Treatment of Traditional Chinese Medicine for Diabetic Peripheral Neuropathy Based on Mitochondrial Quality Control： A Review / 中国实验方剂学杂志

Diabetic peripheral neuropathy（DPN） is a neurodegenerative disease of diabetes mellitus involving peripheral nervous system damage， which is characterized by axonal degenerative necrosis， Schwann cell apoptosis and demyelination of nerve myelin sheath as the main pathological features， this disease is highly prevalent and is a major cause of disability in diabetic patients. Currently， the pathogenesis of DPN may be related to oxidative stress， inflammatory response， metabolic abnormality， and microcirculation disorder. The treatment of DPN in modern medicine mainly starts from controlling blood glucose， nourishing nerves and improving microcirculation， which can only alleviate the clinical symptoms of patients， and it is difficult to fundamentally improve the pathological damage of peripheral nerves. Mitochondrial quality control refers to the physiological mechanisms that can maintain the morphology and functional homeostasis of mitochondria， including mitochondrial biogenesis， mitochondrial dynamics， mitochondrial oxidative stress and mitochondrial autophagy， and abnormal changes of which may cause damage to peripheral nerves. After reviewing the literature， it was found that traditional Chinese medicine（TCM） can improve the low level of mitochondrial biogenesis in DPN， maintain the balance of mitochondrial dynamics， inhibit mitochondrial oxidative stress and mitochondrial autophagy， and delay apoptosis of Schwann cells and neural axon damage， which has obvious effects on the treatment of DPN. With the deepening of research， mitochondrial quality control may become one of the potential targets for the research of new anti-DPN drugs， therefore， this paper summarized the research progress of TCM in treating DPN based on four aspects of mitochondrial quality control， with the aim of providing a theoretical research basis for the discovery of new drugs.

Effect of Huangqi Guizhi Wuwutang on Diabetic Peripheral Neuropathy in MKR Mice via Regulating Endoplasmic Reticulum Stress / 中国实验方剂学杂志

ObjectiveTo investigate the mechanism of Huangqi Guizhi Wuwutang （HQGZWWT） in the treatment of diabetic peripheral neuropathy （DPN） in MKR mice via regulating endoplasmic reticulum （ER） stress. MethodThirty-two 8-week-old MKR mice （half were male and half were female） were fed with a high-fat diet for four weeks， and then 1% streptozotocin （STZ） was injected intraperitoneally for five days. After the blood glucose was stabilized， the mice were housed in the cage covered with ice bags for another one hour stimulation per day for four weeks. Mice with fasting blood glucose （FBG） value ≥11.1 mmol·L-1 were randomly divided into model group ， Huangqi Guizhi Wuwutang in original dosage group （30 g·kg-1·d-1）， Huangqi Guizhi Wuwutang in formula dosage group （6.25 g·kg-1·d-1）， and positive drug group （mecobalamin tablets， 0.17 mg·kg-1·d-1）. Another eight MKR mice of the same age were set as blank group and eight FVB mice were normal group. After four weeks of intragastric administration in each group， the change in FBG was tested， and hematoxylin and eosin （HE） staining and transmission electron microscope were used for observing the morphology of sciatic nerve tissue. In addition， the expression of c-Jun N-terminal kinase （JNK）， phosphorylated c-Jun N-terminal kinase （p-JNK） and inositol requiring enzyme 1α （IRE1α） proteins was determined by immunohistochemical test and Western blot （WB）. ResultCompared with the conditions in the normal group and blank group， the time of paw withdrawal， paw licking and tail flick in the model group was shortened （P<0.01）， and the conduction velocity of sciatic nerve was decreased （P<0.01）. Compared with the conditions in the model group， the behavioral and functional indicators were improved by HQGZWWT （P<0.05，P<0.01）. The immunohistochemical test revealed the JNK expression was elevated in the model group compared with the conditions in the normal group and blank group （P<0.05）， while that was lowered by HQGZWWT compared with the condition in the model group （P<0.05）. However， there was no difference among the treatment groups. According to the WB， the expression of IRE1α and p-JNK in the model group was enhanced compared with the conditions in the normal group and blank group （P<0.05，P<0.01）， while that was decreased by HQGZWWT compared with the condition in the model group （P<0.05，P<0.01）. No difference was observed between the HQGZWWTO and HQGZWWTF groups. ConclusionHQGZWWT can improve the neurophysiological function and pathological damage of sciatic nerve， which may be related to its delaying the ER stress response of sciatic nerve.

