Publications by authors named "Yanming Wei"

38 Publications

Sheng Mai San ameliorated heat stress-induced liver injury via regulating energy metabolism and AMPK/Drp1-dependent autophagy process.

Phytomedicine 2021 Dec 31;97:153920. Epub 2021 Dec 31.

Institute of Traditional Chinese Veterinary Medicine, College of Veterinary Medicine, Gansu Agricultural University, Lanzhou, Gansu 730070, China. Electronic address:

Background: Liver damage is one of the most common complications in humans and animals after heat stress (HS). Sheng Mai San (SMS), a traditional Chinese medicine prescription that originated in the Jin Dynasty, exert a therapeutic effect on HS. However, how SMS prevents liver injury after heat exposure remains unknown.

Purpose: This study aimed to investigate the pharmacological effect and molecular mechanisms of SMS on HS-induced liver injury.

Study Design: A comprehensive strategy via incorporating pharmacodynamics, targeted metabolomics, and molecular biology technology was adopted to investigate energy metabolism changes and the therapeutic mechanisms of SMS in HS-induced rat liver injury.

Methods: First, Sprague-Dawley rats were subjected to HS (38 °C/ 75% RH/ 2 h/ day) for 7 consecutive days to establish the HS model, and SMS was given orally for treatment 2 h before heat exposure. Thereafter, liver function and pathological changes in liver tissue were evaluated. Finally, the underlying mechanisms of SMS were determined using targeted energy metabolomics to comprehensively analyze the metabolic pathways and were further verified through Western-blot and qRT-PCR assays.

Results: Our results showed that SMS alleviated HS-induced liver dysfunction by reducing the alanine aminotransferase (ALT), aspartate aminotransferase (AST), and AST/ALT ratios in serum and improving hepatic pathological damage. Meanwhile, SMS suppressed inflammatory response, oxidative injury, and overexpression of heat shock proteins in liver tissue after heat exposure. With the help of targeted energy metabolomics, we found that SMS could effectively regulate glycolysis and tricarboxylic acid (TCA) cycle to relieve energy metabolism disorder. Furthermore, we confirmed that SMS can facilitate the phosphorylation of AMP-activated protein kinase (AMPK) to maintain mitochondrial homeostasis through a dynamin protein 1 (Drp1)-dependent mitophagy process.

Conclusion: On the basis of energy metabolomics, the present study for the first time systematically illustrated the protective effect of SMS on HS-induced liver injury, and preliminarily confirmed that an AMPK-mediated Drp1-dependent mitophagy and mitochondria rebuilding process plays an important role in SMS intervention on HS-induced rat liver. Together, our study lends further support to the use of SMS in treating HS condition.
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http://dx.doi.org/10.1016/j.phymed.2021.153920DOI Listing
December 2021

PGRMC1 Exerts Its Function of Anti-Influenza Virus in the Central Nervous System.

Microbiol Spectr 2021 10 29;9(2):e0073421. Epub 2021 Sep 29.

State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural Universitygrid.35155.37, Wuhan, People's Republic of China.

The influenza A virus (IAV) infection is usually restricted to the respiratory tract and only rarely enters the central nervous system (CNS) and causes neurological symptoms. However, the roles of host factors involved in IAV infection in the CNS remain largely undetermined. Therefore, we aimed to characterize the host responses to IAV infection in the brain. We isolated a strain of IAV H5N6, which is neurotoxic and highly pathogenic to mice. High-throughput RNA sequencing (RNA-seq) revealed 240 differentially expressed genes in IAV-infected brains. Among the significantly downregulated genes, we focused on the gene encoding progesterone receptor membrane component-1 () and observed that IAV H5N6 infection clearly inhibited in both neuroblastoma and glioma cells. Furthermore, treatment with AG205, a -specific inhibitor, or knockout promoted H5N6 multiplication , while overexpression of resulted in opposite effects. Furthermore, AG205 treatment or knockout significantly inhibited the retinoic acid-inducible gene I (RIG-I)-mediated interferon beta (IFN-β) signaling pathway and reduced the levels of several antiviral proteins (Mx1 and ISG15). In addition, -mediated regulation of IFN signaling relied on inhibition of the expression and ubiquitination of RIG-I. The loss of leads to an increased susceptibility of mice (brain and lung) to influenza A virus infection. Conclusively, our results show for the first time that IAV H5N6 downregulates expression to contribute to virus proliferation by inhibiting RIG-I-mediated IFN-β production in the brain. These findings may offer new insights regarding the interplay between IAV and host factors that may impact IAV pathogenicity in the brain. Central nervous system (CNS) disease is one of the most common extra-respiratory tract complications of influenza A virus (IAV) infections. However, there is still little knowledge about IAV regulating host responses in brain. In this study, we identified progesterone receptor membrane component-1 (PGRMC1) as a novel host factor involved in the replication and propagation of IAV H5N6 in the host brain. We also observed that PGRMC1 antagonism was required for viral evasion from the host immune response during IAV infection via inhibition of the retinoic acid-inducible gene I (RIG-I)-mediated interferon beta (IFN-β) signaling pathway and downstream antiviral gene expression. This study revealed a newly identified regulatory mechanism used by IAV H5N6 to ensure its life cycle in the CNS.
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http://dx.doi.org/10.1128/Spectrum.00734-21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8557870PMC
October 2021

