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   Table of Contents - Current issue
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July-September 2020
Volume 6 | Issue 3
Page Nos. 229-361

Online since Tuesday, September 8, 2020

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REVIEW ARTICLES  

Lanostane tetracyclic triterpenoids as important sources for anti-inflammatory drug discovery Highly accessed article p. 229
Yu-Pei Yang, Shumaila Tasneem, Muhammad Daniyal, Liu Zhang, Yan-Zhe Jia, Yu-Qing Jian, Bin Li, Wei Wang
DOI:10.4103/wjtcm.wjtcm_17_20  
Inflammation is a defensive reaction of the human body to numerous detrimental stimuli, including physical trauma, noxious chemicals, as well as microbial agents. Uncontrolled inflammation is the pathological basis of multiple diseases, such as rheumatoid arthritis (RA), neurodegenerative diseases, liver disease, and lung inflammation. Lanostane triterpenoids are natural tetracyclic triterpenoids with significant anti-inflammatory activity. An extensive review of the published literature regarding the phytochemistry and anti-inflammatory pharmacology of lanostane triterpenoids has been performed and analyzed using several search engines, such as SciFinder, Web of Science, Scopus, PubMed, Google Scholar, and ScienceDirect. This review is devoted to naturally occurring lanostane-type triterpenes with anti-inflammatory activity, including their sources, biosynthesis, and mechanism of action. This review also discusses the inflammation-related diseases and the clinical significance of traditional Chinese medicine as multi-target therapeutic agents for the prevention and treatment of inflammatory diseases. In the past 30 years, more than 100 new lanostane-type triterpenes have been reported from the families Schisandraceae, Ganodermataceae, and Polyporaceae. Six compounds, fomitopinic acid A, fomitosides E and F, obtusifoliol, 4α, l4α-dimethyl-5α-ergosta-7,9(11), 24(28)-trien-3 β-ol, and gramisterol exhibited the most potent anti-inflammatory activity against cyclooxygenase-1 (COX-1) and COX-2, with IC50values ranging from 0.087 to 1.15 μM. Some of these compounds exhibited significant activity by mediating the inhibition of the pro-inflammatory cytokines, inducible nitric oxide synthase, and COX-2 expression. This review provides a basis for identifying anti-inflammatory drugs with high selectivity, high potency, and few adverse effects from lanostane-type triterpenes.
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Effect of acupoints on acupuncture-moxibustion and its therapeutic mechanism Highly accessed article p. 239
Han-Dan Zheng, Zhao-Qin Wang, Shan-Shan Li, Yuan Lu, Yan Huang, Ci-Li Zhou, Yu-Qing Lu, Hui-Rong Liu, Ya-Nan Liu, Huan-Gan Wu
DOI:10.4103/wjtcm.wjtcm_18_20  
The clinical efficacy of acupuncture-moxibustion (AM) mainly depends on acupoints, but the relationship between the acupoints and AM remains unclear. Improving clinical efficacy and clarifying the mechanisms of AM is critical. We found that the specificity and sensitivity of acupoints, the skill of operation, and reasonable amount of stimulation can significantly improve the efficacy of AM. In addition, some studies have shown that Neural-Endocrine-Immune network and metabolites are involved in this process, clarifying the therapeutic mechanism of acupoints. Therefore, how to effectively use acupoints to improve the clinical efficacy of AM is one of the key issues in need of an urgent solution. In summary, this article reviewed the Chinese and English databases on the clinical efficacy and underlying mechanisms of acupoints to clarify the relationship between acupoints and AM efficacy and ultimately improve clinical efficacy through effective and rational use of acupoints.