Effect of Modified Huangqi Biejiatang Combined with Auricular Acupressure on Diabetic Peripheral Neuropathy of Qi-Yin Deficiency Syndrome and Serum MyD88/IκB Signaling Pathway / 中国实验方剂学杂志

Objective:To observe the effects of modified Huangqi Biejiatang combined with auricular acupressure on diabetic peripheral neuropathy （DPN） due to Qi and Yin deficiency and serum myeloid differentiation factor 88/inhibitor of nuclear factor-<italic>κ</italic>B （MyD88/I<italic>κ</italic>B） signaling pathway. Method:One hundred and forty cases were randomly divided into an observation group （<italic>n</italic>=70） and a control group （<italic>n</italic>=70）. In addition to routine treatments like dietary intervention and the regulation of fasting blood glucose （FBG） and blood pressure， the modified Huangqi Biejiatang combined with auricular acupressure was further provided in the observation group， while mecobalamine was administered in the control group. After four-week intervention， the toronto clinical scoring system （TCSS） score， traditional Chinese medicine （TCM） syndrome score， the conduction velocities of motor and sensory nerves （median nerve， common peroneal nerve， tibial nerve， and ulnar nerve）， glucose metabolism indexes ［fasting plasma glucose （FPG）， 2 h postprandial blood glucose （2 h PG）， and hemoglobin A1c （HbA1c）］， intestinal genera （<italic>Clostridium</italic>， <italic>Prauserella</italic>， <italic>Bacteroides</italic>， and <italic>Faecalibacterium</italic>）， as well as the serum MyD88， I<italic>κ</italic>B<italic>α</italic>， and phosphorylated I<italic>κ</italic>B<italic>α </italic>（p-I<italic>κ</italic>B<italic>α</italic>） levels in the MyD88/I<italic>κ</italic>B signaling pathway before and after treatment were observed in the two groups， for comparing their clinical efficacy and safety. Result:The total effective rate of the observation group was 85.3% （58/68）， which was higher than 48.5% （32/66） of the control group （<italic>χ</italic>²=6.143， <italic>P</italic><0.05）. The comparison with the control group revealed that the scores of TCSS and TCM syndrome， the levels of FPG， 2 h PG， HbA1c， MyD88， and p-I<italic>κ</italic>B<italic>α</italic>， as well as the abundances of <italic>Clostridium</italic> and <italic>Prauserella</italic> in the observation group were decreased （<italic>P</italic><0.05）， while the conduction velocities of motor and sensory nerves （median nerve， common peroneal nerve， tibial nerve， and ulnar nerve） were significantly accelerated （<italic>P</italic><0.05）. Besides， the abundances of <italic>Bacteroides</italic> and <italic>Faecalibacterium</italic> and I<italic>κ</italic>B<italic>α</italic> level were significantly elevated （<italic>P</italic><0.05）. The incidence of adverse reactions in the observation group was 1.5% （1/68）， lower than 12.1% （8/66） in the control group （<italic>χ</italic>²=4.328， <italic>P</italic><0.05）. Conclusion:The modified Huangqi Biejiatang combined with auricular acupressure alleviates DPN due to Qi and Yin deficiency， which may be attributed to the regulation of serum MyD88/I<italic>κ</italic>B signaling pathway.

Analysis on Medication Rules of Traditional Chinese Medicine for Treatment of Diabetic Peripheral Neuropathy Based on Clinical Literature / 中国实验方剂学杂志

