Efficacy and Safety of Mulberry Twig Alkaloids Tablet for Treatment of Type 2 Diabetes: A Randomized, Double-Blind, Placebo-Controlled Multicenter Clinical Study / 中国结合医学杂志

OBJECTIVE@#To assess the efficacy and safety of mulberry twig alkaloids (Sangzhi alkaloids, SZ-A) for treatment of type 2 diabetes in a randomized, double-blind, placebo-controlled multicenter clinical trial.@*METHODS@#A total of 200 patients were randomized to receive SZ-A (n=100) or placebo (n=100) for 16 weeks. The data analysis system for electronic data capture clinical trial central randomization system was used for randomization and dispensing of drugs. The primary outcome was the change in glycosylated hemoglobin (HbA1c) level. The secondary outcome included the proportions of cases with HbA1c <7.0% and HbA1c <6.5%, fasting blood glucose (FBG), postprandial blood glucose (PBG), area under curve for the PBG (AUC0-2h), body weight, and body mass index (BMI). Adverse events (AEs), severe adverse events (SAEs), treatment-related adverse events (TAEs), gastrointestinal disorders (GDs), blood pressure, routine blood tests, and liver and kidney function were monitored.@*RESULTS@#Compared with baseline, the change of HbA1c at week 16 was -0.80% (95% CI: -0.98% to -0.62%) and -0.09% (95% CI: -0.27% to 0.09%) in SZ-A group and placebo group, respectively. The proportion of patients with HbA1c <7% and <6.5% was higher in the SZ-A group than in the placebo group (46.8% vs. 21.6% and 29.9% vs. 10.8%). The observed values and changes in FBG, 1 h-PBG, 2 h-PBG, and AUC0-2h differed significantly between groups (P<0.001), but differences were not significant in body weight and BMI (P>0.05). The incidence rates of AEs, TAEs, and GDs differed significantly between groups (P=0.010, P=0.005, and P=0.006, respectively), whereas the incidence rates of SAEs showed no significant differences between groups (P=1.000).@*CONCLUSION@#SZ-A are effective and safe for treatment of type 2 diabetes. The protocol was registered in http://www.chictr.org.cn/showproj.aspx?proj=60117 (ChiCTR2000038550).

Metabolomics in Diabetic Neuropathy / 中国医学科学院学报

Diabetic neuropathy is a common diabetic complication.The application of metabolomics in the research on diabetic neuropathy is beneficial for us to understand the pathophysiological processes and overall metabolic disturbance of the nervous system under the condition of hyperglycemia,decipher the pathogenesis of diabetic neuropathy,and mine the potential biomarkers for clinical diagnosis and treatment.Long-term hyperglycemia may lead to disorders in multiple pathways,such as tricarboxylic acid circle,amino acid metabolism,and lipid metabolism.These metabolic changes are closely associated with the injuries of the peripheral and central nervous system.In the paper,we reviewed the metabolomics-based studies about diabetic neuropathy in the last five years.

Advances in Noninvasive Methods for Screening and Evaluating Diabetic Peripheral Neuropathy / 中国医学科学院学报

Diabetic peripheral neuropathy(DPN),a chronic diabetic microvascular complication with a high incidence among diabetic patients,increases the risk of diabetic foot and amputation.Many methods are available for screening and evaluating DPN,including traditional 10 g monofilament,tuning fork and vibration perception,and tendon reflex tests,which should be combined with some nerve function score systems to improve the detection rate and accuracy for DPN.In recent years,a number of noninvasive new techniques have been developed for the evaluation of nerve injury,such as corneal confocal microscopy,quantitative sensory testing,current perception threshold test,sympathetic sudomotor function evaluation,and quantitative detection of skin advanced glycation end products.This paper reviews these noninvasive methods for screening and evaluating DPN to help clinicians detect and focus on DPN early.