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Clinical effect of tripterygium glycosides combined with glucocorticoids in the treatment of refractory nephrotic syndrome patients: A systematic review and meta-analysis p. 249
Ya-Qing Cheng, Jing Li, Hai-Shun Qu, Xian-Zhi Zhang, Hai-Li Zhang, Jing Zhang, Bo Peng
DOI:10.4103/wjtcm.wjtcm_20_20  
The objective of this study is to evaluate the effectiveness and safety of Tripterygium glycosides combined with glucocorticoids for the treatment of refractory nephrotic syndrome (NS). Computer search of Chinese and English databases, including CNKI, VIP, Wan Fang Database, PubMed, Cochrane Library, Embase, and Sinomed, for randomized controlled trials (RCTs) of Tripterygium glycosides combined with glucocorticoids for refractory NS (RNS) was conducted. Meta-analysis was performed using RevMan5.3. Thirteen RCTs comprising 994 patients were included in the study. Tripterygium glycosides combined with glucocorticoids had a statistical significance on the effective rate (odds ratio [OR] =4.69, 95% confidence interval [CI] 3.29, 6.67, P < 0.00001), 24-h urine protein ( Weighted mean difference (MD) = −0.57, 95% CI [−0.62, −0.51], P < 0.00001), serum albumin (MD = 4.77,95% CI [4.30, 5.24], P < 0.00001), total serum protein (MD = 9.45, 95% CI [8.73, 10.17], P < 0.00001), urea nitrogen (MD = −0.53, 95% CI [−0.90, −0.17], P = 0.005), and serum creatinine (MD = −8.45, 95% CI [−15.32, −1.57], P = 0.02). There was no statistical significance on adverse reactions (OR = 0.68, 95% CI [0.41, 1.12], P = 0.13). Tripterygium glycosides combined with glucocorticoids could improve clinical effective rate, reduce 24-h urine protein, improve serum albumin and total serum protein, and reduce urea nitrogen and serum creatinine levels in patients with RNS. However, the quality of the included literature is poor, and conclusion still needs further verification using larger samples and high-quality randomized, double-blind controlled trials.
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Strategy of systems biology for visualizing the “Black box” of traditional Chinese medicine p. 260
Yu Gu, Gao-Song Wu, Hou-Kai Li, Wei-Dong Zhang
DOI:10.4103/wjtcm.wjtcm_31_20  
Traditional Chinese medicine (TCM) has been practiced for thousands of years in China. TCM formula, usually composed of several or even dozens of herbal medicines, is the main form of TCM practicing, which is extremely complex due to multiple components and therapeutic targets, especially the characteristics of formula compatibility. Thus, it is an enormous challenge for the modernization of TCM. Systems biology is a strategy for investigating the complex interactions between genes, mRNA, proteins, and metabolites by using integrated omics approaches. In recent years, systems biology has been increasingly adopted in TCM study. This review comprehensively summarized status of syndrome and application of TCM formulae in clinical and preclinical studies and discussed the advances of systems biology in TCM research. Then, a “Disease-Syndrome-Formulae-Effect” strategy was proposed for TCM research. Combination of systems biology and “Disease-Syndrome-Formulae-Effect” strategy provided a novel approach to understand the complex interactions among biological systems, drugs, and complex diseases from a network perspective, thus facilitating the modernization of TCM. The objective of this manuscript is to provide comprehensive and up-to-date review on the application of systems biology in TCM research, as well as the perspective of TCM modernization with systems biology.
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Progress of traditional chinese medicine therapy in preventing and treating radiation enteritis p. 271
Cheng Jiang
DOI:10.4103/wjtcm.wjtcm_33_20  
At present, there is no unified clinical approach for the treatment of radiation enteritis (RE). Clinically, its treatment is mainly based on nutritional support, mucosal protective agents, somatostatin, and microecological preparations. On the basis of syndrome differentiation and treatment, traditional Chinese medicine (TCM) is mainly used for internal administration, enteroclysis, acupuncture, and Tuina. It shows significant advantages in relieving the adverse reactions of radiotherapy and exhibits significant preventive and therapeutic effects against RE. This article reviews two aspects of TCM on RE, including internal and external administration, to explore and develop an effective and reliable standardized Chinese medicine program.