Corrigendum to "Characterization and antioxidative activities of polysaccharide in Chinese angelica and its processed products" [Int. J. Biol. Macromol. 67 (2014) 195-200].

Int J Biol Macromol 2021 May 15;178:616. Epub 2021 Apr 15.

Institute of Traditional Chinese Veterinary Medicine, College of Veterinary Medicine, Gansu Agricultural University, Lanzhou 730070, PR China.

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http://dx.doi.org/10.1016/j.ijbiomac.2021.03.095DOI Listing
May 2021

MicroRNAs as crucial mediators in the pharmacological activities of triptolide (Review).

Exp Ther Med 2021 May 17;21(5):499. Epub 2021 Mar 17.

College of Chinese Medicine and Food Engineering, Shanxi University of Chinese Medicine, Jinzhong, Shanxi 030619, P.R. China.

Triptolide is the main bioactive constituent isolated from the Chinese herb Hook F., which possesses a variety of pharmacological properties. MicroRNAs (miRNAs/miRs) are short non-coding RNAs that regulate gene expression post-transcriptionally. miRNAs are implicated in several intracellular processes, whereby their dysregulation contributes to pathogenesis of various diseases. Thus, miRNAs have great potential as biomarkers and therapeutic targets for diseases, and are implicated in drug treatment. Previous studies have reported that specific miRNAs are targeted, and their expression levels can be altered following exposure to triptolide. Thus, miRNAs are emerging as crucial mediators in the pharmacological activities of triptolide. The present review summarizes current literature on miRNAs as target molecules in the pharmacological activities of triptolide, including antitumor, anti-inflammatory, immunosuppressive, renal protective, cardioprotective, antiangiogenesis activities and multiorgan toxicity effects. In addition, the diverse signaling pathways involved are discussed to provide a comprehensive understanding of the underlying molecular mechanisms of triptolide in the regulation of target miRNAs.
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http://dx.doi.org/10.3892/etm.2021.9930DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8005665PMC
May 2021

Transcriptome Profiles of Highly Pathogenic Pure Avian H7N9 Virus-Infected Lungs of BALB/c Mice.

Front Vet Sci 2020 21;7:603584. Epub 2020 Dec 21.

State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, China.

Avian influenza A (H7N9) viruses emerged in China in 2013 and caused a zoonotic disease associated with a high case-fatality ratio of more than 30%. Transcriptional profiles obtained using animal models reveal host responses to the disease, thereby providing insights into disease pathogenesis. Therefore, we aimed to characterize the host responses of the H7N9 virus infected-mouse lungs in this study. First, we isolated an avian-originated H7N9 strain, which was shown to be highly pathogenic to both chickens and mice. Genomic analysis results suggested that a 12-nucleotide-insertion was present at the hemagglutinin cleavage site, and both the hemagglutinin and neuraminidase genes belonged to the Yangtze River Delta lineage. RNA sequencing results revealed 566 differentially expressed genes in the H7N9-infected lungs. Moreover, transcriptome analysis revealed that over-activated antiviral signals and intense interferon-stimulated gene products possibly contributed to the high virulence of the virus in mice. Importantly, lung concentrations of inflammatory cytokines, including interleukin-1β and interleukin-6, interferon-β, and tumor necrosis factor-α, were upregulated in response to H7N9 virus infection. Overall, the present study provided a comprehensive understanding of H7N9 virus pathogenicity and correlated host immune responses.
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http://dx.doi.org/10.3389/fvets.2020.603584DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7779551PMC
December 2020

Screening study of blood-supplementing active components in water decoction of processed with yellow rice wine based on response surface methodology.

