: The application of ABPPk markedly enhanced the viability of SH-SY5Y cells and primary dopaminergic neurons treated with neurotoxic agent MPP+ . In an in vivo MPTP-induced PD model, ABPPk significantly improved behavioural performances and prevented tyrosine hydroxylase loss in the substantia nigra pars compacta and striatum. Furthermore, we showed that MPTP-induced astrocyte and microglia activation were largely attenuated by ABPPk, leading to low levels of neuroinflammation and a downregulation of the apoptotic signalling pathway. CONCLUSION AND IMPLICATIONS: Taken together, our data show that ABPPk protects dopaminergic neurons from apoptosis, suggesting that ABPPk might be an effective intervention for treating the neuron loss associated with disorders such as PD.

An active component of Achyranthes bidentata polypeptides provides neuroprotection through inhibition of mitochondrial-dependent apoptotic pathway in cultured neurons and in animal models of cerebral ischemia.

An active component has been isolated by reverse-phase high performance liquid chromatography (HPLC) from Achyranthes bidentata Blume polypeptides that are extracted from Achyranthes bidentata Blume, a Chinese medicinal herb. The active component is called ABPPk based on the order of HPLC elution. In this study, we used in vitro and in vivo experimental models of cerebral ischemia to investigate the possible neuroprotective effect of ABPPk. ABPPk treatment promoted neuronal survival and inhibited neuronal apoptosis in primary cortical neurons exposed to oxygen and glucose deprivation and in rats subjected to transient middle cerebral artery occlusion. The role of ABPPk in protection against ischemia-induced neuronal damage might be mediated by mitochondrial-dependent pathways, including modulation of apoptosis-related gene expression, regulation of mitochondrial dysfunction through restoring mitochondrial membrane potential, reducing release of mitochondrial apoptogenic factors, and inhibiting intracellular ROS production. The neuroprotective effect of ABPPk may suggest the possible use of this agent in the treatment and prevention of cerebral ischemic stroke.

Neurotrophic and neuroprotective actions of Achyranthes bidentata polypeptides on cultured dorsal root ganglia of rats and on crushed common peroneal nerve of rabbits.

We have isolated Achyranthes bidentata Blume polypeptides (ABPP) from the aqueous extract of A. bidentata Blume, a traditional Chinese medicine with multiple therapeutic applications. In this study, we aimed to investigate neurotrophic effects of ABPP on cultured dorsal root ganglia (DRGs) of rats and neuroprotective effects on crushed common peroneal nerve of rabbits. Immunochemistry and Western blot analysis indicated that ABPP (0.01, 0.1, and 1.0 µg/ml) encouraged neurite outgrowth from cultured DRG explants/neurons in a concentration-dependent manner through activation of ERK1/2. After crush injury to rabbit common peroneal nerve, animals received daily administration of ABPP for 5 weeks. Electrophysiological assessments and histomorphological evaluation showed that 6.0mg/kg ABPP significantly enhanced nerve regeneration and function restoration. Our findings suggest that ABPP could be used as a neurotrophic and neuroprotective agent to treat peripheral nerve crush injury.

The Achyranthes bidentata polypeptide k fraction enhances neuronal growth in vitro and promotes peripheral nerve regeneration after crush injury in vivo.

We have previously shown that Achyranthes bidentata polypeptides (ABPP), isolated from Achyranthes bidentata Blume (a medicinal herb), exhibit neurotrophic and neuroprotective effects on the nervous system. To identify the major active component of ABPP, and thus optimize the use of ABPP, we used reverse-phase high performance liquid chromatography to separate ABPP. We obtained 12 fractions, among which the fraction of ABPPk demonstrated the strongest neuroactivity. Immunocytochemistry and western blot analysis showed that ABPPk promoted neurite growth in cultured dorsal root ganglion explant and dorsal root ganglion neurons, which might be associated with activation of Erk1/2. A combination of behavioral tests, electrophysiological assessment, and histomorphometric analysis indicated that ABPPk enhanced nerve regeneration and function restoration in a mouse model of crushed sciatic nerve. All the results suggest that ABPPk, as the key component of ABPP, can be used for peripheral nerve repair to yield better outcomes than ABPP.

Achyranthes bidentata polypeptides confer neuroprotection through inhibition of reactive oxygen species production, Bax expression, and mitochondrial dysfunction induced by overstimulation of N-methyl-D-aspartate receptors.

