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05 July 2018, Volume 3 Issue 4 Previous Issue    Next Issue
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Special Issue on the Modern Chinese Herbs
Continuous ban on injections of traditional Chinese medicines 
Editor Group of TMR
Traditional Medicine Research. 2018, 3 (4)  
Abstract ( 601 )     PDF (175KB) ( 86 )  
Recently, the State Drug Administration of the People's Republic of China issued a series of notifications to ban certain herbal injections or modify the instructions for their use:
May 29, 2018: A contraindication was added in the Caihu injection manual: forbidden for use in children!
June 11, 2018: A contraindication was added in the Shuanghuanglian injection manual: forbidden for use in children aged 4 years and under and pregnant women!
June 12, 2018: A contraindication was added in the Danseng injection manual: forbidden for use in newborns, infants, and pregnant women!
   In addition to the inclusion of prohibition of use by children, allergic reactions were clearly emphasized in the adverse reactions. Besides the abovementioned injections, there are also a few other commonly used traditional Chinese medicine (TCM) injections that need attention: Yinzhihuang injection, Xiyanping injection, Chuanhuning injection, Yanhuning injection, Shengmai injection, Lianbizhi injection, Qingkailing injection, Yuxingcao injection, Honghua injection, Compound Pugongying injection, etc. 
Since 2005, restrictions have been imposed on the clinical use of at least 45 kinds of TCM injections, or orders have been issued for modifications in their contraindications and matters needing attention. Therefore, according to the “Opinions on Deepening the Reform of Examination and Approval system and Encouraging the Innovation of Drug and Medical Devices" issued by the General Office of the Communist Party of China Central Committee and the General Office of the State Council, the re-evaluation of TCM injections in the market needs to be carried out to ensure their safety and efficacy.
   Since TCM injections contain many biological macromolecules and impurities as well as several unidentified components, new impurities or insoluble granules are easily generated during their storage. This makes them prone to becoming potential allergens that result in allergic reactions and even lead to shock, especially in children. The present special issue on the modern Chinese herbs will focus on the latest research on the efficacy and mechanism of TCM.


Editor Group of TMR

Modernization of Traditional Medicine
Long-term effect of Chinese herbal medicine Tianqi Capsule on the incidence of diabetes: an 8-year cohort study protocol
Bing Pang, Chun-Yong Han, Qing-Hu He, Jing Liu, Qing-Wei Li, Yu-Jiao Zheng, Feng-Mei Lian, Xiao-Lin Tong
Traditional Medicine Research. 2018, 3 (4): 166-172.   https://doi.org/10.12032/TMR201812075
Abstract ( 3125 )   HTML ( 27 )     PDF (449KB) ( 405 )  

Highlights
The protocol attempted to systematically assess the long-term efficacy of Tianqi capsule for prevention of T2DM.

Editor’s Summary
Tianqi capsule is an approved natural TCM compound in China (Approved No. Z20020089). This study may provide evidence for the long-term effect of Tianqi capsule intervention to prevent T2DM in people with impaired glucose tolerance.

Abstract
Background:The rapid growth of type 2 diabetes mellitus (T2DM) remains a big challenge for clinicians worldwide. Traditional Chinese medicine may bring a new approach for solving this problem. The Tianqi Capsule Diabetes Prevention Study (REDUCES Study) reported that 1 years of therapy with Tianqi capsule reduced the risk of diabetes by 32.1% compared with the placebo. Here we aimed to assess the long-term effect of Tianqi capsule on prevention of T2DM in people with impaired glucose tolerance after discontinuation of active intervention. Methods/design: 420 subjects will be followed-up for 8 years to assess the long-term effect of Tianqi capsule intervention. The causes of death and the status of living subjects will be investigated. Follow-up data for living subjects will be collected by personal interview and clinical examination and medical record review to determine diabetes status. Questionnaires will be given to all the subjects to investigate the factors that probably affect the diabetes status during the 8-year of discontinuation of intervention. The primary outcome is the incidence of T2DM, and the secondary outcomes are body mass index, blood glucose, blood lipids and blood pressure. The Cox proportional hazards model will be used to estimate the hazard ratio for diabetes incidence. Analyses will be done with SAS 8.2 software package. Discussion: Results from this study may provide evidence for the long-term efficacy of Tianqi capsule in patients with prediabetes. The findings will provide a basis for further confirmatory studies. Ethics: The protocol has been approved by the Medical Ethics Committee of Guang’anmen Hospital of China Academy of Chinese Medical Sciences (approval number 2016-046-KY-01). Study registration number: ClinicalTrials.gov; NCT02848053.