Pharm Biol 2020 Dec;58(1):1167-1176

College of Veterinary Medicine, Gansu Agricultural University, Lanzhou, P. R. China.

Context: (Oliv.) Diels (Apiaceae) (syn. Maxim var. Oliver) processed with yellow rice wine (WAS) has a blood-supplementing effect.

Objective: To establish an optimal technology for preparing water decoction of WAS (WASD), and screen blood-supplementing fractions.

Materials And Methods: Ferulic acid and crude polysaccharide were used in optimizing the preparation technology for WASD through response surface methodology. The independent variables were liquid-solid ratio, soaking time, and extraction time. Eighty Kunming mice were randomly divided into normal control, model, and six intervention groups ( = 10). The intervention groups were given different WASD fractions by gavage (5 or 10 g/kg). The model intervention groups received acetylphenyl hydrazine (subcutaneous injection) and cyclophosphamide (intraperitoneal injection). Duration of study, 9 days. The components of blood-supplementing fractions were analyzed.

Results: The optimum extraction parameters were liquid-solid ratio, 7.69:1 mL/g; soaking time, 119.78 min; and extraction time, 143.35 min. The optimal OD value was 0.8437. RBC, WBC, and Hb in the water fraction (5, 10 g/kg) and -butanol fraction (10 g/kg) intervention groups increased significantly compared with the model group ( < 0.05). Polysaccharide and caffeic acid contents of water fraction were 252.565 and 0.346 μg/mg, respectively; ferulic acid was not detected. Caffeic acid and ferulic acid contents of -butanol fraction were 1.187 and 0.806 μg/mg, respectively, polysaccharide was not detected.

Conclusions: The optimum preparation technology of WASD was obtained, and the water, -butanol fractions were blood-supplementing fractions. This study provides a theoretical foundation for further application of WAS in the pharmaceutical industry.
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http://dx.doi.org/10.1080/13880209.2020.1844760DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7877401PMC
December 2020

Tandem Mass Tag-Based Quantitative Proteome Analysis of Porcine Deltacoronavirus (PDCoV)-Infected LLC Porcine Kidney Cells.

ACS Omega 2020 Sep 27;5(35):21979-21987. Epub 2020 Aug 27.

State Key Laboratory of Veterinary Etiological Biology, Key Laboratory of Animal Virology of Ministry of Agriculture, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou 730046, China.

Porcine deltacoronavirus (PDCoV) is a newly emerging porcine pathogenic enteric coronavirus that can cause diarrhea, vomiting, dehydration, and a high mortality rate in piglets. At present, the understanding of PDCoV pathogenesis is very limited, which seriously hinders effective prevention and control. In this study, liquid chromatography tandem-mass spectrometry (LC-MS/MS) combined with tandem mass tag (TMT) labeling was performed to compare the differential expression of proteins in PDCoV-infected and mock-infected LLC-PK cells at 18 h post-infection (hpi). In addition, the parallel reaction monitoring (PRM) technique was used to verify the quantitative proteome data. A total of 4624 differentially expressed proteins (DEPs) were quantitated, of which 128 were significantly upregulated, and 147 were significantly downregulated. Bioinformatics analysis revealed that these DEPs were involved mainly in the defense response, apoptosis, and the immune system, and several DEPs may be related to interferon-stimulated genes and the immune system. Based on DEP bioinformatics analysis, we propose that PDCoV infection may utilize the apoptosis pathway of host cells to achieve maximum viral replication. Meanwhile, the host may be able to stimulate the transcription of interferon-stimulated genes (ISGs) through the JAK/STAT signaling pathway to resist the virus. Overall, in this study, we presented the first application of proteomics analysis to determine the protein profile of PDCoV-infected cells, which provides valuable information with respect to better understanding the host response to PDCoV infection and the specific pathogenesis of PDCoV infection.
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http://dx.doi.org/10.1021/acsomega.0c00886DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7482077PMC
September 2020

Mechanism of Huang-lian-Jie-du decoction and its effective fraction in alleviating acute ulcerative colitis in mice: Regulating arachidonic acid metabolism and glycerophospholipid metabolism.

