Publications by authors named "Yan-Yan Chen"

133 Publications

Potential medicinal value of celastrol and its synthesized analogues for central nervous system diseases.

Biomed Pharmacother 2021 Apr 14;139:111551. Epub 2021 Apr 14.

Key Laboratory of Shaanxi Administration of Traditional Chinese Medicine for TCM Compatibility, and State Key Laboratory of Research & Development of Characteristic Qin Medicine Resources (Cultivation), and Shaanxi Key Laboratory of Chinese Medicine Fundamentals and New Drugs Research, and Shaanxi Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Shaanxi University of Chinese Medicine, Xi'an 712046, Shaanxi Province, China. Electronic address:

The central nervous system (CNS) is a vital part of the human nervous system, and the incidence of CNS disease is increasing year by year, which has become a major public health problem and a prominent social problem. At present, the drugs most commonly used in the clinic are receptor regulators, and neurotransmitter inhibitors, but they are accompanied by serious side effects. Therefore, the identification of new drugs and treatment strategies for CNS disease has been a research hotspot in the medical field. Celastrol, a highly bio-active pentacyclic triterpenoid isolated from Tripterygium wilfordii Hook. F, has been proved to have a wide range of pharmacological effects, such as anti-inflammation, immunosuppression, anti-obesity and anti-tumor activity. However, due to its poor water solubility, low bioavailability and toxicity, the clinical development and trials of celastrol have been postponed. However, in recent years, the extensive medical value of celastrol in the treatment of CNS diseases such as nervous system tumors, Alzheimer's disease, Parkinson's disease, cerebral ischemia, multiple sclerosis, spinal cord injury, and amyotrophic lateral sclerosis has gradually attracted intensive attention worldwide. In particular, celastrol has non-negligible anti-tumor efficacy, and as there are no 100% effective anti-tumor drugs, the study of its structural modification to obtain better leading compounds with higher efficiency and lower toxicity has aroused strong interest in pharmaceutical chemists. In this review, research progress on celastrol in CNS diseases and the synthesis of celastrol-type triterpenoid analogues and their application evaluation in disease models, such as CNS diseases and autotoxicity-related target organ cancers in the past decade are summarized in detail, in order to provide reference for future better application in the treatment of CNS diseases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.biopha.2021.111551DOI Listing
April 2021

Dysiarenone from Marine Sponge Attenuates ROS and Inflammation via Inhibition of 5-LOX/NF-κB/MAPKs and Upregulation of Nrf-2/OH-1 in RAW 264.7 Macrophages.

J Inflamm Res 2021 25;14:587-597. Epub 2021 Feb 25.

Shenzhen Key Laboratory of ENT, Institute of ENT and Longgang ENT Hospital, Shenzhen, 518172, People's Republic of China.

Background: Marine natural products harbor a variety of pharmacological activities, and the sea species have been becoming a main source of new drug candidate. In pursuit of safer and more effective anti-inflammation drug, the anti-inflammatory activities, anti-oxygenation effects and underlying molecular mechanisms of compound dysiarenone from were investigated via LPS-induced RAW 264.7 cell model.

Methods: Firstly, RAW 264.7 cells have been stimulated with LPS and treated with dysiarenone, and the cell viability of the LPS-treated RAW 264.7 cells was examined. One-step method, DCFH-DA fluorescence probe method was used to detect reactive oxygen species (ROS). The modulation of dysiarenone on anti-inflammation was detected by enzyme-linked immunosorbent assay by measuring the release of inflammatory cytokines (TNF-α and IL-6), and inflammatory mediators (LTB4). Further, the underlying anti-inflammatory mechanism of dysiarenone was explored by determining the expression of inducible 5-LOX, MAPKs, p-Akt, and p-NF-κB p65. Oxidative stress is tightly connected with inflammation, which was also evaluated through nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (OH-1) signaling pathway.

Results: Our study unraveled that dysiarenone between 2 and 8 µM reduces the inflammation responses via suppressing the production of inflammatory cytokines (TNF-α and IL-6) and inflammatory mediators (LTB). Dysiarenone down-regulated the protein levels of inducible 5-LOX via the inhibition of phosphorylation of MAPKs (including p38, ERK), Akt and NF-κB p65. Additionally, dysiarenone decreases ROS accumulation by upregulating HO-1 expression via nuclear translocation of Nrf2.

Conclusion: In conclusion, we demonstrated that dysiarenone possesses anti-inflammation and anti-oxidation activity via inhibiting 5-LOX/NF-κB/MAPK and Nrf2/HO-1 signaling pathway. Dysiarenone might be a promising lead compound for inflammatory diseases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/JIR.S283745DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7921866PMC
February 2021

[Research progress on processing history evolution as well as effect on chemical compositions and traditional pharmacological effects of Rhei Radix et Rhizoma].

Zhongguo Zhong Yao Za Zhi 2021 Feb;46(3):539-551

Key Laboratory of Shaanxi Administration of Traditional Chinese Medicine for TCM Compatibility, Shaanxi University of Chinese Medicine Xianyang 712046, China.

Rhei Radix et Rhizoma(RRR) is a commonly used traditional Chinese medicine, with extensive pharmacological effects and clinical applications. This paper summarized processing history evolution of RRR and its effect on chemical compositions and pharmacological effects, and provided feasible insights for further studies on the chemical compositions and pharmacological effects of RRR before and after processing. Relevant information demonstrated that RRR has a long history of processing and various methods. At pre-sent, Chinese Pharmacopoeia mainly records four processing methods: cleaning(raw RRR), wine processing(RRR stir-fried with wine), steaming processing(RRR wine steaming), fried charcoal(RRR charring). RRR has a good effect in clearing heat effect, hemostatic effect and blood promoting effect, and its main chemical components are anthraquinone/anthrones, stilbene, phenylbutanone, chromogens, flavonoids and tannin compounds. This paper reviewed the history evolution of RRR and its effect on chemical composition and pharmacological changes, and put forward further study ideas, with the aim to provide a basic reference for processing mechanism, effective material basis and clinical application of RRR.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.19540/j.cnki.cjcmm.20201105.601DOI Listing
February 2021

Estimating Bus Cross-Sectional Flow Based on Machine Learning Algorithm Combined with Wi-Fi Probe Technology.

Sensors (Basel) 2021 Jan 27;21(3). Epub 2021 Jan 27.

Department of Beijing Key Laboratory of Traffic Engineering, Beijing University of Technology, Beijing 100124, China.

With expansion of city scale, the issue of public transport systems will become prominent. For single-swipe buses, the traditional method of obtaining section passenger flow is to rely on surveillance video identification or manual investigation. This paper adopts a new method: collecting wireless signals from mobile terminals inside and outside the bus by installing six Wi-Fi probes in the bus, and use machine learning algorithms to estimate passenger flow of the bus. Five features of signals were selected, and then the three machine learning algorithms of Random Forest, K-Nearest Neighbor, and Support Vector Machines were used to learn the data laws of signal features. Because the signal strength was affected by the complexity of the environment, a strain function was proposed, which varied with the degree of congestion in the bus. Finally, the error between the average of estimation result and the manual survey was 0.1338. Therefore, the method proposed is suitable for the passenger flow identification of single-swiping buses in small and medium-sized cities, which improves the operational efficiency of buses and reduces the waiting pressure of passengers during the morning and evening rush hours in the future.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/s21030844DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7865710PMC
January 2021

Quantitative evaluation of Danqi tablet by ultra-performance liquid chromatography coupled with triple quadrupole mass spectrometry integrated with bioassay.