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Systematic review and meta-analysis of shenfu injection on treating acute exacerbation of chronic obstructive pulmonary disease p. 276
Jian-Guo Lin, Jian Lyu, Meng-Hua Sun, Xing Liao, Yan-Ming Xie
DOI:10.4103/wjtcm.wjtcm_30_20  
The objective of the study was to systematically evaluate the efficacy and safety of Shenfu injection in the treatment of patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). A total of 15 randomized controlled trials involving 1198 patients were included. The results of meta-analysis showed that compared with the control group, the experimental group can improve the total clinical effective rate in AECOPD patients (relative risk = 1.15, 95% confidence interval [CI] [1.09, 1.21], P < 0.000 01), improve the pulmonary function levels: forced expiratory volume in one second (FEV1) (standardized mean difference = 1.88, 95% CI [0.89, 2.88], P = 0.000 2) and the FEV1/forced vital capacity (FVC) ratio (FEV1/FVC) (mean difference [MD] = 3.96, 95% CI [2.74, 5.19], P < 0.000 01); improve the arterial blood oxygen partial pressure (MD = 6.03, 95% CI [4.58, 7.48], P < 0.000 01), and reduce the arterial blood partial pressure of carbon dioxide (MD = −4.59, 95% CI [−6.91, −2.26], P = 0.000 01), and the white blood cell count in pulmonary infection may be improved (MD = −1.16, 95% CI [−1.63, −0.68], P < 0.000 01). The study showed that the efficacy of experimental group in the treatment of AECOPD is better than control group. Due to the limitation of the number and quality of included studies, this conclusion needs more high quality studies to confirm.
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ORIGINAL ARTICLES Top

Ginsenoside Rb1 pretreatment attenuates myocardial ischemia by reducing calcium/calmodulin-dependent protein kinase II-medicated calcium release p. 284
Wen-Jun Zhou, Juan-Li Li, Qian-Mei Zhou, Fei-Fei Cai, Xiao-Le Chen, Yi-Yu Lu, Ming Zhao, Shi-Bing Su
DOI:10.4103/wjtcm.wjtcm_24_20  
Objective: The aim of this study was to investigate the protective effects of ginsenoside Rb1 and assess whether these protective effects are related to calcium/calmodulin-dependent protein kinase II (CaMKII).Methods: A myocardial ischemia (IS) rat. model and a myocardial H9C2 cell hypoxia model were established. MI was induced by occluding the left anterior descending artery for 120 min. Ginsenoside Rb1 (10 mg/kg) was administered 30 min before ischemia induction, and the treatment continued for 7 days. Results: In the rat IS injury model, ginsenoside Rb1 reduced myocardial infarct size, mean left ventricular diastolic pressure, incidence of arrhythmia, and levels of serum creatine kinase, lactate dehydrogenase, and malondialdehyde. However, the mean left ventricular systolic pressure, and maximal rising and falling rates of ventricular pressure (±dp/dtmax) increased. In the myocardial H9C2 cell hypoxia model, ginsenoside Rb1 reduced intracellular calcium concentrations ([Ca2+ ]i) during hypoxia, and markedly reversed the hypoxia-induced decrease in cell survival. Ginsenoside Rb1 was involved in the downregulation of CaMKII and the ryanodine receptor, as well as hypoxia-induced H9C2 cell survival. Conclusion: The findings of the present study suggest that ginsenoside Rb1 attenuates MI injury in rats, partially through the downregulation of CaMKII expression.
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Guidelines for Chinese medicine rehabilitation of chronic obstructive pulmonary disease p. 295
Jian-Sheng Li
DOI:10.4103/wjtcm.wjtcm_44_20  
Chronic obstructive pulmonary disease (COPD) is a common, chronic, frequently occurring, and difficult disease of the respiratory system and is a huge disease burden. Pulmonary rehabilitation is an important part of clinical treatment. Chinese medicine lung rehabilitation (CMLR), which is based on Chinese medicine theory and practice, is a comprehensive rehabilitation measure that can prevent and treat pulmonary diseases and preserve physical and mental functions. Its aim is to promote the return of patients to society as soon as possible. To better guide the clinical practice of COPD rehabilitation, the Specialty Committee of Pulmonary Rehabilitation of World Federation of Chinese Medicine Societies established a panel for formulating guidelines, systematically retrieved domestic and foreign literature, performed systematic evaluation after expert consultation and on-site discussion, and finally, formed the guidelines in accordance with the development standard of international evidence-based guidelines. The guideline has seven parts, which are the preface, introduction, scope, normative references, terms and definitions, types of disease syndromes, diseases assessment, CMLR techniques, and annex. The techniques of CMLR include 11 techniques in seven species, such as Simplified Taijiquan, Baduanjin, and Liuzijue. The guideline defines the technical points (time, frequency, course, etc.), optimal applicable population, use of drugs, common acupoints, operation methods, and so on for each technique. The release of the guidelines is helpful to improve the rehabilitation technique standardization and to improve the curative effect and level of rehabilitation.