Objective:To investigate the medication rules of traditional Chinese medicine (TCM) for the treatment of diabetic peripheral neuropathy (DPN).Method:The literature published in China Knowledge Resource Integrated Database (CNKI), Wanfang Database, China Biomedical Literature Service System (SinoMed), VIP Database and PubMeb from 2008 to 2019 were retrieved by setting the topics of diabetic peripheral neuropathy and TCM. After screening, a database was established to analyze the medication rules (efficacy, frequency, flavor and meridian tropism, common couplet medicinals and core medicines) of TCM by frequency statistics, association rules and data statistical methods of constructing complex networks.Result:A total of 461 papers for treatment of DPN were included in this study, including 275 kinds of TCM and a total frequency of 6 361 times. Astragali Radix had the highest frequency. Among all kinds of medicinal materials, activating blood circulation and removing stasis was the most commonly used medicine, followed by Qi-invigorating medicine. Flavor of medicines was mainly sugariness and warm, and most of their meridian tropism was liver meridian. After the analysis by association rules, the couplet medicinals with the highest support was Astragali Radix-Angelicae Sinensis Radix. The core medicines obtained by complex network analysis were Astragali Radix, Angelicae Sinensis Radix, Chuanxiong Rhizoma, Spatholobi Caulis, Cinnamomi Ramulus, Carthami Flos, Pheretima, Paeoniae Radix Rubra, Salviae Miltiorrhizae Radix et Rhizoma and Persicae Semen.Conclusion:This study comprehensively analyzes the medication rules of TCM clinical treatment of DPN. The main treatment methods of TCM for DPN are invigorating Qi and blood, activating blood circulation and removing stasis, activating meridians to stop pain, which can provide guidance for the TCM clinical use and new Chinese medicines research and development of DPN.

Effect of Huangqi Guizhi Wuwutang on AGEs/RAGE/NF-κB Signaling Pathway in Diabetic Peripheral Neuropathy Rats / 中国实验方剂学杂志

Objective:To study the effect of Huangqi Guizhi Wuwutang on receptor of advanced glycation end products(AGEs)/advanced glycation endproducts (RAGE)/nuclear transcription factor-kappa B p65 (NF-κB p65) signaling pathway in the diabetic peripheral neuropathy rats through an animal modeling experiment, and discuss the mechanism of Huangqi Guizhi Wuwutang in alleviating diabetic peripheral neuropathy. Method:Rat model of diabetic peripheral neuropathy was established by high-fat diet and intraperitoneal injection with streptozotocin (STZ). After successful modeling, Huangqi Guizhi Wuwutang intervention began in the fifth week. The patients in high-dose group (19.40 g∙kg-1∙d-1), middle-dose group (4.85 g∙kg-1∙d-1) and low-dose group (2.43 g∙kg-1∙d-1) were given by gavage continuously for 12 weeks. The western medicine control group was given 25 mg∙kg-1∙d-1 by gavage. After the experiment, serum interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) were detected by enzyme-linked immunosorbent assay (ELISA). Real-time fluorescent quantitative polymerase chain reaction (Real-time PCR) was used to detect RAGE and NF-κB p65 mRNA expressions in sciatic nerve tissue. The expressions of RAGE, NF-κB and phosphorylation(p)-NF-κB p65 proteins in sciatic nerve tissues were detected by Western blot (WB). Result:Compared with the normal group, serum IL-1β and TNF-α protein levels, RAGE mRNA and NF-κB p65 mRNA levels, RAGE protein, NF-κB p65 protein and p-NF-κB p65 protein levels were significantly increased in the model group (P<0.01), the ratio of p-NF-κB p65 to NF-κB p65 was increased, and the phosphorylation of NF-κB p65 was enhanced (P<0.01). After the intervention of Huangqi Guizhi Wuwutang, compared with the model group, serum IL-1β and TNF-α protein levels, RAGE and NF-κB p65 mRNA levels, RAGE protein, NF-κB p65 protein and p-NF-κB p65 protein levels were all decreased (P<0.01), the ratio of p-NF-κB p65 to NF-κB p65 was decreased in high-dose group (P<0.01). The effect was obvious with the increase of dose of astragalus cassia twig. Conclusion:Huangqi Guizhi Wuwutang can alleviate diabetic peripheral neuropathy, and its mechanism may be related to blocking the expression of RAGE on tissue cell surface in AGEs/RAGE/NF-κB signaling pathway, inhibiting the activation of NF-κB and inducing TNF-α triggered oxidative stress and excessive inflammatory response, so as to avoid cell damage and dysfunction.

