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ORIGINAL ARTICLES
Kigelia africana fruit: Constituents, bioactivity, and reflection on composition disparities
Ahmed Galal Osman, Zulfiqar Ali, Amar G Chittiboyina, Ikhlas A Khan
October-December 2017, 3(4):1-6
DOI:10.4103/wjtcm.wjtcm_15_17  
Objective: Kigelia africana, a tropical tree, which has long been used in African traditional medicine. The objective of the current study has been identifying the constituents of K. africana and verifying its utilities in traditional medicine. Materials and Methods: The methanol extract of K. africana fruits was subjected to chromatographic fractionation utilizing different techniques. The methanol extract together with the isolated compounds were tested for their bioactivities in a series of cell-based assays. Results: The current work led to isolation and characterization of nine constituents including iridoid glycosides, phenylpropanoid derivatives, and a eucommiol derivative. The hexanes extract caused inhibition of the opportunistic yeast; Cryptococcus neoformans Pinh. The chloroform extract exhibited substantial antileishmanial activity of Leishmania donovani. Verminoside (1) showed weak inhibition of the CB1, CB2, and Kappa opioid receptors. Compound 4 exhibited weak inhibition of the Kappa and Mu opioid receptors. The hexanes and the chloroform extracts of K. africana exhibited inhibitory activity against the pathogenic parasite Trypanosoma brucei. The ethyl acetate extract showed the same activity. Conclusions: This is the first report on the isolation of coniferyl 4-O-β-D-glucopyranoside (7), a eucommiol derivative (crescentin IV) (6), and 6-feruloylcatalpol (4) from the genus Kigelia. It is also the first report on the separation of ajugol (2), catalpol (3), and specioside (5) from the fruits of K. africana. Revision of the 1H and 13C-NMR spectra of 6-feruloylcatalop (4) and 6-p-hydroxycinnamoylcatalpol (5, specioside) is described. Further, the results of the in vitro assays corroborate the traditional utility of this plant in medicine.
  2,322 305 1
REVIEW ARTICLES
Xiao chai hu tang for liver diseases: A literature review
Yi Wang, Li Li, Yan-Mei Cheng, Sheng-Liang Zhu
July-September 2017, 3(3):46-50
DOI:10.4103/wjtcm.wjtcm_4_17  
The objective of this study is to summarize the pharmacological effects and the mechanisms of action of Xiao Chai Hu Tang (XCHT, Minor Bupleurum Decoction) on liver diseases, so as to give relevant researchers a valuable insight and benefit patients with hepatopathy. PubMed was used to search for and collect scientific publications related to XCHT and liver diseases from 1986 to 2016. The available scientific results or evidence were read, classified, and analyzed. XCHT showed clinical efficacy in patients with hepatic diseases including hepatitis, hepatic fibrosis, and hepatoma. The mechanisms involved the production of cytokines, the regulation of immune function, the suppression of lipid peroxidation, etc., XCHT might work on the metabolism of some medications such as tolbutamide by the regulation of gastric emptying and intragastric pH. XCHT exhibited a very low toxicity profile, such as interstitial pneumonia due to duration of medication, patients' age, and drug combination. XCHT has been a eutherapeutic supplemental remedy for liver diseases. However, many mechanisms of action and effects of XCHT on new types of liver diseases still remain unclear, so more and more animal experiments and human clinical trials are needed to obtain enough proofs for the clinical use of XCHT in new types of hepatosis such as nonalcoholic fatty liver disease and autoimmune liver disease.
  2,281 187 1
Interactions between traditional chinese medicine and anticancer drugs in chemotherapy
Zhi-Jie Ding, Dan-Qing Xu, Yuan-Zhi Lao, Hong-Xi Xu
July-September 2017, 3(3):38-45
DOI:10.4103/wjtcm.wjtcm_6_17  
Herbal medicines, including traditional Chinese medicines (TCMs), have been used in Eastern countries for treating diseases such as cancer for thousands of years. With the growing knowledge of tumorigenesis and cancer therapy, some natural compounds have been developed as clinical anticancer drugs. In addition, many compounds and TCMs have been characterized as complementary and alternative treatments, with synergetic effects on enhancing the efficacy or reducing the side effects of the therapeutics. In this review, we summarized the recent studies focusing on the combination of natural compounds or TCM decoction with chemotherapeutics. The detailed mechanisms of action of the combinations and the application of analytical methods on TCM development are also discussed.
  1,961 284 -
ORIGINAL ARTICLES
The effects of different compatibilities of Qing'e formula on scopolamine-induced learning and memory impairment in the mouse
Xiao-Ping Zheng, Fang-Di Hu, Li Yang, Yu-Ling Ma, Bo-Lu Sun, Chang-Hong Wang, Zheng-Tao Wang
July-September 2017, 3(3):12-17
DOI:10.4103/wjtcm.wjtcm_8_17  
Background: The Qing'e formula (QEF) is a well-known traditional Chinese prescription that has been clinically employed for treatment of bone disease for hundreds of years. Objective: The present study aims to observe the effects of different compatibilities of QEF on the scopolamine-induced learning and memory impairment in the mouse, and further to explore its action mechanisms and compatibility rationality. Materials and Methods: The learning and memory alterations in the mouse were evaluated using the step-down test and Morris water maze (MWM) test; the acetylcholinesterase (AChE) activity and brain-derived neurotrophic factor (BDNF) expression in the hippocampus were measured using colorimetric method or immunohistochemistry. Results: The results showed that different compatibilities of QEF significantly prolonged latency in the step-down test, shortened escape latency in the navigation test, increased the percentage of residence time, and the percentage of swimming distance in the target quadrant in the probe trial session. In addition, our results also found that different compatibilities of QEF remarkably inhibited AChE activity and increased BDNF expression in the hippocampus of mice. What's more, the group after being treated with whole recipe (QF) showed the highest level of improvement. Conclusions: These findings not only suggest that QEF may effectively ameliorate cognitive deficits through inhibiting AChE activity and increasing BDNF expression in the hippocampus but also elucidate the rationality of QEF.
