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Mechanism analysis of Traditional Chinese Medicine in treatment of Diabetic Nephropathy based on network pharmacology and Traditional Chinese Medicine inheritance support system
Yu-hui Ma, Li-na Zhang, Qian Cui, Lin-feng Li, Guo-wei Zhang
6TMR Modern Herbal Medicine    2019, 2 (2): 64-73.   https://doi.org/10.12032/TMRmhm2017A44
Abstract ( 208 HTML PDF (886KB) ( 94 )  

Diabetic nephropathy is one of the most serious complications of diabetes mellitus. In the early stage, edema and proteinuria are the main clinical manifestations. In the later stage, glomerulosclerosis and interstitial fibrosis will occur. And the prognosis is poor. Nowadays, traditional Chinese medicine has a remarkable curative effect in the treatment of diabetic nephropathy. There are more and more studies on the treatment of diabetic nephropathy with traditional Chinese medicine, but most of them focus on the syndromes of diabetic nephropathy, which are short of in-depth research and summary on the mechanism of Chinese herbal prescriptions. In this paper, the traditional Chinese medicine inheritance support system and network pharmacology BATMAN-TCM software were used to collect and analyze the relevant literature. It was found that the core compatibility of Shanzhuyu, Fuling and Shuyu in the treatment of diabetic nephropathy is closely related to the signal transduction pathway and target of diabetic nephropathy, and has a positive effect on the improvement of clinical symptoms such as proteinuria, glycometabolism disorder, edema, etc. This paper explores the core compatibility of Shanzhuyu, Fuling and Shuyu on diabetic nephropathy, in order to provide reference for clinical treatment.

Highlights
Diabetic nephropathy is one of the most serious complications of diabetes mellitus, which seriously affects the quality of life of patients for the poor prognosis. Nowadays, Traditional Chinese Medicine has a remarkable curative effect in the treatment of diabetic nephropathy, which has brought some enlightenment to our research ideas. Traditional Chinese Medicine Inheritance Assistant Platform System (TCM Inheritance Assistant Platform) is an organic combination of computer science and TCM. By intellectualized processing of disease prescription, the data of disease information, syndrome information and compatibility of TCM can be more intuitive, which make Chinese herbal medicine and drug pairs for treating diseases more specialized and precise. Network pharmacology is based on system biology to analyze multi-target networks of drugs, and can combine Drug targets with diseases, which make the treatment of diseases more targeted. This paper collects and summarizes the prescriptions of traditional Chinese medicine for diabetic nephropathy in the past 10 years from China Knowledge Net, and uses the system of traditional Chinese Medicine Inheritance assistant platform and BATMAN-TCM database of network pharmacology to analyze the medication rules and action signal pathways. We concluded that Shanzhuyu(Cornus officinalis Sieb. et Zucc), Fuling (Poria cocos (Schw.) Wolf) and Shuyu (Dioscorea opposite) have certain positive effects on the compatibility in the prevention and treatment of diabetic nephropathy and hope to provide new ideas for the research and clinical treatment of diabetic nephropathy with TCM.

Pharmacologic mechanisms mining and prediction of Xiaoer Qixing Cha Formulae in the treatment of infantile functional dyspepsia based on chemical analysis by UPLC-QTOF/MS and interactive network pharmacology
Mei-Qi Wang, Zeren Dawa, Yu-Feng Yao, Fang-Le Liu, Run-Jing Zhang, Zi-Yuan Wang, Chen-Chen Zhu
6TMR Modern Herbal Medicine    2019, 2 (2): 48-63.   https://doi.org/10.12032/TMRmhm2017A45
Abstract ( 207 HTML PDF (1413KB) ( 75 )  

