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   2021| July-September  | Volume 7 | Issue 3  
    Online since August 9, 2021

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Reviewing threats to wild rhodiola sachalinensis, a medicinally valuable yet vulnerable species
Josef A Brinckmann, Anthony B Cunningham, David E V. Harter
July-September 2021, 7(3):299-306
Occurring in China, DPR Korea, Japan, and Russian Federation and classified in the Red List of Chinese Flora as a vulnerable species, Rhodiola sachalinensis Boriss. is used increasingly in cosmetics, dietary supplements, and Traditional Chinese Medicines (TCMs). The aim of this study was to evaluate the (i) conservation status, harvesting and trade levels of R. sachalinensis, (ii) current state of experimental and commercial farming, and (iii) evidence of substitution or interchangeable use of R. sachalinensis with other Rhodiola species. We assessed data from multiple disciplines and languages including studies on R. sachalinensis biology and ecology, information on impacts of wild harvest, management measures, and current levels of cultivation. Our assessment shows that while R. sachalinensis is increasingly produced by cultivation, wild populations are decreasing and face multiple threats. These include (a) habitat loss including due to oil and gas infrastructure development on Sakhalin island, (b) climate change impacts on alpine ecosystems, and (c) overexploitation of wild plants to satisfy the growing commercial demand. Assessments of the conservation status of R. sachalinensis should commence in each Range State, as well as resource assessments and monitoring of harvesting and trade of wild R. sachalinensis. Even with increased reliance on cultivation, biodiversity conservation, and genetic diversity in wild populations are relevant to future use of this species.
  1,987 229 -
Phytohormones jasmonic acid, salicylic acid, gibberellins, and abscisic acid are key mediators of plant secondary metabolites
Zong-You Lv, Wen-Jing Sun, Rui Jiang, Jun-Feng Chen, Xiao Ying, Lei Zhang, Wan-Sheng Chen
July-September 2021, 7(3):307-325
Until recently, many studies on the role of phytohormones in plant secondary metabolism focused on jasmonic acid (JA), salicylic acid (SA), gibberellins (GA), and abscisic acid (ABA). It is now clear that phytohormone-induced regulation of signaling occurs via regulation of the biosynthetic pathway genes at the transcriptional level or through posttranslational regulation, or an increase in secondary metabolite deposition (e.g., trichomes). Here, we summarize recent advances, updating the current reports on the molecular machinery of phytohormones JA, SA, GA, and ABA involved in plant secondary metabolites. This review emphasizes the differences and similarities among the four phytohormones in regulating various secondary metabolic biosynthetic pathways and also provides suggestions for further research.
  1,809 164 1
The distribution, uses, and characteristic components of gentianaceae plants in China
Han Cheng, Yue-Bin Ge, Jun Li, Yan Zhang, Xian-Ju Huang, Guo-Xun Chen
July-September 2021, 7(3):287-298
Extracts of Gentianaceae herbs have been widely used as food additives, teas, or medicinal remedies for various human diseases and disorders. Iridoids, secoiridoids, and analogs glycosides, mainly include gentiopicroside, sweroside, swertiamarin, and loganic acid, are the characteristic compounds found in the Gentianaceae plants. The uses of the medicinal herbs containing these secoiridoids have been described in Chinese Materia Medica. Herbal extracts containing iridoids, secoiridoids, and analogs could exert protective effects in multiple human tissues and cells. Some of these medicinal herbs have been studied using modern pharmacological means. The results indicate that they have analgesic, liver protective, anti-inflammatory, antiallergic, anti-pathogeny, and anti-bacterial functions. This review was aimed to summarize the use of Gentianaceae herbs for disease treatments and pharmacokinetic characteristics of the active compounds. In so doing, we hope to demonstrate that Gentianaceae herbs and bioactive compounds in them may have abilities to affect inflammation, hepatic metabolism and cell signaling. In addition, we would like to bring this to the attention of the field about the use and study of compounds derived from Gentianaceae herbs.