  1,974 134 -
REVIEW ARTICLES
Effect of Juzentaihoto/Shi-Quan-Da-Bu-Tang on malignant progression and metastasis of tumor cells
Ikuo Saiki, Satoru Yokoyama, Yoshihiro Hayakawa
October-December 2017, 3(4):26-45
DOI:10.4103/wjtcm.wjtcm_3_17  
A Japanese herbal (Kampo, [INSIDE:1]) medicine, [INSIDE:2] (juzentaihoto/Shi-Quan-Da-Bu-Tang), is one of the nourishing agents, a so-called “[INSIDE:3] (Hozai/Bu-Ji),” that is used for improving disturbance and imbalances in the homeostatic condition of the body. This formulation is orally administered to patients in various weakened states, including postsurgery patients and patients with chronic illness, where it can alleviate general symptoms such as extreme fatigue, pale complexion, loss of appetite, dry or scaly skin, night sweating, and dryness of the mouth. Recently, juzentaihoto/Shi-Quan-Da-Bu-Tang has been shown to have a variety of biological activities, including activation of natural killer cells and macrophages, cytokine induction, antibody production, antitumor effects in combination with surgical excision or other drugs, and protection against the adverse effects of anticancer drugs and radiation, including immunosuppression and bone marrow toxicity. This article focuses on the antitumor and antimetastatic properties of some Kampo medicines and mainly describes the effects of juzentaihoto and its related formulations on tumor development, progression, and metastasis in vivo. We also discuss the inhibitory mechanism of action and the importance of the prescription and constituent crude drugs in determining the efficacy.
  1,630 195 -
Progress of studies on traditional chinese medicine based on complex network analysis
Qian-Ru Zhang, Xiang-Jun Kong, Hai-Yu Xu, Yi-Tao Wang, Yuan-Jia Hu
July-September 2017, 3(3):28-37
DOI:10.4103/wjtcm.wjtcm_7_17  
Traditional Chinese medicine (TCM) is a distinct medical system that deals with the life–health–disease–environment relationship using holistic, dynamic, and dialectical thinking. However, reductionism has often restricted the conventional studies on TCM, and these studies did not investigate the central concepts of TCM theory about the multiple relationships among life, health, disease, and environment. Complex network analysis describes a wide variety of complex systems in the real world, and it has the potential to bridge the gap between TCM and modern science owing to the holism of TCM theory. This article summarizes the current research involving TCM network analysis and highlights the computational tools and analysis methods involved in this research. Finally, to inspire a new approach, the article discussed the potential problems underlying the application of TCM network analysis.
  1,394 205 1
ORIGINAL ARTICLES
New orally active artemisinin dimer antimalarials
Mahmoud A ElSohly, Waseem Gul, Shabana I Khan, Babu L Tekwani
July-September 2017, 3(3):1-11
DOI:10.4103/wjtcm.wjtcm_10_17  
Objective: To synthesize orally bioavailable artemisinin dimers and the evaluation of their in vivo antimalarial activity. Methods: Artemsisin dimers were synthesized and their antimalarial activity was determined in in vitro and in vivo studies (administered orally and IP). Results: Dimers 5 and 6 provided 100% suppression of parastemia throughout the oral administration study, with all animals surviving up to day 28 (the last day of the study). Conclusion: Dimers 4-7 displayed markedly improved in vitro activity against P. falciparum, while the in vivo activity against P. berghei was highly encouraging, with 5 and 6 completely clearing parasitemia from the start of the drug treatment until the end of the study (day 28).
  1,186 181 -
REVIEW ARTICLES
Traditional chinese herbal medicine for perimenopausal depression of chinese women: A meta-analysis
Ying Zhang, Lin-Jie Xu, Yu Zheng, Feng-Quan Xu
July-September 2017, 3(3):51-57
DOI:10.4103/wjtcm.wjtcm_12_17  
Objective: The objective of this study is to evaluate the effectiveness and safety of traditional Chinese herbal medicine (TCHM) in treatment of perimenopausal depression (PD) in China. Methods: To identify randomized controlled trials, an electronic search has been conducted through databases as follows: PubMed, the Cochrane Central Register of Controlled Trials, Web of Science, Chinese Biological Medicine Database, China National Knowledge Infrastructure Database, Chinese Scientific Journal Database, and WanFang Digital Periodicals Database. Methodological quality was evaluated by Cochrane Collaboration's tool which is able to assess the risk of bias in Review Manager Software. What's more, meta-analysis was performed by using Cochrane Collaboration's RevMan 5.2 software, (Nordic Cochrane Centre, Cochrane Collaboration, Copenhagen, and Denmark). Dichotomous data were analyzed by using relative risk (RR) and 95% confidence interval (CI). Continuous variables were analyzed using weighted mean differences (WMDs) and 95% CI. Subgroup analysis was performed by the type of medicine which was used in the experimental group. Results: This meta-analysis includes 11 randomized control trials with 818 patients. Compared to the control group (RR: 1.14, 95% CI: [1.03, 1.26], P = 0.009 and WMD: −2.09, 95% CI: [ −3.58, −0.18]), the experimental group had a significant higher clinical efficacy rate and relatively lower Hamilton Depression Rating Scale (HAM-D) score. For clinical efficacy rate, the results varied depending on the detail treatment measures of the experimental group. In the experimental group with TCHM, no significant difference was observed (RR: 1.14, 95% CI: [0.97, 1.33]), while in the experimental group combined with western medicine, a significant difference in the clinical efficacy rate between the experimental group and control group showed up (RR: 1.15, 95% CI: [1.01, 1.32], P = 0.04). For the HAM-D score, subgroup analyses revealed that the pure TCHM therapy was not associated with significant HAM-D score reduction compared to the control group (WMD: −2.48, 95% CI: [−6.00, 1.03], P = 0.17). However, in the experimental group where western medicine was added to, the HAM-D score decreased statistically compared to the control group (WMD: −1.88, 95% CI: [−3.58, −0.18], P = 0.03). There is no serious adverse event in both groups. Conclusions: Combination therapy of TCHM and western medicine is more effective in treating PD in terms of clinical efficacy rate. However, the results should be interpreted with caution due to the mediocre methodological quality of the included trials.
