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.

Buyang Huanwu decoction up-regulates Notch1 gene expression in injured spinal cord

Expression of genes in the Notch signaling pathway is altered in the injured spinal cord, which indicates that Notch participates in repair after spinal cord injury. Buyang Huanwu decoction, a traditional Chinese herbal preparation, can promote the growth of nerve cells and nerve fibers; however, it is unclear whether Buyang Huanwu decoction affects the Notch signaling pathway in injured spinal cord. In this study, a rat model was established by injuring the T10 spinal cord. At 2 days after injury, rats were intragastrically administered 2 m L of 0.8 g/m L Buyang Huanwu decoction daily until sacrifice. Real-time reverse transcription polymerase chain reaction analysis demonstrated that at 7, 14 and 28 days after injury, the expression of Notch1 was increased in the Buyang Huanwu decoction group compared with controls. These findings confirm that Buyang Huanwu decoction can promote the expression of Notch1 in rats with incomplete spinal cord injury, and may indicate a mechanism to promote the repair of spinal cord injury.

Mechanism of Yinchenhao decoction in the treatment of jaundice based on network pharmacology

Objective:This study aimed to examine the mechanism of classic ancient prescription of Chinese medicine Yinchenhao decoction in treating jaundice based on network pharmacology.Method:An oral bioavailability of≥30%,a drug likeness of≥0.18,and literature studies were used to screen for Yinchen(Artemisiae scopariae herba),Zhizi(Gardeniae fructus),Dahuang(Rhei radix et rhizome)in the Chinese Medicine System Pharmacology Database and Analysis Platform.The active ingredient was introduced into the PubChem database to collect drug component targets and import into the Uniprot database for gene standardization.The target gene of Yinchen(Artemisiae scopariae herba)was screened via Human Gene Database(GeneCards).Then,use the Cytoscape 3.7.2 software was used for network visualization analysis,and the R3.6.1 software was used for gene ontology functional and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses.Results:We collected a total of 47 active constituents of classic ancient prescription of Chinese medicine Yinchenhao decoction,of which 17 were related to jaundice;189,9 targets of jaundice were screened,of which 41 were interdigitated with the targets of classic ancient prescription of Chinese medicine Yinchenhao decoction.Gene ontology functional enrichment analysis revealed 111 biological processes,14 cellular components,and 28 molecular functions,and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis showed 34 Kyoto Encyclopedia of Genes and Genomes pathways including hepatocellular carcinoma,PI3K-Akt signaling pathway,HIF-1 signaling pathway,prolactin signaling pathway,and non-alcoholic fatty liver disease.Conclusion:Based on the network pharmacology,the analysis of jaundice and classic ancient prescription of Chinese medicine Yinchenhao decoction provides a novel idea and direction for the study of classic ancient prescription of Chinese medicine Yinchenhao decoction in the treatment of jaundice.

Is the Chinese Medicinal Formula Guipi Decoction(归脾汤) Effectiveas AnAdjunctive Treatment for Depression？AMeta-Analysis of Randomized Controlled Trials

Objectives： To evaluate the effectiveness and safety of Guipi Decoction（归脾汤, GPD） as an adjunctive in the treatment of depression. Methods： A review of all relevant studies retrieved from a search of the following databases were conducted without any language restriction： Excerpt Medica Database（EMBASE）, Pub Med, Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure（CNKI）, VIP Information, Wanfang Data, and the Chinese Biomedical Literature Database. Papers published until February 2013 were taken into consideration. The analysis was performed using the Cochrane software Revman 5.1. Results： Nine randomized controlled trials involving 620 patients with depression were included in this review. The meta-analysis revealed that compared with antidepressant therapy alone, treatment with a combination of GPD and an antidepressant drug significantly improved the symptoms of depression [weighted mean difference（WMD）： –3.09; 95% confidence interval（CI）： –4.11 to –2.07] and increased the rates of effectiveness（OR： 4.75; 95% CI： 2.66–8.51） as well as recovery（OR： 1.73; 95% CI： 1.17–2.56）. The adverse effects of GPD were not found to be significant in these studies. Conclusions： The findings of this meta-analysis were in keeping with the notion that GPD formulations were effective in the treatment of depression without causing any severe adverse effects. However, currently available evidence was of low quality and therefore inadequate to justify a strong recommendation of using GPD formulations in the management of depression.