Combination of Quercetin, Hirudin and Cinnamaldehyde Promotes Schwann Cell Differentiation and Myelination against High Glucose by Inhibiting ERK Signaling Pathway / 中国结合医学杂志

OBJECTIVE@#To investigate the therapeutic and synergistic effects of QHC (combination of quercetin (Q), hirudin (H) and cinnamaldehyd (C)) on Schwann cell differentiation and myelination against high glucose (HG) induced injury.@*METHODS@#Primary-culture Schwann cells exposed to HG (50 mmol/L) for 72 h and Schwann cell-dorsal root ganglion (DRG) neuron cocultures exposed to HG (50 mmol/L) for 7 days were employed as in vitro model of diabetic neuropathy. The cells were randomly divided into 10 groups: control (CON, 25 mmol/L glucose), HG (50 mmol/L glucose), HG plus 10 μmol/L quercetin (Q), HG plus 0.04 IU/mL hirudin (H), HG plus 100 nmol/L cinnamaldehyd (C), HG plus 10 μmol/L quercetin and 0.04 IU/mL hirudin (QH), HG plus 10 μmol/L quercetin and 50 nmol/L cinnamaldehyd (QC), HG plus 0.04 IU/mL hirudin and 50 nmol/L cinnamaldehyd (HC), HG plus 10 μmol/L quercetin, 0.04 IU/mL hirudin and 50 nmol/L cinnamaldehyd (QHC) or 10 μmol/L U0126. Cell differentiation was evaluated by periaxin immunofluorescence staining. The protein expression levels of myelin protein zero (P0), myelin basic protein (MBP), myelin-associated glycoprotein (MAG), extracellular signal-regulated kinase (ERK), p-ERK, p-c-Jun, c-Jun, notch intracellular domain (NICD) and the mRNA expression levels of P0, MBP, MAG, Krox-20, Notch1 and Jagged1 were detected by Western blotting and real-time quantitative PCR analysis. The secretion of ciliary neurotrophic factor (CNTF) was determined by enzyme-linked immunosorbent assay (ELISA). The number and length of the myelin segments were evaluated by MBP immunofluorescence staining. The expression and the location of p-ERK in cocultures were detected by MAG and p-ERK immunofluorescence double staining.@*RESULTS@#Co-treatment with Q, C, H and their combination promoted Schwann cell differentiation, increased CNTF secretion, up-regulated the protein and mRNA expressions of myelin, and increased the number and length of the myelin segments (P<0.01 or P<0.05). In particular, the combination therapy of Q, H and C was superior to the respective monotherapy (P<0.01). Combination therapy of QHC exhibited higher inhibitory activities for ERK signaling related molecules than each monomer or the combination of the two monomers (P<0.01).@*CONCLUSION@#QHC combination yielded synergy in promoting Schwann cell differentiation and myelination and the protective effect may involve in the inhibition of ERK signaling pathway, providing scientific evidence for better understanding of combination of Q, H and C in clinical applications.

Effects of Mitochondrial Dysfunction via AMPK/PGC-1 α Signal Pathway on Pathogenic Mechanism of Diabetic Peripheral Neuropathy and the Protective Effects of Chinese Medicine / 中国结合医学杂志

Diabetic peripheral neuropathy (DPN) is a progressive neurodegenerative disease of peripheral nervous system with high energy requirement. The adenosine monophosphate-activated protein kinase (AMPK)/peroxisome proliferator-activated receptor- γ coactivator 1 α (PGC-1 α) axis plays a key role in regulating mitochondrial energy metabolism. Increasing preclinical evidences have shown that inhibition of AMPK/PGC-1 α pathway leading to mitochondrial dysfunction in neurons or Schwann cells contributes to neuron apoptosis, distal axonopathy and nerve demyelination in DPN. Some Chinese medicine formulae or extracts from herbs may have potential neuroprotective effects on DPN via activating AMPK/PGC-1 α pathway and improving mitochondrial function.

Humanistic Spirit Contained in Traditional Chinese Medicine should Be Valued / 中国医学科学杂志(英文版)

Medicine is a science studying human's health and diseases as well as the regularity between them. Its research subject is human, who possess natural attribute, psychological attribute and social attribute. Therefore, medicine is bound to possess humanistic attribute. Rooted in Chinese traditional culture, Traditional Chinese Medicine contains abundant humanistic thoughts, for instance, pursuing the unity of human and nature, advocating the vital importance of life, sticking to the virtue of "medicine being humane art", abiding by the principle of "Benevolence prior to interest", complying with the medical rule of "Respecting peers". These are the very concrete reflections of medical humanistic spirit. In this article we aim to explore the humanistic thoughts contained in Traditional Chinese Medicine, and try to inherit and carry forward the spirit to better relieve the tensions between doctors and patients and improve the quality of medical services.