  1,214 139 1
ORIGINAL ARTICLES
Investigation on prescription screening of a polyherbal preparation based on splenocyte proliferation activity and its preparation method
Ahmed Attia Ahmed Abdelmoaty, Yu-Ling Ma, Ruibin Bai, Xiao-Ping Zheng, Fang-Di Hu, Ying-Dong Li
October-December 2017, 3(4):7-14
DOI:10.4103/wjtcm.wjtcm_14_17  
Objective: The present study aims to optimize the extraction conditions of polysaccharides and flavonoids from a polyherbal preparation consisting of three kinds of Chinese medicinal herbs, Codonopsis pilosula, Crataegus pinnatifida, and Lycium barbarum, and evaluation of its immunomodulatory activity in immunosuppressed mice. Materials and Methods: An orthogonal design (L9 [3]4) was constructed to achieve the optimal extraction conditions. The immunomodulatory action of the polyherbal preparation was studied at three doses of 10, 20, and 40 mL/kg/day orally by measuring splenocyte proliferation in mice model of cyclophosphamide-induced immunosuppression. Results: The chosen parameters, including the ratio of solvent-to-raw material, duration of extraction, and extraction times, were the fundamental variables that influenced the extract yields. The highest yield of total polysaccharides content was 54.3 mg/mL when the ratio of solvent-to-raw material, duration of extraction, and number of extractions were 12:1, 1.5 h, and 3, respectively. The maximum extraction yield of the flavonoids was 3.5 mg/mL when the ratio of solvent-to-raw material was 12:1, the extraction time was 2 h, and the number of extractions was 3. The prescription screening showed that the impact of the polyherbal preparation on the splenocyte proliferation capacity was more pronounced than its disassembled components. Oral administration of the polyherbal preparation could significantly increase the concanavalin A-stimulated mouse spleen cells proliferation in a dose-dependent manner. Conclusion: These findings suggested that the polyherbal preparation possesses potential for augmenting the immune activity due to the polysaccharide and flavonoid content in these herbal medicines.
  1,149 142 1
REVIEW ARTICLES
Monoclonal antibody usage strategies for natural products in traditional chinese medicine
Yukihiro Shoyama
July-September 2017, 3(3):18-27
DOI:10.4103/wjtcm.wjtcm_5_17  
Monoclonal antibodies (MAbs) against natural products with low-molecular weights have become an important tool when combined with other analytical systems. Eastern blotting involves a typical staining system wherein, for example, glycosides can be blotted to a membrane and cross-linked and stained using MAbs. An immunoaffinity column combined with a monoclonal antibody allows a one-step purification of hapten compounds or preparation of a knockout extract that removes only the target hapten molecules from a crude extract. Here, we discuss the application of these extracts. Single-chain variable fragment (scFv) proteins have led to novel assay systems such as fluobodies or antibodies coupled with green fluorescent protein for natural products. A typical novel application of a scFv gene would be in the context of plant breeding; this is designated “missile-type” molecular breeding, intended to increase hapten molecule concentrations in transgenic plants.
  1,115 136 -
ORIGINAL ARTICLES
The total flavonoids of Clerodendrum bungei suppress A549 cells proliferation, migration, and invasion by impacting Wnt/β-Catenin signaling
Na Yu, Ke-Jian Zhu, Si-Jing Ma, Hao Tang, Xiao-Ning Tan
October-December 2017, 3(4):15-20
DOI:10.4103/wjtcm.wjtcm_18_17  
Objectives: The objective of this study is to evaluate the effect of the total flavonoids of Clerodendrum bungei (TFCB) on the proliferation, invasion, and metastasis of A549 lung cancer cells through the Wnt signaling pathway. Materials and Methods: A549 cells were transfected with a β-catenin overexpression plasmid and the empty vector pcDNA3.1. The A549 cells were divided into six groups: normal A549 cell group, normal A549 cells with TFCB group, vector control group, vector with TFCB group, β-catenin overexpression group, and β-catenin with TFCB group. We used the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay to detect cell proliferation, a scratch test was used to observe cell migration, and a transwell experiment was employed to evaluate cell invasion. Proteins related to the Wnt pathway were detected with Western blot analysis, including β-catenin, GSK-3 β, P-GSK-3 β, c-Myc, and CyclinD1. Results: The proliferation, invasion, and metastasis of A549 cells were significantly enhanced after being transfected with the β-catenin overexpression plasmid (P < 0.05 or 0.01), accompanied by increased expression of β-catenin, C-Myc, CyclinD1 and reduced expression of Gsk-3 β and P-GSK-3 β. Treatment of cells with TFCB resulted in inhibition of cell proliferation, migration, and invasion; downregulated expression of β-catenin, C-Myc, and CyclinD1; and upregulated expression of GSK-3 β and P-GSK-3 β, especially in the β-catenin overexpression group. Conclusion: TFCB has the potential to inhibit the Wnt/β-catenin pathway by prohibiting the overexpression of β-catenin and regulating its downstream factors.