Objective: To explore the main chemical compounds in Xiaoer Qixing Cha Formulae (XQCF), and investigate its mechanisms for the treatment of infantile functional dyspepsia (IFD). Methods: The chemical components were identified by UPLC-QTOF/MS analytic technique. Targets of the compounds were screened from TCMSP and SWISS database, and disease targets were screened from OMIM and TTD online database. Candidate targets of compounds were mapped to the disease targets as predict therapeutic targets for XQCF. Several networks were constructed and analyzed by Cytoscape ver. 3.2.1. Meanwhile, prescription compatibility in XQCF was interpreted from the network perspective based on distribution of the number of targets. Furthermore, Gene Ontology (GO) enrichment analysis and KEGG pathway analysis were operated via Clue Go to illustrate complex relationships between the potential targets and pharmacological mechanisms. Results: A total of fifty-three compounds were recognized or tentatively characterized belonging to XQCF based on MS data and online chemical database. Sixty-three therapeutic targets were screened. AKT1, FOS, SLC6A4, COMT and 5-HT receptors were focused as therapeutic targets of XQCF. Pathways including carbohydrate digestion and absorption, serotonergic synapse, calcium signaling pathway and cAMP signaling pathway were predicted as significant regulatory pathways. The results indicated that the predicted targets and pathways related in brain-gut axis to a great extent, which could be potential pharmacological mechanism of XQCF for the treatment of IFD. Conclusions: The findings in this study provided the experimental and theoretical basis for further research for XQCF. Those also illustrated a reasonable method worth intensive study on pharmacodynamic mechanisms of TCM Formulae.

Highlights
Chemical components in Xiaoer Qixing Cha Formulae were firstly identified by UPLC-QTOF/MS analytic technique and collated into data source. Then the mechanisms of the Formulae for the treatment of infantile functional dyspepsia were predicted by interactive network pharmacology. The results suggested that targets and pathways related in brain-gut axis might exert regulating effects on digestive process and digestive system function.

Wenxin granule for cardiac arrhythmia: an overview of systematic reviews
Ruijin Qiu, Changming Zhong, Huichan Yuan, Xiaoyi Tang, Ya Huang, Tianmai He, Songjie Han, Manke Guan, Min Li, Jiayuan Hu, Xiaoyu Zhang, Jing Chen, Hongcai Shang
6TMR Modern Herbal Medicine    2019, 2 (2): 91-114.   https://doi.org/10.12032/TMRmhm2017B42
Abstract ( 170 HTML PDF (1104KB) ( 54 )  

Objectives: Evaluating the quality of systematic reviews/meta-analysis of Wenxin granule in treating cardiac arrhythmia to provide evidence for clinical practice, and analyzing the problems in the research to identify potential research priorities for researchers. Method: The systematic reviews of Wenxin granule in treating cardiac arrhythmia were searched from 8 databases. The methodological quality and evidence quality were assessed by AMSTAR and GRADE respectively. Results: Nineteen eligible systematic reviews with 52,905 participants were included. The overall scores of AMSTAR ranged from 3 to 10 with a mean score of 6.5, the median score was 6. There were 9 (9/19, 47.37%) systematic reviews had the score of 7 or more. 6 of them with appropriate information were assessed the quality of evidence by GRADE. The results showed that the overall quality of evidence was limited (range from “very low” to “low”), no “moderate” or “high” quality of evidence existed. For the outcome reporting, no systematic reviews reported endpoints and limited evidence showed that there is causality between Wenxin granule and adverse effects/events. The outcome matrix showed that there are obvious heterogeneity and incompleteness for the outcome reporting in included systematic reviews, so that some included studies cannot be conducted meta-analysis. Meanwhile, there were studies excluded because of inappropriate outcome measures, such as outcome measures did not meet inclusion criteria, treatment time did not meet inclusion criteria, treatment time was unclear, incomplete data or the data cannot be extracted. Conclusions: Wenxin granule have limited efficacy and safety for treating arrhythmia. In the future, high quality of RCTs and systematic reviews should be conducted. Core outcome set for cardiac arrhythmia is needed to improve outcome reporting and decrease waste.