Strategies and Research Progress of Chinese Medicine in Prevention and Treatment of Diabetic Peripheral Neuropathy / 中国结合医学杂志

Diabetic peripheral neuropathy (DPN) seriously affects the quality of life in patients with type 2 diabetes mellitus. This paper reviews the role of Chinese medicine in the main treatment goal of DPN, including protecting pancreatic β-cells, in the use of antioxidation therapy to delay disease progression, and in the endpoint of neural repair and regeneration. We propose that protecting the body from injury caused by high glucose and oxidative stress, and promoting repair and regeneration of nerves should be the research direction for the prevention and treatment of DPN.

Research Advances in Autophagy and Diabetic Neuropathy / 中国医学科学院学报

Recent studies have found that autophagy is involved in the development of many chronic complications of diabetes. However,the specific mechanism between autophagy and diabetic neuropathy(DN)remains unclear. This article reviews the latest research on the pathogenesis of autophagy and DN,with an attempt to find new targets and ideas for the treatment of DN.

New developments in the pharmacodynamics and pharmacokinetics of combination of Chinese medicine and Western medicine / 中国结合医学杂志

It is very common to use Chinese medicine (CM) combined with Western medicine (WM) in clinical practice. The appropriate combination of CM with WM can reduce toxicity and enhance effects in order to make the best use of advantages and bypass the disadvantages. However, an inappropriate combination can not only affect the curative effect but even cause death. Therefore, strengthening the complementary advantages of the CM and WM to improve the therapeutic efficacy and reduce side effects has become an important research topic of clinical medicine and pharmacy. Many researchers try to clarify the effects of combining CM with WM on therapeutic efficacy and absorption, distribution, metabolism and excretion by pharmacodynamics and pharmacokinetics studies, providing evidence for clinical application. This review focuses on the new developments in the pharmacodynamics and pharmacokinetics of the combination of CM with WM in order to give references for clinical treatment.

Combination of quercetin, cinnamaldehyde and hirudin protects rat dorsal root ganglion neurons against high glucose-induced injury through Nrf-2/HO-1 activation and NF-κB inhibition / 中国结合医学杂志

<p><b>OBJECTIVE</b>To examine the effects of the combination of quercetin (Q), cinnamaldehyde (C) and hirudin (H), a Chinese medicine formula on high glucose (HG)-induced apoptosis of cultured dorsal root ganglion (DRG) neurons.</p><p><b>METHODS</b>DRG neurons exposed to HG (45 mmol/L) for 24 h were employed as an in vitro model of diabetic neuropathy. Cell viability, reactive oxygen species (ROS) level and apoptosis were determined. The expression of nuclear factor of Kappa B (NF-κB), inhibitory kappa Bα(IκBα), phosphorylated IκBα and Nf-E2 related factor 2 (Nrf2) were examined using reverse transcription-polymerase chain reaction (RT-PCR) and Western blot assay. The expression of hemeoxygenase-1 (HO-1), interleukin-6 (IL-6), tumor necrosis factor (TNF-α) and caspase-3 were also examined by RT-PCR and Western blot assay.</p><p><b>RESULTS</b>HG treatment markedly increased DRG neuron apoptosis via increasing intracellular ROS level and activating the NF-κB signaling pathway (P<0.05). Co-treatment with Q, C, H and their combination decreased HG-induced caspase-3 activation and apoptosis (P<0.05 or P<0.01). The expressions of NF-κB, IL-6 and TNF-α were down-regulated, and Nrf2/HO-1 expression was up-regulated (P<0.05 or P<0.01). QCH has better effect in scavenging ROS, activating Nrf-2/HO-1, and down-regulating the NF-κB pathway than other treatment group.</p><p><b>CONCLUSIONS</b>DRG neurons' apoptosis was increased in diabetic conditions, which was reduced by QCH formula treatment. The possible reason could be activating Nrf-2/HO-1 pathway, scavenging ROS, and inhibition of NF-κB activation. The effect of QCH combination was better than each monomer or the combination of the two monomers.</p>

