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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).
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Alcaloides , Diabetes Mellitus Tipo 2 , Morus , Glucemia , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Método Doble Ciego , Hemoglobina Glucada , Humanos , Hipoglucemiantes/uso terapéutico , Comprimidos/uso terapéutico , Resultado del TratamientoRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Jinmaitong (JMT) is a prescription of Traditional Chinese Medicine, which is composed of ten herbal drugs and two animal drugs. It has long been used for the treatment of diabetic peripheral neuropathy (DPN). AIM OF STUDY: Wnt/ß-catenin pathway is considered as an essential and direct driver of myelinogenesis. This study aims to evaluate the protective effect of JMT against DPN dynamically during a 16-weeks' treatment, and to investigate the underlying mechanism in which the Wnt/ß-catenin pathway is involved. MATERIALS AND METHODS: Diabetic model was induced by single intraperitoneal injection of Streptozotocin (STZ) using male Sprague-Dawley rats. The model rats were divided into five groups and administrated with JMT at three doses (0.437, 0.875, and 1.75 g/kg per day), neurotropin (positive drug, 2.67 NU/kg per day), and placebo (deionized water), respectively, for continuous 8 weeks (n = 9-10), 12 weeks (n = 8-10), or 16 weeks (n = 7-9). Meanwhile, rats in control group were administrated with placebo (n = 10 for 8 weeks, n = 9 for 12 and 16 weeks, respectively). Blood glucose and body weight were monitored every four weeks. Mechanical allodynia was assessed using mechanical withdrawal threshold (MWT) test. The morphological change of sciatic nerves were observed by transmission electron microscope (TEM) and hematoxylin and eosin (HE) stain. The mRNA and protein levels of targeted genes were evaluated by quantitative real time-PCR and western bolt, respectively. Myelin protein zero (MPZ) and mediators involved in Wnt/ß-catenin pathway, such as ß-catenin, glycogen synthase kinase 3ß (GSK-3ß), and WNT inhibitory factor-1 (WIF-1), were compared among different groups after treatment of 8, 12, and 16 weeks, respectively. RESULTS: The mechanical allodynia and peripheral nerve morphology were degenerated in DPN rats over time, and notably improved after JMT-treatment of 12 and 16 weeks. The decreased MPZ level in DPN rats were also significantly amended by JMT. More importantly, we found that the suppressed Wnt/ß-catenin pathway in sciatic nerves of DPN rats was overtly up-regulated by JMT in a time-dependent manner. Among the three doses, JMT at the middle dose showed the best effect. CONCLUSIONS: JMT effectively ameliorated diabetic-induced peripheral neuropathy, which was mediated by the activation of Wnt/ß-catenin signaling pathway. This study provided new perspective to understand the neuroprotective mechanism of JMT.
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Diabetes Mellitus Experimental/tratamiento farmacológico , Neuropatías Diabéticas/tratamiento farmacológico , Medicamentos Herbarios Chinos/farmacología , Vía de Señalización Wnt/efectos de los fármacos , Animales , Glucemia/efectos de los fármacos , Peso Corporal/efectos de los fármacos , Diabetes Mellitus Experimental/complicaciones , Neuropatías Diabéticas/fisiopatología , Relación Dosis-Respuesta a Droga , Medicamentos Herbarios Chinos/administración & dosificación , Masculino , Fármacos Neuroprotectores/administración & dosificación , Fármacos Neuroprotectores/farmacología , Ratas , Ratas Sprague-Dawley , Nervio Ciático/efectos de los fármacos , Nervio Ciático/metabolismo , EstreptozocinaRESUMEN
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.
