Publications by authors named "Ding-Qiao Xu"

12 Publications

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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

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

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

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

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

4-Octyl itaconate inhibits aerobic glycolysis by targeting GAPDH to exert anti-inflammatory effects.

Nat Commun 2019 11 8;10(1):5091. Epub 2019 Nov 8.

Jiangsu Key Laboratory of Bioactive Natural Product Research and State Key Laboratory of Natural Medicines, School of Traditional Chinese Pharmacy, China Pharmaceutical University, 24 Tong Jia Xiang, 210009, Nanjing, China.

Activated macrophages switch from oxidative phosphorylation to aerobic glycolysis, similar to the Warburg effect, presenting a potential therapeutic target in inflammatory disease. The endogenous metabolite itaconate has been reported to regulate macrophage function, but its precise mechanism is not clear. Here, we show that 4-octyl itaconate (4-OI, a cell-permeable itaconate derivative) directly alkylates cysteine residue 22 on the glycolytic enzyme GAPDH and decreases its enzyme activity. Glycolytic flux analysis by UC glucose tracing provides evidence that 4-OI blocks glycolytic flux at GAPDH. 4-OI thereby downregulates aerobic glycolysis in activated macrophages, which is required for its anti-inflammatory effects. The anti-inflammatory effects of 4-OI are replicated by heptelidic acid, 2-DG and reversed by increasing wild-type (but not C22A mutant) GAPDH expression. 4-OI protects against lipopolysaccharide-induced lethality in vivo and inhibits cytokine release. These findings show that 4-OI has anti-inflammatory effects by targeting GAPDH to decrease aerobic glycolysis in macrophages.
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http://dx.doi.org/10.1038/s41467-019-13078-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6841710PMC
November 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

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

Protection by Huang-Lian-Jie-Du decoction and its constituent herbs of lipopolysaccharide-induced acute kidney injury.

FEBS Open Bio 2017 Feb 11;7(2):221-236. Epub 2017 Jan 11.

State Key Laboratory of Natural Medicines Department of Natural Medicinal Chemistry China Pharmaceutical University Nanjing China.

Sepsis, characterized by systemic inflammation, often leads to end-organ dysfunction, such as acute kidney injury (AKI). Despite of the severity and frequency of septic AKI in clinic, its pathogenesis is still poorly understood. Combined with histopathology evaluations, mortality assessments, biochemical evaluations, reverse transcription (RT) reaction and quantitative real-time PCR, and western blot, H NMR-based metabolomics approach was applied to investigate effects of Huang-Lian-Jie-Du-Decotion (HLJDD), a traditional Chinese medicine prescription, and its four component herbs on lipopolysaccharide (LPS)-induced septic AKI and the underlying mechanism. LPS induced kidney dysfunction via activation of NF-κB and mitogen-activated protein kinases (MAPKs), by excessive production of IL-6, tumor necrosis factor-α, inducible nitric oxide synthase, and COX-2, producing perturbance in energy metabolism and oxidative stress. HLJDD and its component herbs could effectively inhibit LPS-induced AKI in mice by inhibiting NF-κB and MAPK activation and activating the Akt/HO-1 pathway, and by markedly ameliorating disturbances in oxidative stress and energy metabolism induced by LPS. The four-component herbs could complement each other.
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http://dx.doi.org/10.1002/2211-5463.12178DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5292670PMC
February 2017

Rational modification of donepezil as multifunctional acetylcholinesterase inhibitors for the treatment of Alzheimer's disease.

Eur J Med Chem 2016 Nov 25;123:282-297. Epub 2016 Jul 25.

State Key Laboratory of Natural Medicines, Department of Natural Medicinal Chemistry, China Pharmaceutical University, 24 Tong Jia Xiang, NanJing 210009, People's Republic of China. Electronic address:

A series of novel donepezil derivatives was designed, synthesized and evaluated as multifunctional acetylcholinesterase (AChE) inhibitors for the treatment of Alzheimer's disease (AD). The screening results indicated that most of the compounds exhibited potent inhibition of AChE with IC50 values in the nanomolar range. Moreover, these derivatives displayed good antioxidant, Aβ interaction, blood-brain barrier penetration (PAMPA-BBB+) and ADMET properties (in silico). Among them, 5c demonstrated excellent AChE inhibition (IC50: 85 nM for eeAChE, 73 nM for hAChE), metal chelation, and inhibitory effects on self-induced, hAChE-induced and Cu(2+)-induced Aβ1-42 aggregation (18.5%, 72.4% and 46.3%, at 20 μM). Kinetic analysis and molecular modeling studies suggested that 5c could bind simultaneously to the catalytic active site (CAS) and peripheral anionic site (PAS) of AChE. More importantly, 5c exhibited significant neuroprotective potency against Aβ1-42-induced PC12 cell injury. Furthermore, the step-through passive avoidance test showed 5c significantly reversed scopolamine-induced memory deficit and no hepatotoxicity in mice. These results indicated that 5c might be a promising drug candidate for AD therapy.
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http://dx.doi.org/10.1016/j.ejmech.2016.07.052DOI Listing
November 2016

[Exploring the best dried processing condition of fresh Gastrodia elata].

Zhong Yao Cai 2014 Feb;37(2):215-8

Objective: To study the processing conditions that influenced the contents of gastrodine in dried processing of fresh Gastrodia elata.

Methods: The optimized processing condition were established by using single-factor and orthogonal experimental design, which was guided by the contents of gastrodine. Fresh Gastrodia elata were harvested in the day, cleaned sediment, cooked in atmospheric pressure for 25 min, cut into 0.5 - 1.0 cm thick slices and dried in 105 degrees C. The gastrodine content was measured by HPLC.

Results: The gastrodine content was 0.532%, which was higher than that of traditional processing method.

Conclusion: Dried processing condition can influence the content of gastrodine in Gastrodia elata significantly.
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February 2014

[Research the extraction and detection method of gastrodin content in Gastrodia elata].

Zhong Yao Cai 2012 Nov;35(11):1799-804

School of Biological Science and Engineering, Shaanxi University of Technology/The Center of Gastrodia elata B1. and Dogwood Engineering in Shaanxi, Hanzhong 723000, China.

Objective: To improve an extraction and determination method for gastrodin in Gastrodia elata.

Methods: On the basis of single factor experiment, used the method of hot water reflux extraction and applied the response surface methodology to determine the best conditions for extracting gastrodin and using HPLC test.

Results: Under the boiling water condition, pure water as solvent, the solid-liquid ratio was 1:37,extraction 2 times and extraction time 126 min per times,the content of gastrodin was 0.377%. Comparison with the 2010 edition of the China pharmacopoeia of gastrodin extracted in Gastrodia elata, the result showed the gastrodin content was increased by 2. 12 times.

Conclusion: This extraction method of gastrodin dissolution rate is high and can reflect the real content of gastrodin of Gastrodia elata.
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November 2012