J Sep Sci 2021 Apr 2;44(7):1552-1563. Epub 2021 Feb 2.

Key Laboratory of Shaanxi Administration of Traditional Chinese Medicine for TCM Compatibility, and State Key Laboratory of Research & Development of Characteristic Qin Medicine Resources (Cultivation), and Shaanxi Key Laboratory of Chinese Medicine Fundamentals and New Drugs Research, and Shaanxi Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Shaanxi University of Chinese Medicine, Xi'an, P. R. China.

Danqi tablet composed of the dried roots of Salvia miltiorrhiza and Panax notoginseng is a well-known Chinese patent medicine commonly used for the treatment of cardio-cerebrovascular diseases such as coronary heart disease and myocardial ischemia. Numerous chemical constituents belonging to S. miltiorrhiza and P. notoginseng were detectable in Danqi tablet. Here, we established and validated a rapid and sensitive ultra-performance liquid chromatography coupled with triple quadrupole mass spectrometry method for simultaneous quantification of 23 components in Danqi tablet and then successfully applied to assay 12 batches of samples from ten manufacturers. Our results demonstrated that the contents of 23 components in 12 batches of Danqi tablets varied significantly and their quality indeed existed differently based on the principal component analysis. According to the quantitative data and the loading plot of principal component analysis, five abundant compounds in Danqi tablet were selected as characteristic chemical markers possibly responsible for the quality assessment. Among them, salvianolic acid B and ginsenoside Rg were further chosen to be combined at 2:5 ratio to evaluate the anti-thrombotic activity on phenylhydrazine-induced zebrafish heart thrombosis model. Expectedly, this component combination increased the heart red blood cells intensity compared with the model group and the median effective concentration was 123.4 µg/mL, suggestive of its well anti-thrombotic effect. This study contributed to the quantitative evaluation of Danqi tablet and indicated the combination of salvianolic acid B and ginsenoside Rg may be capable of reflecting the effect of Danqi tablet, thereby providing a reference for further investigations on the improvement of quality control and clinical application of Danqi tablet.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jssc.202000932DOI Listing
April 2021

Leonurine, a potential drug for the treatment of cardiovascular system and central nervous system diseases.

Brain Behav 2021 Feb 10;11(2):e01995. Epub 2020 Dec 10.

Key Laboratory of Shaanxi Administration of Traditional Chinese Medicine for TCM Compatibility, State Key Laboratory of Research & Development of Characteristic Qin Medicine Resources (Cultivation), Shaanxi Key Laboratory of Chinese Medicine Fundamentals and New Drugs Research, Shaanxi Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Shaanxi University of Chinese Medicine, Xi'an, China.

Leonurus japonicus Houtt., a traditional Chinese herbal medicine, is often used as a gynecological medicine with the effect of promoting blood circulation, regulating menstruation, clearing heat, and detoxificating. As the most important alkaloid in L. japonicus, leonurine has a wide range of biological activities, such as antioxidation, anti-inflammation, and anti-apoptosis. Cardiovascular system and central nervous system diseases are arrogant killers that threaten human lives and health around the world, but many drugs for treating them have certain side effects. This paper reviews the potential therapeutic effects of leonurine on cardiovascular system and central nervous system diseases, summarizes the previous research progress, and focuses on its therapeutic effect in various diseases. Although leonurine plays a prominent role in the treatment of cardiovascular system and central nervous system diseases, there are still some shortages, such as low bioavailability, weak transmembrane ability, and poor fat solubility. Therefore, the structure modification of leonurine may solve these problems and provide reference value for the development of new drugs. At present, leonurine is in clinical trial, and it is hoped that our summary will help to provide guidance for its future research on the basic science and clinical application.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/brb3.1995DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7882174PMC
February 2021

Pillararene-based AIEgens: research progress and appealing applications.

Chem Commun (Camb) 2021 Jan;57(3):284-301

Key Laboratory of Eco-Environment-Related Polymer Materials, Ministry of Education of China, Research Center of Gansu Military and Civilian Integration Advanced Structural Materials, College of Chemistry and Chemical Engineering, Northwest Normal University, Lanzhou, Gansu 730070, China.

As a photophysical phenomenon, aggregation-induced emission (AIE) was proposed by Tang in 2001. Due to their excellent fluorescence emission performance, AIEgens and AIE-based fluorescence materials have shown great application potential in a wide range of science fields. Hence, exploring new AIEgens and construction of novel AIE materials are especially vital. In addition, as a new class of macrocyclic hosts, pillararenes have shown excellent performance in supramolecular chemistry. Interestingly, pillararenes also exhibited fairly bright application prospects in the AIE area: firstly, some research studies suggested that pillararenes could serve as a novel AIEgen with considerable fluorescence emission in the aggregated state; moreover, they could also participate in the construction of AIE materials and have potential application in various areas. In this review, we summarised the recent development of pillararene-based AIE materials from the following aspects: pillararenes as novel AIEgens, the TPE functionalized pillararene-based AIE materials, the pillararene-based AIE materials constructed by supramolecular assembly, and the functionalized pseudo-pillararene-based AIE materials. It is hoped that this feature article will attract increasing attention and pave a new way for the development and application of pillar[n]arene-based AIE materials in more fields.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/d0cc05776bDOI Listing
January 2021

Therapeutic Potential of Hydroxysafflor Yellow A on Cardio-Cerebrovascular Diseases.

Front Pharmacol 2020 29;11:01265. Epub 2020 Sep 29.

Key Laboratory of Shaanxi Administration of Traditional Chinese Medicine for TCM Compatibility, and State Key Laboratory of Research & Development of Characteristic Qin Medicine Resources (Cultivation), and Shaanxi Key Laboratory of Chinese Medicine Fundamentals and New Drugs Research, and Shaanxi Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Shaanxi University of Chinese Medicine, Xi'an, China.

The incidence rate of cardio-cerebrovascular diseases (CCVDs) is increasing worldwide, causing an increasingly serious public health burden. The pursuit of new promising treatment options is thus becoming a pressing issue. Hydroxysafflor yellow A (HSYA) is one of the main active quinochalcone -glycosides in the florets of L., a medical and edible dual-purpose plant. HSYA has attracted much interest for its pharmacological actions in treating and/or managing CCVDs, such as myocardial and cerebral ischemia, hypertension, atherosclerosis, vascular dementia, and traumatic brain injury, in massive preclinical studies. In this review, we briefly summarized the mode and mechanism of action of HSYA on CCVDs based on these preclinical studies. The therapeutic effects of HSYA against CCVDs were presumed to reside mostly in its antioxidant, anti-inflammatory, and neuroprotective roles by acting on complex signaling pathways.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fphar.2020.01265DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7550755PMC
September 2020

Comparatively Evaluating the Role of Herb Pairs Containing Angelicae Sinensis Radix in Xin-Sheng-Hua Granule by Withdrawal Analysis.

Evid Based Complement Alternat Med 2020 22;2020:9456350. Epub 2020 Sep 22.

Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, and National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, and Jiangsu Key Laboratory for High Technology Research of TCM Formulae, Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu Province, China.

