Publications by authors named "Yikun Sun"

25 Publications

  • Page 1 of 1

Pharmacokinetic and metabolic profiling studies of osmundacetone in rats by UPLC-MS/MS and UPLC-QE-Orbitrap-HRMS.

Biomed Chromatogr 2021 Oct 4:e5251. Epub 2021 Oct 4.

School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China.

Osmundacetone is a potential medicinal substance existing in ferns and has excellent antioxidant effects. This research aims to obtain the pharmacokinetic data for and metabolite products of osmundacetone. An UPLC-MS/MS quantitative method was established for the measurement of osmundacetonein in rat plasma over a linear range of 6.72-860.00 ng/ml. The signal to noise ratio of the lower limit of quantification was 60:1, the precision was <9.74% and the method had good selectivity and stability. The established method was successfully applied to the pharmacokinetic study of osmundacetone for the first time. Osmundacetone reached a peak at 0.25 h with a maximum value of 3283.33 μg/L. The apparent volume of distribution not multiplied by the bioavailability was 127.96 L/kg, and the half-life of osmundacetone was 5.20 h. At the same time, an UPLC-QE-Orbitrap-HRMS method was established to identify metabolites in plasma, urine and feces for the first time. A total of 30 metabolites were identified and the metabolic profile of osmundacetone was defined. In general, we have established a mass spectrometry quantitative method for osmundacetone for the first time and characterized its metabolic characteristics in rats.
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http://dx.doi.org/10.1002/bmc.5251DOI Listing
October 2021

Liquid chromatography-mass spectrometry in-depth analysis and in silico verification of the potential active ingredients of Baihe Dihuang decoction in vivo and in vitro.

J Sep Sci 2021 Sep 2. Epub 2021 Sep 2.

Department of Analysisand Testing, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, P. R. China.

Baihe Dihuang decoction is a commonly used herbal formula to treat depression and insomnia in traditional Chinese medicine. This study established a liquid chromatography-mass spectrometry method to investigate the potential active ingredients and the components absorbed in the blood and brain tissue of mice. Using a new data processing method, 94 chemical components were identified, 33 and 9 of which were absorbed in the blood and brain. More interestingly, we analyzed the substance changes during co-decoction and the characteristics of the compounds absorbed in the blood and brain. The results show that 71 newly generated chemical components were discovered from co-decoction: 38 with fragment information and five absorbed in the blood. Ultimately, the results of molecular docking show that these components have excellent performance in proteins of γ-aminobutyric acid, serotonin and melatonin receptors. The docking results of emodin with Monoamine Oxidase A and Melatonin Receptor 1A, and luteolin with Solute Carrier Family 6 Member 4, Glyoxalase I, Monoamine Oxidase B and Melatonin Receptor 1A, may explain the mechanism of action of Baihe Dihuang decoction in treating insomnia and depression. Overall, our research results may provide novel perspectives for further understanding of the effective substances in Baihe Dihuang decoction.
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http://dx.doi.org/10.1002/jssc.202100434DOI Listing
September 2021

In-depth investigation of the effective substances of traditional Chinese medicine formula based on the novel concept of co-decoction reaction-using Zuojin decoction as a model sample.

J Chromatogr B Analyt Technol Biomed Life Sci 2021 Aug 24;1179:122869. Epub 2021 Jul 24.

School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, China. Electronic address:

Zuojin decoction (ZJD) is a classic pair composed of Coptidis Rhizoma and Evodiae Fructus, which is suitable for treating gastrointestinal diseases and tumours, etc. In recent years, scientists have been widely focused on research into the treatment of liver cancer using ZJD; however, the effective substances have not yet been comprehensively elucidated. The difference between the co-decoction and the single decoction of ZJD is revealed in this paper based on the UPLC-QE-Orbitrap-MS, and the chemical components absorbed into the blood and liver of mice have been analyzed simultaneously. In addition, the combination of prototype components absorbed into the liver with liver cancer-related targets has been performed via molecular docking to explore the mechanism of ZJD in treating liver cancer. By comparing the co-decoction and single decoction of ZJD, 44 new components appeared during co-decoction and 76 known chemical compounds have been identified at the same time. It has been confirmed that 35 known components and 11 new components were absorbed into the blood. Furthermore, 20 known components were discovered from the sample of liver tissue. Molecular docking results showed that 3-O-feruloylquinic acid has good conjugation with Bcl-2, Stat3, mTOR, and mmp9. Catechin has the lowest binding energy with CDK6 and β-catenin. The study provides data for the further confirmation of the material basis and mechanism of ZJD in treating liver cancer, and provides a new idea for the researches on the compatibility mechanism of prescriptions of traditional Chinese medicine.
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http://dx.doi.org/10.1016/j.jchromb.2021.122869DOI Listing
August 2021

Integrated Screening of Effective Anti-Insomnia Fractions of Zhi-Zi-Hou-Po Decoction via and Network Pharmacology Analysis of the Underlying Pharmacodynamic Material and Mechanism.

ACS Omega 2021 Apr 24;6(13):9176-9187. Epub 2021 Mar 24.

School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, China.

