Effectiveness and safety of traditional Chinese medicine decoction for diabetic gastroparesis:A network meta-analysis

BACKGROUND Diabetic gastroparesis(DGP)is a prevalent complication of diabetes that impairs people's quality of life and places a significant financial burden on them.The gastrointestinal symptoms of DGP patients can be improved by several Traditional Chinese Medicine(TCM)decoctions that have been shown to be effective in treating the disease.There are still many unanswered questions regarding the identification of appropriate therapeutic agents for the treatment of DGP in clinical practice.AIM To analyze the efficacy of several TCM decoctions in the treatment of DGP using Bayesian network meta-analysis for reference.METHODS PubMed,EMBASE,Cochrane Library,Web of Science,China National Knowledge Infrastructure,The China Biology Medicine DVD,Wanfang,and CQVIP were searched from inception to September 17,2022,to collect randomized controlled trials(RCTs)about TCM decoctions for DGP.Clinical effects and symptom scores were the primary outcomes.Additionally,we assessed motilin(MOT),somatostatin(SS),gastrin(GAS),gastric emptying rate,gastric emptying time,and adverse drug events as secondary outcomes.RESULTS A total of 67 eligible RCTs involving 4790 DGP patients and 7 TCM decoctions were included.The results of network meta-analysis(NMA)and surface under the cumulative ranking curve showed that with western medicine(WM)as a common control,the Banxia Xiexin Decoction(BXXD)+WM was most effective in clinical effects and enhancing early satiety scores;the Simo decoction(SMD)+WM was most effective in improving nausea and vomiting scores and anorexia scores,bloating scores;the Chaishao Liujunzi Decoction(CSLJD)was most effective in MOT,the Zhishi Xiaopi Decoction(ZSXPD)was most effective in SS and upgrading emptying rate;the Jianpi Xiaozhi Decoction was most effective in GAS;the CSLJD+WM was most effective in improving gastric emptying time.CONCLUSION These NMA results suggest that the BXXD+WM and SMD+WM may be one of the potential optimal treatments.Due to various limitations,further large-sample,double-blind,multi-center randomized RCTs are needed.

Xiangshaliujunzi Decoction for the treatment of diabetic gastroparesis: A systematic review

AIM: To assess the current clinical evidence of the effectiveness of Xiangshaliujunzi Decoction (XSLJZD) for the treatment of diabetic gastroparesis (DGP).

Combination of symptoms, syndrome and disease: Treatment of refractory diabetic gastroparesis

AIM: To assess effect of combination of symptoms, syndrome and disease on treatment of diabetic gastroparesis with severe nausea and vomiting.

Treatment of refractory diabetic gastroparesis: Western medicine and traditional Chinese medicine therapies

Refractory diabetic gastroparesis(DGP),a disorder that occurs in both type 1 and type 2 diabetics,is associated with severe symptoms,such as nausea and vomiting,and results in an economic burden on the health care system.In this article,the basic characteristics of refractory DGP are reviewed,followed by a discussion of therapeutic modalities,which encompasses the definitions and clinical manifestations,pathogenesis,diagnosis,and therapeutic efficacy evaluation of refractory DGP.The diagnostic standards assumed in this study are those set forth in the published literature due to the absence of recognized diagnosis criteria that have been assessed by an international organization.The therapeutic modalities for refractory DGP are as follows:drug therapy,nutritional support,gastricelectrical stimulation,pyloric botulinum toxin injection,endoscopic or surgical therapy,and traditional Chinese treatment.The therapeutic modalities may be used alone or in combination.The use of traditional Chinese treatments is prevalent in China.The effectiveness of these therapies appears to be supported by preliminary evidence and clinical experience,although the mechanisms that underlie these effects will require further research.The purpose of this article is to explore the potential of combined Western and traditional Chinese medicine treatment methods for improved patient outcomes in refractory DGP.