The present study aims to investigate the roles of herb pairs containing Angelicae Sinensis Radix (Danggui) in Xin-Sheng-Hua Granule (XSHG) on hemolytic and aplastic anemia (HAA) mice. HAA model mice were induced by acetyl phenylhydrazine and cyclophosphamide; then the samples of XSHG and its decomposed recipes (DY, DC, DT, DH, DJ, and DZ) were orally administrated to these mice. Indicators of peripheral blood routine, organ index, and ATPase activities were tested. Moreover, the main effective components in these samples were also analyzed by UHPLC-TQ-MS/MS. Clear separation between the control and model groups from score plot of principal component analysis (PCA) was easily seen, indicating that HAA model was successfully conducted. Afterwards, relative distance calculation method between dose groups and control group from PCA score plot was adopted to evaluate the integrated effects of hematinic function of different samples. And the orders of hematinic effects were as follows: XHSG > DJ > DT > DZ > DH > DC > DY. Further analysis of these samples by UHPLC-TQ-MS/MS revealed that XSHG underwent complicated changes when herb pairs containing Danggui were excluded from XSHG, respectively. Compared with XSHG, the vast majority of active compounds in sample DY (formula minus herb pair Danggui-Yimucao) decreased significantly, which could partly explain why herb pair Danggui-Yimucao made great contribution to XSHG. These findings showed that withdrawal analysis method is a valuable tool to analyze the impacts of herb pairs containing Danggui on XSHG, which could lay foundation to reveal the compatibility rules of this formula.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2020/9456350DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7528019PMC
September 2020

Qiju Dihuang Decoction for Hypertension: A Systematic Review and Meta-Analysis.

Evid Based Complement Alternat Med 2020 31;2020:9403092. Epub 2020 Jul 31.

Key Laboratory of Shaanxi Administration of Traditional Chinese Medicine for TCM Compatibility, Shaanxi University of Chinese Medicine, Xi'an 712046, Shaanxi, China.

Objective: To systematically evaluate the efficacy of Chinese herbal medicine Qiju Dihuang Decoction (QDD) for hypertension.

Methods: A comprehensive literature search of randomized controlled trials using QDD to treat hypertension was conducted in 7 electronic databases, including Chinese databases. Subjects and abstracts of the trials were read in NoteExpress for preliminary screening, and the full text was read for further screening. The data extraction table was made for the selected 19 trials, and risk of bias was assessed by using the Cochrane collaboration tool, followed by data analysis using Rev Man 5.3.

Results: The antihypertensive efficacy of QDD is 1.45 times that of antihypertensive drugs and 1.56 times that of conventional therapies, which can also reduce the endothelin level. QPAD exhibits an antihypertensive effect, and its clinical efficacy is 1.34 times and 1.61 times that of antihypertensive drugs, which can not only significantly lower the diastolic blood pressure but also reduce the 24 h mean ambulate blood pressure. At the same time, it can decrease the TCM syndrome score, inhibit the inflammation, protect the renal function, reduce the insulin resistance, and improve the life quality of patients.

Conclusion: QDD can effectively reduce blood pressure and improve the life quality of patients with hypertension, which plays a certain role in preventing hypertension complications. However, due to the methodological deficiencies, more rigorous randomized controlled trials will be needed in the future to provide stronger evidence.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2020/9403092DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7415105PMC
July 2020

The Circumferential Resection Margin Is a Prognostic Predictor in Colon Cancer.

Front Oncol 2020 26;10:927. Epub 2020 Jun 26.

Department of Medical Oncology, School of Medicine, Jingling Hospital, Nanjing University, Nanjing, China.

This study aimed to investigate the potential value of circumferential resection margin (CRM) in colon cancer prognostics. CRM has been extensively studied as an important prognostic factor in rectal and esophageal cancer, but not in colon cancer. Data from 6,681 CRM-positive patients and 25,908 CRM-negative patients diagnosed with colon cancer in 2010-2015 were obtained from the Surveillance, Epidemiology, and End Results database. Statistical analysis methods utilized included the chi-square test, Kaplan-Meier estimates, Cox proportional, and X-tile software analyses. After propensity score matching, CRM positivity was found to be negatively related with survival < 0.001). X-tile software identified 0 and 30 mm as optimal cutoff values ( < 0.001) for prognosis, which was applicable only in stage II-IV patients. A 20 and 33% risk decrease were observed in patients with CRM between 0 and 30 mm [95% confidence interval (CI) = 0.76-0.84], and larger than 30 mm (95% CI = 0.62-0.71), respectively. Chemotherapy strongly benefited prognosis with a hazard ratio of 0.36 (95% CI = 0.34-0.38) for overall survival (OS). Patients with a CRM value of 0-30 mm seemed to benefit most from chemotherapy compared with other groups. CRM and number of regional lymph nodes are independent risk factors, and the latter is a good substitute for CRM in AJCC stage I patients. CRM positivity is a strong unfavorable survival indicator for colon cancer patients. A better outcome is expected with CRM values larger than 30 mm. This cutoff value only applied to stage II-IV patients. For stage I patients, number of regional lymph nodes is a good substitute to predict survival. Chemotherapy was another favorable prognostic factor, especially for patients with a CRM value between 0 and 30 mm.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fonc.2020.00927DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7332859PMC
June 2020

Integration of organ metabolomics and proteomics in exploring the blood enriching mechanism of Danggui Buxue Decoction in hemorrhagic anemia rats.

J Ethnopharmacol 2020 Oct 12;261:113000. Epub 2020 Jul 12.

Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Jiangsu Key Laboratory for High Technology Research of TCM Formulae, National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, Jiangsu Province, China.

Ethnopharmacological Relevance: Danggui Buxue Decoction (DBD), as a classical Chinese medicine prescription, is composed of Danggui (DG) and Huangqi (HQ) at a ratio of 1:5, and it has been used clinically in treating anemia for hundreds of years.

Aim Of The Study: The aim of this study was to explore the treatment mechanisms of DBD in anemia rats from the perspective of thymus and spleen.

Materials And Methods: In this study, a successful hemorrhagic anemia model was established, and metabolomics (UPLC-QTOF-MS/MS) and proteomics (label-free approach) together with bioinformatics (Gene Ontology analysis and Reactome pathway enrichment), correlation analysis (pearson correlation matrix) and joint pathway analysis (MetaboAnalyst) were employed to discover the underlying mechanisms of DBD.

Results: DBD had a significant blood enrichment effect on hemorrhagic anemia rats. Metabolomics and proteomics results showed that DBD regulated a total of 10 metabolites (lysophosphatidylcholines, etc.) and 41 proteins (myeloperoxidase, etc.) in thymus, and 9 metabolites (L-methionine, etc.) and 24 proteins (transferrin, etc.) in spleen. With GO analysis and Reactome pathway enrichment, DBD mainly improved anti-oxidative stress ability of thymocyte and accelerated oxidative phosphorylation to provide ATP for splenocyte. Phenotype key indexes were strongly and positively associated with most of the differential proteins and metabolites, especially nucleosides, amino acids, Fabp4, Decr1 and Ndufs3. 14 pathways in thymus and 9 pathways in spleen were obtained through joint pathway analysis, in addition, the most influential pathway in thymus was arachidonic acid metabolism, while in spleen was the biosynthesis of phenylalanine, tyrosine and tryptophan. Furthermore, DBD was validated to up-regulate Mpo, Hbb and Cp levels and down-regulate Ca level in thymus, as well as up-regulate Fabp4, Ndufs3, Tf, Decr1 and ATP levels in spleen.