J Ethnopharmacol 2020 Sep 14;259:112872. Epub 2020 May 14.

Institute of Traditional Chinese Veterinary Medicine, College of Veterinary Medicine, Gansu Agricultural University, Lanzhou, China. Electronic address:

Ethnopharmacological Relevance: Huang-lian-Jie-du decoction (HLJDD) is a traditional Chinese medicine prescription for clearing away heat, purging fire and detoxifying, which can be used to treat sepsis, stroke, Alzheimer's disease and gastrointestinal diseases. Our previous studies have shown that HLJDD can effectively alleviate acute ulcerative colitis (UC) in mice, and its n-butanol fraction (HLJDD-NBA) is the effective fraction. The aim of this study is to further investigate the mechanism of HLJDD and HLJDD-NBA in relieving UC in mice from a holistic perspective.

Methods: The acute UC model of BABL/c mice was induced by 3.5% (w/v) dextran sodium sulfate drinking water. At the same time of modeling, HLJDD and HLJDD-NBA were given orally for treatment respectively. During the experiment, the clinical symptoms of mice were recorded and the physiological and biochemical indexes of mice were detected after the experiment. In addition, the plasma metabolites of mice in each group were detected and analyzed by ultra-high performance liquid chromatography quadrupole time of flight mass spectrometry and multivariate statistical analysis method. Then, the potential target metabolic pathway of drug intervention was screened through the enrichment analysis of differential metabolites. Finally, we use molecular simulation docking technology to further explore the molecular regulatory mechanism of HLJDD and HLJDD-NBA on potential target metabolic pathways.

Results: HLJDD and HLJDD-NBA intervention can significantly reduce the disease activity index of UC mice, inhibit colon length shortening and pathological damage, and relieve the abnormal changes of physiological and biochemical parameters of UC mice. Moreover, HLJDD and HLJDD-NBA can significantly inhibit the metabolic dysfunction of UC mice by reversing the abnormal changes of 24 metabolites in UC mice, and the arachidonic acid metabolic pathway and glycerophospholipid metabolic pathway are the target metabolic pathways regulated by them. Further literature review and molecular simulation docking analysis showed that HLJDD and HLJDD-NBA may inhibit the disorder of arachidonic acid metabolism pathway and glycerophospholipid metabolism pathway by inhibiting COX-2 protein expression and PLA2, 5-LOX activity.

Conclusions: Our experiments revealed that HLJDD and HLJDD-NBA can alleviate UC of mice by regulating arachidonic acid metabolism and glycerophospholipid metabolism, which points out the direction for further research and development of HLJDD as a new anti-ulcer drug.
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http://dx.doi.org/10.1016/j.jep.2020.112872DOI Listing
September 2020

Rapid and visual detection of porcine deltacoronavirus by recombinase polymerase amplification combined with a lateral flow dipstick.

BMC Vet Res 2020 May 7;16(1):130. Epub 2020 May 7.

State Key Laboratory of Veterinary Etiological Biology, Key Laboratory of Animal Virology of the Ministry of Agriculture, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, 730046, China.

Background: Porcine Deltacoronavirus (PDCoV) is a newly emerging Coronavirus that was first identified in 2012 in Hong Kong, China. Since then, PDCoV has subsequently been reported worldwide, causing a high number of neonatal piglet deaths and significant economic losses to the swine industry. Therefore, it is necessary to establish a highly sensitive and specific method for the rapid diagnosis of PDCoV.

Results: In the present study, a highly sensitive and specific diagnostic method using recombinase polymerase amplification combined with a lateral flow dipstick (LFD-RPA) was developed for rapid and visual detection of PDCoV. The system can be performed under a broad range of temperature conditions from 10 to 37 °C, and the detection of PDCoV can be completed in 10 min at 37 °C. The sensitivity of this assay was 10 times higher than that of conventional PCR with a lower detection limit of 1 × 10 copies/µl of PDCoV. Meanwhile, the LFD-RPA assay specifically amplified PDCoV, while there was no cross-amplification with other swine-associated viruses, including Porcine epidemic diarrhea virus (PEDV), Transmissible gastroenteritis virus (TGEV), Porcine kobuvirus (PKoV), Foot and mouth disease virus (FMDV), Porcine reproductive and respiratory syndrome virus (PRRSV), Porcine circovirus type 2 (PCV2), Classical swine fever virus (CSFV) and Seneca valley virus (SVV). The repeatability of the test results indicated that this assay had good repeatability. In addition, 68 clinical samples (48 fecal swab specimens and 20 intestinal specimens) were further tested by LFD-RPA and RT-PCR assay. The positive rate of LFD-RPA clinical samples was 26.47% higher than that of conventional PCR (23.53%).