Effect of Electroacupuncture on Platelet-derived Growth Factor and the Ultrastructure of Mitochondria in Rats with Diabetic Gastroparesis

Objective To observe the effect of electroacupuncture(EA)at the pressure points Zu San Li(ST36),San Yin Jiao(SP6)and Liang Men(ST21)on platelet-derived growth factor(PDGF)and the ultrastructure of mitochondria in rats with diabetic gastroparesis(DGP).Methods Sixty Sprague Dawley(SD)rats were randomly separated into a normal control group(NC,n=10)and a modeling group(n=50).Rats in the modeling group received an injection of 2%streptozotocin(STZ)and a high-fat and highglucose diet for eight weeks to establish a DGP rat model.At the same time,blood glucose and a general symptom score were recorded every week.After modeling,30 successfully modeled rats were randomly separated into the following groups:the DGP group(n=10),the EA group(n=10)and the metoclopramide(MP)group(n=10).After three weeks of intervention,the gastrointestinal propulsive rate was measured by measuring the optical density(OD).The concentration of Ca2+was determined by fluorescence immunoassay,and levels of serum insulin(INS)and PDGF were determined by ELISA.The ultrastructure of mitochondria was observed with transmission electron microscopy.Results(1)After intervention,levels of blood glucose and the general symptom score were greatly decreased in the EA group compared to the DGP group(P<0.01).Compared with the DGP group,the gastric emptying rate and the intestinal propulsive rate of the EA group was significantly improved(P<0.01),and there was no statistically significant difference between the EA and the NC groups.(2)Compared with the NC group,the levels of INS in the DGP group markedly decreased(P<0.05),but there was no significant difference of INS levels between the EA and the MP roups.(3)Compared with the DGP group,theconcentration of Ca2+in the EA and the MP groups significantly increased(P<0.01,P<0.05,respectively).(4)Compared with the NC group,the average OD of PDGF in the DGP group was significantly higher(P<0.01).Compared with the DGP group,levels of PDGF in the EA group increased significantly(P<0.01).(5)There were abundant mitochondria with a clear structure and complete cristae in the NC group.However,in the DGP group,mitochondria were severely swollen,partly vacuolated,and cristae were either fractured,absent,or shortened.In the EA group,mitochondria were slightly swollen,with clear cristae.Conclusions Electroacupuncture at the points Zu San Li(ST36),San Yin Jiao(SP6)and Liang Men(ST21)may improve gastric motility in DGP by up-regulating the amount of PDGF and improving the ultrastructure of mitochondria.

A meta-analysis of Wendan decoction in the treatment of diabetic gastroparesis

Objective To evaluate the clinical efficacy and safety of Wendan decoction in the treatment of diabetic gastroparesis (DGP). Methods PubMed, MEDLINE, The Cochrane Library, Embase, China Biology Medicine (CBM), Chinese National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database (VIP) and Wanfang databases were searched and eligible randomized controlled clinical trials (RCTs) were included. The quality of the RCTs was evaluated by the Cochrane risk of bias assessment tool, and data analysis were performed with Review Manager 5.3. Results A total of 7 studies were included, including 533 patients. Meta analysis results showed that the effective rate of Wendan decoction in the treatment of diabetic gastroparesis was better than that of the control group [RR=1.30, 95%CI (1.20, 1.40), P<0.001], and the improvement of fasting blood glucose (FBG) was better than that of western medicine [MD =-0.43, 95%CI (-0.91,-0.01), P=0.05]. The recurrence rate in the TCM treatment group was lower than that in the western medicine group[RR = 0.29, 95%CI (0.13, 0.62), P=0.002]. Conclusion Compared with western medicine, Wendan decoction has better curative effect on DGP and can reduce its recurrence rate. However, due to the low quality of the included literatures and the possibility of bias, large-scale and high-quality RCTs are still needed for further confirmation.