Conclusion: DBD might enhance thymus function mainly by reducing excessive lipid metabolism and intracellular Ca level, and promote ATP production in spleen to provide energy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jep.2020.113000DOI Listing
October 2020

The epigallocatechin gallate derivative Y6 reduces the cardiotoxicity and enhances the efficacy of daunorubicin against human hepatocellular carcinoma by inhibiting carbonyl reductase 1 expression.

J Ethnopharmacol 2020 Oct 1;261:113118. Epub 2020 Jul 1.

Pharmaceutical College, Guangxi Medical University, Nanning, China. Electronic address:

Ethnopharmacological Relevance: Green tea is the most ancient and popular beverage worldwide and its main constituent epigallocatechin-3-gallate (EGCG) has a potential role in the management of cancer through the modulation of cell signaling pathways. However, EGCG is frangible to oxidation and exhibits low lipid solubility and bioavailability, and we synthesized a derivative of EGCG in an attempt to overcome these limitations.

Aim Of The Study: The anthracycline antibiotic daunorubicin (DNR) is a potent anticancer agent. However, its severe cardiotoxic limits its clinical efficacy. Human carbonyl reductase 1 (CBR1) is one of the most effective human reductases for producing hydroxyl metabolites and thus may be involved in increasing the cardiotoxicity and decreasing the antineoplastic effect of anthracycline antibiotics. Accordingly, in this study, we investigated the co-therapeutic effect of Y6, a novel and potent adjuvant obtained by optimization of the structure of EGCG.

Material And Methods: The cellular concentrations of DNR and its metabolite DNRol were measured by HPLC to determine the effects of EGCG and Y6 on the inhibition of DNRol formation. The cytotoxic effects of EGCG and Y6 were tested by MTT assay in order to identify non-toxic concentrations of them. To understand their antitumor and cardioprotective mechanisms, hypoxia-inducible factor-1α (HIF-1α) and CBR1 protein expression was measured via Western blotting and immunohistochemical staining while gene expression was analyzed using RT-PCR. Moreover, PI3K/AKT and MEK/ERK signaling pathways were analyzed via Western blotting. HepG2 xenograft model was used to detect the effects of EGCG and Y6 on the antitumor activity and cardiotoxicity of DNR in vivo. Finally, to obtain further insight into the interactions of Y6 and EGCG with HIF-1α and CBR1, we performed a molecular modeling.

Results: Y6(10 μg/ml or 55 mg/kg) decreased the expression of HIF-1α and CBR1 at both the mRNA and protein levels during combined drug therapy in vitro as well as in vivo, thereby inhibiting formation of the metabolite DNRol from DNR, with the mechanisms being related to PI3K/AKT and MEK/ERK signaling inhibition. In a human carcinoma xenograft model established with subcutaneous HepG2 cells, Y6(55 mg/kg) enhanced the antitumor effect and reduced the cardiotoxicity of DNR more effectively than EGCG(40 mg/kg).

Conclusions: Y6 has the ability to inhibit CBR1 expression through the coordinate inhibition of PI3K/AKT and MEK/ERK signaling, then synergistically enhances the antitumor effect and reduces the cardiotoxicity of DNR.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jep.2020.113118DOI Listing
October 2020

Analysis and evaluation of nucleosides, nucleobases, and amino acids in safflower from different regions based on ultra high performance liquid chromatography coupled with triple-quadrupole linear ion-trap tandem mass spectrometry.

J Sep Sci 2020 Aug 20;43(16):3170-3182. Epub 2020 Jul 20.

Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, and Jiangsu Key Laboratory for High Technology Research of TCM Formulae, and National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province, P. R. China.

Safflower has both medicinal and edible values but research on its nutrient composition is still lacking. This study was established for the quantitative determination of 28 nucleosides, nucleobases, and amino acids based on the ultra-performance liquid chromatography coupled with triple-quadrupole linear ion-trap tandem mass spectrometry. Analysis of 30 batches of safflower from different producing areas indicated that the contents of l-proline, l-asparagine, l(+)-arginine, l-serine, l-histidine, uracil, guanosine, and uridine was high in safflower. Principle component analysis and cluster analysis found that samples from different regions could be distinguished well, and samples from the same area could be clustered into one class, different geographical environments may cause the differences of nucleosides, nucleobases, and amino acids in safflower. The analysis of principal component analysis, cluster analysis, and counter propagation artificial neural network show similar results. Then the content of nucleosides, nucleobases, and essential amino acids were compared, and found that the content in safflower from Gansu was higher than those from other regions, and there was a little difference between the samples from Xinjiang, Sichuan, and Yunnan. This research revealed the composition of nucleosides, nucleobases, and amino acids in safflower, and provided a theoretical basis for utilization of safflower.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jssc.202000180DOI Listing
August 2020

An integrated strategy for discovering effective components of Shaoyao Gancao decoction for treating neuropathic pain by the combination of partial least-squares regression and multi-index comprehensive method.

J Ethnopharmacol 2020 Oct 2;260:113050. Epub 2020 Jun 2.

Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Jiangsu Key Laboratory for High Technology Research of TCM Formulae, National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, Jiangsu Province, China.

Ethnopharmacological Relevance: Neuropathic pain, the incidence of which ranges from 5 to 8% in the general population, remains challenge in the treatment. Shaoyao Gancao decoction (SGD) is a Chinese classical formula used to relieve pain for thousands of years and has been applied for neuropathic pain nowadays. However, the effective components of SGD for the treatment of neuropathic pain remains unclear.

Aims Of Study: To investigate the effect and potential mechanism of SGD against neuropathic pain and further reveal the effective components of SGD in the treatment of neuropathic pain.

Materials And Methods: Spared nerve injury (SNI) model rats of neuropathic pain were orally given SGD to intervene, the components in vivo after SGD administration were determined, behavior indicators, biochemical parameters, and metabolomics were applied for assessing the efficacy. Then correlation between components and biomarkers was analyzed by pearson correlation method. To further measure the contribution of components to efficacy, the combination of partial least-squares regression (PLSR) and multi-index comprehensive method was carried out, according to the corresponding contribution degree of the results, the components with large contribution degree were considered as the effective components.

Results: SGD exhibited a significant regulatory effect on neuropathic pain, which could increase the pain threshold and decrease the levels of SP, β-EP, PGE2 and NO. With the high resolution of UPLC-Q-TOF/MS technology, a total of 128 compounds from SGD were identified and 44 of them were absorbed in blood. Besides, 40 serum biomarkers were identified after intervention of SGD and the metabolic pathways were constructed. The key metabolic pathways including Glycerophospholipid metabolism, Linoleic acid metabolism, Alpha-linolenic acid metabolism, Glycosylphosphatidylinositol-anchor biosynthesis and Arachidonic acid metabolism may be related to the regulation of neuropathic pain. Metabolomics combined with PLSR and multi-index comprehensive method was utilized to discover 5 components including paeonol, DL-Arabinose, benzoic acid, hispaglabridin A and paeonilactone C as effective components of SGD in the treatment of neuropathic pain. This strategy was used to explore the effective components of SGD and elucidate its possible analgesic mechanism.