Conclusions: The LFD-RPA assay successfully detected PDCoV in less than 20 min in this study, providing a potentially valuable tool to improve molecular detection for PDCoV and to monitor the outbreak of PDCoV, especially in low-resource areas and laboratories.
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http://dx.doi.org/10.1186/s12917-020-02341-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7203717PMC
May 2020

Huang-Lian-Jie-Du Decoction Ameliorates Acute Ulcerative Colitis in Mice Regulating NF-κB and Nrf2 Signaling Pathways and Enhancing Intestinal Barrier Function.

Front Pharmacol 2019 21;10:1354. Epub 2019 Nov 21.

Institute of Traditional Chinese Veterinary Medicine, College of Veterinary Medicine, Gansu Agricultural University, Lanzhou, China.

Evidence shows that intestinal inflammation, oxidative stress, and injury of mucosal barrier are closely related to the pathogenesis of ulcerative colitis (UC). Huang-lian-Jie-du Decoction (HLJDD) is a well-known prescription of traditional Chinese medicine with anti-inflammatory and antioxidative activities, which may be used to treat UC. However, its therapeutic effect and mechanism are still unclear. In this study, the UC model of BABL/c mice were established by DSS [3.5% (w/v)], and HLJDD was given orally for treatment at the same time. During the experiment, the clinical symptoms of mice were scored by disease activity index (DAI). Besides, the effects of HLJDD on immune function, oxidative stress, colon NF-κB and Nrf2 signaling pathway, and intestinal mucosal barrier function in UC mice were also investigated. The results showed that HLJDD could alleviate body weight loss and DAI score of UC mice, inhibit colonic shortening and relieve colonic pathological damage, and reduce plasma and colon MPO levels. In addition, HLJDD treatment significantly up-regulated plasma IL-10, down-regulated TNF-α and IL-1β levels, and inhibited the expression of NF-κB p65, p-IκKα/β, and p-IκBα proteins in the colon. Moreover, NO and MDA levels in colon tissues were significantly reduced after HLJDD treatment, while GSH, SOD levels and Nrf2, Keap1 protein expression levels were remarkably elevated. Additionally, HLJDD also protected intestinal mucosa by increasing the secretion of mucin and the expression of ZO-1 and occludin in colonic mucosa. These results indicate that HLJDD could effectively alleviate DSS-induced mice UC by suppressing NF-κB signaling pathway, activating Nrf2 signaling pathway, and enhancing intestinal barrier function.
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http://dx.doi.org/10.3389/fphar.2019.01354DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6900672PMC
November 2019

Therapeutic effect of n-butanol fraction of Huang-lian-Jie-du Decoction on ulcerative colitis and its regulation on intestinal flora in colitis mice.

Biomed Pharmacother 2020 Jan 22;121:109638. Epub 2019 Nov 22.

Institute of Traditional Chinese Veterinary Medicine, College of Veterinary Medicine, Gansu Agricultural University, Lanzhou, China. Electronic address:

Huang-lian-Jie-du Decoction (HLJDD) is a classical prescription for clearing away heat and detoxification. In order to screen the effective fraction of HLJDD in the treatment of ulcerative colitis (UC) in mice and explore its effects on intestinal flora in UC mice, we prepared different polar fractions of HLJDD by system solvent extraction method. Subsequently, the contents of 13 active compounds in different polar fractions of HLJDD were determined by HPLC. Further, the UC model induced by dextran sodium sulfate was used to evaluate the therapeutic effects of different polar fractions of HLJDD. Finally, cecal contents were used for sequencing and analysis of bacterial 16S rRNA genes. The results showed that the yield of HLJDD-n-butanol (HLJDD-NBA) fraction was the highest, and the content or proportion of 13 active compounds in HLJDD-NBA fraction were the most similar to HLJDD. In addition, in vivo pharmacodynamic experiments showed that HLJDD-NBA intervention not only significantly alleviated the clinical symptoms of UC mice and ameliorated the pathological damage of colon tissue, but also showed significant anti-inflammatory and antioxidative effects (p < 0.05), which were comparable to HLJDD (p > 0.05). Moreover, both HLDD and HLJDD-NBA treatments can restore the intestinal flora homeostasis of UC mice by inhibiting the growth of intestinal pathogens and preventing the decrease of beneficial bacteria. Meanwhile, they can also significantly correct the dysfunction of intestinal flora in UC mice. In conclusion, we proved that HLJDD-NBA fraction is an effective fraction of HLJDD in treating UC in mice, and it can maintain the intestinal flora homeostasis of UC mice, which increases our understanding of the mechanism of HLJDD in treating UC and lays a foundation for the development of new anti-ulcer drugs.
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http://dx.doi.org/10.1016/j.biopha.2019.109638DOI Listing
January 2020

