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The AMPK/PGC-1α pathway-mediated mitochondrial dysfunction has been supposed to play a crucial role in pathogenesis of diabetic peripheral neuropathy (DPN). The present study investigated the neuroprotective potential of quercetin, a natural AMPK activator. Streptozotocin (STZ)-induced diabetic rats that developed DPN phenotype were orally administrated with quercetin (30 and 60 mg/kg per day) for 6 weeks. The morphologic changes in the sciatic nerves (SN), the pathological structure of neurons in dorsal root ganglion (DRG), and the expressions of myelin proteins were assessed. The ATP content and the mitochondrial ultrastructure were measured. Furthermore, key proteins in the AMPK/PGC-1α pathway were determined. As a result, quercetin administration at both doses improved the paw withdrawal threshold, nerve conduction velocity, and the pathologic changes in SN and DRG of DPN rats. The expressions of myelin basic protein and myelin protein zero were also increased by quercetin. The oxidative stress, decreased ATP generation, and morphological changes of mitochondria were corrected by quercetin. In vitro study found that quercetin treatment significantly decreased the high-glucose-induced generation of reactive oxygen species, as well as attenuated the mitochondrial morphologic injuries and oxidative DNA damages of RSC96 cells. Quercetin treatment promoted the expressions of phosphorylated AMPK, PGC-1α, SIRT1, NRF1, and TFAM under hyperglycemic state in vivo and in vitro. This study revealed that the neuroprotective effect of quercetin was mainly related to mitochondrial protection by activation of the AMPK/PGC-1α pathway for the first time and proved quercetin as a potential therapeutic agent in the management of diabetic neuropathy.

ObjectiveTo investigate the association between serum adiponectin levels and diabetic peripheral neuropathy (DPN) in Chinese type 2 diabetes (T2D) patients.Design and MethodsTwo hundred nineteen T2D patients aged 40–79 years were divided into two groups according to whether they had DPN. The systemic levels of five biomarkers were measured using a human adipokine multiplexed bead-based immunoassay. Diabetic peripheral neuropathy diagnostic criteria included both common DPN symptoms and neurological screening tests.ResultsMost features of DPN (n=98) and non-DPN patients (n=121) are similar, but the DPN patients were slightly older, had longer diabetes duration, higher hemoglobin (Hb) A1c, lower estimated glomerular filtration rates (eGFR), less exercise, and used lipid-lowering drugs more often. Serum adiponectin levels of DPN patients were higher than that of non-DPN patients (8.13 vs. 9.63 mg/ml, P = 0.004). Serum adiponectin levels were positively associated with DPN after adjusting for age, gender, body mass index, hypertension, HbA1c, alcohol intake, smoking status, physical activity, log-transformed low density lipoprotein cholesterol, lipid-lowering drug usage, eGFR, and diabetes duration {odds ratio (OR) 1.72 [95% confidence interval (CI) 1.02-2.89], P = 0.041}. The OR refers to a doubling in biomarkers.ConclusionsSerum adiponectin levels were higher in DPN patients compared to non‑DPN patients in this Chinese T2D population. Serum adiponectin levels were positively associated with DPN presence, independent of multiple confounders.

Background. Numerous studies suggested that chronic pain and depression were closely related and widespread in the population. When patients have symptoms of chronic pain and depression, the corresponding treatment will become difficult. Acupuncture, a unique therapeutic method of traditional Chinese medicine, has been reported to potentially serve as an alternative treatment for patients with comorbid chronic pain and depression by many research studies. Methods. A comprehensive search was conducted through the online database, including the Cochrane Library, PubMed, EMBASE, SinoMed, CNKI, and Wanfang database. Trials were RCTs published in the English or Chinese language, recruiting participants with chronic pain and depression comorbidity. The primary outcomes were the Visual Analogue Scale (VAS) and Hamilton Depression Scale (HAMD). Statistical analyses were conducted using Review Manager 5.3. Each trail was quality appraised with the five-point Jadad Score. Results. 7 eligible RCTs involving 535 patients were included. Better therapeutic effect and safety could be observed in the experimental group compared with the control group. There was a significant decrease in the VAS (mean difference (MD) = −0.68 (−1.24, −0.12), P=0.02) and HAMD (MD = −2.18 (−3.09, −1.26), P

