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Protective effects of Pulsatilla chinensis Regel against isoproterenol-induced heart failure in mice
Huimin Zhang, Congping Su, Wei Wang, Sen Li, Shuzhen Guo
6TMR Modern Herbal Medicine    2020, 3 (1): 21-29.   https://doi.org/10.12032/TMRmhm202003060
Abstract ( 27 PDF (522KB) ( 15 )  
Objective: To study the cardioprotective effect of Baitouwen (Pulsatilla chinensis Regel, PR) in isoproterenol (ISO) induced heart failure in mice, and investigated the molecular targets using network pharmacological prediction and experimental validation. Methods: PR were orally administered to ISO induced HF mice for two weeks. The cardiac function was analyzed by echocardiography. Hematoxylin-eosinstaining (HE) was used to evaluate the pathological changes. The PR targets for HF were predicted by bioinformatics analysis tool (BATMAN-TCM). The expression of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and HF related genes Phosphodiesterase (PDEs), were detected by real-time fluorescence quantitative PCR or Immunohistochemical staining in heart tissues. Results: Cardiac hypertrophy was observed after ISO treatment, and hypertrophic cardiomyocytes were arranged in disorder. Moreover, the expression of ANP and BNP gene in myocardium were upregulated (P < 0.05). Treatment of HF mice with PR aqueous extract improved cardiac function characterized by enhanced ejection fraction (EF) and fraction shortening (FS). Furthermore, PR extract also downregulated the expression of ANP and BNP in the heart tissues. Arrangement of cardiomyocytes was also improved. Furthermore, administration of PR group decreased target genes PDE5 and PDE1C expression in the hearts. In addition, PR treatment also improved myocardial fiber distribution and decreased myocardial thickness in the hearts of HF mice. Conclusion: PR treatment may suppress cardiac hypertrophy and improve myocardial function in HF mice via inhibiting the predicted targets PDE5 expression. These results suggest the potential of using PR in preventing the development of HF.
Identification of prognostic markers by integrating the genome and transcriptomics in ovarian cancer
Xin Wu, Dong-Xin Tang, Xia-Nan Sang, Kui-Long Wang, Min Hao, Gang Cao
6TMR Modern Herbal Medicine    2019, 2 (4): 192-205.   https://doi.org/10.12032/TMRmhm2017A59
Abstract ( 69 PDF (5262KB) ( 58 )  

Objective: In order to find a genetic marker to predict the prognosis of patients with ovarian cancer based on multi-omics data. Methods: We download RNA-Seq SNP, CNV data and clinical follow-up information from TCGA database and randomly divide them into training set and test set. GSE17260 dataset in GEO is taken as an external validation set. Prognosis-related genes, copy number difference genes and mutant genes are screened in the training set. After the integration of genes, the random forest algorithm is further used for feature selection, ultimately obtaining a robust biomarker. On this basis, a gene-related prognostic model is established and verified in the test set and verification set. Results: We have obtained 2097 prognostic related genes, 447 copy amplification genes, 1069 copy deletion genes and 654 significant mutations genes. Through the feature selection of random forest algorithm, five feature genes (PSMB1, COL6A6, SLC22A2, KLHL23 and CD3G) are obtained by integrating these genes, some of which have been reported to be related to tumor progress. Furthermore, the prognostic risk assessment model of 5-gene signature is established by Cox regression analysis. The model can evaluate the risk of patient samples in training set, test set and external verification set. 5-gene signature shows strong robustness and clinical independence. The results of GSEA analysis also show that the pathway of 5-gene signature enrichment is significantly related to the pathway and biological process of the occurrence and development of ovarian cancer. Conclusion: In this study, 5-gene signature is constructed as a new prognostic marker to predict the survival of patients with ovarian cancer.