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Clinical evaluation on xiyanping injection in the treatment of bronchopneumonia in children based on meta-analysis p. 307
Cheng Zhang, Jian Lyu, Yan-Ming Xie, Meng-Hua Sun
DOI:10.4103/wjtcm.wjtcm_29_20  
Objective: The aim of this study is to evaluate the effectiveness and safety of xiyanping injection (XYPI) in the treatment of children with bronchopneumonia. Methods: A systematic and comprehensive search was conducted in the domestic and foreign electronic databases CNKI, SinoMed, VIP, WanFang DATA, PubMed, The Cochrane Library, Embase, Web of Science, Clinical-Trials.gov, and the search date ended on May 30, 2019. Inclusion criteria: (1) the types of studies included were randomized controlled trials; (2) the study participants were infants and children with a clear diagnosis of bronchopneumonia, without gender and ethnic restrictions; (3) the intervention test group was XYPI or the control group plus XYPI. The control group was routine treatment (RT) (basic treatment such as fever, cough and asthma, oxygen inhalation, anti-infection, maintaining water, electrolyte balance, etc.) or other Western medicine or RT + other Western medicine treatment. Except for XYPI, the two groups were consistent in intervention measures. According to the Cochrane Handbook, 5.1 evaluation standard and a meta-analysis of the final included studies was performed using RevMan 5.3 software. Results: A total of 57 studies were included, with a total sample size of 8454 cases, of which 4255 were in the experimental group and 4199 were in the control group. Meta-analysis results showed that (1) Total effective rate: XYPI group was better than the control group (relative risk [RRRT] = 1.25, 95% confidence interval [CI] [1.15, 1.36], P < 0.00001; RRRT+RBVI= 1.18, 95% CI [1.09, 1.29], P < 0.0001; RR antibiotic= 1.16, 95% CI [1.09, 1.24], P < 0.00001, RRRT+antibiotic= 1.22, 95% CI [1.16, 1.27], P < 0.00001); antipyretic time: XYPI group was better than the control group (mean difference [MDRT] = −0.97, 95% CI [−1.17, −0.76], P < 0.00001; MDRT+antibiotic= −2.28, 95% CI [−2.88, −1.67], P < 0.00001; MDRT+RBVI= −1.51, 95% CI [−1.81, −1.21], P < 0.00001; cough disappearing time: XYPI group was better than the control group (MDRT= −1.37, 95% CI [−1.74, −1.00], P < 0.00001; MDRT+antibiotic= −1.71, 95% CI [−2.04, −1.37], P < 0.00001; MDRT+RBVI= −1.51, 95% CI [−2.15, −0.86], P < 0.00001); disappearance time of lung rales: XYPI group was better than the control group (MDRT= −1.11, 95% CI [−1.35, −0.88], P < 0.00001; MDRT+ RBVI= −1.63, 95% CI [−2.23, −1.03], P < 0.00001). The difference was statistically significant; (2) Of the 57 studies (a total of 8454 cases), 29 studies reported adverse reactions, of which 18 studies did not find adverse reactions, and 11 studies reported adverse reactions such as nausea, vomiting, and rash after medication in both groups. (3) The funnel chart indicated potential publication bias. Conclusion: Based on the existing clinical evidence, XYPI can have a certain effect on the treatment of children with bronchopneumonia, and it is not yet possible to conclude its safety evaluation. Moreover, due to the low quality of the included studies, this evidence is still used with cautious clinically.