Anti-oxidative and anti-inflammatory effects of cinnamaldehyde on protecting high glucose-induced damage in cultured dorsal root ganglion neurons of rats / 中国结合医学杂志

<p><b>OBJECTIVE</b>To examine the mechanism underlying the beneficial role of cinnamaldehyde on oxidative damage and apoptosis in high glucose (HG)-induced dorsal root ganglion (DRG) neurons in vitro.</p><p><b>METHODS</b>HG-treated DRG neurons were developed as an in vitro model of diabetic neuropathy. The neurons were randomly divided into five groups: the control group, the HG group and the HG groups treated with 25, 50 and 100 nmol/L cinnamaldehyde, respectively. Cell viability was examined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and apoptosis rate was evaluated by the in situ TdT-mediated dUTP nick end labeling (TUNEL) assay. The intracellular level of reactive oxygen species (ROS) was measured with flow cytometry. Expression of nuclear factor-kappa B (NF-κB), inhibitor of κB (IκB), phosphorylated IκB (p-IκB), tumor necrosis factor (TNF)-α, interleukin-6 (IL-6) and caspase-3 were determined by western blotting and real-time quantitative reverse transcription polymerase chain reaction (RT-PCR). Expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and hemeoxygenase-1 (HO-1) were also measured by western blotting.</p><p><b>RESULTS</b>Cinnamaldehyde reduced HG-induced loss of viability, apoptosis and intracellular generation of ROS in the DRG neurons via inhibiting NF-κB activity. The western blot assay results showed that the HG-induced elevated expressions of NF-κB, IκB and p-IκB were remarkably reduced by cinnamaldehyde treatment in a dose-dependent manner (P <0.01). The HG-induced over-expression of NF-κB p65 mRNA was remarkably attenuated after cinnamaldehyde treatment in a dose-dependent manner (P <0.01). However, the expressions of Nrf2 and HO-1 were not upregulated. Treatment with cinnamaldehyde not only attenuated caspase-3 activation and the caspase cleavage cascade in DRG neurons, but also lowered the elevated IL-6, TNF-α, cyclo-oxygenase and inducible nitric oxide synthase levels, indicating a reduction in inflammatory damage.</p><p><b>CONCLUSIONS</b>Cinnamaldehyde protected DRG neurons from the deleterious effects of HG through inactivation of NF-κB pathway but not through activation of Nrf2/HO-1. And thus cinnamaldehyde may have potential application as a treatment for DPN.</p>

Culturing Schwann Cells from Neonatal Rats by Improved Enzyme Digestion Combined with Explants-culture Method / 中国医学科学院学报

Objective To develop an improved method for culturing Schwann cells(SCs) by using both enzyme digestion and explants-culture approaches and compared with traditional explants-culture method and general hemi-explants-culture method. Methods Bilaterally sciatic nerves and brachial plexus nerves were dissected from 3 to 5-day-old neonatal SD rats and explants-culture method,general hemi-explants-culture method,and improved enzyme digestion combined with explants-culture method were adopted to culture SCs,respectively. SCs were digested and passaged after 7 days in culture and counted under the microscope. The purity of SCs was identified by S-100 immunofluorescence staining. Results The SCs of improved method group grew fastest and the total number of cells obtained was(1.85±0.13)×10(6);the SCs of the hemi-explants-culture method group grew slower than the improved method group and the total number of cells obtained was (1.10±0.10)×10(6);the SCs of the explants-culture method group grew slowest and the total number of cells obtained was (0.77±0.03)×10(6).The total number of cells obtained showed significant difference among the three groups(P<0.01). Immunofluorescence staining showed that the SCs purity was (95.73±1.51)% in the improved method group,(84.66±2.68)% in the hemi-explants-culture method group,and (74.50±4.23)% in the explants-culture method group(P<0.01). Conclusion The improved enzyme digestion combined with explants-culture method can obtain sufficient amount of high-purity SCs in a short time and thus may be applied in further research on peripheral nerve regeneration.