Highlights
1. This is the first overview of systematic reviews for Wenxin granule in treating cardiac arrhythmia, which summarized the efficacy and safety of Wenxin granule in treating cardiac arrhythmia and strictly assessed the quality of methodology and evidence.
2. Besides methodological quality and evidence quality assessment, this overview also analyzed some other problems, such as outcome reporting in systematic reviews and RCTs, so that researchers may identify potential research priorities from the results.
3. The outcome matrix of included reviews showed that there was heterogeneity in outcome reporting, and some clinical trials cannot be included in systematic reviews or cannot be conducted meta-analysis in systematic reviews because of inappropriate outcomes reporting. These problems reduce the value of clinical trials and systematic reviews. This research presents that core outcome set for cardiac arrhythmia is necessary to solve these problems.

The study on neuroprotective mechanism of water extract of Fomitopsis Pinicola on mesencephala dopaminergic neurons induced by MPP+
Shanshan Guo, Wolf Dieter Rausch
6TMR Modern Herbal Medicine    2019, 2 (2): 74-82.   https://doi.org/10.12032/TMRmhm2017A46
Abstract ( 169 HTML PDF (1025KB) ( 45 )  

Objective: To observe the neuroprotective mechanism of water extract of Fomitopsis Pinicola on MPP+ induced apoptosis of mesencephala dopaminergic cells in vitro. Methods: The antioxidant activity of fungi was determined by FRAP method. The anti-inflammatory activity of the fungi was detected by LPS-induced NO release method. Mesencephalic dopaminergic neurons were labeled by TH staining to observe the survival of THir neurons. Results: In the anti-oxidant activity assay, the Trolox equivalent anti-oxidant capacity (TEAC) of water extract of Fomitopsis Pinicola was determined to be (165.80±7.13)μmol Trolox/g extract. Water extracts of Fomitopsis Pinicola treatment(100,50,25,12.5μg/ml) decreased NO formation significantly. MPP+ induced significant chromatin condensation in the nuclei of mesencephala dopaminergic neurons with nuclear lysis,the mitochondrial membrane potential decreased remarkably, and ROS production increased significantly. Compared with the MPP+ control group, the morphological changes of cell nuclei after apoptosis was reversed by water extract of Fomitopsis Pinicola. Water extract of Fomitopsis Pinicola treatment(50,25,12.5μg/ml) dramatically increased relative mitochondrial membrane potential compared with MPP+ control respectively. Compared with the MPP+ control, water extract of Fomitopsis Pinicola treatment (50, 25μg/ml) significantly decreased relative ROS formation respectively. Conclusions:Water extract of Fomitopsis Pinicola showed significant neuroprotective effect on mesencephala dopaminergic cells induced by MPP+. The water extract of Fomitopsis Pinicola showed antioxidant and anti-inflammatory activities. The mechanism of neuroprotective effect of water extract of Fomitopsis Pinicola may be related to inhibitory on mitochondrial oxidative stress.

Highlights
Fomitopsis Pinicola is characterized with anti-oxidant, anti-inflammation and immunostimulant properties. In the present study, primary dopaminergic cell cultures prepared from embryonic mouse mesencephala were used to determine the neuroprotective effects and the potential mechanisms of water extract of Fomitopsis Pinicola on the degeneration of dopaminergic neurons induced by MPP+. The results demonstrated that Water extract of Fomitopsis Pinicola protected dopamine neurons against MPP+. The water extract of Fomitopsis Pinicola showed antioxidant and anti-inflammatory activities. The mechanism of neuroprotective effect of water extract of Fomitopsis Pinicola may be related to inhibitory on mitochondrial oxidative stress.