  1,694 150 -
Panax notoginseng saponins increases the blood concentration of nifedipine by inhibiting CYP3A4 enzyme through PXR- and CAR-Mediated pathway
Qiu-Hong Li, Jiao Zhao, Ai-Xia Ju, Yong Hu, Qing-Song Qie, Hong-Bin Xiao, Guang Xu, Xi-Jun Wang
July-September 2021, 7(3):332-338
  1,346 76 -
Randomized clinical trials of traditional chinese medicines for treating ulcerative colitis: A scoping review
You-You Zheng, Xiao Wang, Jiang-Tao Si, Yu-Xin Sun, Wen-Bin Hou, Jian-Ping Liu, Yuan-Xi Li, Zhao-Lan Liu
July-September 2021, 7(3):326-331
Objective: Traditional Chinese medicines (TCMs) are efficacious against ulcerative colitis (UC). In recent years, the number of randomized clinical trials (RCTs) of TCM has increased. Thus, it is very important to summarize the basic characteristics, quality, and types of TCM interventions in published RCTs. This scoping review was performed to systematically identify and describe the current situations about RCTs of TCMs for treating UC. Hope to express the focus and specifics of nowadays research in TCM interventions in RCTs and evaluate their common disadvantages exposed to help advance in TCM researching. Materials and Methods: A scoping review was conducted according to the PRISMA extension for scoping reviews. We searched two English databases and four Chinese databases from the date of establishment of each database to January 2020. Data from RCTs focusing on any TCM treatment for patients with UC were extracted and evaluated. Selection and characterization were performed by two independent reviewers using predefined forms. All discrepancies were resolved by consensus discussion with a third reviewer. Microsoft Excel 2010 was used to extract the following data from the included studies: (1) basic information of the included studies including research ID, article title, publication language, journal, year of publication, and funding information; (2) patient information including gender, age, disease course, disease stage, severity, sample size; and (3) information on intervention measures, types of intervention measures, drug dosage forms, and treatment courses. Results: The search identified 2225 RCTs published between 1987 and 2020. These studies covered 36 provinces in China. The time frame of the RCTs was <28 days in approximately one-third of the RCTs (647, 29.08%). Only one RCT was published in English. Nearly three-quarters of RCTs (1665, 74.83%) did not report the severity of the disease. Three types of interventions were included in the RCTs: pharmacotherapy (2028, 91.15%), nonpharmacotherapy (57, 2.56%), and a combination of the two (140, 6.29%). The administration modes of the intervention groups were evaluated. Drug therapy involved 12 types of TCM dosage forms, which were decoctions, troches, powders, capsules, granules, pills, suppositories, ointments, injections, gels, oral liquids, and substitute tea according to the frequency of use. Nondrug intervention measures involved 10 treatment options, namely, acupuncture, moxibustion, hemospasia, auricular point, acupoint catgut embedding, acupoint injection, scrapping, tuina, acupoint application, and five-tone therapy according to the frequency of use. Most studies included in this review were low in quality. This underscores the need for improvement in the quality of trial methodology in TCM RCTs.
  1,262 79 2
Intelligent prescription-generating models of traditional chinese medicine based on deep learning
Qing-Yang Shi, Li-Zi Tan, Lim Lian Seng, Hui-Jun Wang
July-September 2021, 7(3):361-369
Objective: This study aimed to construct an intelligent prescription-generating (IPG) model based on deep-learning natural language processing (NLP) technology for multiple prescriptions in Chinese medicine. Materials and Methods: We selected the Treatise on Febrile Diseases and the Synopsis of Golden Chamber as basic datasets with EDA data augmentation, and the Yellow Emperor's Canon of Internal Medicine, the Classic of the Miraculous Pivot, and the Classic on Medical Problems as supplementary datasets for fine-tuning. We selected the word-embedding model based on the Imperial Collection of Four, the bidirectional encoder representations from transformers (BERT) model based on the Chinese Wikipedia, and the robustly optimized BERT approach (RoBERTa) model based on the Chinese Wikipedia and a general database. In addition, the BERT model was fine-tuned using the supplementary datasets to generate a Traditional Chinese Medicine-BERT model. Multiple IPG models were constructed based on the pretraining strategy and experiments were performed. Metrics of precision, recall, and F1-score were used to assess the model performance. Based on the trained models, we extracted and visualized the semantic features of some typical texts from treatise on febrile diseases and investigated the patterns. Results: Among all the trained models, the RoBERTa-large model performed the best, with a test set precision of 92.22%, recall of 86.71%, and F1-score of 89.38% and 10-fold cross-validation precision of 94.5% ± 2.5%, recall of 90.47% ± 4.1%, and F1-score of 92.38% ± 2.8%. The semantic feature extraction results based on this model showed that the model was intelligently stratified based on different meanings such that the within-layer's patterns showed the associations of symptom–symptoms, disease–symptoms, and symptom–punctuations, while the between-layer's patterns showed a progressive or dynamic symptom and disease transformation. Conclusions: Deep-learning-based NLP technology significantly improves the performance of IPG model. In addition, NLP-based semantic feature extraction may be vital to further investigate the ancient Chinese medicine texts.