Conclusion: This study demonstrate that SGD significantly relieved neuropathic pain and elucidated the effective components of SGD for treating neuropathic pain, the strategy as an illustrative case study can be applied to other classical formula and is beneficial to improve the quality and efficacy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jep.2020.113050DOI Listing
October 2020

Clinicopathological characteristics and prognosis of colorectal mucinous adenocarcinoma and nonmucinous adenocarcinoma: a surveillance, epidemiology, and end results (SEER) population-based study.

Ann Transl Med 2020 Mar;8(5):205

Department of Medical Oncology, Jinling Hospital, The First School of Clinical Medicine, Southern Medical University, Nanjing 210002, China.

Background: Mucinous adenocarcinoma (MC) is a rare histological subtype of colorectal adenocarcinoma. Previous studies investigating the prognosis of MC have conflicting results and the proper treatment of MC remains unclear.

Methods: This retrospective study presents the clinicopathological characteristics and prognosis of MC. This cohort study collected data from April 1 through August 01, 2018. This study used data on 107,735 patients with nonmucinous adenocarcinoma (NMC) and 9,494 with MC between 2009 and 2013 from the Surveillance, Epidemiology, and End Results program (SEER). Clinicopathological features were analyzed by chi-square test and survival curves by the Kaplan-Meier method. We used propensity score matching (PSM) to account for potential bias. Logistic regression and Cox proportional hazards models were used to compare and calculate adjusted risks of MC death.

Results: MC was more frequent in patients with older age, large tumor size and moderate tumor grade compared with NMC (P<0.001). Five-year survival was lower for MC patients than NMC patients (P<0.001). Older age, later tumor node metastasis (TNM) stage and multiple tumors indicated a poorer prognosis while surgery gave better survival outcomes [hazard ratio (HR) =0.38; 95% confidence interval (CI), 0.33 to 0.44; P<0.001]. Younger age, left-side colon location and early disease stage were associated with better survival after surgery (P<0.001).

Conclusions: Age, TNM stage, tumor number and treatment were indicators of prognosis and surgery gave better survival for MC patients compared with those without surgery. Our study contributes to their clinical treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.21037/atm.2020.01.52DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7154470PMC
March 2020

Frontline Science: Two flavonoid compounds attenuate allergic asthma by regulating epithelial barrier via G protein-coupled estrogen receptor: Probing a possible target for allergic inflammation.

J Leukoc Biol 2020 07 17;108(1):59-71. Epub 2020 Apr 17.

Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China.

Allergic asthma is a common chronic lung inflammatory disease and seriously influences public health. We aim to investigate the effects of formononetin (FMN) and calycosin (CAL), 2 flavonoids in Radix Astragali, on allergic asthma and elucidate possible therapeutic targets. A house dust mite (HDM)-induced allergic asthma mouse model and TNF-α and Poly(I:C) co-stimulated human bronchial epithelial cell line (16HBE) were performed respectively in vivo and in vitro. The role of G protein-coupled estrogen receptor (GPER) was explored by its agonist, antagonist, or GPER small interfering RNA (siGPER). E-cadherin, occludin, and GPER were detected by western blotting, immunohistochemistry, or immunofluorescence. The epithelial barrier integrity was assessed by trans-epithelial electric resistance (TEER). Cytokines were examined by enzyme-linked immunosorbent assay (ELISA). The results showed that flavonoids attenuated pulmonary inflammation and hyperresponsiveness in asthmatic mice. These flavonoids significantly inhibited thymic stromal lymphopoietin (TSLP), increased occludin and restored E-cadherin in vivo and in vitro. The effects of flavonoids on occludin and TSLP were not interfered by ICI182780 (estrogen receptor antagonist), while blocked by G15 (GPER antagonist). Furthermore, compared with PPT (ERα agonist) and DPN (ERβ agonist), G1 (GPER agonist) significantly inhibited TSLP, up-regulated occludin, and restored E-cadherin. siGPER and TEER assays suggested that GPER was pivotal for the flavonoids on the epithelial barrier integrity. Finally, G1 attenuated allergic lung inflammation, which could be abolished by G15. Our data demonstrated that 2 flavonoids in Radix Astragali could alleviate allergic asthma by protecting epithelial integrity via regulating GPER, and activating GPER might be a possible therapeutic strategy against allergic inflammation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/JLB.3HI0220-342RRDOI Listing
July 2020

The epigallocatechin gallate derivative Y inhibits human hepatocellular carcinoma by inhibiting angiogenesis in MAPK/ERK1/2 and PI3K/AKT/ HIF-1α/VEGF dependent pathways.

J Ethnopharmacol 2020 Sep 9;259:112852. Epub 2020 Apr 9.

Pharmaceutical College, Guangxi Medical University, Nanning, 530021, China. Electronic address:

Ethnopharmacological Relevance: Hypervascularity has been considered as one of the major features of many solid tumors. Green tea is one of the commonly drink resources in China, and its active component, Epigallocatechin gallate (EGCG), exhibits antiangiogenic activities in various experimental tumor models. However, EGCG has many shortages, e.g., relatively unstable, low lipid solubility, poor bioavailability, and short duration of action.

Aim Of The Study: To overcome the shortages of EGCG for antiangiogenic antitumor usage, our study developed a novel EGCG derivate, Y(5,3',4',3″,4″,5″-6-0-ethyl-EGCG). The underlying mechanism was also elucidated.

Material And Methods: we evaluated the effects of EGCG, Y on HCC and angiogenesis in vivo and in vitro. Moreover, to understand their antitumor mechanisms, key factors within angiogenesis-related signaling pathways (MAPK/ERK1/2, PI3K/AKT, HIF-1 VEGF) were analyzed by using western blot, immunohistochemistry (IHC), quantitative real-time quantitative PCR (RT-PCR). HepG2 xenograft model and the chorioallantoic membrane (CAM) were used to investigate the effects of Y and EGCG on tumors and anti-angiogenesis in vivo. Micro-vessel density (MVD) was analyzed by IHC of CD34 staining. IHC, qRT-PCR and Western blot were used to detect the expression of HIF-1α and VEGF protein in tumor tissues. The protein levels of MAPK/ERK1/2, PI3K/AKT, HIF-1α, and VEGF in tumor tissues were detected by western blot.

Results: Our results demonstrated that both EGCG and Y displayed antiangiogenetic and antitumor effects against HCC cells in vitro and in vivo. We found that rather than equal amount of EGCG, Y displayed better abilities in inhibiting the growth of HCC tumor cells, as well as inhibiting the growth of neovascularization in the chick embryos and HepG2 xenograft tumors bearing-mice, based on the data obtained from MTT assay, immunohistochemistry (IHC), chick chorioallantoic membrane (CAM) assays. In the comparison of equivalent dose of EGCG, qRT-PCR data showed that Y induced more significant decrease of the mRNA levels of HIF-1α and VEGF in supernatant-treated SMMC-7721 cells under hypoxic condition, as well as in the in xenograft tumor tissues; whereas Y also significantly reduced the protein levels of MAPK/ERK1/2, PI3K/AKT, HIF-1α, and VEGF to a greater extent than EGCG, determined by western blotting assay.

Conclusions: our work suggests that the new EGCG derivate Y could significantly inhibit tumor growth and angiogenesis which is possibly involved with the signaling intervention of MAPK/ERK1/2 and PI3K/AKT/HIF-1α/VEGF pathways, and is supposed to be a potential therapeutic reagent for anti-angiogenesis treatment of solid tumors.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jep.2020.112852DOI Listing
September 2020

Visible-Light-Promoted Selenylative Spirocyclization of Indolyl-ynones toward the Formation of 3-Selenospiroindolenine Anticancer Agents.