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Acroleína/análogos & derivados , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Hirudinas/farmacología , Vaina de Mielina/metabolismo , Quercetina/farmacología , Células de Schwann/efectos de los fármacos , Acroleína/farmacología , Animales , Células Cultivadas , Nefropatías Diabéticas , Quimioterapia Combinada , Glucosa/metabolismo , Ratas , Ratas Sprague-DawleyRESUMEN
OBJECTIVE: To investigate protective effects of hirudin on oxidative stress and apoptosis of spinal dorsal root ganglion cells in high-glucose rats at the cellular and molecular level. METHODS: Dorsal root ganglion neurons (DRGn) were harvested from embryonic day in 15 SD rats, purified and identificated after primary culture. They were divided into the normal control group, high-glucose (HG) group, positive control (alpha-lipoic acid, ALA) group, low-dose hirudin group (H1), medium-dose hirudin group (H2) and high-dose hirudin group (H3). The control group was cultured by neuron specific culture medium, while the HG group was cultured by neuron specific culture medium and 20 mmol/L glucose (HG medium). The hirudin groups were cultured by HG medium+0.25 IU/mL hirudin (H1), HG medium+0.5 IU/mL hirudin (H2) and HG medium+1 IU/mL hirudin (H3). The ALA group was cultured by HG medium+100 µ mol/L ALA. 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenylt etrazolium bromide (MTT) assay was used to explore the optimum concentration and intervention time. Flow cytometry assay was used to detect the level of reactive oxygen series (ROS). Western blot and quantificational realtime polymerase chain reaction (qRT-PCR) were used to detect the expression of protein and mRNA of nuclear factor erythroid 2-related factor 2 (Nrf-2), hemeoxygence-1 (HO-1), nuclear factor-κ B (NF-κ B) and Caspase-3. TUNEL assay was used to test the apoptosis rate of different groups. RESULTS: After 24 h of culture, the cell activity of hirudin and ALA groups were higher than that of HG group, and there was a statistical difference between the H1 group and HG group (P<0.05). In hirudin groups, the apoptosis rate of cells, the expression of activated Caspase-3 protein and Caspase-3 mRNA were lower than those of HG group (P<0.01), higher than those of ALA group (P<0.01 or P<0.05). The ROS level of hirudin groups was higher than that of ALA group (P<0.01), lower than that of HG group (P<0.01 or P<0.05). The expression of NF-κ B (P65) protein in H3 group were lower than those of HG group (P<0.05). The expression of Nrf-2 protein in hirudin groups was higher than that of HG group (P<0.01), lower than that of ALA group (P<0.01 or P<0.05). The expression of HO-1 protein in hirudin groups was lower than that of ALA group (P<0.01 or P<0.05), higher than that of HG group (P<0.01 or P<0.05). CONCLUSIONS: The activity of DRGn cells can be promoted by hirudin under HG conditions. The effects of hirudin on the inhibition of HG on DRGn cells damage mainly include scavenging ROS, up-regulating Nrf-2/HO-1 pathway, inhibiting activation of NF-κ B pathway, down-regulating the expression of and Caspase-3 and reducing DRGn cell apoptosis.
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Apoptosis/efectos de los fármacos , Ganglios Espinales/efectos de los fármacos , Hirudinas/farmacología , Estrés Oxidativo/efectos de los fármacos , Animales , Caspasa 3/metabolismo , China , Modelos Animales de Enfermedad , Hemo Oxigenasa (Desciclizante)/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Ratas , Ratas Sprague-Dawley , Factor de Transcripción ReIA/metabolismoRESUMEN
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.
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Medicina Tradicional China , Relaciones Médico-Paciente , HumanosRESUMEN
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.
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Proteínas Quinasas Activadas por AMP/metabolismo , Neuropatías Diabéticas/tratamiento farmacológico , Neuropatías Diabéticas/patología , Medicina Tradicional China , Mitocondrias/patología , Fármacos Neuroprotectores/uso terapéutico , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/metabolismo , Transducción de Señal , Humanos , Mitocondrias/metabolismoRESUMEN
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 ß-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.