  992 125 1
A preliminary study on combination therapy of artemisinin dimer oxime and topotecan against nonsmall cell lung cancer in mice
Mohammad K Ashfaq, Mohamed Sadek Abdel-Bakky, Mir Tahir Maqbool, Waseem Gul, Mahmoud A ElSohly
January-March 2018, 4(1):8-14
DOI:10.4103/wjtcm.wjtcm_1_18  
Background: Artemisinin dimer oxime – dimer molecule synthesized from artemisinin possesses high bioavailability and marked in vitro anticancer activities against solid tumor-derived cell lines, endothelial cell proliferation, migration, and angiogenic processes. Numerous murine models have been developed to study human cancer. The most widely used models are the human tumor xenograft mouse model. Materials and Methods: In this study, human tumor cells (NCI-H640, 1 × 107 in 100 μL) are implanted subcutaneously, or 1 × 107 in 50 μL in the thoracic cavity, in athymic nude mice (nu/nu). The implanted cells were allowed to grow for 10 days before initiation of drug treatment (dimer oxime and topotecan, ip). Tumor volume and thoracic/body weight ratio were recorded. Results: We successfully established subcutaneous and thoracic xenografts with human nonsmall cell lung cancer cell line xenografts in athymic nude mice in only 10 days. Using these models, we attempted treatment of xenografts with topotecan – a known anticancer drug and artemisinin dimer oxime or combination of these two drugs. Combination therapy showed a significant reduction in tumor volume and tumor/body weight. Treatments with combination of topotecan and dimer oxime resulted in the reduced mortality rates in comparison with untreated mice. Conclusions: Xenograft tumor models are useful for preclinical screening of new pharmacophores. From this preliminary study, it appears that combination of dimer oxime and topotecan may be used as chemotherapeutic agents against nonsmall cell lung cancer. Further studies are needed to evaluate other combination treatment regimens as well as the mechanism(s) of action.
  959 152 -
The protective effect of Gan Shen Fu Fang on liver endothelial cells in common bile duct-ligated rats
Qing-Hong Du, Yi-Bo Tang, Wei-Hong Li, Ya Xu, Lin Han, Xu Jia, Tong Zhao
October-December 2017, 3(4):21-25
DOI:10.4103/wjtcm.wjtcm_16_17  
Objective: To elucidate the protective effect of Gan Shen Fu Fang (GSFF) on liver endothelial cells in common bile duct-ligated (CBDL) rats. Materials and Methods: Cirrhosis was induced by common bile duct ligation. The rats were divided into three groups: sham group, CBDL group, and GSFF group. After 2 weeks of ligation, rats in the GSFF group were administered GSFF. After 4 weeks, the hydroxyproline (Hyp) content of liver tissues was spectrophotometrically determined. The histological changes were evaluated by H and E and Masson staining. Transmission electron microscopy (TEM) and scanning electron microscopy (SEM) were used to observe the ultrastructural changes in the liver, especially in the liver sinusoidal endothelial cells (LSECs). Results: Hyp synthesis was significantly inhibited by GSFF, which agreed with the results from H and E and Masson staining for liver fibrosis. The TEM observations of CBDL rats revealed reduced hepatocyte microvilli and deposited fibrous tissue underneath LSECs. SEM confirmed the TEM findings and showed that the fenestrae of LSECs decreased and even disappeared in CBDL rats. The morphological results indicated hepatic sinusoid capillarization. GSFF promoted the restoration of fenestrae and reversed hepatic sinusoid capillarization. Conclusion: GSFF can inhibit Hyp synthesis, restore the fenestrae of LSECs, and reverse hepatic sinusoid capillarization in CBDL rats. These results provide a basis for future detailed investigations of the mechanism of action of GSFF in LSECs.
  977 127 -
REVIEW ARTICLE
Network pharmacology: An approach to the analysis of complex systems underlying traditional chinese medicine
Shao Li, Yuan-Jia Hu
October-December 2018, 4(4):135-136
DOI:10.4103/wjtcm.wjtcm_22_18  
  883 211 -
ORIGINAL ARTICLES
Exploring the pathways and targets of Shexiang Baoxin pill for coronary heart disease through a network pharmacology approach
Shou-De Zhang, Zhan-Hai Su, Rui-Hui Liu, Yan-Yan Diao, Shi-Liang Li, Ya-Ping-Hua , Hong-Lin Li, Wei-Dong Zhang
October-December 2018, 4(4):137-146
DOI:10.4103/wjtcm.wjtcm_18_18  
Objective: To investigate the network pharmacology of Shexiang Baoxin pill (SBP) and systematically analyze the mechanisms of SBP. Methods: In this study, we excavated all the targets of 26 constituents of SBP which were identified in rat plasma though literature mining and target calculation (reverse docking and similarity search) and analyzed the multiple pharmacology actions of SBP comprehensively through a network pharmacology approach. Results: In the end, a total of 330 Homo sapiens targets were identified for 26 blood constituents of SBP. Moreover, the pathway enrichment analysis found that these targets mapped into 171 KEGG pathways and 31 of which were more enriched. Among these identified pathways, 3 pathways were selected for analyzing the mechanisms of SBP for treating coronary heart disease. Conclusion: This study systematically illustrated the mechanisms of the SBP by analyzing the corresponding “drug-target-pathway-disease” interaction network.