Chem Asian J 2020 May 7;15(10):1536-1539. Epub 2020 Apr 7.

Pharmacy School, Guilin Medical University, 541004, People's Republic of China, Guilin.

A metal-free and efficient visible-light-induced spirocyclization of indolyl-ynones with diselenides at room temperature under air atmosphere to prepare 3-selenospiroindolenines in moderate to good yields has been developed. The resulting products were tested for in vitro anticancer activity by MTT assay, and compounds 3 c and 3 e showed potent cancer cell-growth inhibition activities.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/asia.202000298DOI Listing
May 2020

Comparison of the performance of two depression rating scales in patients with epilepsy in southern China.

Epilepsy Behav 2020 05 19;106:107025. Epub 2020 Mar 19.

Department of Neurology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang Province, China. Electronic address:

Objective: The aim of this study was to evaluate and compare the performance of the Chinese version of the Neurological Disorder Depression Inventory for Epilepsy (CNDDI-E) with that of the depression subscale of the Hospital Anxiety and Depression Scale (C-HADS-D) as screening tools for depression in the same patients with epilepsy (PWE).

Methods: A total of 213 consecutive PWE were evaluated. Receiver operating characteristic (ROC) analysis was performed using the C-NDDI-E and C-HADS-D as predictors and the Chinese version of the Mini International Neuropsychiatric Interview (C-MINI) as the gold standard.

Results: The area under the curve (AUC) for the C-NDDI-E was 0.870, and the optimal cutoff score was >11 (sensitivity 85.71%, specificity 79.78%); for the C-HADS-D, the AUC was 0.804, and the optimal cutoff score was >5 (sensitivity 85.71%, specificity 62.36%). The AUC for the C-NDDI-E was larger than the AUC for the C-HADS-D, but the comparison of the AUCs revealed no significant differences (P = 0.1444).

Conclusion: Our findings indicate that the C-NDDI-E and C-HADS-D have high validity and support the use of these screening tools for depression in PWE. Moreover, the C-NDDI-E is a better screening scale for diagnosing depression than the C-HADS-D according to the results of this study.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.yebeh.2020.107025DOI Listing
May 2020

Deciphering the Active Compounds and Mechanisms of Qixuehe Capsule on Qi Stagnation and Blood Stasis Syndrome: A Network Pharmacology Study.

Evid Based Complement Alternat Med 2020 27;2020:5053914. Epub 2020 Feb 27.

Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Jiangsu Key Laboratory for High Technology Research of TCM Formulae, National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China.

Background: Qixuehe capsule (QXH), a Chinese patent medicine, has been demonstrated to be effective in the treatment of menstrual disorders. In traditional Chinese medicine (TCM) theory, qi stagnation and blood stasis syndrome (QS-BSS) is the main syndrome type of menstrual disorders. However, the pharmacodynamic effect of QXH in treating QS-BSS is not clear, and the main active compounds and underlying mechanisms remain unknown.

Methods: A rat model of QS-BSS was established to evaluate the pharmacodynamic effect of QXH. Thereafter, a network pharmacology approach was performed to decipher the active compounds and underlying mechanisms of QXH.

Results: QXH could significantly reduce the rising whole blood viscosity (WBV) and plasma viscosity (PV) but also normalize prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), and fibrinogen (FIB) content in QS-BSS rats. Based on partial least-squares-discriminant analysis (PLS-DA), the low-dose QXH-intervened (QXH-L) and the high-dose QXH-intervened (QXH-H) groups seemed the most effective by calculating the relative distance to normality. Through network pharmacology, QXH may improve hemorheological abnormality mainly via 185 compounds-51 targets-28 pathways, whereas 184 compounds-68 targets-28 pathways were associated with QXH in improving coagulopathy. Subsequently, 25 active compounds of QXH were verified by UPLC-Q/TOF-MS. Furthermore, 174 active compounds of QXH were shared in improving hemorheological abnormality and coagulopathy in QS-BSS, each of which can act on multiple targets to be mainly involved in complement and coagulation cascades, leukocyte transendothelial migration, PPAR signaling pathway, VEGF signaling pathway, and arachidonic acid metabolism. The attribution of active compounds indicated that Angelicae Sinensis Radix (DG), Paeoniae Radix Rubra (CS), Carthami Flos (HH), Persicae Semen (TR), and Corydalis Rhizoma (YHS) were the vital herbs of QXH in treating QS-BSS.

Conclusion: QXH can improve the hemorheology abnormality and coagulopathy of QS-BSS, which may result from the synergy of multiple compounds, targets, and pathways.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2020/5053914DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7063220PMC
February 2020

Elucidating the interaction of kansui and licorice by comparative plasma/tissue metabolomics and a heatmap with relative fold change.

J Pharm Anal 2019 Oct 1;9(5):312-323. Epub 2019 Jun 1.

Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, and Jiangsu Key Laboratory for High Technology Research of TCM Formulae, Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu Province, China.

Although compatibility is highly advocated in traditional Chinese medicine (TCM), inappropriate combination of some herbs may reduce the therapeutic action and even produce toxic effects. Kansui and licorice, one of TCM "", are the most representative cases of improper herbal combination, which may still be applied simultaneously under given conditions. However, the potential mechanism of their compatibility and incompatibility is unclear. In the present study, two different ratios of kansui and licorice, representing their compatibility and incompatibility respectively, were designed to elucidate their interaction by comparative plasma/tissue metabolomics and a heatmap with relative fold change. As a result, glycocholic acid, prostaglandin F2a, dihydroceramide and sphinganine were screened out as the principal alternative biomarkers of compatibility group; sphinganine, dihydroceramide, arachidonic acid, leukotriene B4, acetoacetic acid and linoleic acid were those of incompatibility group. Based on the values of biomarkers in each tissue, the liver was identified as the compatible target organ, while the heart, liver, and kidney were the incompatible target organs. Furthermore, important pathways for compatibility and incompatibility were also constructed. These results help us to better understand and utilize the two herbs, and the study was the first to reveal some innate characters of herbs related to TCM "".
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jpha.2019.05.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6951493PMC
October 2019

Comparative pharmacodynamic, pharmacokinetic and tissue distribution of Dahuang-Gancao decoction in normal and experimental constipation mice.

Chin J Nat Med 2019 Nov;17(11):871-880

Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, and National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, and Jiangsu Key Laboratory for High Technology Research of TCM Formulae, Nanjing University of Chinese Medicine, Nanjing 210023, China.