Discussion of acupuncture for diabetic peripheral neuropathy based on blood stasis theory / 中国针灸

Based on the understanding of TCM and western medicine on diabetes mellitus (DM) and diabetic peripheral neuropathy (DPN), the relationship between DPN pathogenesis and blood stasis of TCM is discussed from the perspective of modern medicine. It is indicated blood stasis is the key pathogenesis to DPN, and a two-step acupuncture treatment of DPN from the theory of blood stasis is proposed. The first step is to analyze the pathogenesis of blood stasis, which could block the progress of the disease and diminish the symptoms. The second step is to apply acupuncture for pathological result of blood stasis by following the principle of, as a result, the purpose of treating both symptoms and root cause is achieved.

Rules of acupoint selection for diabetic peripheral neuropathy based on data mining technology / 中国针灸

The rules of acupoint selection for diabetic peripheral neuropathy (DPN) based on data mining technology are analyzed. Literature regarding acupuncture for DPN published in core journals from January of 2005 to December of 2014 was retrieved in CNKI database and Wanfang database to establish a database of acupuncture prescriptions, which were included into the TCM Inheritance Platform software (Version 2.0). The data mining methods, including rule analysis, revised mutual information, etc. were applied to analyze the acupuncture prescriptions and the frequency of each acupoint was calculated. The results indicated Zusanli (ST 36), Sanyinjiao (SP 6), Quchi (LI 11), Yanglingquan (GB 34), Hegu (LI 4), Shenshu (BL 23), etc. were mostly selected in acupuncture for DPN; in addition, 19 acupoint combinations were acquired. It is concluded that acupuncture for DPN applied reinforcing methods as main rules, accompanied with promoting blood andcirculation; the acupoint selection focused onmeridians and back-points.

Association between serum uric acid level and diabetic peripheral neuropathy in middle-aged and elderly ;population / 中国糖尿病杂志

Objective To investigate the association between serum uric acid (SUA ) level and diabetic peripheral neuropathy (DPN ) in middle‐aged and elderly population. Methods A total of 207 middle‐aged and elderly patients with T2DM were enrolled in this study. All the subjects were divided into two groups:T2DM only group and DPN group. The DPN group was further divided into three subgroups (mild ,moderate and severe group) according to TCSS score. Pearson correlation analysis was used to evaluate each index ,and binary logistic regression was used for statistical analysis of risk factors for DPN.Results SBP ,UACR ,BUN ,Scr ,TC ,LDL‐C and SUA were significantly higher in DPN group than in T2DM group. SUA were significantly increased together with the increase of the severity of DPN [(279.66 ± 56.53)vs(308.93 ± 52.96)vs(330.24 ± 48.79) μmol/L](P<0.05). Conclusion SUA level is an risk factor for the development of DPN in the middle‐aged and elders with T2DM. SUA is positively correlated with the severity of DPN.

The changes of serum stromal cell-derived factor-1α in patients with diabetic peripheral neuropathy and the ;influence of mouse nerve growth factor / 中国糖尿病杂志

Objective To investigate the changes of serum stromal cell‐derived factor‐1α (SDF‐1α) in patients with diabetic peripheral neuropathy (DPN) and the influence of mouse never growth factor (MNGF) on the levels of serum SDF‐1α. Methods 180 patients with type 2 diabetes (T2DM ) were divided into T2DM with DPN (DPN group ,n=92) and T2DM without DPN (T2DM group ,n=88). 90 healthy people were select as normal control (NC group). DPN group was divided into 47 cases of MNGF treatment (A) subgroup and 45 cases of basic treatment (B) subgroup. The levels of serum SDF‐1αwere measured using ELISA method. The relationships between the levels of serum SDF‐1αand SOD ,TGF‐β1 , hsC‐RP ,and GAP‐43 were analyzed. After treatment ,the levels of serum SDF‐1α in A and B subgroups were compared. Results Compared with NC group [(0.91 ± 0.37)μg/L] ,the levels of serum SDF‐1αin T2DM and DPN group were higher [(2.58 ± 0.58) μg/L and(1.71 ± 0.43)μg/L ,respectively ,P0.05] .Multiple stepwise regression analysis showed that HbA1c ,hsC‐RP and PSCV were the independent factors related with the levels of SDF‐1αin DPN patients. Conclusion The levels of serum SDF‐1αin DPN patients are lower than in T2DM patients without DPN. MNGF may increase the level of serum SDF‐1α.