  938 148 -
An integrated study for the utilization of anthraquinone compounds extract “Heshouwu” In vivo and their comparative metabolism in liver microsomes using UPLC-ESI-Q-TOF/MSn
Sha Chen, Hong-Yu Ma, Zhe Deng, Jun Zhang, Jin-Tang Cheng, Chang Chen, An Liu
January-March 2018, 4(1):21-27
DOI:10.4103/wjtcm.wjtcm_2_18  
Objective: Anthraquinone (AQ), a major bioactive component of the traditional Chinese medicine HeShouWu, has widespread applications in industry and medicine. The objective of the current study is to explore the differences in the bioavailability of anthraquinones in vivo and the metabolism in liver microsomes. Materials and Methods: In vivo, we used a reliable UPLC-ESI-QqQ-MS/MS method to measure seven AQ compounds in the jugular vein plasma of rats following oral administration of HeShouWu. Furthermore, in order to quantify the bioavailability of AQs in vivo and to further understand the metabolism of these compounds, we compared the in vitro metabolism of AQ in different species with respect to metabolic profiles, the enzymes involved, and catalytic efficiency using liver microsomes from human (HLM), mouse (MLM), rat (RLM), and beagle dog (DLM). Results: We identified two metabolic pathways, including the hydroxylation and glucuronidation of AQ, in the liver microsomes of humans and other species using UPLC-ESI-Q-TOF. We found that substitutions on the AQ ring were crucial to the activity and regioselectivity of its hydroxylation. In general, hydroxylation activity decreased greatly with β-COOH (rhein) and enhanced dramatically with β-OH (emodin). We also found that glucuronidation of the compound emodin-8-O-β-D-glucoside acts as the main isoform in AQ hydroxylation in HLM and DLM. Total microsomal intrinsic clearance values for AQ were greatest in mouse microsomes, followed by those in dog, human, and rat microsomes. Conclusion: The absorption of different anthrquinone compounds varied based on the compound structure, the metabolism types and products of anthraquinones in liver microsomes were different in different species. These findings provide vital information for a deeper unuunderstanding of the metabolism of AQs.
  968 116 -
Network pharmacology-based study of the active constituents of Chinese medicinal formulae for antitumor mechanism
Bao-Yue Zhang, Yi-Fu Zheng, Xiao-Cong Pang, Zhe Wang, Hong Ding, Ai-Lin Liu
April-June 2018, 4(2):43-53
DOI:10.4103/wjtcm.wjtcm_6_18  
Objective: To investigate the network pharmacology of anti-tumor Chinese medicinal formulae and explain the synergistic mechanism of various active ingredients of Chinese medicinal formulae. Methods: We collected the anti-tumor Chinese medicinal formulae and chose several single herbs with the top frequency for further study. The chemical constituents of these herbs were downloaded from databases CNPC and Traditional Chinese Medicine Systems Pharmacology and were analyzed to set up the anti-tumor material basis. The genes regulated by these constituents were retrieved in Traditional Chinese Medicine integrated database and Comparative Toxicogenomics database. Results: We collected 65 anti-tumor Chinese medicinal formulae, and 4 single herbs were selected, including Licorice, Radix astragali, Panax ginseng, and Radix scutellariae, which consist of 172, 70, 293, and 92 known constituents, respectively. The constituent–gene network, protein–protein interaction network, gene–pathway enrichment network, and gene–disease network were constructed. Moreover, molecular docking was employed to clarify the interactions between active constituents and key drug targets (PTG2, epidermal growth factor receptor, peroxisome proliferator-activated receptor gamma, estrogen receptor 1, mammalian target of rapamycin, AKT1, mitogen-activated protein kinase 1 [MAPK1], peroxisome proliferator-activated receptor alpha, and MAPK8). Most of the constituents could act on multiple targets, whose structures mainly belong to alkaloids, flavonoids, and their glycosides, organic acids, or dianthrone, and their representative chemical constituents include narcissus glycosides, rutin, dauricine, scutellarin, baicalin, isoschaftoside, and leucovorin. Conclusion: The network mechanism of the effective constituents from traditional Chinese medicines (TCMs) for anti-tumor therapy was partially uncovered by using statistical methods, network pharmacology methods, and molecular docking methods. This study will provide important information for new drug design with multiple targets for anti-tumor therapy.