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Neuropatías Diabéticas/prevención & control , Neuropatías Diabéticas/terapia , Medicina Tradicional China , Antioxidantes/uso terapéutico , Citoprotección , Neuropatías Diabéticas/patología , Progresión de la Enfermedad , Humanos , Células Secretoras de Insulina/patologíaRESUMEN
OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
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Acroleína/análogos & derivados , Ganglios Espinales/patología , Glucosa/toxicidad , Hemo-Oxigenasa 1/metabolismo , Hirudinas/farmacología , Factor 2 Relacionado con NF-E2/metabolismo , FN-kappa B/antagonistas & inhibidores , Quercetina/farmacología , Acroleína/farmacología , Animales , Apoptosis/efectos de los fármacos , Caspasa 3/metabolismo , Supervivencia Celular/efectos de los fármacos , Fluoresceínas/metabolismo , Ganglios Espinales/efectos de los fármacos , Ganglios Espinales/metabolismo , Proteínas I-kappa B/metabolismo , Interleucina-6/metabolismo , FN-kappa B/metabolismo , Fármacos Neuroprotectores/farmacología , Fosforilación/efectos de los fármacos , Ratas Sprague-Dawley , Especies Reactivas de Oxígeno/metabolismo , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
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.
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Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/farmacocinética , Medicina Tradicional China , Antibacterianos/farmacología , Circulación Sanguínea/efectos de los fármacos , Quimioterapia Combinada , HumanosRESUMEN
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.
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Medicamentos Herbarios Chinos/farmacología , Ganglios Espinales/metabolismo , Factor de Crecimiento Nervioso/metabolismo , Tirosina/análogos & derivados , Animales , Glucemia , Peso Corporal , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Experimental/patología , Ganglios Espinales/efectos de los fármacos , Inmunohistoquímica , Umbral del Dolor , Distribución Aleatoria , Ratas , Tirosina/metabolismoRESUMEN
OBJECTIVE: To observe the deregulation of autophagy in diabetic peripheral neuropathy (DPN) and investigate whether Jinmaitong ( JMT) alleviates DPN by inducing autophagy. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.
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Autofagia , Diabetes Mellitus Experimental/complicaciones , Diabetes Mellitus Experimental/tratamiento farmacológico , Neuropatías Diabéticas/complicaciones , Neuropatías Diabéticas/tratamiento farmacológico , Medicamentos Herbarios Chinos/uso terapéutico , Animales , Autofagia/efectos de los fármacos , Axones/efectos de los fármacos , Axones/patología , Beclina-1/metabolismo , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Diabetes Mellitus Experimental/patología , Neuropatías Diabéticas/patología , Regulación hacia Abajo/efectos de los fármacos , Medicamentos Herbarios Chinos/farmacología , Glucosa/farmacología , Inmunohistoquímica , Masculino , Ratas Wistar , Células de Schwann/efectos de los fármacos , Células de Schwann/patología , Nervio Ciático/efectos de los fármacos , Nervio Ciático/patología , Nervio Ciático/ultraestructura , Coloración y EtiquetadoRESUMEN
OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
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Acroleína/análogos & derivados , Antiinflamatorios/farmacología , Ganglios Espinales/patología , Glucosa/toxicidad , Neuronas/patología , Fármacos Neuroprotectores/farmacología , Acroleína/administración & dosificación , Acroleína/farmacología , Animales , Apoptosis/efectos de los fármacos , Western Blotting , Caspasa 3/metabolismo , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Ganglios Espinales/efectos de los fármacos , Ganglios Espinales/metabolismo , Hemo Oxigenasa (Desciclizante)/metabolismo , Proteínas I-kappa B/metabolismo , Interleucina-6/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , FN-kappa B/metabolismo , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Oxidación-Reducción/efectos de los fármacos , Fosforilación/efectos de los fármacos , Ratas Sprague-Dawley , Especies Reactivas de Oxígeno/metabolismo , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