Dahuang-Gancao decoction (DGD) is a classical formula, which is commonly used for reliving constipation in Chinese clinic. The aim of this study was to investigate the pharmacodynamic, pharmacokinetic and tissue distribution alternations of DGD in normal and constipation mice. DGD exhibited stronger purgative effect in constipation mice by the increased fecal excretion and reduced first defection time compared with normal mice. The C, AUC and MRT of rhein, aloe-emodin, rhein-8-O-β-D-glucoside, sennoside A, and glycyrrhizic acid as main bio-active components in DGD were markedly increased in constipation mice. The tissue distribution of the analytes in constipation mice were higher than those in normal mice with rhein > rhein-8-O-β-D-glucoside > aloe-emodin > glycyrrhizic acid > emodin in liver, and glycyrrhizic acid > rhein-8-O-β-D-glucoside > liquitin > sennoside A > rhein > aloe-emodin > emodin in colon. The kidney concentrations of the analytes showed a descending order of rhein > rhein-8-O-β-D-glucoside > sennoside A > glycyrrhizic acid > aloe-emodin > emodin, most of them were higher while rhein was lower in constipation mice than normal mice. The higher exposure of the anthraquinones in plasma, liver and colon may result in the stronger purgative effect in the constipation mice than normal mice. Rhein is mainly excreted through the kidney, the decreased level of rhein in constipation mice may explain the alleviated side effects. Accumulation of glycyrrhizic acid in colon may related with the moderate property of licorice. These results provided the experimental basis for understanding the therapeutic effects and metabolite profile of DGD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/S1875-5364(19)30104-9DOI Listing
November 2019

[Administrative village-based spatial distribution specificity of and its relationship with water systems in Hubei Province].

Zhongguo Xue Xi Chong Bing Fang Zhi Za Zhi 2019 Sep;31(4):374-381

Hubei Center for Disease Control and Prevention, Wuhan 430079, China.

Objective: To investigate the spatial distribution of snail habitats at the administrative village scale in schistosomiasis-endemic areas of Hubei Province, so as to provide scientific bases for precise control of snails in the province.

Methods: Data regarding snail distribution at the village level in Hubei Province in 2017 were collected to create a spatial analysis database of snail distribution in Hubei Province. The spatial aggregations of distribution were analyzed using Moran's index and Local Moran's index. In addition, the distances from schistosomiasis-endemic villages to the Yangtze River were captured using the software ArcGIS 13.0, and their correlations with area of snail habitats were examined with the Spearman correlation method.

Results: snails were mainly distributed in 5 450 endemic villages from 63 counties of 13 cities in Hubei Province in 2017. The global spatial autocorrelation analysis showed spatial aggregations in the areas of historically accumulated snail habitats, current areas of snail habitats, areas of snail habitats outside the embankment and snail habitats inside the embankment (all Scores > 0, all values < 0.05), and no spatial aggregation was seen in the areas of snail habitats in hilly areas ( Score > 0, > 0.05). There were four types of spatial distribution of historically accumulated areas of snail habitats, areas of current snail habitats, areas of snail habitats outside the embankment and snail habitats inside the embankment, including the high-high type (H-H type), high-low type (H-L type), low-high type (L-H type) and random distribution type, and a high percentage of the H-H type was found. There were 340, 125 and 110 endemic villages with the H-H type of areas of historically accumulated snail habitats, current areas of snail habitats and areas of snail habitats outside the embankment, and these villages were mainly concentrated in Wuhan and Jingzhou cities, with almost consistent spatial aggregation locations. There were 319 endemic villages with the H-H type of distribution of snail habitats inside the embankment, which were mainly distributed in Jingzhou, Xiaogan and Huangshi cities. In addition, the areas of historically accumulated snail habitats, current areas of snail habitats and areas of snail habitats outside the embankment negatively correlated with the distance from the endemic villages to the Yangtze River ( = -0.094, < 0.01; = -0.225, < 0.01; = -0.177, < 0.01).

Conclusions: The clustering areas of snail habitats along the Yangtze River Basin, notably the villages near the Yangtze River are key regions for snail monitoring and control in Hubei Province.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.16250/j.32.1374.2018296DOI Listing
September 2019

Pharmacodynamics and pharmacokinetics of Danshen in isoproterenol-induced acute myocardial ischemic injury combined with Honghua.

J Ethnopharmacol 2020 Jan 8;247:112284. Epub 2019 Oct 8.

Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Jiangsu Key Laboratory for High Technology Research of TCM Formulae, Nanjing University of Chinese Medicine, Nanjing, 210023, China.

Ethnopharmacological Relevance: Herb pair, the most fundamental and simplest form of herb compatibility, serves as the basic building block of traditional Chinese medicine formulae. The Danshen-Honghua herb pair (DH), composed of Salviae Miltiorrhizae Radix et Rhizoma (Danshen in Chinese) and Carthami Flos (Honghua in Chinese), has remarkable clinical efficacy to cure cardio-cerebrovascular diseases. This study was designed to investigate the pharmacodynamics of DH in comparison with single herbs and pharmacokinetics of DH relative to Danshen in acute myocardial ischemic injury.

Materials And Methods: Sixty male Wistar rats were divided into control, model and drug treated groups. The acute myocardial ischemia rat model was induced by administering 85 mg/kg/d isoproterenol (ISO) subcutaneously for two consecutive days. For pharmacodynamic study, histopathological and biochemical analysis were performed to assess the anti-myocardial ischemic effects. While for pharmacokinetic study, a UPLC-MS/MS method was developed for determination of nine main active ingredients, namely danshensu, protocatechuic acid, protocatechualdehyde, caffeic acid, lithospermic acid, rosmarinic acid, salvianolic acid B, salvianolic acid A and salvianolic acid C in rat plasma.

Results: The histopathological and biochemical analysis revealed that DH exerted enhanced anti-myocardial ischemic effects against the ISO-induced myocardial ischemia compared with single herbs. The pharmacokinetic study indicated that DH could significantly increase the t of danshensu, T, AUC and MRT of protocatechuic acid in comparison with Danshen alone in normal rats, but more importantly elevate systemic exposure level and prolong t of protocatechualdehyde, caffeic acid, T of danshensu in acute myocardial ischemia rats.

Conclusions: Our findings demonstrated the greater effects of DH after the compatibility in ISO-induced acute myocardial ischemia rats at pharmacodynamic and pharmacokinetic levels and provided valuable information for clinical application of herb pairs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jep.2019.112284DOI Listing
January 2020

[Research thoughts and methods on grading identification and transmission change law of traditional Chinese medicine(TCM) Q-marker].

Zhongguo Zhong Yao Za Zhi 2019 Jul;44(14):3116-3122

Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization,Nanjing University of Chinese Medicine Nanjing 210023,China.

The quality marker( Q-maker) of traditional Chinese medicine( TCM) has been the core concept of TCM quality evaluation and control in recent years. Based on the knowledge and long-term practice of the researches on TCM quality,we put forward that " Taking the effectiveness as the core,the measurability and peculiarity as necessary conditions,and considering compatibility for TCM formulae,TCM Q-makers are selected and confirmed,and then the transmission and traceability should be investigated as its functional attributes". Selecting the commonly used representative TCM as the research object,based on the score of TCM effectiveness,measurability and peculiarity,a layered three-dimensional integrated technology was adopted for the quantitative evaluation and grading identification of the Q-markers for TCM. And after Q-markers for TCM are selected and confirmed,the transmission variation of the Q-markers is studied in the whole process from the formation of TCM to its function representation. Based on TCM chemical and biological characteristics as well as effectiveness,and integrating multidisciplinary techniques and methods,researches on innovative methods for system identification and confirmation of the TCM Q-makers are developed emphatically to form representative and exemplary extensive application,which will provide significant theoretical and methodological support for effectively improving the quality control level of TCM.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.19540/j.cnki.cjcmm.20190408.201DOI Listing
July 2019

Gut microbiota modulation with traditional Chinese medicine: A system biology-driven approach.

Pharmacol Res 2019 10 18;148:104453. Epub 2019 Sep 18.