Insomnia is an anabatic epidemiology, while the mechanism is extremely complicated; it remains one of the major scientific challenges in life sciences. Because of the advantage of having a similar genetic background and circadian rhythm as those of humans, the model organism is hugely popular in sleep-related drug screening studies. Seven-day-old virgin was used to establish the sleep deprivation model by repeated light stimulation at night. Using PySolo activity monitoring system and activity as indices, the effective fractions of Zhi-Zi-Hou-Po decoction (ZZHPD) for insomnia were screened; the content of monoamine neurotransmitters dopamine (DA), 5-hydroxyindole-3-acetic acid (5-HIAA), Homovanillic acid (HVA), and 5-hydroxytryptamine (5-HT) in the brain of were determined by high-performance liquid chromatography-electro-chemical detection. The herb-compound-target-disease target network were further constructed through network pharmacology to identify the potential targets and pathways of ZZHPD in the intervention of insomnia. Finally, the molecular docking method was used for evaluating the binding characteristics of important compounds from ZZHPD with related targets. The results showed that a certain dose of ZZHPD and its petroleum ether, dichloromethane, ethyl acetate, and -butanol fractions could improve sleep. The dichloromethane fraction from ZZHPD extracts showed the best anti-insomnia effect among all extracts. It can also reduce the content of DA and HVA in the brain of and increase 5-HT and 5-HIAA levels. The network pharmacology showed that the main active ingredients in ZZHPD included magnolol, honokiol, hesperidin, and so forth. According to the screening conditions, there were 71 targets and the result of KEGG enrichment analysis revealed that 73 pathways were associated with insomnia, which were primarily involved in inflammatory response, central neurotransmitter regulation, and apoptosis to relieve insomnia. The molecular docking results clarified that naringenin and apigenin have an intimate relationship with GABA receptor, histamine H1, orexin receptor type 2, and interleukin-6. The mechanism of relieving insomnia is the result of the interaction of multi-components, multi-targets, and multi-pathways, which provides a certain theoretical basis for the treatment of insomnia and related diseases as well as clinical research.
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http://dx.doi.org/10.1021/acsomega.1c00445DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8028125PMC
April 2021

Integrating UPLC-QE-Orbitrap-MS technology and network pharmacological method to reveal the mechanism of Bailemian capsule to relieve insomnia.

Nat Prod Res 2021 Mar 17:1-5. Epub 2021 Mar 17.

School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China.

Bailemian capsule (BLMC) is a Chinese patent drug for treating insomnia with excellent curative effects. But there are few researches on it. In this research, a rapid separation and identification method using UPLC-QE-Orbitrap-MS was established, and 228 identified compounds were separated within 18 min. The structures of compounds were preliminarily determined by comparing the retention time and fragmentation law. Furthermore, multiple databases were used to integrate the compound targets of BLMC and the disease targets related to insomnia. After the intersection of the two sets of targets, a protein-protein interaction network and a drug-target-disease pharmacological network were established, then using the DAVID database to perform GO analysis and KEGG analysis on the common targets to find related pathways. Finally, a total of 289 common targets and 136 pathways were found to participate in the mechanism.
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http://dx.doi.org/10.1080/14786419.2021.1900176DOI Listing
March 2021

LC-MS-Based Qualitative Analysis and Pharmacokinetic Integration Network Pharmacology Strategy Reveals the Mechanism of H.W.Li Treatment of Pneumonia.

ACS Omega 2021 Feb 1;6(6):4495-4505. Epub 2021 Feb 1.

School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, China.

H.W.Li Radix (R) is a rare traditional Tibetan medicine, and it is widely used in the Chinese Tibetan region for the treatment of pharyngitis, pneumonia, and so forth. Nevertheless, there is very little research on its modern pharmacy, and the active ingredients and mechanisms against these diseases remain unknown. In this study, we employed the qualitative analysis and pharmacokinetic based on LC-MS technology and network pharmacology to explore the active ingredients and mechanisms of R for treatment of pneumonia. Ultraperformance liquid chromatography coupled with time-of-flight mass spectrometry (UPLC-Q-TOF/MS) methodology was applied to identify the chemical composition of R. Meanwhile, a UPLC-MS/MS method was developed to quantify three active constituents (sesamoside, shanzhiside methyl ester, and barlerin) in rat plasma for the pharmacokinetic analysis after oral administration of R. Finally, in order to clarify the anti-pneumonia mechanism of this rare Tibetan medicine, a comprehensive network pharmacology strategy was applied. As a result, a total of 23 compounds were identified in R, including 14 iridoid glycosides, 7 phenylethanoid glycosides, and 2 other kinds of compounds. Pharmacokinetic studies have shown that the three compounds exhibit extremely similar pharmacokinetic characteristics, possibly due to their highly analogous chemical structure. We speculate that the iridoid glycosides may be the main active component in R. Then, the three iridoid glycoside constituents absorbed into blood were subjected to network pharmacology analysis for treatment of pneumonia. Compound-target-disease, gene ontology bioanalysis, KEGG pathway, and other network pharmacology analysis methods were applied to reveal that five main targets of the three iridoid glycosides, namely, GAPDH, ALB, MAPK1, AKT1, and EGFR, were significant in the regulation of the above bioprocesses and pathways. These results provide a basis for elucidating the bioactive compounds and the pharmacological mechanisms of H.W.Li radix under clinical applications.
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http://dx.doi.org/10.1021/acsomega.0c06201DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7893793PMC
February 2021

Xuesaitong exerts long-term neuroprotection for stroke recovery by inhibiting the ROCKII pathway, in vitro and in vivo.

J Ethnopharmacol 2021 May 20;272:113943. Epub 2021 Feb 20.