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Analysis of phytochemical constituents of zuogui wan in rat serum and its effects on early embryonic development of mice p. 324
Ya-Fei Guo, Kai-Xia Xu, Jie-Wei Hong, Shuang Yin, Xin Niu, Qian-Jin Feng, Ying-Li Wang
DOI:10.4103/wjtcm.wjtcm_34_20  
Objective: Zuogui Wan (ZGW) has been used as a typical prescription for tonifying kidney essence in traditional Chinese medicine. The objective of this study is to elucidate the phytochemical constituents of ZGW-treated rat serum (ZGWRS) using ultra-performance liquid chromatography-electrospray ionization/quadrupole-time-of-flight high-definition mass spectrometry (UPLC-ESI-Q-TOF-MS). Methods: ZGW was administered to rats, and the phytochemical constituents in rat serum were determined using UPLC-ESI-Q-TOF-MS. MetaboLynx analysis in negative ion mode was adopted to characterize the chemical constituents of ZGWRS. Orthogonal partial least squares discriminant analysis was applied for the discovery of constituents of ZGW that entered the serum of rats. The fertilized eggs collected from the same experiment were randomly divided into four groups, including the normal, 40 mmol/L glucose, 40 mmol/L glucose 5% control rat serum, and 40 mmol/L glucose 5% ZGWRS groups. They were cultivated at 37°C and 5% CO2in a saturated humidity CO2incubator. The blastocyst rate and two-cell rate were used to evaluate the effects of ZGWRS on embryonic development. Results: Thirteen constituents were identified in the ZGWRS, among which sweroside, loganin, morroniside, loganic acid, and 8-epiloganic acid were from Fructus Corni (Shan Zhu Yu). 5-Hydroxymethyl-2-furfural-glucuronide, 2-H-5-hydroxymethyl-2-furfural-glucuronide, 3-hydroxy-2,6,6-trimethyl-1-cyclohexene-1-carboxylic acid, and β-D-ribofuranuronic acid methyl ester triacetate were from Radix Rehmanniae Preparata (Shu Di Huang). Coumaric acid was from Fructus Lycii (Gou Qi Zi). Kaempferol-3-beta-O-glucuronide and cuscutamine were from Semen Cuscutae (Tu Si Zi). The embryonic development was significantly inhibited using 40 mmol/L glucose. Compared with the normal group, the blastocyst rate of the glucose group was decreased. The blastocyst rate of the 40 mmol/L glucose 5% ZGWRS group was significantly higher than that of the glucose group, indicating that ZGWRS negates the effect of glucose on mouse embryonic development. Conclusion: The results verified that a rapid and robust UPLC-ESI-Q-TOF-MS-based platform had been successful for identifying multiple constituents of ZGW. ZGWRS is rich in active constituents of iridoid glycosides. The results of this study also showed that ZGWRS could negate the effect of glucose on mouse embryonic development.
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The mechanisms of pei-yuan-tong-nao capsule as a therapeutic agent against cerebrovascular disease p. 331
Yu Wei, Xiao-Jing Fan, Ming-Hui Zhang, Mai-Qiu Wu, Wei Li, Ping Wang, Wei Xiong, Jian-Ping Lin
DOI:10.4103/wjtcm.wjtcm_45_20  
Objective: Pei-Yuan-Tong-Nao (PYTN) capsule has been widely used for the treatment of cerebrovascular disease (CVD), including cerebral ischemia. However, due to the complexity of traditional Chinese Medicine (TCM) and the lack of proper inspection methods, the pharmacological mechanisms of the actions of PYTN capsule on CVD remain ambiguous. In this investigation, a network pharmacology method was used to investigate the mechanism of action of PYTN capsule in the treatment of CVD. Methods: In this method, a chemical similarity ensemble approach was employed to predict putative targets for chemicals derived from PYTN capsule. Results: Thus, a total of 351 compounds and 650 proteins were identified as potential active ingredients and putative CVD-related targets. In addition, two interaction networks were constructed, including a network between putative targets of PYTN capsule and known CVD-related targets, and a network between candidate active compounds and putative CVD-related targets. Conclusion: The mechanism of PYTN capsule in the treatment of CVD was found to be based on three functional modules, namely, antioxidation, anti-inflammation, and antiapoptosis modules through multiple signaling pathways, such as PI3K-Akt, mitogen-activated protein kinase, and TNF signaling pathways. We hope that this work can provide insight into the pharmacological mechanisms of TCMs in the treatment of CVD and provide a basis for further development and the discovery of more effective clinical strategies for the treatment of complicated diseases.
