Huangqi Guizhi Wuwu Decoction for treating diabetic peripheral neuropathy：a meta-analysis of 16 randomized controlled trials

OBJECTIVE：This meta-analysis was performed to systematically assess the efficacy and safety of the Chinese herbal medicine Huangqi Guizhi Wuwu Decoction（HGWWD） for treating diabetic peripheral neuropathy.DATA SOURCES：Six electronic databases,including the Cochrane Library,MEDLINE database,Chinese Biomedical Database,Chinese National Knowledge Infrastructure Database,Chinese Science and Technique Journals Database,and the Wanfang Database,were search ed on the internet for randomized controlled trials published up until 1 December 2015.The search terms included ＂Chinese herbal medicine＂,＂diabetic peripheral neuropathy＂ and ＂randomized controlled trials＂ in Chinese and in English.DATA SELECTION：We included randomized controlled trials using HGWWD/modified HGWWD for the treatment group,without restriction for the control group.We assessed literature quality in accordance with the Cochrane Review Handbook.A random or a fixed effects model was used to analyze outcomes using Rev Man 5.2 software.OUTCOME MEASURES：The primary outcomes were changes in symptoms and nerve conduction velocities.The secondary outcomeswere fasting blood glucose and hemorheological indexes.RESULTS：Sixteen randomized controlled trials,with a total of 1,173 patients,were included.Meta-analysis revealed that the efficacy of HGWWD for diabetic peripheral neuropathy was significantly superior compared with the control treatment（i.e.,control group）（risk ratio = 0.36,95% confidence interval（CI）：0.29–0.46,Z =8.33,P 〈 0.00001） Compared with the control group,there was an increase in median motor nerve conduction velocity（mean difference（MD） = 3.46,95%CI：1.88–5.04,Z = 4.30,P 〈 0.01） and median sensory nerve conduction velocity（MD = 3.30,95%CI：2.04–4.56,Z = 5.14,P 〈 0.01）.There was also an increase in peroneal motor nerve conduction velocity（MD = 3.22,95%CI：2.45–3.98,Z = 8.21,P 〈 0.01） and peroneal sensory nerve conduction velocity（MD = 3.05,95%CI：2.01–4.09,Z = 5.75,P 〈 0.01） in the treatment groups.No significant difference in fasting blood glucose was found between the treatment groups and the control groups（MD =-0.12,95%CI：-0.42–0.19,Z = 0.76,P = 0.45）.Plasma viscosity was significantly decreased after treatment（MD =-0.11,95%CI：-0.21 to-0.02,Z = 2.30,P = 0.02）.No significant difference in fibrinogen was detectable（MD =-0.53,95%CI：-1.28–0.22,Z = 1.38,P = 0.17）.Four trials reported that treatment groups experienced no adverse reactions.Adverse events were not mentioned in the other 12 trials.No trial reported the incidence of complications,quality of life outcomes,or health economics.CONCLUSION：HGWWD treatment improves diabetic neurologic symptoms and ameliorates nerve conduction velocities.Our study suggests that HGWWD may have significant therapeutic efficacy for the treatment of diabetic peripheral neuropathy.However,the methodological quality of the randomized controlled trials was generally low.Larger and better-designed randomized controlled trials are required to more reliably assess the clinical effectiveness of HGWWD.

Clinical Study of Jiawei Huangqi Guizhi Wuwu Decoction (加味黄芪桂枝五物汤) in Preventing and Treating Peripheral Neuro-sensory Toxicity Caused by Oxaliplatin

Objective： To evaluate the efficacy of Jiawei Huangqi Guizhi Wuwu Decoction （加味黄芪桂枝五物汤, JHGWD） in treating neuro-sensory toxicity induced by oxaliplatin. Methods： A randomized controlled self-crossover trial was performed. Thirty-one patients were randomly divided into AB and BA groups. Patients in A cycle belonged to the treated group, who were treated with chemotherapy combined with oxaliplatin plus JHGWD. Patients in B cycle belonged to the control group and were treated with chemotherapy alone. The peripheral neuro-sensory toxicity was observed and analyzed. Results： The main neurotoxicity was cold-induced paresthesia after the use of oxaliplatin, which included hyperaesthesia, chill, anaesthesia in the extremities, electrified sensation, formication, foreign body sensation and pain that might be exacerbated by exposure to cold. Twenty patients （64.5 % ） suffered from neuro-sensory toxicity in the treated group and 27 cases （87.1% ） in the control group. Symptoms were more serious and lasted longer in the control group than those in the treated group （P〈0.01）. Conclusion： JHGWD could prevent and reduce the occurence and intensity of acute peripheral neuro-sensory toxicity caused by oxaliplatin.

Potential Mechanism of Huangqi Guizhi Wuwu Decoction for Cervical Spondylosis treatment based on Network Pharmacology