Key Laboratory of Shaanxi Administration of Traditional Chinese Medicine for TCM Compatibility, and State Key Laboratory of Research & Development of Characteristic Qin Medicine Resources (Cultivation), and Shaanxi Key Laboratory of Chinese Medicine Fundamentals and New Drugs Research, and Shaanxi Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Shaanxi University of Chinese Medicine, Xi'an 712046, China; Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, and Jiangsu Key Laboratory for High Technology Research of TCM Formulae, and National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China. Electronic address:

With the development of system biology, traditional Chinese medicine (TCM) is drawing more and more attention nowadays. However, there are still many enigmas behind this ancient medical system because of the arcane theory and complex mechanism of actions. In recent decades, advancements in genome sequencing technologies, bioinformatics and culturomics have led to the groundbreaking characterization of the gut microbiota, a 'forgotten organ', and its role in host health and disease. Notably, gut microbiota has been emerging as a new avenue to understanding TCM. In this review, we will focus on the structure, composition, functionality and metabolites of gut microbiota affected by TCM so as to conversely understand its theory and mechanisms. We will also discuss the potential areas of gut microbiota for exploring Chinese material medica waste, Chinese marine material medica, add-on therapy and personalized precise medication of TCM. The review will conclude with future perspectives and challenges of gut microbiota in TCM intervention.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.phrs.2019.104453DOI Listing
October 2019

Comparative analysis of the main active constituents from different parts of Leonurus japonicus Houtt. and from different regions in China by ultra-high performance liquid chromatography with triple quadrupole tandem mass spectrometry.

J Pharm Biomed Anal 2020 Jan 10;177:112873. Epub 2019 Sep 10.

Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, and Jiangsu Key Laboratory for High Technology Research of TCM Formulae, and National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, Jiangsu Province, China.

A rapid, sensitive and convenient analytical method of ultra-performance liquid chromatography coupled with triple-quadrupole linear ion-trap tandem mass spectrometry (UPLC-QTRAP®/MS) was proposed for the simultaneous determination of characteristic alkaline and acidic components covering many structure types including alkaloids, phenolic acids, phenylpropanoids and flavonoids in Leonurus japonicus Houtt. (LJ). The proposed method was first reported and validated by assessing the matrix effects, linearity, limit of detections, limit of quantifications, precision, repeatability, stability and recovery of target components. The developed UPLC-QTRAP®/MS was successfully applied to simultaneously determine all target compounds in 38 batches of LJ from 11 different producing regions in China and five organs (including root, caulis, branch, flower and leaf) of LJ from the same stand planting base in Jiangsu Province (China). The result showed that LJ in different regions with different geographical position would affect the accumulation of different compounds, and the significant discrepancies of some target compounds were also observed in different organs of LJ due to different biosynthetic pathway and enzymes in different organs. Furthermore, both hierarchical clustering analysis and principal components analysis were performed to classify the 38 batches of LJ samples from different producing regions on the basis of target compounds. As a result, the samples could be mainly clustered into different groups, which were similar with areas classification. Overall, the presented method would be helpful for the comprehensive utilization and development of LJ resources.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jpba.2019.112873DOI Listing
January 2020

The Comprehensive Evaluation of Safflowers in Different Producing Areas by Combined Analysis of Color, Chemical Compounds, and Biological Activity.

Molecules 2019 Sep 17;24(18). Epub 2019 Sep 17.

Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, and Jiangsu Key Laboratory for High Technology Research of TCM Formulae, and National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China.

In the present study, a new strategy including the combination of external appearance, chemical detection, and biological analysis was proposed for the comprehensive evaluation of safflowers in different producing areas. Firstly, 40 batches of safflower samples were classified into class I and II based on color measurements and K-means clustering analysis. Secondly, a rapid and sensitive analytical method was developed for simultaneous quantification of 16 chromaticity-related characteristic components (including characteristic components hydroxysafflor yellow A, anhydrosafflor yellow B, safflomin C, and another 13 flavonoid glycosides) in safflowers by ultra-performance liquid chromatography coupled with triple-quadrupole linear ion-trap tandem mass spectrometry (UPLC-QTRAP/MS). The results of the quantification indicate that hydroxysafflor yellow A, anhydrosafflor yellow B, kaempferol, quercetin, and safflomin C had significant differences between the two types of safflower, and class I of safflower had a higher content of hydroxysafflor yellow A, anhydrosafflor yellow B, and safflomin C as the main anti-thrombotic components in safflower. Thirdly, chemometrics methods were employed to illustrate the relationship in multivariate data of color measurements and chromaticity-related characteristic components. As a result, kaempferol-3--rutinoside and 6-hydroxykaempferol-3--β-d-glucoside were strongly associated with the color indicators. Finally, anti-thrombotic analysis was used to evaluate activity and verify the suitability of the classification basis of safflower based on the color measurements. It was shown that brighter, redder, yellower, more orange-yellow, and more vivid safflowers divided into class I had a higher content of characteristic components and better anti-thrombotic activity. In summary, the presented strategy has potential for quality evaluation of other flower medicinal materials.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/molecules24183381DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6767200PMC
September 2019

An integrated metabolomics strategy to reveal dose-effect relationship and therapeutic mechanisms of different efficacy of rhubarb in constipation rats.

J Pharm Biomed Anal 2020 Jan 26;177:112837. Epub 2019 Aug 26.

Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, and National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, and Jiangsu Key Laboratory for High Technology Research of TCM Formulae, Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu Province, China. Electronic address:

The ambiguity of dose-effect relationship of many traditional Chinese medicines (TCMs) has always influenced their rational use in TCM clinic. Rhubarb, a preferred representative of cathartic TCM, is currently widely used that results in a diversity of its dosage. The aim of this study was to use an integrated metabolomics strategy to simultaneously reveal dose-effect relationship and therapeutic mechanisms of different efficacy of rhubarb in constipation rats. Six doses of rhubarb (0.135, 0.27, 0.81, 1.35, 4.05, and 8.1 g/kg) were examined to elucidate the laxative and fire-purging effects by pathological sections and UPLC-Q-TOF/MS. The results showed that there existed serious lesions in the stomach and colon of model rats. And conditions were basically improved to some extent in rhubarb-treated groups. Through relative distance calculation based on metabolomics score plots, it suggested that the effective dose threshold (EC-EC range) of rhubarb was from 0.31 to 4.5 g/kg (corresponding to 3.44-50.00 g in the clinic) in rat serum and 0.29-2.1 g/kg (corresponding to 3.22-23.33 g in the clinic) in feces. Then, 33 potential biomarkers were identified in total. Functional pathway analysis revealed that the alterations of these biomarkers were associated with 15 metabolic pathways, mainly including arachidonic acid metabolism, glycerophospholipid metabolism, steroid biosynthesis, primary bile acid biosynthesis and sphingolipid metabolism. Of note, different doses of rhubarb could alleviate endogenous disorders to varying degrees through regulating multiple perturbed pathways to the normal state, which might be in a dose-dependent manner and involved in therapeutic mechanisms. To sum up, integrated serum and fecal metabolomics obtained that rhubarb ranging from 0.31 to 2.1 g/kg is safe and effective for constipation treatment. Also, our findings showed that the robust metabolomics techniques would be promising to be more accurately used in the dose-effect studies of complex TCM, and to clarify syndrome pathogenesis and action mechanisms in Chinese medicine.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jpba.2019.112837DOI Listing
January 2020