Relationship between HbA1 c and CIMT,carotid arterial stiffness of diabetic peripheral neuropathy patients / 中国糖尿病杂志

Objective To explore the relationship between HbA1 c and carotid artery intima‐media thickness (CIMT) ,carotid arterial stiffness in diabetic patients with peripheral neuropathy. Methods A total of 220 subjects were enrolled in this study and divided into three groups:T2DM group (n=60) ,DPN group (n=100) ,and healthy individuals as NC group (n=60). Serum HbA1c ,CIMT and carotid arterial stiffness were measured. Results HbA1c [(8.62 ± 2.71)% ] ,CIMT [(1.01 ± 0.11)mm] and carotid arterial stiffness [(827.6 ± 123.7)]was significantly higher in DPN group than in NC group [(4.20 ± 0.47)% ,(0.70 ± 0.07) mm ,(521.2 ± 89.3)] and T2DM group [(7.95 ± 1.98) % ,(0.81 ± 0.09) mm , (629.3 ± 113.5)] respectively (P< 0.05).The duration was significantly longer in DPN group than in T2DM group(P<0.05). CIMT [(1.11 ± 0.09)mm] and arotid arterial stiffness [(901.5 ± 241.5)] was higher in patients with HbA1 c≥10.0% than in patients with HbA1 c between 8.0% ~10.0% [(0.94 ± 0.07)mm ,(724.5 ± 159.9)] and patients with HbA1c between 7.0% ~ 8.0% [(0.73 ± 0.06)mm , (574.1 ± 145.3 )] respectively ( P< 0.05 ).Association analysis showed that HbA1 c had a positive correlation with CIMT and carotid arterial stiffness (r= 0.107 ,0.213 ,P< 0.05). Conclusion CIMT and carotid stiffness are positively correlated with HbA1 c in DPN patients.HbA1 c is a risk factor for CIM T and carotid stiffness.

The progression on the research of haem oxygenase-1 and diabetic peripheral neuropathy / 中国糖尿病杂志

[Summary] The pathogenesis of diabetic peripheral neuropathy (DPN ) is the result of complex multiple concurrent pathogenic factors ,among which oxidative stress and inflammation play important roles. Multiple data have indicated that haem oxygenase‐1 (HO‐1) and its degradation products products possess the functions of anti‐oxidation ,anti‐inflammation ,anti‐apoptosis and pro‐angiogenesis ,which now becomes a new target for the treatment of DPN. We will briefly review the progression on the research of HO‐1 and DPN.

Study on differentiation of symptoms and signs and treatment in diabetic peripheral neuropathy / 中华中医药杂志

The pathogenesy of diabetic peripheral neuropathy(DPN) is approached according to collaterals diseases theory in this study,indicated that defi ciency of both vital energy and yin is the chief pathologic foundation and obstruction of collaterals by blood stasis and phlegm is the critical element in DPN.Furthermore,highlight of differentiation of symptoms and signs,therapeutic principle and diagnosis and treatment based on differentiation are illuminated.This study has supplied a new idea for precaution and treatment of DPN.

A comparative study of motor conduction velocity and F-wave parameters between diabetes mellitus and healthy subjects / 中国糖尿病杂志

0 1). (4)75 2% of all the patients in DM group showed one or more abnormalities in MCV or F wave parameters, and electrophysiological abnormalitis correlated with, or precede to clinical findings in 175 of 190 patients (92 1%). Conclusion MCV and F wave parameters are sensitive measures for detection of DPN. Among these parameters, FwPL, F MIPL from all the four nerves are the most sensitive. To improve diagnostic accuracy, all the MCV and F wave parameters recorded should be considered.

Effects of puerar in injection on diabetic peripheral neuropathy / 中国糖尿病杂志

ObjectiveTo investigate the effects of puerar in injection on the diabetic preipheral neuropathy (DPN).MethodsComparing sixty-six cases in puerar treat group with twenty-two cases in mecobalamin control group.And observing the effects of puerar in injection on the electromyo graphy,FBG,HbAlc,hemorheology and erythrocyte polyol.ResultsMarked effective rate:51.51% (treat group);22.72% (control group) (P005);HbA1c decreased markedly (P<001);hemorheology improved evidently;erythrocyte polyol decreased conspicuously (P<001).ConclusionPuerar in injection has a good effect in DPN remedy.