Effects of Wenxiao Ⅱ Decoction on the expression of MCP-1 and VCAM-1 in atherosclerotic rabbits

OBJECTIVE:To observe the effects of different doses of Wenxiao Ⅱ Decoction on the expression of monocyte chemoattractant protein-1(MCP-1) and vascular cell adhesion molecule-1(VCAM-1) in an experimental model of atherosclerosis in rabbits and to explore the mechanism by which it alleviates atherosclerosis.METHODS:Sixty 3-4 month-old New Zealand rabbits of both sexes were randomly divided into six groups:simvastain;model;blank;and high-dose,mid-dose,and low-dose Wenxiao Ⅱ Decoction groups.Except for those in the blank group,all rabbits were fed a high-cholesterol diet.Carotid atherosclerosis was established by balloon-induced injury to the endothelium of the carotid artery in conjunction with consumption of a high-cholesterol diet.After 8 weeks,all rabbits were killed to evaluate the expression of MCP-1 and VCAM-1 by immunohistochemical staining.RESULTS:Expressions of MCP-1 and VCAM-1 were significantly decreased in all groups except the blank group compared with the model group(P<0.05).When compared with the simvastain group only variation of MCP-1 expression in low-dose group was not appreciable,and the differences were indistinct(P<0.05).When comparing among Wenxiao Ⅱ Decoction groups,MCP-1 expression in the mid-and high-dose groups was significantly lower than that seen in the low-dose group(P<0.01),but there were no differences among three dosage groups with respect to VCAM-1 expression(P>0.05).CONCLUSION:These data suggested that high,mid,and low doses of Wenxiao Ⅱ Decoction can inhibit the expression of MCP-1 and VCAM-1,which may prevent the formation of or stabilize atherosclerotic plaques.There may be a direct relationship between the dosage of Wenxiao Ⅱ Decoction and its therapeutic efficacy.

Anti-Inflammatory Effect of Qingwen Baidu Decoction (清瘟败毒饮) in Sepsis Rats

Objective：To explore the pharmacological anti-inflammatory mechanism of Chinese formula Qingwen Baidu Decoction（清瘟败毒饮,QBD） from the view of holistic biology.Methods：The rats were randomly divided into a normal conrol group,a lipopolysaccharide（LPS） group,the low- and high-dose QBD groups,and a dexamethasone（DXM） group.NR8383 cells were treated with culture fluid containing 6%serum from rats of each group respectively.Inflammatory mediators were detected by reverse transcription polymerase chain reaction（RT-PCR）,Western blotting hybridization,enzyme linked immunosorbent assay（ELISA）,polymerase chain reaction（PCR） gene array and antibody array.Results：It is showed that the levels of interleukin（IL）-1 α,IL-4 and IL-12 were enhanced in the low-dose QBD group;levels of IL-1 α,IL-12 and IL-18 were augmented in the high-dose QBD group,compared with the LPS group after ELISA detection.Western blot showed that IL-1β and tumor necrosis factor（TNF）-α expression of the control group were lower than other groups.IL-1 βlevel of the low-dose and high-dose QBD groups detected by RT-PCR was higher in early stage but lower after24 h than that of the control group（P〈0.01）.Expression of 84 main inflammatory cytokines and receptors was detected by rat inflammatory cytokines and receptors PCR array.Up-regulation genes were 22 in both the LPS group and the low-dose QBD group,among which 16 up-regulating genes were the same.In these 16 genes,the up-regulating amplitude of 9 genes in the low-dose QBD group was less than that in the LPS group,4 were similar to and 3 were more.Twenty-nine main cytokines were inspected by rat cytokine antibody array.Intergroup gray value differences were found in 7 expressed cytokines.The levels of these 7 cytokines in the lowdose QBD group were all lower than those in the the LPS group.Conclusions：QBD has anti-inflammatory effect on sepsis by changing the level of inflammatory mediators.

Decomposition and Reformulation of Banxia Baizhu Tianma Decoction:A Vasodilatory Approach

Objective To decompose and reformulate Banxia Baizhu Tianma Decoction（BBT） in order to optimize its ratio for vasodilatory effect.The fingerprints of these six component herbs were also studied via Tri-step FTIR analysis.Methods The herbal components of BBT were extracted separately with different solvents,such as 95%ethanol,50%ethanol,and distilled water.The vasodilatory effect of the extracts was studied using the in vitro pre-contracted aortic ring model.Among these extracts,the water extracts of Pinellia ternata[PT（W）]and Citri reticulatae[CR（W）],50%ethanol extracts of Castrodia elata[GE（50）]and Clycyrrhiza uralensis[GU（50）],and 95%ethanol extracts of Atractylodes macrocephala[AM（E）],and Poria cocos[PC（E）]were selected for the orthogonal stimulus-response compatibility group study due to their high effectiveness in vasodilation.Results The best combination ratio（G2） was GE（50）,GU（50）,AM（E）,PC（E）,CR（W）,and PT（W） at EC0,EC5,EC5,EC5,EC5,and EC5,with EC50 of（0.06 ± 0.01） mg/mL.Comparison between the vasodilatory effects of extracts derived from G2 and BBT were also studied.From the results,the 50%ethanol extract following G2 ratio was found to be most potent extract with the highest vasodilatory effect compared with other extracts derived from G2 or BBT,with EC50 of（0.05 ±0.005） mg/mL.Conclusion The optimum ratio and appropriate extraction method for the new BBT formulae are obtained.G2 is determined as the best formulae with the highest potency in producing the vasodilatory effect on isolated rat aortic rings.The results obtained suggest that 50%ethanol is found to be the best solvent to extract the vasoactive compounds of G2 in order to exhibit the highest efficacy of vasodilatory effect.