Key Laboratory of Chinese Internal Medicine of Educational Ministry and Beijing, Dongzhimen Hospital, Beijing University of Chinese Medicine, 100700, Beijing, China; Department of Neurology, Dongzhimen Hospital, Beijing University of Chinese Medicine, 100700, Beijing, China. Electronic address:

Ethnopharmacological Relevance: Xuesaitong (XST) is a traditional Chinese medicine injection with neuroprotective properties and has been extensively used to treat stroke for many years. The main component of XST is Panax notoginseng saponins (PNS), which is the main extract of the Chinese herbal medicine Panax notoginseng.

Aim Of The Study: In this study, we investigated whether XST provided long-term neuroprotection by inhibiting neurite outgrowth inhibitor-A (Nogo-A) and the ROCKII pathway in experimental rats after middle cerebral artery occlusion (MCAO) and in SH-SY5Y cells exposed to oxygen-glucose deprivation/reperfusion (OGD/R).

Materials And Methods: Rats with permanent MCAO were administered XST, Y27632, XST plus Y27632, and nimodipine for 14 and 28 days. Successful MCAO onset was confirmed by 2,3,5-triphenyl tetrazolium chloride (TTC) staining. Neurological deficit score (NDS) was used to assess neurological impairment. Hematoxylin-eosin (HE) staining and immunohistochemical (IHC) analysis of synaptophysin (SYN) and postsynaptic density protein-95 (PSD-95) were performed to evaluate cerebral ischemic injury and the neuroprotective capability of XST. Nogo-A levels and the ROCKII pathway were detected by IHC analysis, western blotting, and quantitative real-time polymerase chain reaction (qRT-PCR) to explore the protective mechanism of XST. OGD/R model was established in SH-SY5Y cells. Cell counting kit 8 (CCK8) was applied to detect the optimum OGD time and XST concentration. The expression levels Nogo-A and ROCKII pathway were determined using western blotting.

Results: Our results showed that XST reduced neurological dysfunction and pathological damage, promoted weight gain and synaptic regeneration, reduced Nogo-A mRNA and protein levels, and inhibited the ROCKII pathway in MCAO rats. CCK8 assay displayed that the optimal OGD time and optimal XST concentration were 7 h and 20 μg/mL respectively in SH-SY5Y cells. XST could evidently inhibit OGD/R-induced Nogo-A protein expression and ROCKII pathway activation in SH-SY5Y cells.

Conclusions: The present study suggested that XST exerted long-term neuroprotective effects that assisted in stroke recovery, possibly through inhibition of the ROCKII pathway.
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http://dx.doi.org/10.1016/j.jep.2021.113943DOI Listing
May 2021

Correction to: Shuangxia decoction alleviates p-chlorophenylalanine induced insomnia through the modification of serotonergic and immune system.

Metab Brain Dis 2020 Dec;35(8):1433

School of Chinese Material Medica, Beijing University of Chinese Medicine, The Yangguang South Street and Baiyang East Road, Fangshan district, Beijing, 102488, China.

The original article contains mistake. The authors want to add Wenhui Pei as first co-author and Fang Fang as co-corresponding author.
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http://dx.doi.org/10.1007/s11011-020-00612-4DOI Listing
December 2020

Anti-inflammatory and immunomodulatory effects of baicalin in cerebrovascular and neurological disorders.

Brain Res Bull 2020 11 26;164:314-324. Epub 2020 Aug 26.

Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing, Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine, 100700, Beijing, China. Electronic address:

Inflammatory responses play an extraordinary role in the pathogenesis of cerebrovascular and neurological disorders. Baicalin is one of the important flavonoids, which is extracted from Scutellaria baicalensis Georgi. Recently, numerous in vivo and in vitro studies have shown that baicalin has salutary effects for anti-inflammatory and immunomodulatory and has been demonstrated to exert beneficial therapeutic properties in cerebrovascular and neurological diseases. In this review, we aim to discuss that baicalin exerts anti-inflammatory effects through multiple pathways and targets, thus affecting the production of a variety of inflammatory cytokines and neuroprotective process of neurological diseases; furthermore, the related targets of the anti-inflammatory effects of baicalin were analyzed via using the tools of network pharmacology, to provide theoretical basis and innovative ideas for the future clinical application of baicalin.
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http://dx.doi.org/10.1016/j.brainresbull.2020.08.016DOI Listing
November 2020

In Vitro Evaluation of the Neuroprotective Effect of Saponins by Activating the EGFR/PI3K/AKT Pathway.

Evid Based Complement Alternat Med 2020 31;2020:1403572. Epub 2020 Jul 31.

Key Laboratory of Chinese Internal Medicine of Educational Ministry and Beijing, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China.

Objective: This study investigated whether saponins (PNS) extracted from (Bruk.) F. H. Chen played a neuroprotective role by affecting the EGFR/PI3K/AKT pathway in oxygen-glucose deprived (OGD) SH-SY5Y cells.

Materials And Methods: Different groups of OGD SH-SY5Y cells were treated with varying doses of PNS, PNS + AG1478 (a specific inhibitor of EGFR), or AG1478 for 16 hours. CCK8, Annexin V-FITC/PI apoptosis analysis, and LDH release analysis were used to determine cell viability, apoptosis rate, and amounts of LDH. Quantitative real-time PCR (q-RT-PCR) and western blotting were used to measure mRNA and proteins levels of p-EGFR/EGFR, p-PI3K/PI3K, and p-AKT/AKT in SH-SY5Y cells subjected to OGD.