To investigate effect of icariin on apoptosis in hippocampal neurons cultured in high glucose, and the possible mechanism behind the action.Hippocampus was obtained from newborn 24 h Sprague-Dawley rats and then primarily cultured. Then hippocampal neurons were divided into normal control group, high glucose group, icariin group, icariin + protein kinase B (Akt) inhibitor group and Akt agonist group. After each group was cultured in different conditioned medium for 72 h, we detected the apoptosis of neurons with flow cytometry, and the expression of Akt, p-Akt, B-cell lymphoma-2 (Bcl-2) and Bcl-2 associated X protein (Bax) with western blot.Compared with the normal control group, the apoptosis rate of hippocampal neurons increased significantly (P0.01), and p-Akt/Akt and Bcl-2/Bax decreased significantly (P0.01) in high glucose group. Compared with the high glucose group, the apoptosis rate of hippocampal neurons decreased significantly (P0.01), and p-Akt/Akt and Bcl-2/Bax increased significantly (P0.05)in icariin group and Akt agonist group. Compared with the icariin + Akt inhibitor group, the apoptosis rate of hippocampal neurons decreased significantly (P0.01), and p-Akt/Akt and Bcl-2/Bax increased significantly (P0.01) in icariin group.Icariin could reduce the apoptosis of neurons cultured in high glucose, which may be achieved by increasing the phosphorylation of Akt protein in Akt signal pathway, then increasing the expression of Bcl-2 and inhibiting the expression of Bax.

Objective To investigate the neuroprotective effect of puerarin on rat hippocampal neurons cultured in high glucose medium, and to examine the role of the p38 mitogen activated protein kinase (p38 MAPK) and c-Jun N-terminal kinase (JNK) signaling pathways in this effect. Methods Primary cultures of hippocampal neurons were prepared from newborn Sprague Dawley rats. Neuron-specific enolase immunocytochemistry was used to identify neurons. The neurons were cultured with normal medium (control group) or with high-glucose medium (high-glucose group), and puerarin (puerarin group), a p38 MAPK inhibitor (SB239063; p38 MAPK inhibitor group) or a JNK inhibitor (SP600125; JNK inhibitor group) were added. After 72 h of treatment, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay was performed to detect apoptosis, and western blotting was used to assess protein levels of p-p38, p38, p-JNK and JNK. Results In the high-glucose group, the neuronal apoptosis rate and the p-p38/p38 and p-JNK/JNK ratios were higher than in the control group. The p38 MAPK and JNK inhibitors prevented this increase in the apoptosis rate. The apoptosis rates in the puerarin group, the p38 MAPK inhibitor group and the JNK inhibitor group were significantly decreased compared with the high-glucose group. Moreover, protein levels of p-p38 and p-JNK were significantly reduced, and the p-p38/p38 and p-JNK/JNK ratios were decreased in the puerarin group compared with the high-glucose group. In addition, compared with the high-glucose group, p-p38 levels and the p-p38/p38 ratio were reduced in the p38 MAPK inhibitor group, and p-JNK levels and the p-JNK/JNK ratio were decreased in the JNK inhibitor group. Conclusion Puerarin attenuates neuronal apoptosis induced by high glucose by reducing the phosphorylation of p38 and JNK.

Background. Diabetic cognitive impairment (DCI), a serious complication of diabetes mellitus (DM), is gaining more acceptance and attention. The learning and memory function of diabetics always decreases. Traditional Chinese medicine (TCM) has been demonstrated to be effective in treating the symptoms in China, and thereinto Chinese medicinal herbs (CMH) are the most widely used. The objective of the present study was to review and analyze the existing data about reducing the symptoms in CMH treatment for DCI. Methods. Electronic literature databases (PubMed, EMBASE, CNKI, SinoMed, and Wan fang) were searched for randomized controlled trials conducted in China, comparing CMH with western medicines in the treatment of DCI, up to April 1, 2018. We applied standard meta-analytic techniques to analyze data from papers that reached acceptable criteria. Result. Nine randomized controlled trials (n = 576) on CMH were included. We found moderate evidence that CMH used alone or in combination with western medicines was more effective than western medicines alone in reliving the symptoms for DCI (total effective rate, odds radio (OR) = 4.64 (2.60, 8.29), and 95% confidence interval, P

The problem of cognitive impairment resulting from diabetes is gaining more acceptance and attention. Both type 1 and type 2 diabetes mellitus have been proved to be associated with reduced performance on numerous domains of cognitive function. Although the exact mechanisms of cognitive impairments in diabetes have not been completely understood, hyperglycemia and insulin resistance seem to play significant roles. And other possible risk factors such as hypoglycemia, insulin deficiency, vascular risk factors, hyperactive HPA axis, depression, and altered neurotransmitters will also be examined. In the meanwhile, this review analyzed the role of the active ingredient of Chinese herbal medicine in the treatment of diabetes cognitive impairments.