Effect of ultrasound on binding interaction between emodin and micellar casein and its microencapsulation at various temperatures.

Ultrason Sonochem 2020 Apr 5;62:104861. Epub 2019 Nov 5.

College of Science, Gansu Agricultural University, Lanzhou 730070, China.

Emodin is a bioactive compound with strong anti-inflammatory and antioxidant properties. Micellar casein is casein concentrates close to the native state of casein micelles. The interaction of emodin and micellar casein under heat treatment in the absence and presence of ultrasound was investigated, and the properties of microencapsulated emodin in micellar casein were compared. Fluorescence experiments proved that the major interaction between emodin and micellar casein was through hydrophobic forces under heat treatment in the absence and presence of ultrasound. However, ΔH, ΔS and ΔG of emodin-casein complexation without sonication were higher than those with sonication, in contradiction to binding constants. The particle sizes of emodin-casein complexes in the presence of ultrasound were smaller than those without sonication, while the specific surface area showed an opposite trend. As to encapsulation, emodin-casein capsules under heat-sonication treatment showed higher antioxidant properties than those of heat treatment alone under similar experimental conditions. Interestingly, micellar casein-emodin encapsulation in the presence of ultrasound showed a lower release rate of emodin in gastrointestinal conditions than that without ultrasound at the emdoin concentration of 10 μmol per gram casein. Ultrasound has been shown to be a potential processing technology for customizing the release kinetics of bioactive compounds.
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http://dx.doi.org/10.1016/j.ultsonch.2019.104861DOI Listing
April 2020

Prevalence and Characteristics of Quinolone Resistance in Isolated from Retail Foods in Lanzhou, China.

J Food Prot 2019 Sep;82(9):1591-1597

Institute of Traditional Chinese Veterinary Medicine, College of Veterinary Medicine, Gansu Agricultural University, Lanzhou 730070, People's Republic of China.

The aim of this study was to determinate the prevalence of in retail foods and its resistance to quinolones in retail foods in Lanzhou, People's Republic of China. In this work, 2,182 food samples, collected from March 2015 to December 2018, were analyzed to detect and then analyzed for serotype distribution, quinolone resistance, and quinolone-resistant gene detection. The findings demonstrate that the overall prevalence of in these food categories was low. A total of 41 (1.9%) of 2,182 food samples were found to be positive for . Ten distinct serovars were identified, and Derby, Anatum, and Enteritidis were the most prevalent serovars. According to the broth microdilution test, the resistance percentages were 90.2% to nalidixic acid, 39.0% to enrofloxacin, 41.5% to ciprofloxacin, 29.3% to ofloxacin, and 26.8% to levofloxacin. Among the quinolone-resistant isolates, 12 strains had a single mutation in at codon 83 (Ser→Phe) or codon 87 (Asp→Asn or Asp→Gly). Five isolates had one mutation (Ser80→Arg) and one or two hot spot mutations. genes were found in seven isolates (five and two ), and the gene in seven isolates. Two isolates carry both and genes. Based on these results, a low prevalence of contamination in retail foods was found, but it might play a potential risk factor in the spread of quinolone-resistant strains in the Lanzhou region.
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http://dx.doi.org/10.4315/0362-028X.JFP-19-001DOI Listing
September 2019

Cellular Interleukin Enhancer-Binding Factor 2, ILF2, Inhibits Japanese Encephalitis Virus Replication In Vitro.

Viruses 2019 06 17;11(6). Epub 2019 Jun 17.

State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan 430070, China.

