Publications by authors named "Yu-Ping Tang"

199 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.
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http://dx.doi.org/10.1016/j.biopha.2021.111551DOI Listing
April 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.
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http://dx.doi.org/10.19540/j.cnki.cjcmm.20201105.601DOI Listing
February 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.
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http://dx.doi.org/10.1002/jssc.202000932DOI Listing
April 2021

A two-photon multi-emissive fluorescent probe for discrimination of Cys and Hcy/GSH via an aromatic substitution-rearrangement.

Talanta 2021 Mar 30;224:121833. Epub 2020 Oct 30.

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

Cys (Cysteine), Hcy (homocysteine), and GSH (glutathione) are three important kinds of biothiols, playing crucial roles in the variety of pathological and physiological processes. It is greater challenges to simultaneously identify different biothiols due to their similar molecular structures and chemical characteristics. In this work, we employed a multi-emissive fluorescent probe by sulfonyl benzoxadiazole (SBD) with halogen chloride unit as the interaction site based on aromatic substitution-rearrangement strategy to discriminate Cys and Hcy/GSH. The response of probe 1 to Cys would generate FRET and cause a red-shift of fluorescence emission, while Hcy/GSH only lead to different degrees of fluorescence enhancement owing to PET. The probe showed good selectivity, high sensitivity, and low detection limits to three biothiols (Cys: 0.86 μM, Hcy: 0.48 μM and GSH: 0.54 μM). Such capability of the probe could be demonstrated to successfully quantitatively detect the concentrations of Cys/Hcy/GSH in human plasmas. In addition, the probe was also successfully applied for imaging biothiols in lysosomes and real-time monitoring GSH changes in living cells through two-photon fluorescence microscopy.
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http://dx.doi.org/10.1016/j.talanta.2020.121833DOI Listing
March 2021

Comparison of content-toxicity-activity of six ingenane-type diterpenoids between Euphorbia kansui before and after stir-fried with vinegar by using UFLC-MS/MS, zebrafish embryos and HT-29 cells.

J Pharm Biomed Anal 2021 Feb 7;195:113828. Epub 2020 Dec 7.

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 and Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, No. 138, Xianlin Road, Qixia District, Nanjing, 210023, PR China. Electronic address:

The dried roots of Euphorbia kansui (EK) are especially beneficial for the treatment of edema, but the severe toxicity limits their clinical applications. Euphorbia kansui stir-fried with vinegar (VEK) is traditionally employed to reduce the toxicity of EK. However, the material basis for the toxicity reduction with effectivity conservation is still unclear. Therefore, in this study, a rapid, sensitive, and reliable ultra-fast liquid chromatography tandem mass spectrometry (UFLC-MS/MS) method was firstly established to simultaneously determine six ingenane-type diterpenoids, i.e. kansuiphorin C (1), 5-O-benzoyl-20-deoxyingenol (2), 20-deoxyingenol (3), 3-O-(2'E,4'E-decadienoyl)-20-O-acetylingenol (4), 20-O-(2'E,4'Z-decadienoyl)ingenol (5), and ingenol (6), in EK and VEK based on the processing conversion. Then, the toxicity evaluation on zebrafish embryos and modulation of the expression of aquaporin-3 (AQP3) proteins in HT-29 cells were employed to investigate the toxicity-activity of six compounds. Chromatographic separation was obtained on Waters BEH RP18 column (2.1 mm × 100 mm, 2.5 μm) with the mobile phase composed of 0.1 % formic acid in acetonitrile and water, respectively. The column temperature was 35 ℃ at a flow rate of 0.4 mL min. Multiple reaction monitoring was conducted in both positive and negative modes for quantitative analysis. The method was then successfully used for the determination of six compounds in EK and VEK. In addition, 1, 2, 4, and 5 had evident cardiotoxicity, intestinal irritation and nutrient absorption disorders on zebrafish larvae, while no in-vivo toxicity was seen for groups given 3 and 6 (LC > 200 μM). Meanwhile, 1, 2, 4, 5, and 6 significantly increased the expression of AQP3 protein (p < 0.05) to promote the excretion of water in the colon. This study demonstrated that toxic ingenane-type diterpenoids converted into the less toxic compounds with the same core structure through the breakage of multiple ester bonds in the side chain. At the same time, the laxative effect was retained, providing useful information for the optimization of the process of EK and quality evaluation of other similar toxic Chinese herbal medicines.
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http://dx.doi.org/10.1016/j.jpba.2020.113828DOI Listing
February 2021

Association between thyroid function and risk of gestational diabetes mellitus in assisted pregnancies: A retrospective cohort study.