  918 153 -
Relationship between free fatty acid spectrum, blood stasis score, and macroangiopathy in patients with Type 2 Diabetes
De-Liang Liu, Shu-Fang Chu, Hui-Lin Li, Heng-Xia Zhao, Xue-Mei Liu, Xin Qu, Yi-Nan Zhou, Zhe Chen, Xue-Wen Zhang
January-March 2018, 4(1):28-35
DOI:10.4103/wjtcm.wjtcm_5_18  
Objective: Our aim was to investigate the correlation between free fatty acid (FFA) spectrum, blood stasis (BS) score, and macroangiopathy in type 2 diabetic patients with or without BS, as well as the possible relationship between BS and lipotoxicity. Methods: A total of 50 type 2 diabetes (T2D) patients with or without BS were enrolled from June to December 2014 in Shenzhen Traditional Chinese Medicine (TCM) Hospital, with 25 patients allocated to each of two groups. Basic information, BS score, blood glucose, blood lipids, etc., were measured for each patient. In addition, we tested the levels of interleukin (IL)-6, tumor necrosis factor α (TNF-α), and IL-18 with enzyme-linked immunosorbent assay. The macroangiopathy status of patients in the two groups was examined by color ultrasound and all factors related to BS scores were analyzed. Gas chromatography-mass spectrometry was used to explore the difference in the serum FFA spectra between the two different groups. In addition, the relationship between FFA spectra, BS scores, and macroangiopathy was analyzed. Results: BS scores, total cholesterol (TC), total triglyceride (TG), low-density lipoprotein cholesterol, IL-6, TNF-α, IL-18, carotid and femoral artery plaque, carotid intima-media thickness, carotid plaque area, and femoral artery plaque area were all significantly increased in T2D patients with BS syndrome (P < 0.05). A positive correlation was observed between age, duration of diabetes, carotid intima-media thickness, carotid plaque area, femoral artery plaque area, and BS score (P < 0.05). A total of 21 fatty acids were found in the serum, and total FFA (TFFA), saturated fatty acid (SFA), lauric acid (C12:0), palmitic acid (16:0), stearic acid (C18:0), arachidonic acid (C20:4n6), behenic acid (C22:0), and lignoceric acid (C24:0) scores were all found to contribute to the difference between FFA spectrums of the two groups; of the fatty acids, C12:0, C16:0, C18:0, C22:0, TFFA, and SFA positively correlated with BS scores as evaluated by Pearson's or Spearman's correlation analysis (P < 0.05). Only SFA entered the regression equation in the multiple linear regression analysis. C12:0, C16:0, C18:0, C20:4n6, TFFA, and SFA were positively correlated with carotid plaque area, whereas linoleic acid (C18:3n3), Cis-5, 8, 11, 14, and 17-eicosapentaenoic acids (C20:5n3) were negatively correlated (P < 0.05). C16:0 was positively correlated with the femoral artery plaque area and C18:3n3, cis-4, 7, 10, 13, 16, and 19-docosahexaenoic acids (C22:6) and nervonic acid were negatively correlated (P < 0.05). Conclusion: Serum FFA spectra were significantly different between T2D patients with BS and those without, and long-chain SFA made the greatest contribution. Serum FFA spectra were correlated with BS scores and diabetic macroangiopathy, which means that lipotoxicity and BS are correlated in T2D.
  919 117 -
Cloning and expression analysis of two dehydrodolichyl diphosphate synthase genes from Tripterygium wilfordii
Lin-Hui Gao, Ping Su, Yi-Feng Zhang, Li-Chan Tu, Yu-Jun Zhao, Tian-Yuan Hu, Jia-Wei Zhou, Bao-Wei Ma, Wei Gao, Lu-Qi Huang
January-March 2018, 4(1):15-20
DOI:10.4103/wjtcm.wjtcm_4_18  
Objective: To clone and investigate two dehydrodolichyl diphosphate synthase genes of Tripterygium wilfordii by bioinformatics and tissue expression analysis. Materials and Methods: According to the T. wifordii transcriptome database, specific primers were designed to clone the TwDHDDS1 and TwDHDDS2 genes via PCR. Based on the cloned sequences, protein structure prediction, multiple sequence alignment and phylogenetic tree construction were performed. The expression levels of the genes in different tissues of T. wilfordii were measured by real-time quantitative PCR. Results: The TwDHDDS1 gene encompassed a 873 bp open reading frame (ORF) and encoded a protein of 290 amino acids. The calculated molecular weight of the translated protein was about 33.46 kDa, and the theoretical isoelectric point (pI) was 8.67. The TwDHDDS2 encompassed a 768 bp ORF, encoding a protein of 255 amino acids with a calculated molecular weight of about 21.19 kDa, and a theoretical isoelectric point (pI) of 7.72. Plant tissue expression analysis indicated that TwDHDDS1 and TwDHDDS2 both have relatively ubiquitous expression in all sampled organ tissues, but showed the highest transcription levels in the stems. Conclusions: The results of this study provide a basis for further functional studies of TwDHDDS1 and TwDHDDS2. Most importantly, these genes are promising genetic targets for the regulation of the biosynthetic pathways of important bioactive terpenoids such as triptolide.
  897 123 -
Comparison of granules for prescription and classical decoctions by high-performance thin-layer chromatography-fingerprint analysis
Katharina Schiller, Jörg Heilmann, Detlef Manns, Gerhard Franz
January-March 2018, 4(1):1-7
DOI:10.4103/wjtcm.wjtcm_11_17  
Objective: The so-called granules for prescription have been developed about 20 years ago as a new form of modernizing and simplification of the classical decoction common in Traditional Chinese Medicine (TCM) practice. Due to actual problems in Germany/Europe, which are caused by the lack of quality monographs and judicial classification of granules for prescription, the aim of the study was a comparison of the chemical composition of commercial granules versus decoctions. Taking an example, decoctions, commercial granules, and organic extracts of two well-established TCM herbal drugs, Scrophulariae Radix and Xanthii Fructus, were examined in their specific composition. Methods: Using high-performance thin-layer chromatography (HPTLC) for fingerprint analysis of different batches of herbal drugs and samples from various suppliers of Xanthii Fructus and Scrophulariae Radix were critically examined. The decoctions were prepared according to traditional rules, while the granules were dissolved in water in accordance with actual regulations. Furthermore, organic extracts of the plant material were examined and compared with aqueous extracts. Results: It could be demonstrated, that in some cases, there are remarkable differences in the specific composition between granules from different suppliers, the classical aqueous decoction and the organic extract used for the HPTLC fingerprinting. On the other hand, few examples exist for good comparability of decoctions and commercial granules. Conclusion: After critical evaluation of the above results, it can be questioned, if there is a so-called phytoequivalence between decoctions and commercial granules for prescription used in TCM practice.