Japanese encephalitis virus (JEV) is a zoonotic mosquito-borne flavivirus which is the leading causative agent of viral encephalitis in endemic regions. JEV NS3 is a component of the viral replicase complex and is a multifunctional protein. In this study, interleukin enhancer-binding factor 2 (ILF2) is identified as a novel cellular protein interacting with NS3 through co-immunoprecipitation assay and LC-MS/MS. The expression of ILF2 is decreased in JEV-infected human embryonic kidney (293T) cells. The knockdown of endogenous ILF2 by special short hairpin RNA (shRNA) positively regulates JEV propagation, whereas the overexpression of ILF2 results in a significantly reduced JEV genome synthesis. Further analysis revealed that the knockdown of ILF2 positively regulates viral replication by JEV replicon system studies. These results suggest that ILF2 may act as a potential antiviral agent against JEV infection.
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http://dx.doi.org/10.3390/v11060559DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6631381PMC
June 2019

Metabolomics study on promoting blood circulation and ameliorating blood stasis: Investigating the mechanism of Angelica sinensis and its processed products.

Biomed Chromatogr 2019 Apr 9;33(4):e4457. Epub 2019 Jan 9.

Institute of Traditional Chinese Veterinary Medicine, College of Veterinary Medicine, Gansu Agricultural University, Lanzhou, 730070, China.

Angelica sinensis (Danggui, DG) parched with alcohol (Jiu Danggui, JDG) and charred DG are the main processed products of DG, which are used to treat blood stasis syndrome (BSS). However, their therapeutic effect and mechanisms are still unclear. Based on an acute rat BSS model, the intervention effects of DG and its processed products (DGPPs) were evaluated by the hemorheology and coagulation function parameters. Meanwhile, plasma and urine metabolites were detected and analyzed by liquid chromatography coupled to quadrupole time-of-flight mass spectrometry and multivariate statistical analysis method. The results of hemorheology, coagulation function parameters and metabolomics all showed that the BSS model was successfully established, DGPPs intervention could significantly relieve rats BSS and the therapeutic effect of JDG was best. Moreover, 23 differential metabolites (14 in plasma and nine in urine) were identified that were closely related to the BSS, involving seven potential target metabolic pathways. DGPP intervention showed different degrees of reverse effect on these metabolites. JDG was the most effective owing to extensive regulation effect on differential metabolites. This study provides a reference for understanding the pathological mechanism of BSS and the mechanism of DGPPs, which lays a theoretical foundation for the rational use of DGPPs in clinical practice.
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http://dx.doi.org/10.1002/bmc.4457DOI Listing
April 2019

Fructose-1,6-bisphosphate aldolase of Mycoplasma bovis is a plasminogen-binding adhesin.

Microb Pathog 2018 Nov 22;124:230-237. Epub 2018 Aug 22.

College of Veterinary Medicine, Gansu Agricultural University, 1 Yingmencun, Lanzhou 730070, China.

Mycoplasma bovis is an extremely small cell wall-deficient pathogenic bacterium in the genus Mycoplasma that causes serious economic losses to the cattle industry worldwide. Fructose-1,6-bisphosphate aldolase (FBA), a key enzyme in the glycolytic pathway, is a multifunctional protein in several pathogenic bacterial species, but its role in M. bovis remains unknown. Herein, the FBA gene of the M. bovis was amplified by PCR, and subcloned into the prokaryotic expression vector pET28a (+) to generate the pET28a-FBA plasmid for recombinant expression in Escherichia coli Transetta. Expression of the 34 kDa recombinant rMbFBA protein was confirmed by electrophoresis, and enzymatic activity assays based on conversion of NADH to NAD+ revealed Km and Vmax values of 48 μM and 43.8 μmoL/L/min, respectively. Rabbit anti-rMbFBA and anti-M. bovis serum were generated by inoculation with rMbFBA and M. bovis, and antigenicity and immunofluorescence assay demonstrated that FBA is an immunogenic protein expressed on the cell membrane in M. bovis cells. Enzyme-linked immunosorbent assays revealed equal distribution of FBA in the cell membrane and cytoplasm. Complement-dependent mycoplasmacidal assays showed that rabbit anti-rMbFBA serum killed 44.1% of M. bovis cells in the presence of complement. Binding and ELISA assays demonstrated that rMbFBA binds native bovine plasminogen and in a dose-dependent manner. Fluorescent microscopy revealed that pre-treatment with antibodies against rMbFBA decreased the adhesion of M. bovis to embryonic bovine lung (EBL) cells. Furthermore, adherence inhibition assays revealed 34.4% inhibition of M. bovis infection of EBL cells following treatment with rabbit anti-rMbFBA serum, suggesting rMbFBA participates in bacterial adhesion to EBL cells.
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http://dx.doi.org/10.1016/j.micpath.2018.08.032DOI Listing
November 2018

Urinary metabolomics study the mechanism of Taohong Siwu Decoction intervention in acute blood stasis model rats based on liquid chromatography coupled to quadrupole time-of-flight mass spectrometry.