Results: PNS significantly enhanced cell viability, reduced apoptosis, and weakened cytotoxicity by inhibiting the release of LDH. The mRNA expression profiles of EGFR, PI3K, and AKT showed no difference between model and other groups. Additionally, ratios of p-EGFR, p-PI3K, and p-AKT to EGFR, PI3K, and AKT proteins expression, respectively, all increased significantly.

Conclusions: These findings indicate that PNS enhanced neuroprotective effects by activating the EGFR/PI3K/AKT pathway and elevating phosphorylation levels in OGD SH-SY5Y cells.
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http://dx.doi.org/10.1155/2020/1403572DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7415117PMC
July 2020

Rapid characterization the chemical constituents of Bergenia purpurascens and explore potential mechanism in treating osteoarthritis by ultra high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry combined with network pharmacology.

J Sep Sci 2020 Aug 24;43(16):3333-3348. Epub 2020 Jun 24.

School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, P. R. China.

In recent years, direct and indirect evidence has been found of the efficacy of the traditional Chinese medicine Bergenia purpurascens in treating arthritis and osteoarthritis. Several major components, such as bergenin and 11-O-galloylbergenin, have good anti-inflammatory activity. Since research on the chemical components of Bergenia purpurascens and related mechanisms for the treatment of osteoarthritis has never been performed, this study aimed to analyze the chemical components of Bergenia purpurascens through ultra high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry technology and the UNIFI screening platform to predict the underlying mechanisms in treating osteoarthritis by analyzing the network pharmacology. In total, 43 chemical constituents were identified, mainly flavonoids (18), phenolic glycosides (13), and organic acids (7). Among them, 16 components were found in Bergenia purpurascens for the first time. Through the analysis of network pharmacology, several potential candidate targets and pathways were initially predicted, including AKT1, MAPK1, and MAPK3, as well as the apoptosis, estrogen, and MAPK signaling pathways. Bergenin, 11-O-galloylbergenin, arbutin, catechin-3-O-gallate, and other components play a synergistic role in treating osteoarthritis. This study analyzed the chemical components of Bergenia purpurascens and preliminarily revealed potential mechanisms of treating osteoarthritis, providing a basis for further evaluating the drug's efficacy.
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http://dx.doi.org/10.1002/jssc.201901284DOI Listing
August 2020

Shuangxia decoction alleviates p-chlorophenylalanine induced insomnia through the modification of serotonergic and immune system.

Metab Brain Dis 2020 02 30;35(2):315-325. Epub 2019 Nov 30.

School of Chinese Material Medica, Beijing University of Chinese Medicine, The Yangguang South Street and Baiyang East Road, Fangshan district, Beijing, 102488, China.

As a Traditional Chinese Medicine (TCM), Shuangxia Decoction (SXD) has been used to treat insomnia in oriental countries for more than thousands of years and it presents remarkable clinical effects. However, its active pharmacological fraction and the mechanism of sedative-hypnotic effects have not been explored. In this paper, we investigated active pharmacological fraction and revealed the detailed mechanisms underlying the sedative-hypnotic effects of SXD. It showed that SXD water extract compared to ethanol extract possessed better sedative effects on locomotion activity in normal mice and increased sleep duration in subhypnotic dose of sodium pentobarbital-treated mice. SXD alleviated p-chlorophenylalanine (PCPA) -induced insomnia by increasing the content of 5-HT in cortex [F (4, 55) = 12.67], decreasing the content of dopamine (DA) and norepinephrine (NE). Furthermore, SXD enhanced the expression of 5-HT and 5-HT receptors in hypothalamic and reduced serum levels of IL-1,TNF-α [F (5, 36) = 15.58]. In conclusion, these results indicated that SXD produced beneficial sedative and hypnotic bioactivities mediated by regulating the serotonergic and immune system.
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http://dx.doi.org/10.1007/s11011-019-00499-wDOI Listing
February 2020

Hypoxia-associated circDENND2A promotes glioma aggressiveness by sponging miR-625-5p.

Cell Mol Biol Lett 2019 2;24:24. Epub 2019 Apr 2.

1Department of Neurosurgery, Chinese PLA General Hospital, Medical School of Chinese PLA, Beijing, People's Republic of China.

Background: As a newfound type of non-coding RNA, circular RNAs (circRNAs) are involved in various physiological and pathological processes via regulation of gene expression. Increasing evidence shows that aberrantly expressed circRNAs play a crucial role in the initiation and progression of many tumors. However, the functions of different circRNAs in gliomas remain elusive.

Methods: The levels of circRNAs, miRNAs, and mRNAs were quantified by qPCR. The interaction between circDENND2A and miR-625-5p was determined by luciferase reporter and pull-down assays. The migratory and invasive capabilities of glioma cells were examined by wound healing and Transwell assays. Immunohistochemistry was performed to analyze the HIF1α level in glioma tissues.