Banxia Xiexin Decoction(半夏泻心汤)Treats Diabetic Gastroparesis through PLC-IP3-Ca^2+/NO-cGMP-PKG Signal Pathway

Objective To test the effect of Banxia Xiexin Decoction(半夏泻心汤,BXD)on the contraction and relaxation of gastric smooth muscle(SM)in diabetic gastroparesis(DGP)model rats,and to explore the mechanism of BXD in the prevention and treatment of DGP through experiments of signal pathway both in vivo and in vitro.Methods Sixty Sprague-Dawley rats were divided into 6 groups according to a random number table:control group,model group,high-,medium-and low-dose BXD groups(9.2,4.6 and 1.8 g/(kg·d),respectively),and domperidone group(10 mg/(kg·d)),10 rats per group.DGP model was established initially by a single intraperitoneal injection of streptozotocin(STZ),and was confirmed by recording gastric emptying,intestinal transport velocity and gastric myoelectric activity of rats after 2 months.Each group was treated with a corresponding drug for 4 weeks.The mRNA and protein expressions of phospholipase C(PLC),inositol triphosphate(IP3),neuronal nitric oxide synthase(nNOS),and cyclic guanosine monophosphate(cGMP)dependent protein kinase G(PKG)were detected by reverse transcription-polymerase chain reaction and Western blot,respectively,while nitric oxide(NO)and cGMP expressions were detected by enzyme-linked immunosorbent assay.Gastric tissues were obtained from rats for primary cell culture preparation.Gastric SM cells were treated with 0.8µmol/L of STZ or STZ plus 1,000,500 and 200µg/mL of BXD or STZ plus 2.5µmol/mL of domperidone for 24,48,72 or 96 h,respectively.The length of gastric SM cells and intracellular Ca^2+concentration([Ca^2+]i)before and after BXD treatment was measured.Results Compared with the model group,high-and medium-dose BXD and domperidone significantly increased the expressions of PLC,IP3,NO,nNOS,cGMP and PKG in rat’s gastric tissue(P<0.01).Gastric SM cells treated with BXD showed a time-and dose-dependent increase in cell viability(P<0.01).The treatment with high-and medium-dose BXD and domperidone inhibited the increase in gastric SM cells length and increased[Ca^2+]i compared with the model cells(P<0.01).Conclusions Treatment with high-and medium-dose BXD significantly attenuated STZ-induced experimental DGP in rats.The therapeutic effect of BXD on DGP rats might be associated with the PLC-IP3-Ca^2+/NO-cGMP-PKG signal pathway.

Analysis of the Relationship between Helicobacter pylori Infection and Diabetic Gastroparesis

Background： Whether Helicobacter pylori infection is associated with diabetic gastroparesis （DGP） is unclear. This study aimed to investigate the potential correlation between H. pylori infection and DGP. Methods： In this study, 163 patients with type 2 diabetes mellitus and 175 nondiabetic patients who were treated in our department were divided into DGP, simple diabetes, non-DGP （NDG）, and normal groups based on their conditions. The H. pyh）ri infection rate in each group was calculated. H. pylori eradication therapy was performed for patients with H. pylori infection in each group. The eradication rates were compared between the groups, and the improvements in gastroparesis-associated symptoms were compared before and after treatment in patients with DGP. Results： The tl. pylori infection rate was 74.6% in the DGP group, which was significantly higher than that in the simple diabetes （51.1%, P 〈 0.01）, NDG （57.7%, P 〈 0.05）, and normal groups （48.0%, P 〈 0.01）. With increased disease course, the incidence of DGP and the H. pylori infection rate gradually increased （P 〈 0.05）. In the DGP group, the incidences of upper abdominal pain and distention, early satiety, and anorexia were 75.5%, 66.0%, and 67.9%, respectively, before eradication treatment; and 43.4%, 35.8%, and 39.6%, respectively, after eradication treatment, and the difference was statistically significant （P 〈 0.01）. In patients with DGP with successful H. pylori eradication, the number of barium strips discharged after eradication was 5.9 ± 1.0, which was significantly larger than that before treatment （4.1 ± 0.7, P 〈 0.01）. In addition, the number of barium strips discharged was significantly larger in patients with DGP with successful H. pylori eradication than those with failed H. pylori eradication （P 〈 0.01 ）. Conclusions： DGP development might be associated with H. pylori infection. H. pylori eradication can effectively improve dyspepsia-associated symptoms and delayed gastric emptying in patients with DGP.