Effect of Xuebijing injection on hematopoietic homeostasis of LPS induced sepsis in mice
Ping Wang, Jun Wang, Ying Hao, Xiao-Rui Li, Ya-Ru Feng, Lan Wang, Hong-Cai Shang, Jian-Xun Wang
6TMR Modern Herbal Medicine    2019, 2 (4): 206-214.   https://doi.org/10.12032/TMRmhm2017A60
Abstract ( 72 PDF (1088KB) ( 66 )  
Objective: To explore the effect and mechanism of Xuebijing injection (XBJ) on the hematopoietic homeostasis of bone marrow (BM) in septic mice. Methods: BM cells stimulated with XBJ were analyzed by inverted optical microscope and qPCR, to evaluate the effect of XBJ on differentiation function of BM cells in vitro. Lipopolysaccharide (LPS) 055:B5 at the dose of 20mg/kg was used to establish the sepsis model. To determine the hematopoietic stem cells homeostasis affected by LPS in mice, BM cells were isolated and analyzed by flow cytometry based on the immunophenotypic surface markers. 20ml/kg of XBJ was administered by tail vein once/day after peritoneal injection of LPS. All animals were sacrificed on the fifth day. The frequency of hematopoietic stem cells (HSC) and immune cells in mice were quantified by flow cytometry. The gene expression of transcription factors were detected by qPCR. Results: XBJ promoted myeloid differentiation of BM cells in vitro, which may be related to the mRNA expression of the transcription factors. The results in vivo showed the percentage of BM Lin-SCA-1+c-KIT+ (LSK) cells, and Long-term HSCs (LT-HSC) were significantly increased in LPS group. But the percentage of multipotential progenitors (MPPs), granulocyte-monocyte progenitor (GMP) and megakaryocytic-erythroid precursor (MEP) were significantly decreased in LPS group. Whereas, XBJ improved the immune function in sepsis mice by suppression the LSK expansion in vivo. The result of qPCR showed that LSD1 and PU.1 mRNA expression in XBJ group were significantly higher than LPS group and control group respectively. Conclusion: Xuebijing injection can improve immune function in sepsis mice by regulating hematopoietic homeostasis. Its mechanism may be related to the up-regulation of LSD1 and PU.1 gene expressions.
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 ( 123 PDF (859KB) ( 64 )  
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.
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 ( 186 HTML PDF (921KB) ( 104 )  

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.

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 ( 159 HTML PDF (652KB) ( 85 )  

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.

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 ( 122 HTML PDF (647KB) ( 61 )  

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.

Clinical metabolic analysis combined with traceability of biosynthetic pathway: a new approach to quality marker of Chinese materia medica
Yang Zhi-Rui, Wang Ai-Ting, Liu Juan, Yang Xin-Yu, Wang Xiao-Fang, Zhang Lei, Guo Na, Zi Jia-Chen, Peng Cheng, Yan Shu-Xun, Yan Dan
6TMR Modern Herbal Medicine    2019, 2 (1): 3-10.   https://doi.org/10.12032/TMRmhm2017A39
Abstract ( 289 HTML PDF (920KB) ( 124 )  

Quality marker (Q-marker) of Chinese materia medica (CMM) plays an important role in quality control of CMM products. However, its research strategy and technique remain unclear. Based on the fact that quality standard of CMM should be associated with clinical efficacy, taking Jinqi Jiangtang tablet treating type 2 diabetes as an example, the Q-marker related to activity via the reverse analysis of drug metabolism in clinic and traceability of botanic biosynthetic pathways is discovered and validated. Therefore, we proposed a new research strategy of Q-marker of CMM with "Discovery of clinical active constituents as guidance, Reverse analysis of metabolic transformations as link, and Traceability of biosynthesis pathways as key", to improve quality control of CMM products.

Highlights:
"Discovery of clinical active constituents as guidance, Reverse analysis of metabolic transformations as link, and Traceability of biosynthesis pathways as key", a new research strategy for discovering quality marker of Chinese materia medica (CMM), promotes quality standard of CMM.