Jinmaitong alleviates the diabetic peripheral neuropathy by inducing autophagy / 中国结合医学杂志

<p><b>OBJECTIVE</b>To observe the deregulation of autophagy in diabetic peripheral neuropathy (DPN) and investigate whether Jinmaitong ( JMT) alleviates DPN by inducing autophagy.</p><p><b>METHODS</b>DPN models were established by streptozotocin-induced diabetic rats and Schwann cells (SCs) cultured in high glucose medium. The pathological morphology was observed by the improved Bielschowsky's nerve fiber axonal staining and the Luxol fast blue-neutral red myelin staining. The ultrastructure was observed by the transmission electron microscopy. Beclin1 level was detected by immunohistochemistry and Western blot. The proliferation of cultured SCs was detected by methylthiazolyldiphenyl-tetrazolium bromide.</p><p><b>RESULTS</b>Diabetic peripheral nerve tissues demonstrated pathological morphology and reduced autophagic structure, accompanied with down-regulation of Beclin1. JMT apparently alleviated the pathological morphology change and increased the autophagy [in vivo, Beclin1 integral optical density (IOD) value of the control group 86.6±17.7, DM 43.9±8.8, JMT 73.3 ±17.8, P<0.01 or P<0.05, in vitro Beclin1 IOD value of the glucose group 0.47±0.25 vs the control group 0.88±0.29, P<0.05]. Consequently, inhibition of autophagy by 3-methyladenine resulted in a time- and concentration-dependent decrease of the proliferation of SCs (P<0.05, P<0.01).</p><p><b>CONCLUSIONS</b>Down-regulation of autophagy in SCs might contribute to the pathogenesis of DPN. JMT alleviates diabetic peripheral nerve injury at least in part by inducing autophagy.</p>

Effects of Chinese Medicinal Compound Jinmaitong on the Expression of Nitrotyrosine andNerve Growth Factor in the Dorsal Root Ganglia of Diabetic Rats / 中国医学科学院学报

Objective To study the effects of Chinese medicinal compound Jinmaitong(JMT) on the expressions of nitrotyrosine (NT) and nerve growth factor (NGF) in dorsal root ganglia of diabetic rats. Methods Experimental rat diabetic models were established by the intraperitoneal injection of streptozotocin. Rat models were then randomly divided into four groups including normal control group (Con group),diabetes mellitus group (DM group),Jinmaitong group(JMT group)(treated with JMT similar to the fifteen-fold dose of adult recommended dosage),and taurine group(Tau group)(treated with Taurine similar to the fifteen-fold dose of adult recommended dosage),with 10 rats in each group. The Con and DM groups were treated with distilled water at a daily dose of 1 ml/100 g. All rats were given intragastric administration for 16 weeks and then killed. Body weight and blood glucose were detected before and at the 4th,8th,12th,and 16th week after treatment. The pain threshold to mechanical stimulation with von Frey filament were carried out before death. The expressions of NT and NGF in dorsal root ganglion were detected by immunohistochemistry and Western blot analysis,respectively. Results Immunohistochemistry showed that the average optical density (AOD) of NT expression in DM group were significantly higher than those in control group (P=0.000),and the AOD of NGF was significantly lower than the control group (P=0.006).The AOD of NT(P=0.000,P=0.000) in both treatment groups decreased significantly and the AOD of NGF(P=0.000, P=0.004)significantly increased compared with DM group. The AOD of NT in JMT group was significantly lower than Tau group (P=0.004). Western blot analysis showed that the protein level of NT in DM group was significantly higher than that in control group (P=0.000),and the protein level of NGF was significantly lower than that in control group (P=0.000). Compared with the DM group,the protein level of NT in both treatment groups significantly decreased (P=0.001,P=0.000),and the protein level of NGF increased significantly (P=0.000,P=0.001). Conclusion Traditional Chinese medicine JMT can obviously up-regulate the expressions of NGF and reduce the NT levels in dorsal root ganglia of diabetic rats.

Advances in the Relationship between Adipokines and β-cell Failure in Type 2 Diabetes Mellitus / 中国医学科学院学报

β-cell failure coupled with insulin resistance plays a key role in the development of type 2 diabetes mellitus (T2DM). Changed adipokines in circulating level form a remarkable link between obesity and both β-cell failure and insulin resistance. Some adipokines have beneficial effects,whereas others have detrimental properties. The overall contribution of adipokines to β-cell failure mainly depends on the interactions among adipokines. This article reviews the role of individual adipokines such as leptin,adiponectin,and resistin in the function,proliferation,death,and failure of β-cells. Future studies focusing on the combined effects of adipokines on β-cells failure may provide new insights in the treatment of T2DM.