Diabetes Res Clin Pract 2021 Jan 9;171:108590. Epub 2020 Dec 9.

Department of Obstetrics, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, No. 2699, West Gaoke Road, Shanghai 201204, People's Republic of China. Electronic address:

Aims: To explore the association between thyroid function and gestational diabetes mellitus (GDM) risk in assisted pregnancies.

Methods: We screened 57,386 pregnant women treated from February 2013 to October 2017, and 2211 patients were retrospectively enrolled, and their data were analyzed based on quintile groups constituted based on serum thyroid-stimulating hormone (TSH), free thyroxine (FT4), and thyroid peroxidase antibody (TPOAb) levels. Odds ratios (ORs) of GDM were analyzed by multivariate logistic regression, adjusted for maternal age and pre-pregnancy body mass index (BMI).

Results: The prevalence rate of GDM was 20.1%. Lower FT4 levels were associated with an increased risk of GDM (OR = 1.512, 95% confidence interval [CI] 1.073-2.132, p = 0.018; OR = 1.620, 95% CI 1.161-2.261, p = 0.005), but this association disappeared after adjustments. TPOAb+ titer was associated with an increased risk of GDM (aOR = 1.472, 95% CI 1.068-2.028, p = 0.018). Higher TSH (aOR = 2.882, 95% CI 1.919-6.975, p = 0.019) or lower FT4 (aOR = 3.156, 95% CI 1.088-9.115, p = 0.034) levels were associated with an increased risk of GDM in assisted pregnancies for TPOAb+ patients.

Conclusion: TPOAb+ is an independent risk factor for GDM in patients with assisted pregnancies. Higher TSH or lower FT4 levels, with TPOAb+ detection, are risk factors for GDM in assisted pregnancies.
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http://dx.doi.org/10.1016/j.diabres.2020.108590DOI Listing
January 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.
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http://dx.doi.org/10.1002/brb3.1995DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7882174PMC
February 2021

Drug repurposing for COVID-19: could vitamin C combined with glycyrrhizic acid be at play by the findings of Li et al.'s database-based network pharmacology analysis?

Brief Bioinform 2021 03;22(2):1508-1510

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

The outbreak and pandemic of SARS-CoV-2 in 2019 has caused a severe public health burden and will challenge global health for the future. The discovery and mechanistic investigation of drugs against Coronavirus disease 2019 (COVID-19) is in deadly demand. The paper published by Li and colleagues proposed the hypothesis that vitamin C combined with glycyrrhizic acid in treating COVID-19 and its mechanistic investigation was performed by a database-based network pharmacology. In this letter, we present critical comments on the limitations and insufficiencies involved, from both the perspective of network pharmacology and current evidence on COVID-19.
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http://dx.doi.org/10.1093/bib/bbaa330DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7799235PMC
March 2021

Toxicity reduction and water expelling effect preservation of Shizaotang after its toxic members processing with vinegar on rats with malignant pleural effusions.

J Ethnopharmacol 2021 Mar 13;268:113583. Epub 2020 Nov 13.

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

Ethnopharmacological Relevance: Shizaotang (SZT), consisted of Euphorbia kansui S.L.Liou ex S.B.Ho (EK), Euphorbia pekinensis Rupr. (EP), Daphne genkwa Sieb. et Zucc. (DG,fried) and Ziziphus jujuba Mill. (ZJ), is usually used for treating malignant pleural effusions (MPE), but the toxicity of EK and EP limits its clinical safe application. It was reported that vinegar processing can reduce the toxicity of EK and EP. Whether EK and EP processing with vinegar can cause the reduced toxicity and retained pharmacological effects of SZT, it still remains unknown.

Aim Of The Study: We aimed to evaluate whether using vinegar processed EK and EP would reduce toxicity and preserve water expelling effect of SZT.

Materials And Methods: Network pharmacology and qualitative analysis of SZT/VSZT were used to construct compound-target-pathway network of their effects and toxicity. Pleural fluid weight, urine volume, uric electrolyte, pH, pro-inflammatory cytokines in pleural fluid, serum Renin-Angiotensin-Aldosterone System (RAAS), anti-diuretic hormone (ADH) and intestinal aquaporin 8 (AQP8) protein were used to evaluate the effect mechanisms involved in rats experiments. And liver damage, oxidative damage and HE staining (liver, stomach, and intestine) were used to determine the toxicity.