The Protective Effect of Jiujiuguiyi, a Medicine and Food Homologous Formula, on Acute Alcohol Poisoning Mice
Yang-Fan Zhou, Tian-Ze Zhang, Si-Qi Deng, Meng Zhang, Yu-Jiao Zhan, Yi-Fang Li, Rong-Rong He
6TMR Modern Herbal Medicine    2019, 2 (3): 121-130.   https://doi.org/10.12032/TMRmhm2017A49
Abstract ( 168 HTML PDF (921KB) ( 93 )  

Abstract

Background: Nowadays, acute alcoholic intoxication has become the third public problem in China, and the anti-inebriation products mainly aimed at increasing the activity of enzyme involved in the alcohol metabolism, which is a single mechanism that can accelerate alcohol metabolism. Thus, a new formula, Jiujiuguiyi (JJGY) which could protect liver, relieve the abnormal excitability of the center and improve muscle retardation at the same time is designed by us. Methods: The model of acute alcoholic intoxication was established by intragastric administration with 0.12 ml/10g 50% alcohol in mice. JJGY was orally administrated (gavage) once a day for 20 consecutive days before the establishment of acute alcoholic model. Mice were randomly divided into 8 groups with 8 each: blank control group (CON), model group (M), Haiwangjinzun positive control group (HWJZ), experimental groups (AL, AH, BL, BH, AB). Giant, crawling time on the rota-rod, the activities of aspartate amino trans- ferase (AST), alanine amino transferase (ALT) and superoxide dismutase (SOD) in both liver and serum, alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH), glutathione peroxidase (GSH-PX) in liver as well as the HE staining of liver slices, the formation of malondialdehyde (MDA) in serum were determined after acute alcoholic intoxication. Results: Compared with model group, JJGY significantly decreased the AST and ALT activity in liver and serum and MDA activity in serum. Meanwhile, it enhanced the ADH and ALDH level in liver as well as the hepatic and serous SOD activity, indicating more efficient metabolism of alcohol and less hepatic injury. HE staining results also proved that JJGY could reduce alcoholic liver cell injury, and the effect was more obvious in the group medicated before alcohol administration. Moreover, JJGY significantly prolonged the crawling time on the rota-rod and improved the gait of mice and the effect was proved to be better than the widely used health product Haiwangjinzun. Conclusions: This study suggests that JJGY is able to protect liver, relieve the abnormal excitability of the center and improve muscle retardation after acute alcoholic intoxication. Its liver protection effect is likely related to its modulation on the alcohol metabolizing and antioxidant enzymes.

Highlights

In the present study, a new compound Chinese herbal medicine formula, Jiujiuguiyi, was designed by using the medicine and food homology theory. The formula aims at protecting liver, relieving the abnormal excitability of the center and improving muscle retardation at the same time. Acute alcoholic intoxication model in mice was built, then the ethology test and biochemical test were conducted to exam the efficacy of the formula in different preparations. The results suggest that JJGY can protect the acute alcoholic intoxication mice through multiple mechanisms, providing a new way to develop antialcoholismic drug homologous food.

Terahertz spectral analysis of Yunpian Lurong
Li-Na Zhang, Yu-Hui Ma, Kai-Xuan Hou, Ze-Jia Zhang, Yan-Ming Wu, Guo-Wei Zhang
6TMR Modern Herbal Medicine    2019, 2 (2): 83-90.   https://doi.org/10.12032/TMRmhm2017A47
Abstract ( 147 HTML PDF (510KB) ( 58 )  

Objective: Provide a rapid and simple method to identify Yunpian Lurong. Method: Terahertz spectroscopy was used to detect Yunpian Lurong. Result: Compared with the reference wave, the spectral amplitude of Yunpian Lurong decreases significantly. The frequency - domain spectra of Yunpian Lurong are different from conventional Lurong. Compared with the spectrum of free space, both of them have obvious absorption to THz wave, but the intensity and location of absorption are different, which provides a basis for the identification of Yunpian Lurong. The refractive index of the two samples is obviously different, which may be related to the different internal structure and composition content of the samples. The absorption coefficient of the two samples are different as well, when the frequency ranges from 0 to 2.4 THz, the absorption coefficients of the two kinds of Lurong samples have obvious difference, which makes it easy to distinguish the Yunpian Lurong. Conclusion: This study proves that terahertz spectroscopy can be used as an efficient and convenient method to identify Yunpian Lurong.