Achyranthes bidentata polypeptides (ABPP), the important constituents separated from the aqueous extract of Achyranthes bidentata, have been shown to attenuate N-methyl-D-aspartate (NMDA)-induced cell apoptosis in cultured hippocampal neurons through differential modulation of NR2A- and NR2B-containing NMDA receptors. The present study sought to investigate the possible mechanism underlying the neuroprotective effect of ABPP on NMDA-induced cell death. Western blot analysis and colorimetric enzymatic assay demonstrated that ABPP pretreatment inhibited NMDA-induced increase of Bax protein expression or caspase-3 activity in cultured hippocampal neurons. Fluorescence measurements after staining with 2,7-dichlorofluorescin diacetate and rhodamine 123 showed that ABPP treatment also reversed NMDA-induced intracellular radical oxygen species (ROS) elevation and mitochondrial membrane potential depression in cultured hippocampal neurons. Furthermore, the in vivo effects of ABPP on cerebral neuronal damage during focal ischemia-reperfusion were also investigated. In rat middle cerebral artery occlusion (MCAO) model, ABPP attenuated the increase in the neurological deficit and cerebral infarction induced by focal ischemia-reperfusion, showing in vivo neuroprotective effects. The results collectively suggest that ABPP might exert neuroprotective actions through inhibiting Bax protein expression, caspase-3 activity, ROS production, and mitochondrial dysfunction that are all caused by overstimulation of NMDA receptors.

The protective effects of Achyranthes bidentata polypeptides in an experimental model of mouse sciatic nerve crush injury.

We have separated the active polypeptides from aqueous extracts of Achyranthes bidentata Blume (ABPP), a commonly prescribed Chinese medicinal plant with a range of pharmaceutical properties. We investigated the effects of ABPP administration on peripheral nerve regeneration in a mouse sciatic nerve crush injury model. After nerve crush, the mice received daily tail vein injections of 1, 4, and 16 mg/kg of ABPP, 65 microg/kg of methylcobalamin, and vehicle saline, respectively, over a 21-day period. At 1, 3, 6, 9, 12, 15, 18 and 21 days after nerve crush, the animals were subjected to walking track analysis for evaluating the sciatic functional index (SFI) values. At day 21 the animals were anesthetized, and the compound muscle action potential and nerve conduction velocity were respectively recorded. After the animals were killed, the sciatic nerve was examined with immunohistochemistry and electron microscopy, and gastrocnemius muscle was analyzed with Masson trichome staining. The results indicated that treatment with ABPP at a dose range (1-16 mg/kg) promoted histological regeneration and functional recovery of the injured sciatic nerve and its target muscle, yielding a desired efficacy greater than that by vehicle treatment and close to that by methylcobalamin (65 microg/kg). These findings suggest that plant polypeptides, ABPP, may be a potential agent in ameliorating of neuropathy caused by sciatic nerve crush.

Achyranthes bidentata Blume extract protects cultured hippocampal neurons against glutamate-induced neurotoxicity.

UNLABELLED: We have prepared an aqueous extract of Achyranthes bidentata Blume, a Chinese medicinal herb commonly prescribed for arthritis treatment or immnopotentiation, and have found that Achyranthes bidentata extract promotes nerve growth and prevents neuronal apoptosis. AIM OF THE STUDY: To investigate the protective effect of Achyranthes bidentata extract against glutamate-induced neurotoxicity in primary culture of rat hippocampal neurons. MATERIALS AND METHODS: We accomplished MTT assay for cell viability, Hoechst 33342 staining, and flow cytometry for cell apoptosis analysis to examine the effects of Achyranthes bidentata extract on glutamate-induced neurotoxicity, and also used Fluo 4-AM measurement, RT-PCR and Western blot analysis to determine the changes in intracellular calcium concentration [Ca(2+)](I), and mRNA and protein levels of Bcl-2, respectively, concurrently accompanied with the influences of Achyranthes bidentata extract. RESULTS: Achyranthes bidentata extract was found to inhibit glutamate-induced neuronal damage in a dose- and time-dependent manner. On the other hand, Achyranthes bidentata extract depressed glutamate-induced elevation of intracellular calcium concentration [Ca(2+)](i), and also antagonized glutamate-evoked decreases in Bcl-2 expression at mRNA and protein levels. CONCLUSION: The results suggest that Achyranthes bidentata extract prevents glutamate-induced cell damage in primarily cultured hippocampal neurons by inhibiting an increase in [Ca(2+)](i), and reversing the down-regulation of Bcl-2.

The protective effects of Achyranthes bidentata polypeptides against NMDA-induced cell apoptosis in cultured hippocampal neurons through differential modulation of NR2A- and NR2B-containing NMDA receptors.