Results: Network pharmacology analysis reviewed inflammation-related pathways of the effect and toxicity of SZT/VSZT: VEGF-PI3K-AKT pathway inhibited MPE by changing the vasopermeability; PI3K-Akt/Mitogen-activated protein kinase (MAPK)/TNF-NF-κB signaling pathway inhibited MPE by up-regulating expression of AQP8 protein. In vivo experiments displayed that SZT/VSZT could reduce pleural fluid, increase urine volume, lower pro-inflammatory cytokines levels and up-regulate AQP8 protein expression significantly (P < 0.05, P < 0.01). In addition, disorders on electrolyte (Na, K and Cl) and pH were ameliorated (P < 0.05, P < 0.01). The levels of RAAS and ADH were significantly dose-dependently called back (P < 0.01). These findings were partly consistent with the results of network pharmacology analysis. Results of toxicity experiments demonstrated that SZT and VSZT exhibited certain toxicity on normal rats, and VSZT had lower toxicity than that of SZT. Interestingly, SZT and VSZT exerted alleviation effect to the liver damage and oxidative damage on model rats.

Conclusion: SZT/VSZT improved MPE by regulating associated inflammation pathways. Besides, compared to SZT, VSZT showed lower toxicity and equivalent expelling MPE effect. This study may provide scientific basis for guiding the clinical application of SZT.
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http://dx.doi.org/10.1016/j.jep.2020.113583DOI Listing
March 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.
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http://dx.doi.org/10.3389/fphar.2020.01265DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7550755PMC
September 2020

The water expelling effect evaluation of 3-O-(2'E,4'Z-decadienoyl)-20-O-acetylingenol and ingenol on H22 mouse hepatoma ascites model and their content differences analysis in Euphorbia kansui before and after stir-fried with vinegar by UPLC.

J Ethnopharmacol 2021 Mar 22;267:113507. Epub 2020 Oct 22.

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

Ethnopharmacological Relevance: Malignant ascites (MA) effusion is mainly caused by hepatocellular, ovarian, and breast cancer etc. It has been reported that Euphorbia kansui (EK), the root of Euphorbia kansui S.L.Liou ex S.B.Ho, possessing a therapeutic effect on MA. However, the clinical applications of EK are seriously restricted for its severe toxicity. Although studies demonstrated that vinegar-processing can reduce the toxicity and retain the water expelling effect of EK, its specific mechanism remains unknown.

Aim Of The Study: This study aims to explore the underlying mechanisms of toxicity reduction without compromising the pharmacological effects of EK stir-fried with vinegar (VEK).

Materials And Methods: 3-O-(2'E,4'Z-decadienoyl)-20-O-acetylingenol (3-O-EZ), a major diterpenoid of EK, could convert into ingenol after processing EK with vinegar. The H22 mouse hepatoma ascites model was replicated, and were given 3-O-EZ and ingenol seven days (110.14, 50.07 and 27.54 mg/kg). The histopathological observation, serum liver enzymes, serum Renin-Angiotensin-Aldosterone System (RAAS) levels, ascites volumes, pro-inflammatory cytokines levels and H22 cells apoptosis in ascites were examined. Then the intestine (Aquaporin 8, AQP8) and kidney (Aquaporin 2, AQP2; Vasopressin type 2 receptor, V2R) protein expression were detected, as well as the metabolomics of serum were analyzed. Finally, the content of 3-O-EZ and ingenol in EK and VEK were investigated.

Results: 3-O-EZ and ingenol can relieve hepatic and gastrointestinal injuries, reduce ascites volumes, enhance the H22 cells apoptosis, ameliorate abnormal pro-inflammatory cytokines and RAAS levels, and down-regulate the expression of AQP8, AQP2, V2R. The involved metabolic pathways mainly included glycerophospholipid metabolism and arachidonic acid metabolism. And the decreasing rate of 3-O-EZ in VEK was 19.14%, the increasing rate of ingenol in VEK was 92.31%.