  824 163 -
Bioinformatics and expression analysis of NAC transcription factor genes in Scutellaria baicalensis
Juan Liu, Ti-Ying Chen, Yuan Yuan, Jun-Hui Zhou, Yu-Yang Zhao, Lu-Qi Huang
April-June 2018, 4(2):37-42
DOI:10.4103/wjtcm.wjtcm_7_18  
Background: NAC, as a unique transcription factor to plants, plays important roles in multiple biological functions, such as regulation of plant growth and development, hormone levels, and responses to various kinds of stresses. However, there is a lack of research of NAC genes in Chinese herbs. Objective: The study aimed to evaluate the potential functions of NAC genes in Scutellaria baicalensis by bioinformatics and expression analysis, and provide evidence of the molecular regulation mechanism involved in flavonoid biosynthesis in S. baicalensis. Methods: The genes of NAC transcription factors in S. baicalensis were obtained from cDNA library and their functions were explored using bioinformatic methods. The NAC genes were screened from the cDNA library of S. baicalensis using BLAST comparison software. Then, the open reading frame (ORF) finder online tool was used to predict the full-length ORFs of NAC genes and their protein characteristics were explored by bioinformatic methods. The expression of NAC genes was then detected by quantitative polymerase chain reaction in different parts of S. baicalensis and different leaves treated by gibberellin GA3 treatment. Results: Six genes of NAC transcription factors were cloned, two of which had complete ORFs. NAC genes cloned in this study were mainly expressed in the flowers of S. baicalensis. The expression levels of NAC2, NAC3, NAC4, NAC5, NAC6 were increased firstly and then decreased gradually after 100 μM GA3 treatment. Meanwhile, some NACs and PAL2 in S. baicalensis showed strong correlation. Conclusion: This study suggested that NACs cloned in this study were mainly regulated the flavonoid biosynthesis in the flowers of S. baicalensis; NAC6 in S. baicalensis might be involved in the regulation of PAL2 transcription and affected the accumulation of flavonoids in the root of S. baicalensis. Our results provided a basis for further understanding the molecular regulation mechanism of flavonoid biosynthesis in S. baicalensis.
  832 144 -
Compound-target-pathway network analysis and effective mechanisms prediction of Bu-Shen-Jian-Pi formula
Xiao-Yan Li, Meng-Die Yang, Xue-Qing Hu, Fei-Fei Cai, Xiao-Le Chen, Qi-Long Chen, Shi-Bing Su
October-December 2018, 4(4):170-175
DOI:10.4103/wjtcm.wjtcm_19_18  
Objective: The aim of this study was to predict the active compounds, therapy targets, and diseases of Bu-Shen-Jian-Pi formula (BSJPF) through the system pharmacology-based approach. Methods: Traditional Chinese Medicine Systems Pharmacology (TCMSP) and TCM Database@Taiwan Databases were used to obtain Chinese herbal medicine compounds. Oral bioavailability (OB) and drug-likeness (DL) based on the TCMSP database were used to screen the active compounds of BSJPF and related diseases. Therapy targets were defined according to the DrugBank database. The compounds-targets-disease network was constructed by Cytoscape and function and signaling pathways were also analyzed. Results: A total of 143 of 2106 compounds in BSJPF were screened out (OB ≥30%, DL index ≥0.18). Two hundred and sixty-five targets were found and 334 diseases were enriched. The diseases such as cancer, Alzheimer's disease, inflammation, and asthma were most closely correlated with the formula. BSJPF, Liu-Wei-Di-Huang decoction (LWDHD), and Si-Jun-Zi decoction (SJZD) could regulate cell proliferation and apoptosis; LWDHD also regulated biological processes and cellular processes and regulated stress on chemical stimuli and SJZD focused on the regulation of anabolic reaction. All had enriched the signaling pathways in cancer, nonsmall cell lung cancer, and thyroid cancer pathways. There were more pathways in both BSJPF and LWDHD, mainly including cancer, colorectal cancer pathways, toll-like receptors, T-cell receptors and P53 signaling pathways, and apoptosis. LWDHD was also involved in Wnt, natural killer cell cytotoxicity, and lymphocyte migration signaling pathways. SJZD had no separate pathways. In the tumor-related pathways, targets were more concentrated in the PI3K/Akt pathway and the MAPK/ERK signaling pathway. Conclusions: BSJPF owns multiple targets and pathways to treat various diseases under the guidance of “treating different diseases with the same method.”
  842 120 -
REVIEW ARTICLES
Meta-analysis of clinical efficacy of traditional chinese medicine in the treatment of aplastic anemia
Le-Min Xia, Le-Le Cui, Yi-Ling Jiang, Zheng Qin, Mei-Hong Luo
October-December 2017, 3(4):46-50
DOI:10.4103/wjtcm.wjtcm_13_17  
Background: The “Diagnosis and Treatment Guidelines for Chinese Medicine Internal Common Diseases” issued by the Chinese Institute of traditional Chinese medicine (TCM) offers many methods for the treatment of aplastic anemia (AA). However, there is a lack of corresponding evidence. Objective: The study aimed to evaluate the clinical efficacy of TCM in the treatment of AA, and provide evidence for the development of guidelines for the diagnosis and treatment of AA using TCM. Methods: Data of randomized or semi-randomized control trials of AA treatments with TCM were retrieved, and the selected literature was scored using the Jadad scale. The data were extracted, and RevMan 5.2.6 software was used for the meta-analysis. Results: Two studies on the treatment of AA using Liuwei Dihuang pills combined with compound Zaofan pill were included. The results of the meta-analysis showed that there were no statistically significant differences in the efficacy between Liuwei Dihuang pills combined with compound Zaofan pill and androgen in the treatment of AA (P = 0.65). However, there were less adverse reactions, including liver damage and the hirsutism of women, with the former than the latter (P < 0.05). Other studies on the treatment of AA with TCM did not include reports from clinical trials. Conclusion: TCM had a certain curative effect when used to treat AA. However, the quality of the literature is generally low, and the sample size is small, which makes the validation of the results poor. Further high-quality studies are needed to provide high-level evidence.