Neuroprotective Effects of Tongmai Yizhi Decoction(通脉益智汤)against Alzheimer's Disease through Attenuating Cyclin-Dependent Kinase-5 Expression

Objectives： To explore the protective effects of Tongmai Yizhi Decoction（通脉益智汤, TYD）, a Chinese herb complex prescription against the impairment of cognitive functions and memory loss in amyloid beta 1–40（Aβ1-40） peptide and ibotenic（IBO）-induced Alzheimer＇s disease（AD） model rats. Methods： The in vivo model was established by injecting Aβ1-40 and IBO into left hippocampal CA1 area of Sprague-Dawley（SD） rat to mimic AD. Totally 32 SD rats were divided into 4 groups, including sham operation group, AD model group, TYD group [AD rats treated with TYD at the dosage of 19.44 g/（kg·d） for 4 weeks] and huperzine A group [AD rats treated with huperzine A at the dosage of 40.5 μg/（kg·d） for 4 weeks]. Spatial learning and memory level was detected by Morris Water Maze test. Histological morphology in the hippocampus was tested by hematoxylin-eosin（HE） staining. Cyclin-dependent kinase-5（Cdk5） protein and gene expression level were investigated by Western blot analysis and real-time quantitative polymerase chain reaction（RT-q PCR）, respectively. Results： Aβ1-40 and IBO treatment induced longer escape latency of rats, compared with sham operation group from day 25（P〈0.01）. However, TYD and huperzine A obviously shortened the escape latency from day 26（P〈0.01）. Moreover, the effect of TYD was similar to huperzine A（P〉0.05）. Furthermore, HE staining also showed that TYD and huperzine A reversed the neuropathological changes in the hippocampus triggered by Aβ1-40 and IBO. TYD and huperzine A effectively reduced the expression levels of Cdk5 protein and gene located in rat hippocampus, compared with the AD model group（P〈0.01）. Conclusion： TYD could be a promising neuroprotective agent for protecting neuron from AD injury through inhibiting Cdk5 expression.

Short-Term Efficacy of Treating Hepatitis B Virus-Related Acute-on-Chronic Liver Failure Based on Cold Pattern Differentiation with Hot Herbs: A Randomized Controlled Trial

Objective： To evaluate the clinical efficacy and safety of Yinchen Zhufu Decoction（茵陈术附汤, YCZFD） in the treatment of acute-on-chronic liver failure caused by hepatitis B virus（HBV-ACLF） with cold pattern in Chinese medicine（CM）. Methods： This is a multi-center randomized controlled trial of integrative treatment of CM and Western medicine（WM） for the management of HBV-ACLF patients. A total of 200 HBV-ACLF patients with cold pattern were equally randomly assigned to receive YCZFD and WM（integrative treatment） or WM conventional therapy alone respectively for 4 weeks. The primary end point was the mortality for HBV-ACLF patients. Secondary outcome measures included Model for End-Stage Liver disease（MELD） score, liver biochemical function, coagulation function and complications. Adverse events during treatment were reported. Results： The mortality was decreased 14.28% in the integrative treatment group compared with WM group（χ^2=6.156, P=0.013）. The integrative treatment was found to significantly improve the MELD score（t=2.353, P=0.020）. There were statistically significant differences in aspartate transaminase, total bilirubin, indirect bilirubin, direct bilirubin and prothrombin time between the two groups（P〈0.05 or P〈0.01）. The complications of ascites（χ^2=9.033, P=0.003） and spontaneous bacteria peritonitis（χ^2=4.194, P=0.041） were improved significantly in the integrative treatment group. No serious adverse event was reported. Conclusions： The integrative treatment of CM and WM was effective and safe for HBV-ACLF patients with cold pattern in CM. The Chinese therapeutic principle ＂treating cold pattern with hot herbs＂ remains valuable to the clinical therapy.（Trial registration No. Chi CTR-TRC-10000766）