Conclusion: 3-O-EZ and ingenol possess significant effect in treating MA effusion, while ingenol has lower toxicity compared with 3-O-EZ. And provide evidence for the mechanism of attenuation in toxicity without compromising the pharmacological effects of VEK.
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http://dx.doi.org/10.1016/j.jep.2020.113507DOI Listing
March 2021

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

Simultaneous determination of twelve quinones from Rubiae radix et Rhizoma before and after carbonization processing by UPLC-MS/MS and their antithrombotic effect on zebrafish.

J Pharm Biomed Anal 2020 Nov 17;191:113638. Epub 2020 Sep 17.

Nanjing University of Chinese Medicine Hanlin College, 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 and Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, Nanjing, 210023, China. Electronic address:

Rubiae Radix et Rhizoma (called "Qiancao", QC), the root and rhizome of Rubia cordifolia L., has been widely used in clinical practice for its excellent performance in removing blood stasis and haemostasis. However, after carbonization processing, significant changes occurred in chemical components of the charcoal of Rubiae Radix et Rhizoma (called "Qiancaotan", QCT), which enhanced the performance in haemostasis and weakened the performance in removing blood stasis in clinic. In order to study the material basis of function variation during processing, a rapid, reliable, accurate and validated UPLC-MS/MS approach was established to determine twelve quinones in QC and QCT simultaneously. Meanwhile, the antithrombotic effect of target components on zebrafish thrombus model induced by phenylhydrazine (PHZ) was investigated. Chromatographic separation was accomplished on an ACQUITY UPLC Ccolumn with acetonitrile-water containing 0.2 % (v/v) formic acid as mobile phase, at a flow rate of 0.30 mL/min. Quantitation was performed using multiple reaction monitoring (MRM) in positive and negative ion electrospray ionization (ESI). Furthermore, the activity evaluation studies showed that the reduction of removing blood stasis effect of QCT was due to the decrease of dehydro-α-lapachone, lapachol, rubioncolin C and mollugin. This study demonstrated that the method has been successfully applied to determine the content of twelve quinones responsible for the function variation of QCT, and provided a new insight into the material basis and the effect of eliminating stasis before and after processing of QC.
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http://dx.doi.org/10.1016/j.jpba.2020.113638DOI Listing
November 2020

Increases in tumor markers are associated with primary Sjögren's syndrome-associated interstitial lung disease.

Ther Adv Chronic Dis 2020 30;11:2040622320944802. Epub 2020 Jul 30.

Department of Rheumatology, The Second Hospital of Shanxi Medical University, 382 Wuyi Road, Xinghualing District, 030000, Taiyuan, Shanxi, China.

Aims: Interstitial lung disease (ILD) is the most common type of pulmonary involvement of extraglandular complication in patients with primary Sjögren's syndrome (pSS), but the diagnosis of pSS-associated ILD (pSS-ILD) is still challenging. This study aimed to investigate the levels of serum tumor markers in pSS patients with or without ILD (pSS-non-ILD) and explore its diagnostic value for pSS-ILD.

Methods: A total of 168 pSS-ILD patients and age- and sex-matched 538 pSS-non-ILD were recruited. The levels of peripheral tumor markers, including carbohydrate antigen (CA)153, CA125, CA19-9, carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), β-human chorionic gonadotropin, alpha fetoprotein, CA724, and complexed prostate specific antigen, the clinical manifestations, and general laboratory indicators were measured and collected.

Results: Compared with pSS-non-ILD, pSS-ILD patients had higher levels of disease activity indicators, such as EULAR Sjögren's syndrome disease activity index, ESR, and CRP, and elevated serum levels of tumor markers: NSE, CEA, CA125, and CA153. The serum levels of CA153 [odds ratio (OR) = 4.521, 95% confidence interval (CI) = [1.871, 10.928)] and CEA [OR = 2.879, 95% CI = (1.305, 6.353)] were significantly correlated with the onset of SS-ILD. CA153 was the only tumor marker with area under receiver operating characteristic curve (AUC) over 0.7 [AUC = 0.743, 95% CI = (0.70, 0.79)].

Conclusion: Tumor markers increased in serum of pSS-ILD patients. Higher CA153 levels are significantly correlated to the increased risk of ILD in patients with pSS and may be directly involved in the pathogenesis of pSS-ILD. Serum CA153 had the best diagnostic value in those tumor markers for pSS-ILD without malignancy.
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http://dx.doi.org/10.1177/2040622320944802DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7418474PMC
July 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.
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http://dx.doi.org/10.1155/2020/9403092DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7415105PMC
July 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.
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http://dx.doi.org/10.1016/j.jep.2020.113000DOI Listing
October 2020

The database-based strategy may overstate the potential effects of traditional Chinese medicine against COVID-19.