Achyranthes bidentata Blume is a commonly prescribed Chinese medicinal herb with a variety of pharmaceutical properties. From its aqueous extract we have separated important constituents, referred to as A. bidentata polypeptides (ABPP). In this study, the neuroprotective effect of ABPP against N-methyl-d-aspartate (NMDA)-induced cell apoptosis was investigated in cultured rat hippocampal neurons. The results of MTT assay, Hoechst/PI double staining and DNA ladder detection indicated that ABPP significantly attenuated, in a concentration-dependent manner, apoptotic cell damage induced by exposure of cultured hippocampal neurons to NMDA (100 µM) for 30 min. The intracellular calcium measurement with fluo-3/AM revealed that ABPP antagonized the excess intracellular calcium triggered by NMDA. Furthermore, in addition to inhibiting the action of NR2B-containing NMDA receptors, ABPP can enhance the function of NR2A-containing NMDA receptors. Our data might suggest that ABPP may also prove to be a potential neuroprotective therapy owing to its differential modulation of NR2A- and NR2B-containing NMDA receptors.

Neuroprotective effects of salidroside in the PC12 cell model exposed to hypoglycemia and serum limitation.

The hypoglycemia and serum limitation-induced cell death in cultured PC12 cells represents a useful in vitro model for the study of brain ischemia and neurodegenerative disorders. Salidroside is a phenylpropanoid glycoside isolated from Rhodiola rosea L., a traditional Chinese medicinal plant, and has displayed a broad spectrum of pharmacological properties. In this study, MTT assay, Hoechst 33342 staining, and flow cytometry with annexin V/PI staining collectively showed that pretreatment with salidroside attenuated, in a dose-dependent manner, cell viability loss, and apoptotic cell death in cultured PC12 cells induced by hypoglycemia and serum limitation. RT-PCR, Western blot analysis, and enzymatic colorimetric assay indicated the changes in expression levels of Bcl-2, Bax, and caspase3 in PC12 cells on exposure to hypoglycemia and serum limitation with and without salidroside pretreatment, respectively. Rhodamine 123 staining and flow cytometry with 2',7'-Dichlorofluorescin diacetate staining revealed the changes in the mitochondrial membrane potential and radical oxygen species (ROS) production in PC12 cells on exposure to hypoglycemia and serum limitation with and without salidroside pretreatment, respectively. The experimental results suggest that salidroside protects the PC12 cells against hypoglycemia and serum limitation-induced cytotoxicity possibly by the way of the modulation of apoptosis-related gene expression, the restoration of the mitochondrial membrane potential, and the inhibition of the intracellular ROS production. Our findings might raise a possibility of potential therapeutic applications of salidroside for preventing and treating cerebral ischemic and neurodegenerative diseases.

The repair effects of Achyranthes bidentata extract on the crushed common peroneal nerve of rabbits.

In this study the effect of the Achyranthes bidentata root aqueous extract on regeneration of the crushed common peroneal nerve in rabbits by using a combination of electrophysiological assessment and histological aspect were investigated. The examined functional and morphological parameters suggest that A. bidentata extract could accelerate peripheral nerve regeneration in a dose-dependent manner (10-20 microg/kg, i.v.).

Biocompatibility evaluation of silk fibroin with peripheral nerve tissues and cells in vitro.

Silk-based materials have been used in the field of bone or ligament tissue engineering. In order to explore the feasibility of using purified silk fibroin to construct artificial nerve grafts, it is necessary to evaluate the biocompatibility of silk fibroin material with peripheral nerve tissues and cells. We cultured rat dorsal root ganglia (DRG) on the substrate made up of silk fibroin fibers and observed the cell outgrowth from DRG during culture by using light and electron microscopy coupled with immunocytochemistry. On the other hand, we cultured Schwann cells from rat sciatic nerves in the silk fibroin extract fluid and examined the changes of Schwann cells after different times of culture. The results of light microscopy, MTT test and cell cycle analysis showed that Schwann cells cultured in the silk fibroin extract fluid showed no significant difference in their morphology, cell viability and proliferation as compared to that in plain L15 medium. Furthermore, no significant difference was found in expression of the factors secreted by Schwann cells, such as nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) and S-100, between Schwann cells cultured in the silk fibroin extraction fluid and in plain L15 medium by the aid of immunocytochemistry, RT-PCR and Western analysis. Collectively, these data indicate that silk fibroin has good biocompatibility with DRG and is also beneficial to the survival of Schwann cells without exerting any significant cytotoxic effects on their phenotype or functions, thus providing an experimental foundation for the development of silk fibroin as a candidate material for nerve tissue engineering applications.