Results: We predicted circDENND2A (has_circ_0002142) to be a hypoxia-responsive circRNA in glioma via a bioinformatic analysis. We found that hypoxia induced the expression of circDENND2A, which promoted migration and invasion of glioma cells. To understand the behaviors of circDENND2A in glioma, we studied the putative miRNAs targeted by circDENND2A and identified circDENND2A as an efficient sponge of miR-625-5p in glioma cells. Phenotype experiments verified that circDENND2A was required for the hypoxia-induced migration and invasion of glioma cells and that this occurred by sponging of miR-625-5p. Notably, glioma tissues overexpressing HIF1α exhibited a high expression of circDENND2A as well as a low expression of miR-625-5p. circDENND2A was negatively correlated with miR-625-5p.

Conclusion: circDENND2A is required for the hypoxia-induced malignancy of glioma cells and functions by sponging miR-625-5p.
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http://dx.doi.org/10.1186/s11658-019-0149-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6446274PMC
May 2019

The up-regulation of two identified wound healing specific proteins-HSP70 and lysozyme in regenerated Eisenia fetida through transcriptome analysis.

J Ethnopharmacol 2019 Jun 19;237:64-73. Epub 2019 Mar 19.

School of Chinese Material Medica, Beijing University of Chinese Medicine, Yangguang South Road, Fangshan District, Beijing, China. Electronic address:

Ethnopharmacological Relevance: Disposed earthworm has been used to treat various common ailments including burns, arthritis, itching, and inflammation for thousands of years in China. As their remarkable ability to fully regenerate in a scar-free manner, regenerated tissue homogenate of amputated Eisenia fetida (E. fetida) have been considered as an excellent wound repair therapy in our previous study. We have demonstrated that regenerated earthworm (G-90') can perform higher wound repair ability to non-regeneration tissue (G-90) through significant promotion of cutaneous wound repair in mice after their administration into wound beds.

Objective: In the present study, we aimed to reveal the mechanism of G-90' and to explore a potential wound healing accelerated strategy.

Methods And Results: Two functional proteins- HSP70 and lysozyme in G-90' were confirmed by cross-identification of LC-MS/MS and transcriptome analyses. Followed with semi-quantitative PCR and western blot, their expression were validated to up-regulate in 3-day regenerated tissues (G-90').

Conclusion: This study implies the therapeutic potency of G-90' for wound recovery and provides a new strategy to assess other natural materials targeting wound healing with the tail-amputated E .fetida as a model organism.
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http://dx.doi.org/10.1016/j.jep.2019.03.047DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7126112PMC
June 2019

The Effects of Tai Chi Training in Patients with Heart Failure: A Systematic Review and Meta-Analysis.

Front Physiol 2017 7;8:989. Epub 2017 Dec 7.

Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing, Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine, Beijing, China.

Heart Failure (HF) is associated with significantly high morbidity and mortality. We performed a meta-analysis and updated new evidences from randomized controlled trials (RCTs) to determine the effects of Tai Chi (TC) in patients with HF. Electronic literature search of Medline, PubMed, EMBASE, the Cochrane Library, China national knowledge infrastructure (CNKI), and Wan Fang Database was conducted from inception of their establishment until 2017. And we also searched Clinical Trials Registries (https://clinicaltrials.gov/ and www.controlled-trials.com) for on-going studies. A total of 11 trials with 656 patients were available for analysis. The results suggested that TC was associated with an obviously improved 6-min walk distance [6MWD, weighted mean difference (WMD) 65.29 m; 95% CI 32.55-98.04] and quality of life (Qol, WMD -11.52 points; 95% CI -16.5 to -6.98) and left ventricular ejection fraction (LVEF, WMD 9.94%; 95% CI 6.95 to 12.93). TC was shown to reduce serum B-type natriuretic peptide [BNP, standard mean difference (SMD) -1.08 pg/mL; 95% CI -1.91 to -0.26] and heart rate (HR, WMD -2.52 bpm; 95% CI -3.49 to -1.55). In summary, our meta-analysis demonstrated the clinical evidence about TC for HF is inconclusive. TC could improve 6MWD, Qol and LVEF in patients with HF and may reduce BNP and HR. However, there is a lack of evidence to support TC altering other important long-term clinical outcomes so far. Further larger and more sustainable RCTs are urgently needed to investigate the effects of TC.
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http://dx.doi.org/10.3389/fphys.2017.00989DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5770613PMC
December 2017

The identification of functional proteins from amputated lumbricus Eisenia fetida on the wound healing process.

Biomed Pharmacother 2017 Nov 21;95:1469-1478. Epub 2017 Sep 21.

School of Chinese Material Medica, Beijing University of Chinese Medicine, No. 6 Zhonghuan South Road, Wangjing, Chaoyang District, Beijing, China. Electronic address:

Earthworm has a long history of being used for medical purposes in many countries. This study investigated the therapeutic effects of earthworm extract (G-90') from head-regenerating tissue of Eisenia fetida on wound healing process in vitro and in vivo. Among three salting out parts (ES1-ES3) of G-90', ES2 displayed the significant wound healing ability via promoting proliferation of fibroblast and keratinocyte as well as stimulating the expression of fibroblast growth factor and vascular endothelial growth factor in wound area. The wound healing-specific proteins in ES2 were further analysed by "bottom-up" proteomic analytic method. Two proteins in ES2 were identified through "bottom-up" analysis, but their effects on wound healing process remains enigmatic. The bioactive proteins (ES2) in G-90' enhance the proliferative phase in acute wound healing process, providing a new concept for transforming this natural material for use in wound therapy.
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http://dx.doi.org/10.1016/j.biopha.2017.09.049DOI Listing
November 2017

A Systematic Review and Meta-Analysis on the Treatment of Cerebral Hemorrhage with NaoXueShu Oral Liquid.