Objective:To study the potential mechanism of Huangqi Guizhi Wuwu Decoction in the treatment of cervical spondylosis based on the network pharmacological method,and to provide a basis for clinical application and pharmacological research.Methods:TCMSP search was used to screen the main active compounds and related action targets of Huangqi Guizhi Wuwu Decoction,the standard names of action targets were obtained through the Uniprot database,and the"drug-target"interaction network was constructed by using Cytoscape3.6.1 software.The related targets of cervical spondylosis were obtained by searching GeneCards,OMIM,DisGeNET,and CTD databases,and the disease targets and drug targets were mapped by the Venny platform,and the intersection genes of them were the potential targets for drug treatment of this disease.Then,the intersection genes were input into the STRING database and Cytoscape 3.6.1 software,and the protein-protein interactions(PPI)network of"drug-disease intersection targets"was constructed,and we screened the core targets.Finally,GO biological function analysis and KEGG signaling pathway analysis of core targets were carried out through the DAVID database.Results:According to the screening conditions,74 effective compounds and 138 drug action targets of Huangqi Guizhi Wuwu Decoction were obtained,12179 genes related to cervical spondylosis were obtained,and the Venny platform analysis obtained 105 intersecting targets.With visual network processing by Cytoscape software,33 core targets were obtained by analyzing and calculating the core target degree values,which were JUN,PTGS2,NR3C1,TNF,IL6,TP53,EGFR,VEGFA,NOS3,IL1B,and so on.GO analysis showed that there were 133 items(P<0.05),involving adrenergic receptor activation,neurotransmitter receptor activation,nuclear receptor activation,catecholamine binding,etc.KEGG analysis obtained a total of 139 pathways(P<0.05),involving IL-17 signaling pathway,and tumor necrosis factor signaling pathway,relaxin signaling pathway,AGE-RAGE signaling pathway of diabetic complications,fluid shear stress,and atherosclerosis.Conclusion:the active components in Huangqi Guizhi Wuwu decoction may act on the core targets such as JUN,PTGS2,NR3C1,TNF,IL6,TP53,VEGFA through IL-17 signal pathway,tumor necrosis factor signal pathway,and AGE-RAGE signal pathway of diabetic complications,and exert their therapeutic effects.The research results can provide a basis for future basic and clinical research.

Application of Huangqi Guizhi Wuwu Decoction in Orthopaedics and Traumatology

The Huangqi Guizhi Wuwu Decoction(HQGZWWT)is composed of Huangqi(Astragali Radix),Shaoyao(Paeoniae Radix Alba),Guizhi(Cinnamomi Ramulus),Shengjiang(Zingiberis Rhizoma Recens),and Dazao(Jujubae Fructus)which has various pharmacological anti-inflammatory,analgesic,antioxidant,antitumor,lipid-lowering,and immunity-regulating activities.It has certain advantages in the treatment of orthopaedic diseases,such as cervical spondylosis,scapulohumeral periarthritis,lumbar disc herniation,knee osteoarthritis,rheumatoid arthritis,myofascial pain syndrome,etc.,with outstanding clinical efficacy,few adverse reactions,and high patient compliance.However,modern pharmacological researches on the whole prescription of HQGZWWT are insufficient and the therapeutic targets are not clear which needs further exploration.Besides,this prescription cannot treat ll orthopaedic diseases,so we should adhere to the thinking of four diagnostics in traditional Chinese medicine(TCM),select prescriptions based on syndrome differentiation,closely follow the pathogenesis,innovate and expand its scope of application,reflect the application advantages of this prescription in orthopaedics and traumatology and improve the total clinical efficiency.

Huangqi Guizhi Wuwu Decoction suppresses inflammation and bone destruction in collagen-induced arthritis mice

Objective: Rheumatoid arthritis(RA) is a chronic inflammatory and destructive arthritis, characterized by inflammatory infiltration and bone destruction. Huangqi Guizhi Wuwu Decoction(HGWD) is traditional Chinese medicine, which has been applied in the treatment of RA in clinical. The aim of this study was to investigate the therapeutic effect of HGWD on collagen-induced arthritis(CIA) mouse model.Methods: DBA/1J female mice were used to establish the collagen-induced arthritis(CIA) model. HGWD was administered intragastrically once a day for four weeks starting on the 22nd day after the first immunization. The body weight, hind paw thickness and clinical score were measured every five days. Gait analysis, histopathological staining, enzyme-linked immunosorbent assay(ELISA), ultrasound imaging and micro-computed tomography imaging were performed to determine the effects of HGWD treatment on inflammation and bone structure in this model. Moreover, Real-time PCR and Western blot analysis were used to detect inflammatory factors m RNA and protein levels after HGWD intervention in RAW264.7 cells.Results: HGWD attenuated symptoms of arthritis, suppressed inflammatory synovium area and the serum levels of inflammatory factors, inhibited joint space enlargement in the knee and ankle joints,reduced numbers of osteoclasts, protected bone destruction, as well as improved motor function.HGWD decreased the expression of m RNA for inflammatory factors and the protein expression levels of p-NF-ΚB and IL-17.Conclusion: These results suggested that HGWD suppresses inflammation, attenuates bone erosion and maintains motor function in collagen-induced arthritis mice.

Simultaneous determination of two bioactive components of Huangqi Guizhi Wuwu Decoction in rat plasma using UPLC-MS/MS and its application to a pharmacokinetic study

A rapid, sensitive and selective UPLC-MS/MS method was developed to determine paeoniflorin and astragaloside IV, This method was validated via a pharmacokinetic study using rat plasma. The internal standard was clarithromycin. A simple one-step deproteinization procedure was used to prepare plasma samples. Separation was achieved on a CAPCELL CORE ADME CI8 column with a gradient mobile phase consisting of solution A （water containing 0.1% formic acid） and solution B （acetonitrile） at a flow rate of 0.3 mL/min. Multiple reaction monitoring （MRM） was used with an electrospray ionization source （ESI） in positive mode. A good linear response was observed within the ranges of 0.01 to 5.00 ~g/mL for paeoniflorin and 0.000l to 0.05 ~tg/mL for astragaloside IV. The accuracy （RE） was within the range of-3.5% to 6.3%, and the intra- and inter-day precisions （RSD） were within 14.2%. The extraction recoveries were all above 78.9%. The pharmacokinetic study of the two analytes in rats after oral administration of Huangqi Guizhi Wuwu Decoction （HGWD） was successfully completed through this method. The method develooed in this studv will fill a gap in oharmacokinetic studies of HGWD.