  1,077 74 -
Exploration of bioactive constituents and immunoregulatory mechanisms of a hanshi-yufei formulation for treating COVID-19
Wen-Long Wei, Shi-Fei Wu, Zhen-Wei Li, Hao-Jv Li, Hua Qu, Chang-Liang Yao, Jian-Qing Zhang, Jia-Yuan Li, Gao-Le Zhang, Wan-Ying Wu, De-An Guo
July-September 2021, 7(3):339-346
Objective: The objective of this study was to characterize the chemical compounds of a Hanshi-Yufei formulation (HSYF; a modified formulation of a traditional Chinese medicine used for treating COVID-19) to elucidate the mechanism of action and to evaluate potential anti-inflammatory effects of HSYF. Materials and Methods: The chemical constituents of HSYF extract were characterized using UPLC-Q-TOF/MS. Subsequently, a set of TCM network pharmacology methods was applied to identify disease-associated genes and to predict target profiles and pharmacological actions associated with the constituents of HSYF. Then, the antiviral effects of HSYF on H1N1 were assessed in RAW264.7 cells using MTT assays. Expression levels of pro-inflammatory cytokines interleukin (IL)-6 and tumor necrosis factor (TNF)-α following infection of RAW264.7 cells with H1N1 were measured using an enzyme-linked immune sorbent assay (ELISA), and expression levels of inflammatory-related factors were detected using western blotting. Results: In total, 165 chemical constituents (including glycosides, tannins, volatile oils, amino acids, triterpenoids, polyphenols, phenylpropanoids, sesquiterpenes, alkaloids, and flavonoids, among others) were tentatively identified in HSYF. Network pharmacology demonstrated that HSYF can regulate immunomodulatory- and anti-inflammatory-related targets of multiple pathways through its active ingredients, suggesting potential anti-COVID-19 effects. Furthermore, cell viability assays and ELISA showed that HSYF significantly inhibited H1N1 replication in RAW64.7 cells and markedly reduced expression of pro-inflammatory cytokines TNF-α and IL-6 at the proteins level. Conclusions: The results of the present study help improve our understanding of the therapeutic effects of HSYF in COVID-19 treatment from multi-level perspectives.
  1,042 83 -
Screening safflower injection for constituents with activity against stroke using comprehensive chemical profiling coupled with network pharmacology
Xin-Yue Shi, Qiu-Yun Miao, Xin-Guang Liu, Ping Li, Wen Gao
July-September 2021, 7(3):347-360
Objective: This study aimed to explore safflower injection (SI) for constituents with activity against ischemic stroke using a combination of chemical analysis and a network pharmacology strategy. Materials and Methods: The main ingredients of SI were comprehensively identified using ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry, and the core targets and pathways associated with stroke were predicted using PharmMapper and Kyoto Encyclopedia of Genes and Genomes analysis. Cytoscape software was used to visualize and analyze the active compound-target-pathway network of SI regulating ischemic stroke. Results: A total of 76 chemical compounds were identified from the SI sample, including 63, which regulated 88 targets that were ultimately enriched in 12 key ischemia stroke-related signaling pathways. Kaempferol-3-O-sophoroside, kaempferol-3-O-rutinoside, carthamoside B6, neoeriocitrin, and 6-hydroxykaempferol-3-O-rutinoside-6-O-glucoside were determined to be important for stroke treatment because they had a higher degree value in the network than other constituents did. Moreover, the characteristic components isolated from SI showed protective effect mainly by acting on multiple targets including AKT1, epidermal growth factor receptor, transforming growth factor-beta receptor (TGFBR), Ras homolog, mTORC1 binding, caspase 3, and glycogen synthase kinase 3 beta, which were involved in different signaling pathways including phosphoinositide 3-kinase-Akt, mitogen-activated protein kinase, neurotrophin, ErbB, mechanistic target of rapamycin, and tumor necrosis factor. Conclusions: This study proposed a network pharmacology and chemical component profiling strategy for the systematic understanding of the therapeutic material basis of using SI against ischemic stroke.
  942 60 -
Molecular docking-based research on the potential anti-encephalopathy effect of gentianine
Awais Wahab, Jian-Xin Chen, Cai-Xia Jia, Ghulam Murtaza, Chuan-Hong Wu, Na Wang
July-September 2021, 7(3):377-382
Objective: Encephalopathy is increasingly threatening human health. It is correspondingly one of the concerns of society and medical community. As a natural source, traditional Chinese medicine has tremendous beneficial outcomes in various diseases including encephalopathy. Gentianine, a Chinese herbal compound, shows effectiveness in many diseases exclusively in inflammation. Therefore, this in vitro research was carried out to find its effectiveness in encephalopathy. Methodology: Ligand and proteins were searched and downloaded from ChemDraw and protein database, respectively. Sybyl-X2.0 docking software and its various functions were used to prepare ligand and proteins. Finally, gentianine was docked with proteins using Sybyl-X2.0 docking software. Results: Gentianine was docked with 20 protein targets. Compounds with C-score of 5 were selected. A total of three kinds of protein docked with gentianine (ABCC1, C-reactive protein [CRP], and NKX5-2) were selected. ABCC1 was expressed in the brain and was related to seizures and stroke. CRP was an inflammatory biomarker and related to seizures, epilepsy, stroke, and Parkinson's disease. NKX2–5 was also known as cardiac transcription and related to cerebral palsy, Alzheimer's disease, and stroke. All these targets were related to encephalopathy. Conclusion: Molecular docking findings in this study lead to the suggestion that gentianine might be helpful in treating encephalopathy. This study is expected to provide a solution to find potential anti-encephalopathy compounds.