Diabetic peripheral neuropathy (DPN) is a common chronic complication of diabetes. Jinmaitong (JMT), a Traditional Chinese Medicine, improves certain symptoms of DPN, such as limb pain and numbness. The aim of the present study was to investigate the effects of JMT on DNA oxidative damage and apoptosis in the sciatic nerve of diabetic rats. The rats were divided into a normal and a diabetic group. Diabetes was induced using streptozotocin (60 mg/kg). The diabetic model (DM) rats received vitamin C (0.05 g/kg/day) or JMT [low-dosage (L), 0.44 g/kg/day; medium-dosage (M), 0.88 g/kg/day or high-dosage (H), 1.75 g/kg/day]. After 16 weeks, the mechanical pain threshold of the rats was evaluated. The expression of 8-hydroxy-deoxyguanosine (8-OHdG), nicotinamide adenine dinucleotide phosphate (NADPH) oxidase p22phox, B-cell lymphoma 2 (Bcl-2), caspase 3 and cleaved-poly(ADP-ribose) polymerase 1 (PARP-1) in the sciatic nerve tissues was measured using the reverse transcription-quantitative polymerase chain reaction, immunohistochemistry and western blotting. JMT had no effect on body weight and fasting blood glucose levels. Following treatment, the rats in the JMT groups had an improved pain threshold compared with the DM controls (JMT-L, 52.9±6.5 g; JMT-M, 74.7±9.3 g; and JMT-H, 61.7±2.0 g vs. DM control, 35.32±12.06 g; all P<0.01), while the threshold in the JMT-M rats was similar to that of normal controls (P>0.05). 8-OHdG and NADPH oxidase p22phox expression was significantly decreased in the three JMT groups compared with that in the DM controls (all P<0.05). Following JMT treatment, Bcl-2 levels were increased, while caspase 3 and cleaved-PARP-1 levels were decreased compared with those in the DM controls (all P<0.01). In conclusion, JMT may reduce DNA oxidative damage to the sciatic nerve in diabetic rats, as well as regulate genes involved in peripheral neuronal cell apoptosis, suggesting that JMT could be used to prevent or treat DPN in diabetic patients.
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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.
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Antioxidantes/administración & dosificación , Coptis/química , Diabetes Mellitus/tratamiento farmacológico , Medicamentos Herbarios Chinos/administración & dosificación , Animales , Diabetes Mellitus/metabolismo , Humanos , Peroxidación de Lípido/efectos de los fármacosRESUMEN
OBJECTIVE: To assess the efficacy and safety of Astragalus membranaceus Injection combined with conventional therapy in the treatment of viral myocarditis. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
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Astragalus propinquus/química , Medicamentos Herbarios Chinos/uso terapéutico , Miocarditis/tratamiento farmacológico , Miocarditis/virología , Ensayos Clínicos Controlados Aleatorios como Asunto , Medicamentos Herbarios Chinos/efectos adversos , Humanos , Inyecciones , Miocarditis/diagnóstico por imagen , Miocardio/enzimología , Miocardio/patología , Fitoterapia , Resultado del Tratamiento , UltrasonografíaRESUMEN
OBJECTIVE: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.
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Apoptosis/efectos de los fármacos , Medicamentos Herbarios Chinos/farmacología , Glucosa/farmacología , Células de Schwann/citología , Suero/metabolismo , Animales , Cápsulas , Caspasa 3/genética , Caspasa 3/metabolismo , Proliferación Celular/efectos de los fármacos , Forma de la Célula/efectos de los fármacos , Regulación de la Expresión Génica/efectos de los fármacos , Masculino , Proteínas Proto-Oncogénicas c-bcl-2/genética , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Ratas , Ratas Wistar , Proteínas S100/metabolismo , Células de Schwann/efectos de los fármacos , Células de Schwann/enzimologíaRESUMEN
OBJECTIVE: 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). METHODS: 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. RESULTS: 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. CONCLUSION: 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.
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Factor Neurotrófico Ciliar/metabolismo , Diabetes Mellitus Experimental/tratamiento farmacológico , Medicamentos Herbarios Chinos/uso terapéutico , Nervio Ciático/patología , Animales , Glucemia/efectos de los fármacos , Peso Corporal/efectos de los fármacos , Factor Neurotrófico Ciliar/genética , Diabetes Mellitus Experimental/patología , Medicamentos Herbarios Chinos/farmacología , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Masculino , ARN Mensajero/genética , ARN Mensajero/metabolismo , Ratas , Ratas Wistar , Nervio Ciático/efectos de los fármacos , Nervio Ciático/ultraestructuraRESUMEN
OBJECTIVE: To study the effects of Jinmaitong capsule on oxidative stress and cell apoptosis of dorsal root ganglion (DRG) in rats with diabetic peripheral neuropathy. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.