Progress in study of antioxidant effects of Coptis chinensis and its major contributions to diabetes treatment/therapy / 中国中药杂志

Coptis chinensis, a traditional Chinese medicine, has been found to have multiple pharmacological effects recently. Some research showed that C. chinensis has antioxidant effects, including scavenging oxygen free radicals, alleviating lipid peroxidation, enhancing activity of antioxidant enzymes, et al. C. chinensis may inhibit several classical pathological pathways in diabetes. C. chinensis is a potential medicine to prevent and treat diabetes mellitus and its complications. This review focuses on the recent research progress in the study of antioxidant effects of C. chinensis and its major contributions to diabetes treatment/therapy.

Astragalus membranaceus injection combined with conventional treatment for viral myocarditis: a systematic review of randomized controlled trials / 中国结合医学杂志

<p><b>OBJECTIVE</b>To assess the efficacy and safety of Astragalus membranaceus Injection combined with conventional therapy in the treatment of viral myocarditis.</p><p><b>METHODS</b>Randomized controlled trials (RCTs) of A. membranaceus Injection combined with conventional treatment compared with conventional treatment alone were included. Study population characteristics and outcome results were extracted independently by two assessors. Meta-analysis was performed for data available.</p><p><b>RESULTS</b>Six RCTs, involving 639 participants, were included in this study. The methodological quality of the included trials was generally low, and there was high risk of publication bias in the included trials. The total effective rate of A. membranaceus Injection combined with conventional treatment was significantly higher than that of conventional treatment alone. Compared with conventional treatment, the cointervention treatment group showed significant recovery in myocardium enzyme levels and electrocardiography. Two RCTs reported there were no adverse effects from A. membranaceus Injection combined with conventional treatment.</p><p><b>CONCLUSION</b>A. membranaceus Injection combined with conventional treatment appeared to be more efficacious compared with conventional treatment alone for treating viral myocarditis. However, this conclusion should be cautiously interpreted due to low methodological quality, small sample size, limited number of trials, and high risk of publication bias and other unidentified risks of bias. The safety of A. membranaceus Injection combined with conventional treatment remains uncertain.</p>

Effect of serum containing Jinmaitong Capsule on rats' Schwann cell apoptosis induced by high glucose concentration / 中国结合医学杂志

<p><b>OBJECTIVE</b>To evaluate the effect of serum containing Jinmaitong Capsule (JMT) on apoptosis of Schwann cells (SCs) that are cultured in high glucose at the cellular and molecular levels.</p><p><b>METHODS</b>SCs were cultured in Dulbecco's modified Eagle's medium (control group), high glucose (50 mmol/L) medium supplemented with 20% rat serum (HG group), and 50 mmol/L glucose medium supplemented with serum containing JMT (JMT group). SC apoptosis was detected using a terminal deoxynucleotidyl transferase dUTP nick end labeling kit. The expression of Bcl-2 and the caspase-3 p20 subunit in SCs were detected by realtime fluorogenic quantitative polymerase chain reaction and confocal laser scanning microscopy, respectively.</p><p><b>RESULTS</b>No apoptosis was detected in SCs that were cultured in the control group. The percentage of apoptosis of SCs cultured in the HG group was much higher than that in the control group. The apoptosis of SCs in the JMT group was lower than that in the HG group. Fluorescence intensity of Bcl-2 and the expression of Bcl-2 mRNA in SCs that were cultured in the HG group were much lower than those in the control group and much higher than those in the JMT group (P<0.01). The fluorescence intensity of caspase-3 p20 and the expression of caspase-3 p20 mRNA in SCs that were cultured in the HG group were much higher than those in the control group (P<0.01), and they were remarkably lower in the JMT group (P<0.01).</p><p><b>CONCLUSIONS</b>JMT effectively prevents SC apoptosis that is induced by high glucose. This effect may be because of increased expression of Bcl-2 mRNA and protein and decreased expression of caspase-3 p20 mRNA and protein.</p>