Highlights
Yunpian Lurong is one of the "four wonders of Qizhou". It is of great significance to develop the method for testing its commercial specifications. At present, many scholars have applied the fingerprint technology of traditional Chinese medicine to identify the LuRong, which is complex, time-consuming and costly for sample pretreatment is needed before testing. Therefore, it is necessary to establish a nondestructive and rapid detection and analysis method to identify Yunpin Lurong. In the experiment, under the constant and dry room temperature, we used the terahertz spectroscopy to detect Yunpin Lurong, analyzed and compared the differentiation of erahertz time domain spectroscopy, frequency domain spectroscopy, refractive index and absorption spectroscopy between Yunpin Lurong and the conventional Lurong. The results show that Yunpin Lurong can be quickly identified by terahertz spectroscopy without destroying its surface and internal structure or complicated pretreatment. As a new detection technology, it has the advantages of simple operation, short time-consuming, low cost and pollution-free and a positive meaning for the rapid detection of Yunpian Lurong, which is a nondestructive testing method for quality analysis or identification of Chinese medicinal herb with a promising prospect.

Effect of Tanshinone IIA on LPS-induced inflammatory response in a ROS-NLRP3 inflammasome dependent manner in RAW264.7 cells
Dan Li, Shan Gao, Sarhene Michael, Yu-Ying Guo, Hao Deng, Shi-Xin Xu, Guan-Wei Fan
6TMR Modern Herbal Medicine    2019, 2 (3): 131-139.   https://doi.org/10.12032/TMRmhm2017A48
Abstract ( 142 HTML PDF (652KB) ( 70 )  

Abstract

Emerging evidence has demonstrated that Tanshinone IIA (Tan IIA) prevents cardiomyocytes injury, cardiac fibroblasts and atherosclerosis. However, the molecular mechanism underlying the effects of Tan IIA is still unclear. To investigate the role of Tan IIA in inflammatory response in a ROS-NLRP3 inflammasome dependent manner, RAW264.7 cells stimulated with LPS were recruited to produce a cell model of inflammatory response. Our results indicated that the production of NO was significantly increased after stimulated by LPS, and Tan IIA treated significantly decreased the level of NO. The mRNA expression of NLRP3, IL-1β and TNF-α was significantly inhibited by Tan IIA compared with LPS treated cells. The protein expression of NLRP3, IKBα, pp65/p65 and pp38/p38 was significantly decreased by Tan IIA, compared with LPS or LPS+ATP stimulated groups. Meanwhile, Tan IIA significantly inhibited the level of ROS induced by LPS+ATP. And NAC, a ROS inhibitor, could also inhibit the protein expression of NLRP3. Based on these findings, it could be speculated that the mechanism underlying the effect of Tan IIA may involve the regulation of ROS-NF-κB/ P38-NLRP3 pathway. This study further characterized the molecular mechanism of Tan IIA, and provided new thoughts to its clinical therapy.

Highlights

Tan IIA could inhibit the inflammatory response and NLRP3 expression stimulated by LPS or LPS+ATP. Acetylcysteine (N-acetyl-l-cysteine, NAC), a ROS inhibitor, could inhibit LPS+ATP-induced increase in NLRP3 level. The mechanism underlying the effects of Tan IIA may involve the regulation of ROS-NF-κB/ P38-NLRP3 pathway. This study further characterized the molecular mechanism of Tan IIA, and provided new thoughts to its clinical therapy.