Influence of astragalus polysaccharide on kidney status and fibrosis indices of a rat model of streptozotocin-induced diabetic nephropathy
Yue Ji, Xue-Rou Yan, Hong-Tao Yang, Kang Yang, Qing-Yun Zhao, Shou-Ci Hu, Qi-Hang Su
Traditional Medicine Research. 2018, 3 (4): 173-180.   https://doi.org/10.12032/TMR201812076
Abstract ( 1319 )   HTML ( 19 )     PDF (779KB) ( 393 )  

Highlights
Though no down-regulation effect on blood sugar was observed, astragalus polysaccharide could improve renal tubular interstitial injury in diabetic nephropathy rats and the early stage of renal function damage, which may be related to downregulation of the TGF-β1 and α-SMA.

Editor’s Summary
The application of traditional Chinese medicine in the protection and treatment of the complication of diabetic nephropathy needs further research.

Abstract
Object:To examine the effect of astragalus polysaccharide (APS) on kidney status and fibrosis indices of rats with diabetic nephropathy. Methods:72 male rats were randomly divided into three groups: negative control group (NC, n = 24); diabetic nephropathy model group (DNM, n = 24); and diabetic nephropathy model with APS group (DNM + APS, n = 24). Rats of the DNM and DNM + APS groups were subjected to both unilateral nephrectomy and administered streptozotocin (STZ) injection (65 mg/kg). DNM + APS group rats were administered 50 IU/kg/d APS by subcutaneous injection from the first week after operation until death. The NC and DNM group rats were subcutaneously injected with an identical volume of physiological saline. At weeks 3, 8, and 13 after the operation, 6 rats from each group were randomly sacrificed and blood was collected to measure serum creatinine and blood urea nitrogen. On the day before sacrifice, the rats were placed in a metabolic cage for 24 h to collect urine. At week 14 after the operation, 6 rats from each group were randomly selected to measure body weight and kidney index. Blood was collected to measure blood glucose. The kidneys were harvested to detect pathological changes by hematoxylin and eosin staining. Results:Histological assessment of DNM rats suggested damage symptoms as evidenced by hyperplasia of the glomerular mesangial matrix, atrophia of the kidney tubules, and thickening of the basement membrane. In contrast, STZ-induced diabetic nephropathy rats treated with APS (50 IU/kg/d) showed significantly improved histological results, suggesting that APS has beneficial effect on renal tissues in STZ-induced DNM rats. Our results also indicated that APS relieved renal injury and effectively improved body weight in DNM rats. The ratio of kidney weight to body weight was reduced and the early stage of renal function damage was improved after APS treatment. In the later stages of the disease, the 24 h urinary protein significantly decreased. Moreover, APS down-regulated TGF-β1 and α-SMA expression of the kidney.

Study on alantolactone-induced differentiation of mesenchymal stem cells into vascular cells
Yan-Jiao Lu, Qiong Lu, Ruo-Ke Su, Gang Wang, Rui Tan
Traditional Medicine Research. 2018, 3 (4): 181-190.   https://doi.org/10.12032/TMR201812077
Abstract ( 770 )   HTML ( 10 )     PDF (1455KB) ( 429 )  

Highlights
The present study demonstrates the reliability of the highly efficient system for screening of active drug molecules with vascular induction function from Chinese medicines and confirmed the vascular induction function of alantolactone.

Editor’s Summary
This cell screening model and verification experiment may provide methods for the rapid screening of more drug molecules with vascular induction function from Chinese medicines and verifying the potential of rMSCs to differentiate into blood vessels with suitable stimulants.

Abstract
To promote efficient screening of active angiogenic drugs from traditional medicines, we constructed a human embryonic kidney-293 cell model using vascular endothelial growth factor (VEGF) gene promoter as the drug target. In this model, VEGF gene promoter may regulate the expression of the luciferase reporter gene by responding to the stimulation of drug molecules. This cell model allows rapid and efficient screening of vascular-inducing active components from several drug monomer molecules. Furthermore, we used rat bone marrow mesenchymal stem cells (rMSCs) to conduct a preliminary study on the activity of alantolactone. Using simvastatin as a positive control, we investigated the effects of alantolactone on the expression of vascular-related cell marker molecules such as VEGF and α-smooth muscle actin (α-SMA) in rMSCs. According to our results, 0.1, 1, 3 and 5 μM of alantolactone upregulated the transcriptional luciferase gene activity of VEGF promoter, and a significant difference from that in the control group was observed. Among them, 3μM of alantolactone showed the better effect than that of 3 μM of simvastatin (P = 0.036) and other concentrations of alantolactone and simvastatin showed similar effects. Compared with that in the control group, rMSCs induced with 1μM alantolactone for 3 days showed a significant increase in the relative mRNA expressions of VEGF and α-SMA genes. However, these effect of 5 μM alantolactone were weaker than those of 5 μM simvastatin (P < 0.05); rMSCs treated with 1 μM alantolactone for 3 days showed brighter green fluorescence (FITC marker) of α-SMA and VEGF in situ expression than that observed in the control group and similar fluorescence intensity than that of simvastatin group in an immunoradiometric assay. The above results demonstrate the reliability of the highly efficient system for screening of active drug molecules and confirmed the vascular induction function of alantolactone at the gene and protein levels.