Pharmacol Res 2020 09 23;159:105046. Epub 2020 Jun 23.

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 Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Shaanxi University of Chinese Medicine, Xi'an, 712046, China. Electronic address:

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http://dx.doi.org/10.1016/j.phrs.2020.105046DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7309793PMC
September 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.
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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.
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http://dx.doi.org/10.1016/j.jep.2020.113050DOI Listing
October 2020

Muscle BDNF improves synaptic and contractile muscle strength in Kennedy's disease mice in a muscle-type specific manner.

J Physiol 2020 07 29;598(13):2719-2739. Epub 2020 May 29.

Neuroscience Program, Michigan State University, 108 Giltner Hall, East Lansing, MI, 48824-1115, USA.

Key Points: Muscle-derived neurotrophic factors may offer therapeutic promise for treating neuromuscular diseases. We report that a muscle-derived neurotrophic factor, BDNF, rescues synaptic and muscle function in a muscle-type specific manner in mice modelling Kennedy's disease (KD). We also find that BDNF rescues select molecular mechanisms in slow and fast muscle that may underlie the improved cellular function. We also report for the first time that expression of BDNF, but not other members of the neurotrophin family, is perturbed in muscle from patients with KD. Given that muscle BDNF had divergent therapeutic effects that depended on muscle type, a combination of neurotrophic factors may optimally rescue neuromuscular function via effects on both pre- and postsynaptic function, in the face of disease.

Abstract: Deficits in muscle brain-derived neurotrophic factor (BDNF) correlate with neuromuscular deficits in mouse models of Kennedy's disease (KD), suggesting that restoring muscle BDNF might restore function. To test this possibility, transgenic mice expressing human BDNF in skeletal muscle were crossed with '97Q' KD mice. We found that muscle BDNF slowed disease, doubling the time between symptom onset and endstage. BDNF also improved expression of genes in muscle known to play key roles in neuromuscular function, including counteracting the expression of neonatal isoforms induced by disease. Intriguingly, BDNF's ameliorative effects differed between muscle types: synaptic strength was rescued only in slow-twitch muscle, while contractile strength was improved only in fast-twitch muscle. In sum, muscle BDNF slows disease progression, rescuing select cellular and molecular mechanisms that depend on fibre type. Muscle BDNF expression was also affected in KD patients, reinforcing its translational and therapeutic potential for treating this disorder.
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http://dx.doi.org/10.1113/JP279208DOI Listing
July 2020

Hydrophilic interaction chromatography combined with ultrasound-assisted ionic liquid dispersive liquid-liquid microextraction for determination of underivatized neurotransmitters in dementia patients' urine samples.

Anal Chim Acta 2020 Apr 13;1107:74-84. Epub 2020 Feb 13.

Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, And Jiangsu Key Laboratory for High Technology Research of TCM Formulae, Nanjing University of Chinese Medicine, Nanjing, 210023, China. Electronic address:

A sensitive, rapid, precise and specific analytical method of hydrophilic interaction ultra-performance liquid chromatography coupled with triple-quadrupole linear ion-trap tandem mass spectrometry (HILIC-UHPLC-QTRAP®/MS) combined with a high-efficiency and easy sample preparation technology of ultrasound-assisted ionic liquid dispersive liquid-liquid microextraction (UA-IL-DLLME) was developed to investigate neurotransmitters (NTs) in mild cognitive impairment, mild dementia and moderate dementia patients' urine samples. Firstly, the UA-IL-DLLME parameters were optimized using Plackett-Burman screening and rotatable central composite design, and the main optimal conditions were obtained: ultrasound power of 307 W, ultrasound time of 4.3 min and agitation time of 4.8 min. Secondly, HILIC-UHPLC-QTRAP®/MS method was developed to simultaneously determine 15 underivatized NTs in urine samples. The analysis results of clinical samples showed that some NTs such as γ-aminobutyric acid (GABA), acetylcholine (Ach) and glutamic acid (Glu) presented significant differences in different dementia stages. Finally, multivariate analysis based on the combination of principal component analysis and supervised counter propagation artificial neural network was developed for comprehensive analysis of the obtained clinical data sets. As a result, GABA and Glu were simultaneously presented meaningful contribution for classification of samples, and might be considered as potential differential compounds to the urine samples from cluster patients with different dementia stages. In summary, the presented strategy of preparation, analysis and statistics might be used to investigate NTs in different clinical biological fluids.
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http://dx.doi.org/10.1016/j.aca.2020.02.027DOI Listing
April 2020

Design, synthesis, antitumor activity and theoretical calculation of novel PI3Ka inhibitors.