ER stress and ER stress-induced apoptosis are activated in gastric SMCs in diabetic rats

AIM: To investigate the gastric muscle injury caused by endoplasmic reticulum (ER) stress in rats with diabetic gastroparesis.

Gastric nNOS reduction accompanied by natriuretic peptides signaling pathway upregulation in diabetic mice

AIM: To investigate the relationship between neuronal nitric oxide synthase (nNOS) expression and the natriuretic peptide signaling pathway in the gastric fundus of streptozotocin (STZ)-induced diabetic mice.

Effect of acupuncture combined with Chinese medicine on the expression of interstitial cells of Cajal, substance P and nerve nitric oxide synthase in diabetic mice with gastroparesis antrum

Objective To explore the effect of acupuncture combined with Chinese medicine on expression of interstitial cells of Cajal（ICC）, substance P（SP） and nerve nitric oxide synthase（nNOS） in diabetic gastroparesis mice. Methods Eighty Kunming male mice were randomly divided into normal group（group A, 15 mice）, diabetic gastroparesis model mice group（group B, 12 mice）, acupuncture combined with Chinese medicine group（group C, 12 mice）, Chinese medicine group（group D, 13 mice） and western medicine group（group E, 13 mice）. The mice were intraperitoneally injected with steptozotocin and fed with high-fat diet-induced irregular except the normal group mice, that made mouse model of diabetic gastroparesis. And then, the ACM group were treated by acupuncture at the acupoints of Housanli（后三里 ST 36） and Zhōngw n（中脘 CV 12） combined with Chinese medicine, the CM group were only treated by Chinese medicine; the WM group were treated by domperidone and vitamin B 6. Numbers and expression of ICC, SP and n NOS were detected by immunohistochemical methods. Results After treatment, compared with normal group, ICC and SP indexes of model group were significantly reduced. Compared with model group, all indexes in ACM and CM groups were improved significantly（P0.05, P0.01）, but only the positive area and average optical density value in c-Kit and SP in WM group increased obviously（P0.05）. Compared with ACM group, no significant difference in c-Kit and SP of CM group were observed（P0.05）, but expression of nNOS were increased markedly（P0.01）. Besides, c-Kit and SP expressions of WM group were significantly induced was increased remarkably（P0.01）. Conclusion Acupuncture combined with Chinese medicine have much better therapeutic effects for diabetic gastroparesis mice, which may be due to repairing ICC damage, upregulating the expression of SP and lowering the expression of nNOS.

Delayed Postprandial Hypertriglyceridemia,Slow Gastrointestinal Transit and Possible Links Between Them in Alloxan-Induced Diabetic Mice

Both postprandial hypertriglyceridemia and diabetic gastroparesis are common dysfunctions af-fecting diabetes mellitus; however, whether diabetic gastroparesis has an influence on postprandial hypertriglyceridemia still remains undetermined. Delayed postprandial hypertriglyceridemia, diabetic gastroparesis, and the possible links between them were investigated using alloxan-induced diabetic mice. After the oral administration of olive oil, delayed and exaggerated postprandial hypertriglyceridemia and diabetic gastroparesis were markedly presented in alloxan-induced diabetic mice. Domperidone shortened the time of triglycerides (TG) peak levels in diabetic mice. After intraperitoneal and intraduodenal administration of olive oil, no delay of TG peak levels occurred in diabetic mice. Simultaneously, serum post-heparin lipoprotein lipase activities significantly decreased just at the time of prolonged and elevated TG peak levels resulting from diabetic gastroparesis, and further deteriorated postprandial hypertriglyceridemia in diabetic mice. The results indicate that diabetic gastroparesis can be one of the important reasons for delayed and exaggerated postprandial hypertriglyceridemia in diabetes mellitus.