Jianpi Qingchang Decoction-containing serum regulates the autophagy of interstitial cells
Yan-Cheng Dai, Ya-Li Zhang, Lie Zheng, You-Lan Chen, Xuan Chen, De-Liang Chen, Zhi-Peng Tang
Traditional Medicine Research. 2018, 3 (4): 191-201.   https://doi.org/10.12032/TMR201812078
Abstract ( 810 )   HTML ( 12 )     PDF (7321KB) ( 196 )  

Highlights
Jianpi Qingchang Decoction can antagonize rapamycin-induced autophagy in ICCs by promoting the phosphorylation of PI3K/AKt pathway.

Editor’s Summary
The modulation on autophagy of interstitial cells may become the new therapeutic strategy in the treatments of ulcerative colitis with traditional Chinese medicine.

Abstract
Objective:To investigate the effects of Jianpi Qingchang Decoction-containing serum (JQD-CS) on interstitial cells of Cajal (ICCs) autophagy and cell cycle arrest in vitro. Methods:ICCs were collected from the small intestines of mice and analyzed using an anti-c-Kit antibody. ICCs were divided into five groups: the blank group, the rapamycin group (an autophagy inducer), the 5% (rapamycin + 5% JQD-CS), the 20% (rapamycin + 20% JQD-CS) JQD-CS groups, and the 3-Methyladenine (3-MA) group (rapamycin + 3-MA; positive control). Transmission electron microscopy was used to observe the ultrastructure of ICCs. Western blotting was used to detect the expression of microtubule-associated protein 1 light chain 3 (LC3-II), Beclin-1, phosphatidylinositol 3-kinase (PI3K), p-PI3K, protein kinase B (AKt), p-AKt, mammalian target of rapamycin (mTOR), and p-mTOR. Ca2+ current was examined by patch-clamp experiments. Cell cycle was detected by flow cytometry. Results:Unlike in the rapamycin group, the ICC structures were more integrated and a lower number of autophagic vacuoles were observed in the 20% JQD-CS group. Moreover, the expression of LC3-II and Beclin-1 decreased, the expression of c-Kit, p-PI3K, p-AKt increased, the maximum current density value decreased, and the number of cells in the G1 phase increased while those in the G2/M phase decreased, with the addition of 20% JQD-CS. Conclusion:JQD-CS can antagonize rapamycin-induced autophagy in ICCs in vitro by promoting the phosphorylation of PI3K/AKt pathway, inhibiting Ca2 + inflow, and regulating the cell cycle.

Review
Research progress on anti-tumor properties of Marsdenia tenacissima
Yan-Lan Hu, Shao-Hui Wang, Cui-Wei He, Tong-Xiang Liu
1Traditional Medicine Research. 2018, 3 (4): 202-213.   https://doi.org/10.12032/TMR201812079
Abstract ( 1088 )   HTML ( 17 )     PDF (639KB) ( 407 )  

Highlights
This review summaries the recent progress on the main anti-tumor mechanism of Tongguanteng (Marsdenia tenacissima) and its extract.

Editor’s Summary
Editor’s Summary Tongguanteng (Marsdenia tenacissima) belongs to the family Asclepiadaceae, which mainly distributed in the Guizhou, Yunnan, Sichuan, and Guangxi provinces of China and other areas in Southeast Asia.

Abstract
Tongguanteng (Marsdenia tenacissima), which is mainly distributed in the Yunnan and Guizhou provinces of China, was first recorded in Diannanbencao by Lan Mao of the Ming dynasty of China. According to recent pharmacological studies, the chemical composition of Tongguanteng (Marsdenia tenacissima) is complex and contains C21 steroidal saponins, polysaccharides, alkaloids, and other molecules, which show anti-cancer effects on various tumor cell lines. It inhibits tumor cell proliferation and growth mainly by increasing the expression of apoptosis- and cell cycle-related proteins to promote apoptosis and arrest tumor cells in the G2/M or S phase. Downregulation of the expression of vascular endothelial growth factor-2/A and matrix metalloprotease-2/9 suppresses the formation of the tumor microvasculature, leading to tumor malnutrition, increased expression of interleukin-2, glutathione peroxidase, catalase, and superoxide dismutase, and decreased interleukin-10 and malondialdehyde expression, thereby enhancing immunity and antioxidation in the body. Additionally, inhibition of epidermal growth factor receptor, hepatocyte growth factor receptor, and tyrosine-protein kinase receptor activation enhances the anti-tumor efficacy of epidermal growth factor receptor-tyrosine kinase inhibitors as well as inhibits P-glycoprotein and cytochrome P450 to increase the concentration of anti-tumor drugs in tumor cells.

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