Bioorg Chem 2020 05 9;98:103737. Epub 2020 Mar 9.

Shaanxi Key Lab Basic & New Herbal Medicament Research Center, College of Pharmacy, Shaanxi University of Chinese Medicine, China. Electronic address:

PI3Kα has been identified as an ideal target to treat with PIK3CA gene mutation disease, including drugs such as Alpelisib and Copanlisib. Five purine analogues and four thiazole analogues were designed and synthesized. Their enzymaticactivity against PI3Ka/β/γ/δ were tested, respectively. All compounds showed excellent selectivity in modulating PI3Ka activity, and parts of the compounds showed good inhibition. Meanwhile, we used Autodock 4.2 to explore the binding mode of the most potential compound Tg with the target protein. In addition, DFT was used to calculate the HOMO-LUMO maps of the compounds Tf, Tg and positive control. This paper will provide some useful information for further drug design of PI3Kα inhibitors.
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http://dx.doi.org/10.1016/j.bioorg.2020.103737DOI 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.
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http://dx.doi.org/10.1155/2020/5053914DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7063220PMC
February 2020

Effect of the vinegar-process on chemical compositions and biological activities of Euphorbia kansui: A review.

J Ethnopharmacol 2020 Apr 10;252:112557. Epub 2020 Jan 10.

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

Ethnopharmacological Relevance: In traditional Chinese medicine (TCM) the root of Euphorbia kansui S.L.Liou ex S.B.Ho (EK), is used for treating edema and ascites but is also of toxicological concerns. And the clinical applications of EK have been seriously restricted for its severe toxicity. To reduce its toxicity, a commonly used clinical practice is processing it with vinegar.

Aim Of The Review: This review aimed to summarize and discuss updated information on biological activities and phytochemistry of EK before and after vinegar-processing, and provide feasible insights for further research on the chemical composition, toxicity and pharmacological effects of EK before and after vinegar-processing.

Materials And Methods: The relevant information on chemical compositions and biological activities of EK before and after vinegar-processing was collected from scientific databases (Google Scholar, PubMed, CNKI, SpringerLink, Web of Science, Wiley Online Library and SciFinder). Additionally, published and unpublished Ph.D. and MSc. dissertations were also obtained from online databases.

Results And Discussions: Diuretic and purgative effect of EK are well documented pharmacologically as are acute, irritant and organic toxic effects. Some of about terpenoids reported have antiproliferative effects on cancer cells and potential antiviral effect. After processing with vinegar, the contents of terpenoids mostly were reduced (ingenane and jatrophane type) with some new compounds being generated (unclear). Also, the toxicity of EK was decreased (using mice, rats and zebrafish embryos model), while the diuretic and purgative effects were retained (using cancerous ascites model rats and mice).

Conclusions: While some evidence exists for the reduction of toxicity without compromising the pharmacological effects of EK after vinegar processing, the specific mechanism of action remains unknown. Consequently, further research is necessary to investigate the mechanisms and the relationship between vinegar processing and changes in the chemical composition as well as pharmacological effects/toxicity. This is essential before a safe clinical use can be endorsed.
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http://dx.doi.org/10.1016/j.jep.2020.112557DOI Listing
April 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 "".
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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.
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http://dx.doi.org/10.1016/S1875-5364(19)30104-9DOI Listing
November 2019

Kansuiphorin C and Kansuinin A ameliorate malignant ascites by modulating gut microbiota and related metabolic functions.

J Ethnopharmacol 2020 Mar 22;249:112423. Epub 2019 Nov 22.

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 and Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, No.138, Xianlin Road, Qixia District, Nanjing, 210023, PR China. Electronic address:

Ethnopharmacological Relevance: Euphorbia kansui is a toxic Chinese herbal medicine and exhibits promising treatment to the malignant ascites (MA) in its traditional use. Ingenane-type and jastrophane-type diterpenes are demonstrated to be responsible for the toxicity and efficacy of kansui. Two representative compounds, kansuiphorin C (KPC) and kansuinin A (KA) in each type were proved to effectively reduce the ascites. The biological and toxicological effects are closely associated with the gastrointestinal tract, but the possible mechanism and related metabolic functions of KPC and KA treating MA through modulating the gut microbiota remain unclear.