  926 63 1
Network pharmacology study of yuebi plus banxia decoction in treating asthma
Wen-Jie Song, Zheng Hao
July-September 2021, 7(3):370-376
Objective: The objective of the study was to study the potential biological mechanism of Yuebi plus Banxia Decoction (YBD) in the treatment of asthma based on network pharmacology. Materials and Methods: Literature databases were used to collect information on the chemical components and pharmacokinetics of YBD as comprehensively as possible. According to pharmacokinetic information and effective ingredient screening criteria, effective chemical components of YBD were screened, and the target genes corresponding to the effective components were collected by the ligand prediction method. At the same time, literature databases including five disease target gene databases were used to collect asthma disease target genes. Then, the effective component target network of YBD and the asthma disease target network can be constructed using Cytoscape 3.2.1 software. The core targets of YBD for the treatment of asthma were screened according to topological analysis based on degree parameters. Through the analysis of Kyoto Encyclopedia of Genes and Genomes (KEGG) signal pathway, the main mechanisms of YBD in treating asthma were found out. Results: A161 active ingredients of YBD and 136 core targets for the treatment of asthma were screened out. The effective signaling pathways of YBD in the treatment of asthma were mainly focused on ErbB, MAPK, Estrogen, PI3K-Akt, Neurotrophin, Hippo, HIF-1, TGF-, FoxO, Wnt, Chemoking, Toll-like receptor, vascular endothelial growth factor (VEGF), GnRH, and Notch. Conclusion: YBD has the characteristics of multiple targets and multiple pathways in the treatment of asthma. Its main biological mechanism is related to ErbB, MAPK, Estrogen, PI3K-Akt, neurotrophin, Hippo, HIF-1, TGF-, FoxO, Wnt, Chemoking, Toll-like receptor, VEGF, GnRH, and Notch.
  914 73 -
Protective effect of ginsenoside rd on lipopolysaccharide-induced acute lung injury through its anti-inflammatory and anti-oxidative activity
Jv Chen, Wan-Xian Fang, Shao-Jin Li, Shui-Xiu Xiao, Hai-Jian Li, Yong-Li Situ
July-September 2021, 7(3):383-390
Background: Inflammation and oxidation stress are key factors in the mechanism of acute lung injury (ALI). Therefore, suppression of the inflammatory response and oxidative stress could be a potential strategy to treat lipopolysaccharide (LPS)-induced ALI. Ginsenoside Rd (Rd), a natural Ginseng extract, alleviates inflammation and oxidative stress in several diseases such as Alzheimer's disease and cerebral ischemia, but its effect on ALI is still unclear. Aims and Objectives: To explore the protective effect of Rd on LPS-induced ALI and explored associated mechanisms. Materials and Methods: Mice were divided into five groups: A sham-operated group, a LPS-induced ALI group, and three LPS groups pretreated with Rd doses of 20, 40, and 80 mg/kg, respectively. The pathological changes of lung, collagen deposition, pulmonary edema, inflammatory cytokine, oxidative stress and the expression levels of TLR4 and NF-κB were detected. Results: The oral administration of Rd dose dependently attenuated histopathologic changes in the lung, lung edema, pulmonary collagen deposition, protein concentration in bronchoalveolar lavage fluid (BALF), myeloperoxidase (MPO) activity, and inflammatory cell infiltration. In addition, Rd suppressed the LPS-induced inflammatory cytokines tumor necrosis factor-α, interleukin (IL)-6, and IL-1 β in BALF. The productions of oxidative stress-related enzymes (catalase, superoxide dismutase, and glutathione peroxidase) in lung tissue were significantly upregulated by Rd administration. However, malondialdehyde and pulmonary MPO activity was reduced in the Rd-pretreated groups when compared with LPS-induced ALI group. Rd treatment also dose dependently suppressed LPS-induced NF-κB activation and TLR4 expression. Conclusion: Overall, these findings provide evidence that Rd pretreatment inhibits LPS-induced ALI through anti-inflammatory and antioxidative actions, suggesting that it could be a promising protective drug for LPS-induced ALI.
  914 64 -