Biomed Res Int 2017 29;2017:8542576. Epub 2017 May 29.

Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing, Key Office of Encephalopathy TCM Research, Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine, Beijing 100700, China.

NaoXueShu oral liquid invigorates Qi and promotes blood circulation, which is mainly used for treating the acute stage of the meridian of hemorrhagic apoplexy and acute blood stasis syndrome during early convalescence. Its main clinical manifestations include hemiplegia, mouth askew, hemianesthesia, and inarticulateness. It is used mainly in patients with lobar hemorrhage, basal ganglia, and thalamus of the small amount of bleeding without disturbing consciousness of hypertensive cerebral. The purpose of this study was to evaluate the efficacy and adverse effects of NaoXueShu oral liquid on the treatment of cerebral hemorrhage. In this study, literature on randomized controlled trials was collected from seven databases to evaluate the clinical efficiency of the treatment of cerebral hemorrhage alone or combined with Western medicine. The methodologic quality of the included studies was assessed using a standard Cochrane system review and analyzed using RevMan 5.3.0 software. The study included 14 eligible randomized controlled trials. The results showed that the use of NaoXueShu oral liquid alone or combined with other drugs or auxiliary methods can play a significant role in the treatment of cerebral hemorrhage, especially hypertensive intracerebral hemorrhage.
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http://dx.doi.org/10.1155/2017/8542576DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5467282PMC
March 2018

Ultra high performance liquid chromatography with tandem mass spectrometry for rapid separation and identification of main constituents in Chinese herbal formula Xuan Hu Suo San.

Nat Prod Res 2017 Jul 15;31(14):1620-1624. Epub 2017 Feb 15.

a School of Chinese Materia Medica , Beijing University of Chinese Medicine , Beijing , China.

Xuan Hu Suo San (XHSS) is a traditional Chinese medicine that has been extensively applied in the treatment of osteoarthritis for many years, however, its chemical composition has not yet been elucidated. Thus, a rapid, efficient, and precise method based on ultra high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry was applied in both positive- and negative-ion modes to rapidly separate and identify the main chemical ingredients in XHSS for the first time. Finally, with the optimised separation and detection method, a total of 57 compounds were simultaneously separated within 13 min, among which 14 compounds were confirmed by comparing retention time and MS data with reference standards and others were tentatively identified by comparing with reference literatures. This rapid and sensitive approach is highly useful for the identification and characterisation of chemical constituents, and provides fundamental and extensive information supporting further metabolic and pharmacokinetic studies of XHSS.
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http://dx.doi.org/10.1080/14786419.2017.1285296DOI Listing
July 2017

Panax notoginseng saponins provide neuroprotection by regulating NgR1/RhoA/ROCK2 pathway expression, in vitro and in vivo.

J Ethnopharmacol 2016 Aug 8;190:301-12. Epub 2016 Jun 8.

Key Laboratory of Chinese Internal Medicine of Educational Ministry and Beijing, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China. Electronic address:

Ethnopharmacological Relevance: Panax notoginseng saponins (PNS) extracted from a traditional Chinese herbal medicine, Panax notoginseng (Burkill) F.H. Chen (Araliaceae), which has been extensively used in treating coronary heart disease, ischemic cerebrovascular disease and hemorrhagic disorders in China over hundreds of years.

Aims Of The Study: This study explored whether panax notoginseng saponins (PNS) provided neuroprotective effects by inhibiting the expressions of NgR1, RhoA, and ROCK2 following middle cerebral artery occlusion in rats and oxygen-glucose deprivation/reoxygenation (OGD/R) injury in SH-SY5Y cells.

Materials And Methods: 2,3,5-Triphenyltetrazolium chloride staining was used to determine successful middle cerebral artery occlusion establishment in sham-operated and operated Sprague-Dawley rats 1 day after injury. The rats were randomly separated into sham, model, NEP1-40, PNS, and NEP1-40 plus PNS (N+P) groups. After 7 days of treatment, body mass and neurological deficit scores were analyzed. Tissues were harvested and analyzed by hematoxylin-eosin staining and immunohistochemical analysis, western blotting, and quantitative real-time PCR (qRT-PCR). The optimal drug concentration of NEP1-40 and PNS on SH-SY5Y cells exposed to OGD/R injury was determined by CCK8 analysis. qRT-PCR was used to measure mRNA expression profiles of NgR1, RhoA, and ROCK2 in SH-SY5Y cells subjected to OGD/R.

Results: The results showed that MCAO surgery successfully produced an infarct, and the PNS, NEP1-40, and N+P groups exhibited increased body mass and ameliorated neurological deficits compared with the model group. NEP1-40 treatment markedly reduced NgR1 and RhoA overexpression when compared to the model group, although there was no significant difference in ROCK2 expression. PNS and N+P treatment significantly decreased NgR1, RhoA, and ROCK2 overexpression compared with the model group. However, N+P treatment did not result in a synergistic effect, as assessed by immunohistochemistry, western blotting, and qRT-PCR. Following optimal administration of PNS (160μg/ml) and NEP1-40 (10ng/ml) on SH-SY5Y cells exposed to OGD/R injury, cell viability in the NEP1-40, PNS, and N+P groups significantly increased compared with the model group, as assessed by CCK8 analysis. Additionally, NgR1, RhoA, and ROCK2 mRNA expression profiles were significantly less in the NEP1-40, PNS, and N+P groups compared with the model group.