Effects of Dingjifumai Decoction on Electrocardiogram and sodium potassium pump of rats with ventricular arrhythmia
Fu Ling, Liao Hui-Ling, Zhou Yan, Zou Fei-Hu, Luo Ling
6TMR Modern Herbal Medicine    2019, 2 (1): 11-18.   https://doi.org/10.12032/TMRmhm2017A37.
Abstract ( 249 HTML PDF (537KB) ( 106 )  

Objective: To investigate the effect of Dingjifumai Decoction (DJFM) on Electrocardiogram (ECG) and sodium potassium pump in rats with ventricular arrhythmia. Methods: Forty healthy male SD rats (200 ± 20g) were randomly divided into blank group, model group, Metoprolol group and DJFM group. Ten rats in each group were fed with normal diet and free drinking water. Each group was given gavage, and the amount of gavage in each group was calculated according to body weight. In the model group, 0.001% Aconitine was injected into the tail vein at 30ug/kg. In the Metoprolol group, Metoprolol suspension was given according to the standard of 5.2mg/kg per day. In the DJFM group, DJFM was given at 17.6g/kg per day. After 2 weeks of administration, the biologic experiment system BL-420F was used to monitor the II lead ECG curve, and the ECG changes were observed and recorded. Then, the left ventricle of the rat was taken, and part of the heart tissue sodium potassium pump was detected. Results: (1) The effect of DJFM on ECG of rats with ventricular arrhythmia: After intravenous injection of aconitine, the incidence of Ventricular Premature beat (VP), Ventricular Tachycardia (VT), Ventricular Fibrillation (VF) in the model group was 100%, suggesting that the model building of rats with ventricular arrhythmia was successful. (2) VP, VT, and VF time: Compared with model group, DJFM group and Metoprolol group can significantly delay the VP, VT and VF, the difference was statistically significant (P < 0.05). The effect of DJFM group and Metoprolol group on delaying the appearance of VP, VT and VF was the same, there was no significant difference (P > 0.05). (3) The effect of DJFM on sodium potassium pump in rat ventricular arrhythmia heart tissues: Compared with the blank group, the sodium potassium pump value in the model group was significantly decreased, and the difference was statistically significant (P < 0.05). Compared with the model group, the sodium potassium pump value of the tissues in the Metoprolol group and the DJFM group increased, and the difference was statistically significant (P < 0.05). There was no significant difference in sodium potassium pump between the Metoprolol group and the DJFM group (P > 0.05). Conclusion: 1. The rat model of ventricular arrhythmia can be successfully prepared by intravenous injection of Aconitine. 2. DJFM can prolong the occurrence time of cardiac arrhythmias caused by aconitine in rats, such as VP, VT, VF, et al. The mechanism may be related to fast Na+ channel, and it may prevent and control arrhythmias by inhibiting Na+ influx and reducing the fast response cellular self-discipline. 3. DJFM can protect the myocardial tissue sodium potassium pump, which can protect the myocardial cells and improve the myocardial metabolism.

Highlights
In this study, the effects of Dingjifumai Decoction (DJFM) on Electrocardiogram and sodium potassium pump of rats with ventricular arrhythmia were observed, and the effects and mechanism of DJFM on ventricular arrhythmia were discussed. We found that DJFM can prolong the occurrence time of cardiac arrhythmias caused by aconitine in rats, such as VP, VT, VF, et al. The mechanism may be related to fast Na+ channel, and it may prevent and control arrhythmias by inhibiting Na+ influx and reducing the fast response cellular self-discipline. DJFM can protect the myocardial tissue sodium potassium pump, which can protect the myocardial cells and improve the myocardial metabolism

Survey of dose-effect relationship in Chinese materia medica
Kao Hsiu-Ying, Jiang Yong
TMR Modern Herbal Medicine    2018, 1 (4): 249-258.   https://doi.org/10.12032/TMRmhm2017B33
Abstract ( 371 HTML PDF (980KB) ( 198 )  

The research on the dose-effect relationship in Chinese materia medica is delayed due to the complexity of its composition, multi-efficacy, multi-targeting and other factors. Many experts put forward relevant research ideas and methods and worked out more and more research results in literature, experimental and clinical categories because of the progress of statistical methods and scientific and technological means in recent years. In this paper, these results were preliminarily combed to show the basic situation of dose-effect relationship research in Chinese materia medica.

Highlights

The research on the dose-effect relationship in Chinese materia medica was delayed due to the complexity of its composition, multi-efficacy, multi-targeting and other factors. However, there are more and more research results in literature, experimental and clinical categories because of the progress of statistical methods and scientific and technological means in recent years. This paper aimed to present the current basic situation.

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