Aim Of The Study: To investigate the possible mechanism and related metabolism of KPC and KA ameliorating malignant ascites through modulating gut microbiota.

Materials And Methods: MA rats and normal rats were divided into different groups and administrated with KPC, KA, and positive drug, respectively. 16S rDNA gene sequencing and metagenomes analysis combined with the quantification of short-chain fatty acids of feces were performed to reflect the modulation of gut microbiota. Then, the metabolites of KPC and KA in rat feces under the normal and pathological circumstances were detected by ultra-fast liquid chromatography coupled with MS/MS detector (UFLC-MS/MS) to explore the in-vivo bacterial biotransformation.

Results: KPC and KA were modulatory compounds for gut microbiota. The richness of Lactobacillus and the decreased abundance of Helicobacter involved in the carbohydrate metabolism and amino acid metabolism could be responsible for their prohibitory effects on malignant ascites. KPC exhibited stronger modulation of gut microbiota through making the abundance of Helicobacter about 3.5 times lower than KA. Besides, in-vivo microbial biotransformation of KPC and KA contained oxidation, hydrolysis, dehydration, and methylation to form metabolites of lower polarity. Besides, at the dosage of 10 mg kg, the toxicity of both compounds had weaker influences on the gut microbiota of normal rats.

Conclusion: KPC and KA could ameliorate malignant ascites by modulating gut microbiota mainly containing the increase of Lactobacillus and the decrease of Helicobacter and related carbohydrate and amino acid metabolism, providing a basis for their promising clinical usage.
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http://dx.doi.org/10.1016/j.jep.2019.112423DOI Listing
March 2020

Toxicity Reduction of Stir-Fried with Vinegar Based on Conversion of 3--(2',4'-Decadi-enoyl)-20--acetylingenol.

Molecules 2019 Oct 22;24(20). Epub 2019 Oct 22.

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

The dried roots of S.L.Liou ex S.B.Ho have long been used to treat edema in China. However, the severe toxicity caused by (EK) has seriously restricted its clinical application. Although EK was processed with vinegar to reduce its toxicity, the detailed mechanisms of attenuation in toxicity of EK stir-fried with vinegar (VEK) have not been well delineated. Diterpenoids are the main toxic ingredients of EK, and changes in these after processing may be the underlying mechanism of toxicity attenuation of VEK. 3--(2',4'-decadienoyl)-20--acetylingenol (3-O-EZ) is one of the diterpenoids derived from EK, and the content of 3-O-EZ was significantly reduced after processing. This study aims to explore the underlying mechanisms of toxicity reduction of VEK based on the change of 3-O-EZ after processing with vinegar. Based on the chemical structure of 3-O-EZ and the method of processing with vinegar, simulation experiments were carried out to confirm the presence of the product both in EK and VEK and to enrich the product. Then, the difference of peak area of 3-O-EZ and its hydrolysate in EK and VEK were detected by ultra-high-performance liquid chromatography (UPLC). Furthermore, the toxicity effect of 3-O-EZ and its hydrolysate, as well as the underlying mechanism, on zebrafish embryos were investigated. The findings showed that the diterpenoids (3-O-EZ) in EK can convert into less toxic ingenol in VEK after processing with vinegar; meanwhile, the content of ingenol in VEK was higher than that of EK. More interestingly, the ingenol exhibited less toxicity (acute toxicity, developmental toxicity and organic toxicity) than that of 3-O-EZ, and 3-O-EZ could increase malondialdehyde (MDA) content and reduce glutathione (GSH) content; cause embryo oxidative damage by inhibition of the succinate dehydrogenase (SDH) and superoxide dismutase (SOD) activity; and induce inflammation and apoptosis by elevation of IL-2 and IL-8 contents and activation of the caspase-3 and caspase-9 activity. Thus, this study contributes to our understanding of the mechanism of attenuation in toxicity of VEK, and provides the possibility of safe and rational use of EK in clinics.
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http://dx.doi.org/10.3390/molecules24203806DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6832248PMC
October 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.
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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.
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http://dx.doi.org/10.19540/j.cnki.cjcmm.20190408.201DOI Listing
July 2019