Conclusion: PNS provided neuroprotective effects in a rat model of cerebral ischemia and SH-SY5Y cells exposed to oxygen/glucose deprivation injury by inhibiting the overexpression of NgR1, RhoA, and ROCK2.
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http://dx.doi.org/10.1016/j.jep.2016.06.017DOI Listing
August 2016

A Network Pharmacology Approach to Uncover the Pharmacological Mechanism of XuanHuSuo Powder on Osteoarthritis.

Evid Based Complement Alternat Med 2016 24;2016:3246946. Epub 2016 Mar 24.

School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100102, China.

As the most familiar type of arthritis and a chronic illness of the joints, Osteoarthritis (OA) affects a great number of people on the global scale. XuanHuSuo powder (XHSP), a conventional herbal formula from China, has been extensively applied in OA treatment. Nonetheless, its pharmacological mechanism has not been completely expounded. In this research, a network pharmacology approach has been chosen to study the pharmacological mechanism of XHSP on OA, and the pharmacology networks were established based on the relationship between four herbs found in XHSP, compound targets, and OA targets. The pathway enrichment analysis revealed that the significant bioprocess networks of XHSP on OA were regulation of inflammation, interleukin-1β (IL-1β) production and nitric oxide (NO) biosynthetic process, response to cytokine or estrogen stimuli, and antiapoptosis. These effects have not been reported previously. The comprehensive network pharmacology approach developed by our research has revealed, for the first time, a connection between four herbs found in XHSP, corresponding compound targets, and OA pathway systems that are conducive to expanding the clinical application of XHSP. The proposed network pharmacology approach could be a promising complementary method by which researchers might better evaluate multitarget or multicomponent drugs on a systematic level.
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http://dx.doi.org/10.1155/2016/3246946DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4823500PMC
April 2016

The Clinical Relevance of Serum NDKA, NMDA, PARK7, and UFDP Levels with Phlegm-Heat Syndrome and Treatment Efficacy Evaluation of Traditional Chinese Medicine in Acute Ischemic Stroke.

Evid Based Complement Alternat Med 2015 11;2015:270498. Epub 2015 Oct 11.

Department of Neurology, Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine, Beijing 100700, China.

According to the methods of Patient-Reported Outcome (PRO) based on the patient reports internationally and referring to U.S. Food and Drug Administration (FDA) guide, some scholars developed this PRO of stroke which is consistent with China's national conditions, and using it the feel of stroke patients was introduced into the clinical efficacy evaluation system of stoke. "Ischemic Stroke TCM Syndrome Factor Diagnostic Scale (ISTSFDS)" and "Ischemic Stroke TCM Syndrome Factor Evaluation Scale (ISTSFES)" were by "Major State Basic Research Development Program of China (973 Program) (number 2003CB517102)." ISTSFDS can help to classify and diagnose the CM syndrome reasonably and objectively with application of syndrome factors. Six syndrome factors, internal-wind syndrome, internal-fire syndrome, phlegm-dampness syndrome, blood-stasis syndrome, qi-deficiency syndrome, and yin-deficiency syndrome, were included in ISTSFDS and ISTSFES. TCM syndrome factor was considered to be present if the score was greater than or equal to 10 according to ISTSFDS. In our study, patients with phlegm-heat syndrome were recruited, who met the diagnosis of both "phlegm-dampness" and "internal-fire" according to ISTSFDS. ISTSFES was used to assess the syndrome severity; in our study it was used to assess the severity of phlegm-heat syndrome (phlegm-heat syndrome scores = phlegm-dampness syndrome scores + internal-fire syndrome scores).
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http://dx.doi.org/10.1155/2015/270498DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4619909PMC
November 2015

Qingkailing Suppresses the Activation of BV2 Microglial Cells by Inhibiting Hypoxia/Reoxygenation-Induced Inflammatory Responses.

Evid Based Complement Alternat Med 2014 28;2014:696218. Epub 2014 Apr 28.

Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing, Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine, Beijing 100700, China.

Qingkailing (QKL) is a well-known composite extract used in traditional Chinese medicine. This extract has been extensively administered to treat the acute phase of cerebrovascular disease. Our previous experiments confirmed that QKL exerts an inhibitory effect on cerebral ischemia-induced inflammatory responses. However, whether QKL suppresses the activation of microglia, the primary resident immune cells in the brain, has yet to be determined. In this study, BV2 microglial cells were used to validate the protective effects of QKL treatment following ischemia-reperfusion injury simulated via hypoxia/reoxygenation in vitro. Under these conditions, high expression levels of ROS, COX-2, iNOS, and p-p38 protein were detected. Following ischemia/reperfusion injury, QKL significantly increased the activity of BV2 cells to approximately the basal level by modulating microglial activation via inhibition of inflammatory factors, including TNF- α , COX-2, iNOS, and p-p38. However, QKL treatment also displayed dose-dependent differences in its inhibitory effects on p38 phosphorylation and inflammatory factor expression.
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http://dx.doi.org/10.1155/2014/696218DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4020462PMC
May 2014

The Correlation between High-Sensitivity C-Reactive Protein, Matrix Metallopeptidase 9, and Traditional Chinese Medicine Syndrome in Patients with Hypertension.