Effects of Jinmaitong capsule on oxidative stress and cell apoptosis of dorsal root ganglion in diabetic rats / 中国医学科学院学报

<p><b>OBJECTIVE</b>To study the effects of Jinmaitong capsule on oxidative stress and cell apoptosis of dorsal root ganglion (DRG) in rats with diabetic peripheral neuropathy.</p><p><b>METHODS</b>Sixty male SD rats were randomly divided into normal group and model groups. The diabetic rat models were established using Streptozotocin (STZ) method (60 mg/kg of intraperitoneal injection), and then randomly divided Jinmaitong low, middle, and high-dose groups and vitamin C group. All the experimental rats were sacrificed at 16-week and then the DRG was isolated. The morphological changes of DRG were observed using the Nissl's staining, and the NADPH oxidase subunit p22-phox, Cyt C, Bcl-2, and Caspase-3 of DRG in rats were detected by immunohistochemistry and quantitative reverse transcription PCR (qRT-PCR). Cell apoptosis was detected by TUNEL.</p><p><b>RESULTS</b>Compared with the model group, the expressions of NADPH oxidase subunit p22-phox protein, Cyt expression of C protein, Caspase-3 protein, and mRNA cell apoptosis rate in each treatment group significantly decreased whereas the expressions of Bcl-2 mRNA and protein significantly increased (P<0.05 or P<0.01). The Jinmaitong high-dose group had the best effect and was significantly different from that of the vitamin C group (P<0.01).</p><p><b>CONCLUSIONS</b>Jinmaitong capsule can prevent the nerve injury in rats with diabetic peripheral neuropathy by inhibiting oxidative stress and decreasing the apoptosis. The high-dose Jinmaitong capsule has the best effect and is superior to vitamin C.</p>

Effects of Jinmaitong Capsule () on ciliary neurotrophic factor in sciatic nerves of diabetes mellitus rats / 中国结合医学杂志

<p><b>OBJECTIVE</b>To study the effects of the Chinese medicine Jinmaitong Capsule (, JMT) on the pathomorphology of sciatic nerves, ciliary neurotrophic factor (CNTF), and the mRNA expressions of CNTF in rats with streptozotocin-induced diabetes mellitus (STZ-DM).</p><p><b>METHODS</b>The animal model was established by one time intraperitoneal injection of streptozotocin. The rats were simply divided by random into 5 groups including model group, low-dose JMT group (JL), medium-dose JMT group (JM), high-dose JMT group (JH) and neurotropin group. For each of the above 5 groups, a group of 10 normal Wistar rats matched in body weight, age and gender were set as normal group. Intragastric administrations were started after the animal model established. The JL group were administered with five times the JMT dose recommended for a human adult; the JM group were administered with ten times the JMT dose recommended for a human adult; the JH group were administered with twenty times the JMT dose recommended for a human adult. The neurotropin group was administered with ten times the neurotropin dose recommended for a human adult. All rats were given intragastric administration for 16 weeks and then killed. In the 4th, 8th, 12th, 16th week, body weight and blood glucose level were detected before and after the intervention. The morphologic changes of the sciatic nerves were observed by optical microscope and transmission electron microscope. The CNTFmRNA expressions were detected by real-time fluorescent quantitative polymerase chain protein, and the CNTF protein expressions were detected by immunohistochemical method.</p><p><b>RESULTS</b>The blood glucose levels of the STZ-DM rats were much higher than normal group (P<0.01), and there was no apparent difference between any treatment groups and the model group (P>0.05). Before and after the intervention in the 4th, 8th, 12th, 16th week, there were no significant differences in the body weight among all the groups (P>0.05). The sciatic nerves of STZ-DM rats might have pathomorphological changes in axons, myelin sheaths, and interstitium. The levels of CNTF and CNTF-mRNA expressions in the STZ-DM rats were both significantly decreased (P<0.01). The sciatic nerves of STZ-DM rats might have pathomorphological changes in axons, myelin sheaths, and interstitium.</p><p><b>CONCLUSION</b>JMT could improve the pathomorphology of sciatic nerves by increasing CNTF's and CNTF-mRNA expressions in sciatic nerve tissues, and promote the repair and regeneration of damaged nerve fibers.</p>