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Network pharmacology approach to determine active compounds and potential targets associated with the anti-abortion effects of scutellariae radix p. 341
Lei Ma, Qi-Lin Lei, Qing Su
DOI:10.4103/wjtcm.wjtcm_35_20  
Background: It is widely accepted that the causes and mechanisms of abortion are very complicated. In China, Scutellariae Radix (SR) (Scutellaria baicalensis Georgi) is widely used as a traditional Chinese herbal medicine with anti-abortion effects. However, the chemical components and pharmacologic profiles of SR have not been elucidated. The network pharmacology approach can provide a system-level perspective to explore the components, targets, and mechanism of herbal medicines. Thus, this approach was employed to identify the absorbable compounds, potential targets, and signaling pathways associated with SR. Materials and Methods: In this study, we used the Lipinski rule and an oral bioavailability of >30% to identify the bioactive compounds in SR. Targets of the anti-abortion activity of SR were obtained from the PharmMapper website server database. The Search Tool for the Retrieval of Interacting Genes and DAVID databases were utilized to perform protein–protein interaction analysis and pathway enrichment analysis, respectively. Finally, Cytoscape software was used to visualize the active compound–target–Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway network of SR. Results: In total, 286 chemical compounds were identified in SR; of these, 27 compounds could be absorbed into the blood, and 10 compounds that had a high docking score with their corresponding targets were determined. These potentially active compounds of SR regulated 142 targets and clearly affected 29 KEGG pathways. From these targets, a total of 11 targets, which were expressed in the breast and female reproductive system, were associated with the anti-abortion effects of SR: EGFR, HRAS, HSP90AA1, ESR1, PRKACA, SRC, GSK3B, JAK2, IGF1R, CDK2, and AR. In the KEGG pathway analysis, five pathways were related to the anti-abortion effect of SR, including the estrogen signaling pathway, the prolactin signaling pathway, progesterone-mediated oocyte maturation, and oocyte meiosis. Conclusions: The network pharmacology approach used in our study attempted to explain the mechanism of the anti-abortion effects of SR and has provided an alternative approach for the investigation of the effects of this complex compound.
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The antitumor activity and mechanism of MCL3 in G422 glioblastoma p. 353
Qian-Qian Du, Mei Tang, Lu-Lu Huang, Ru Zhao, Chen Yan, Yan Li, Xian-Dao Pan
DOI:10.4103/wjtcm.wjtcm_46_20  
Objective: Parthenolide (PTL) induces anti-tumor effects via the nuclear factor kappa B (NF-κB) signaling pathway. MCL3, a PTL derivative, is a sesquiterpene lactone synthesized by the rearrangement and subsequent oxidation of PTL. The aim of this study was to elucidate the antitumor activity and mechanism of action of MCL3 in glioblastoma (GBM). Materials and Methods: The effects of MCL3 on G422 cell proliferation, apoptosis, invasion, and angiogenesis in vitro were measured using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, flow cytometry, the cell invasion, and tube formation assays. The subcutaneously transplanted G422 xenograft model was used to detect the effect of MCL3 on tumor growth in vivo. Pathological changes were analyzed by immunohistochemical staining. The effects of MCL3 on NF-κB and Stat3 transcriptional activities were examined using a dual-luciferase reporter assay. Protein levels related to the NF-κB/ interleukin (IL)-6/Stat3 signaling pathway were determined using western blot analysis. Results: MCL3 inhibited GBM cell proliferation, invasion, and angiogenesis in a concentration-dependent manner. Moreover, MCL3 decreased the transcriptional activities of NF-κB and Stat3. MCL3 suppressed tumor growth in the subcutaneously transplanted G422 xenograft model, while the inhibition rate was 79% in tumor weight at 40.0 mg/kg. MCL3 blocked the NF-κB/IL-6/Stat3 signaling pathway in G422 cells and tumor tissues, resulting in the downregulation of Stat3 target genes related to apoptosis, invasion, etc., Conclusion: The results show that MCL3 might inhibit G422 GBM growth partly due to the inhibition of the NF-κB/IL-6/Stat3 signaling pathway.
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