Evid Based Complement Alternat Med 2013 28;2013:780937. Epub 2013 Mar 28.

Key Laboratory of Chinese Internal Medicine of Ministry of Education, Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine, Beijing 100700, China.

Hypertension is a common disease affecting millions of people throughout the world. Currently, there is a growing interest in the traditional Chinese medicine (TCM) for patients with hypertension mainly due to the personalized therapy of TCM in many countries. Clinical treatment of patients relies on the successful differentiation of a specific TCM syndrome for hypertension. However, it is difficult to understand that TCM syndrome classifications depend on the clinical experience of a TCM practitioner. Therefore, discovering an objective biomarker associated with TCM syndrome may be beneficial for TCM syndrome classifications. This paper focused on high sensitivity C-reactive protein (HCRP), matrix metallopeptidase 9 (MMP9), and TCM syndrome, and aimed to investigate the relationships between TCM syndrome and the two inflammatory biomarkers in patients with essential hypertension. The result showed that both HCRP and MMP9 are positively correlated with syndrome of wind and phlegm turbidity. Detection of the serum levels of HCRP and MMP9 is beneficial for TCM syndrome classification and prediction of cardiovascular and cerebrovascular risk events in hypertensive patients.
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http://dx.doi.org/10.1155/2013/780937DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3625612PMC
April 2013

[Effect of Astragali Radix injection on myocardial cell mitochondrial structure and function in process of reversing myocardial cell hypertrophy].

Zhongguo Zhong Yao Za Zhi 2012 Apr;37(7):979-84

Key Laboratory of Chinese Internal Medicine of Ministry of Education, Dongzhimen Hospital Affiliated to Beijing University of Traditional Chinese Medicine, Beijing 100700, China.

Objective: To study pathological and therapeutical problems concerning myocardial cell mitochondria changes during myocardial cell hypertrophy by culturing rat primary myocardial cells.

Method: Primary myocardial cells were seperated and cultured together with angiotensin II (Ang II) for 72 or 96 hours. The total protein content with the BCA method and the photography and measurement of cell diameter with inverted microscope reflected myocardial cell proliferation. The mitochondrial membrane potential (Delta Psi m) with fluorescence microscope, the mitochondrial single amine oxidase (MAO) activity with spectrophotometer, the mitochondrial cytochrome oxidase (COX) activity and the injury percentage of mitochondrial outer membrane with microplate reader and the contents of ATP, ADP, AMP with high performance liquid chromatography reflected the injury and energy metabolism of myocardial cell mitochondrial structure and function when being cultured together with Ang II. On that basis, cells were treated with Astragali Radix injection and valsartan for observing pharmacological effects on mitochondrial structure and function in restructured myocardial cells.

Result: In 72 h and 96 h, compare with the control group, the model group showed significantly increased total protein content and enlarged myocardial cell diameter. During the course of proliferation, the myocardial cell MAO activity and the injury percentage of mitochondrial outer membrane were significantly increased, with significant decrease in mitochondrial COX activity, mitochondrial Delta Psi m and the content of ATP, ADP and rise in the content of AMP. Astragali Radix injection and valsartan reduced myocardial cell total protein content and cell diameter caused by Ang II, decreased myocardial cell MAO activity, significantly increased mitochondrial COX activity and the content of ATP and ADP, and decreased the content of AMP.

Conclusion: During the process of myocardial hypertrophy, the injury of mitochondrial structure and function and the changes in myocardial cell energy metabolism injury occurred after the injury of mitochondria. Astragali Radix injection and valsartan can reverse myocardial cell mitochondrial structure and function during myocardial cell hypertrophy caused by Ang II. Reversion of myocardial cell hypertrophy and restructuring of myocardial cells helps improve energy metabolism of the myocardial cells.
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April 2012

Nasal recombinant hirudin-2 delivery: absorption and its mechanism in vivo and in vitro studies.

Biol Pharm Bull 2005 Dec;28(12):2263-7

Department of Chinese Pharmacy, P.O.B.3, Beijing University of Traditional Chinese Medicine, China.

The objective of this study was to investigate the feasibility of systemic absorption of recombinant hirudin-2 (rHV2) by nasal delivery, and its possible absorption mechanism. The degradation of rHV2 in the nasal tissue homogenate and extracts of mucosae of rabbit, as well as the degradation inhibition of enzyme inhibitor (bacitracin) was evaluated. The bioavailability of rHV2 and the improvement with enhancers, after nasal administration in rats was investigated. For further understanding of the transport and uptake characteristics of rHV2, in vitro transport experiment under various conditions using diffusion chamber technique in excised rabbit nasal epithelium was performed. It was found that rHV2 underwent rapid degradation in rabbit nasal homogenate, but it was more stable in the extracts of nasal mucosae surface. Bacitracin was able to inhibit the degradation of rHV2 to certain extent. rHV2 was detected in the rat plasma by chromogenic substrate assay after nasal administration and some enhancers also significantly increased the nasal absorption of rHV2. The transport and uptake of rHV2 across nasal epithelium was concentration-dependent and unsaturated, and was significantly inhibited by low temperature, NaN(3), DNP and colchicines, while was less affected by alteration of transport direction. These results demonstrate that the possible absorption mechanism of rHV2 by nasal mucosa appears to be associated with the endocytosis as well as passive diffusion process.
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http://dx.doi.org/10.1248/bpb.28.2263DOI Listing
December 2005
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