  826 104 -
ORIGINAL ARTICLES
Traditional Chinese medicine based on Zheng differentiation versus angiotensin receptor blocker/angiotensin-converting enzyme antagonist in efficacy of treating diabetic kidney disease: A meta-analysis of randomized clinical trials
Wei-Jun Huang, Tao Yang, Chuan-Jiang Liu, Yong-Hua Xiao, Qiang Fu, Qing Gong, Hua Zhang, Fan Shao, Hong Yue, Shi-Dong Wang, Jin-Xi Zhao
January-March 2019, 5(1):18-28
DOI:10.4103/wjtcm.wjtcm_27_18  
Objective: To compare the efficacy of traditional Chinese medicine (TCM) based on Zheng differentiation with angiotensin receptor blocker/angiotensin-converting enzyme inhibitor (ARB/ACEI) in treating diabetic kidney disease (DKD) from the aspects of decreasing urinary microalbumin, declining 24-h urinary protein, reducing endpoint events, and renal function protection. Methods: The Chinese Biomedical Literature Database (CBM), the Chinese Academy of Sciences database (CNKI), the VIP Chinese journal database, Wanfang DATA, Medline database, Cochrane library, excerpt medical database (Embase), and Web of science were used for literature searching. The reviewer manager 5.3 software was utilized to analyze the data. Results: Twenty-four studies including 1956 participants were involved in this review. Results showed that TCM had a better effect (mean difference [MD], −23.20, 95% confidence interval [CI], −30.60 to −15.79, P < 0.00001) than ARB/ACEI on lowering urinary albumin excretion rate (UAER) and urine albumin-to-creatinine ratio (MD −4.56 mg/mmol, 95% CI, −5.76 to −3.36, P < 0.00001). Moreover, the advantage of decreasing UAER was greater as the follow-up period become longer (P = 0.04). TCM also had a better effect in 24-h urinal protein, decreasing 0.36 g/24 h (95% CI, −0.45 to −0.27, P < 0.00001) more than the control in shorter follow-up period (ranged from 12 to 24 weeks) subgroup but only 0.08 g/24 h (95% CI, −0.13 to −0.03, P = 0.0006) in the longer follow-up period (>24 weeks) subgroup. TCM worked as well as ACEI/ARB in reducing endpoint events (relative risk, 0.67, 95% CI, 0.20–2.224, P = 0.51) and decreasing urinary albumin concentration (UAC) (MD, −16.50, 95% CI, −46.28–13.28, P = 0.28). As for protecting renal function, TCM had an equal effect to AECI/ARB in improving creatinine clearance ratio (MD, −3.30, 95% CI, −6.66–0.03, P = 0.05) or estimated glomerular filtration rate (MD, 1.00, 95% CI, −0.59–2.58, P = 0.22). However, TCM had a better effect in releasing the glomerular hyperfiltration state (MD, −9.64, 95% CI, −14.45 to −4.84, P < 0.0001). Conclusions: TCM based on Zheng differentiation can work as well as ACEI/ARB in treating DKD and even better in decreasing urinary microalbumin and releasing glomerular hyperfiltration. It is a good alternative treatment of DKD.
  819 80 2
A network pharmacology approach to decipher the mechanisms of anti-depression of Xiaoyaosan formula
Yao Gao, Li Gao, Jun-Sheng Tian, Xue-Mei Qin, Xiang Zhang
October-December 2018, 4(4):147-162
DOI:10.4103/wjtcm.wjtcm_20_18  
Objective: Depression is one of the prevalent and prominent complex psychiatric diseases, and the number of depressed patients has been on the rise globally during the recent decades. Xiaoyaosan, as a famous Chinese herbal formula, has been widely used in depression patients for a long time. However, the therapeutic mechanisms remain uncertain because of the difficulty of depression pathophysiology and the lack of bioinformatic approach to understand the molecular connection. Materials and Methods: In this thesis, we applied a network pharmacology approach to explain the potential mechanisms between Xiaoyaosan and depression involved in oral bioavailability screening, drug-likeness assessment, caco-2 permeability, blood–brain barrier target recognition, and network analysis. Results: Sixty-six active compounds in Xiaoyaosan formula with favorable pharmacokinetic profiles are predicted as active compounds for antidepression treatment. Network analyses showed that these 66 compounds target 40 depression-associated proteins including especially HTR2A, NR 3C1, monoamine oxidase inhibitor B, XDH, and CNR2. These proteins are mainly involved in the neuroactive ligand–receptor interaction, serotonergic synapse, cAMP signaling pathways, and calcium signaling pathways. Conclusion: The integrated network pharmacology method can provide a new approach for understanding the pathogenesis of depression and uncovering the molecular mechanisms of Xiaoyansan, which will also facilitate the application of traditional Chinese herbs in modern medicine.
  748 140 -