Clinical research progress of ischemic heart failure and prospect of traditional Chinese medicine
Man-Ke Guan, Jia-Yuan Hu, Xiao-Yu Zhang, Yang Sun, Hong-Cai Shang
6TMR Modern Herbal Medicine    2019, 2 (2): 115-120.   https://doi.org/10.12032/TMRmhm2017B43
Abstract ( 141 HTML PDF (394KB) ( 50 )  

As one of the most common types of heart failure, the diagnosis and treatment of Ischemic heart failure are the main focus of clinic. In recent years, the studies on biomarkers have provided supports for clinical diagnosis, prognosis evaluation and stratification. The clinical application of new drugs and the development of non-drug treatment methods have brought more choices conventional treatment. At the same time, under the guidance of Traditional Chinese Medicine syndrome differentiation theory, Traditional Chinese Medicine therapy also plays an increasingly important role and shows its broad prospects .

Highlights
As the most common type of heart failure, the morbidity of ischemic heart failure is increasing year by year. Although physicians attach great importance to the study of ischemic heart failure, the clinical treatment and diagnosis of ischemic heart failure are still relatively lack of systematicness and pertinence. In this article, we will outline some clinical studies on ischemic heart failure in recent years, including diagnosis and treatment. We will also introduce the progress and the unique prospect of Traditional Chinese Medicine in the treatment of this disease.

Bio-characteristic profiling related to clinic: A new technology platform for quality evaluation of Chinese materia medic
Li-Na Wen, Ai-Ting Wang, Na Guo, Yumei Han, Can Yan, Dan Yan
6TMR Modern Herbal Medicine    2019, 2 (4): 215-224.   https://doi.org/10.12032/TMRmhm2017B54
Abstract ( 103 PDF (859KB) ( 52 )  
Quality evaluation is a bottleneck restricting the modernization and internationalization of Chinese materia medica (CMM). Due to characteristics of multi-component, multi-efficacy, multi-target, the existing quality evaluation system still cannot fully meet quality control needs of CMM. Hence, the author put forward “Bio-characteristic profiling related to clinic, BPRC” academic concept, meanwhile, fully take the advantage of analysis method with clinical monitoring superiority or profiling characteristics, build up "BPRC" new technology platform, in order to realize “real-time, dynamic and full-range monitoring” new technologies of CMM quality evaluation system and promote the further development of CMM industry.
Mitochondrial membrane stabilization by Angelica sinensis polysaccharide in murine aplastic anemia
Ping Zhong, Xing Cui
6TMR Modern Herbal Medicine    2019, 2 (3): 151-157.   https://doi.org/10.12032/TMRmhm2017A50
Abstract ( 102 HTML PDF (647KB) ( 54 )  

Abstract

In order to investigate the mechanism of mitochondrial membrane stabilization by Angelica sinensis polysaccharide (ASP) in murine aplastic anemia (AA).ICR mice were randomly divided into control, AA and ASP-treated groups. The AA group mice were treated with 60Coγand intraperitoneal injections of cyclophosphamide and chloramphenicol. The control animals were treated with lead shielding irradiation and saline injection. The treated AA mice were fed with ASP for 2 wk. Mitochondrial ultrastructure of the bone marrow was observed by transmission electron microscopy, and the transmembrane potential of bone marrow-nucleated cells (BMNC)was examined by fluorescence spectrophotometry. The Cox and MDH contents of the medium were also studied in the three groups.The mitochondrial number and transmembrane potential of BMNC in the bone marrow decreased in the AA group as compared to the control group, but improved in the ASP-treated group as compared to the AA group. Complete mitochondrial cleavage in the ASP-treated group was significantly delayed (P < 0.05) as compared to the AA group. We conclude that ASP might improve mitochondrial membrane stabilization, and suppress the downregulation of transmembrane potential and apoptosis of BMNC in AA.

Highlights

Acquired deletions of mtDNA and abnormal mitochondrial function are crucial reasons in some blood disease include aplastic anemia. Angelica sinensis helps in tonifying the blood and promoting its circulation via anti-oxidative and neuroprotective effects. In this paper, we demonstrated that Angelica sinensis polysaccharide can improve improve the mitochondrial ultrastructure, and suppress the downregulation of transmembrane potential and apoptosis of myeloid element to cure bone marrow failure.

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