J Chromatogr B Analyt Technol Biomed Life Sci 2018 Feb 2;1074-1075:51-60. Epub 2018 Jan 2.

Institute of Traditional Chinese Veterinary Medicine, College of Veterinary Medicine, Gansu Agricultural University, Lanzhou 730070, PR China. Electronic address:

Taohong Siwu Decoction (TSD) is a classic prescription in traditional Chinese medicine and is widely used to promote blood circulation to remove blood stasis. However, the effect mechanisms are not yet well understood. Here, a urinary metabolomic approach based on liquid chromatography coupled to quadrupole time-of-flight mass spectrometry (LC/Q-TOF-MS) was conducted to explore the changes in the endogenous metabolites and to assess the integral efficacy of TSD on acute blood stasis model rats. Then, parameters for hemorheology and coagulation functions were detected. Principal component analysis (PCA) and orthogonal partial least squares discriminate analysis (OPLS-DA) was used to investigate the global metabolite alterations and to evaluate the preventive effects of TSD in rats. Potential metabolite markers were found using OPLS-DA and t-test. Furthermore, metabolic pathway analysis was performed to construct metabolic networks. The results showed that TSD could significantly decrease whole blood viscosity and plasma viscosity. It also significantly prolonged partial thromboplastin time (APPT) and prothrombin time (PT), increased thrombin time (TT) and lowered fibrinogen content (FIB). Moreover, 24 potential metabolite markers of acute blood stasis were screened, and the levels were all reversed to different degrees after TSD administration. In metabolic networks, amino acid metabolism (arginine and proline metabolism; histidine metabolism; alanine, aspartate, and glutamate metabolism; phenylalanine, tyrosine, and tryptophan biosynthesis; phenylalanine metabolism) and lipid metabolism (glycerophospholipid metabolism; linoleic acid metabolism; alpha-linolenic acid metabolism) were closely related with the intervention mechanism of TSD on acute blood stasis. The urinary metabolomic approach can be applied to clarify the mechanism of TSD in promoting blood circulation to remove acute blood stasis and to provide the theoretical basis for further research on the therapeutic mechanism of TSD in clinical practice.
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http://dx.doi.org/10.1016/j.jchromb.2017.12.035DOI Listing
February 2018

A novel approach using metabolomics coupled with hematological and biochemical parameters to explain the enriching-blood effect and mechanism of unprocessed Angelica sinensis and its 4 kinds of processed products.

J Ethnopharmacol 2018 Jan 25;211:101-116. Epub 2017 Sep 25.

Institute of Traditional Chinese Veterinary Medicine, College of Veterinary Medicine, Gansu Agricultural University, Lanzhou 730070, PR China.

Ethnopharmacological Relevance: Angelica sinensis (AS), root of Angelica sinensis (Oliv.) Diels, an important kind of Chinese traditional herbal medicine, has been used for women to enrich the blood for thousands of years. It is mainly distributed in Gansu province of China. According to Traditional Chinese medicine usage, unprocessed AS (UAS) and its 4 kinds of processed products (ASs) are all used to treat different diseases or syndromes. The difference among the enriching-blood effects of ASs is unclear. And their exact mechanisms of enriching the blood are not fully understood.

Aim Of The Study: In this study, our aim is to compare the enriching-blood effect and explain the related mechanism of ASs, to lay the foundation for the blood deficiency diagnosis and the rational use of ASs in the clinic.

Materials And Methods: ASs were used to intervene the blood deficiency syndrome model mice induced by acetyl phenylhydrazine (APH) and cyclophosphamide (CTX). A novel approach using metabolomics coupled with hematological and biochemical parameters to explain the enriching-blood effect and mechanism of ASs was established. The blood routine examination, ATPase, glucose-6-phosphate dehydrogenase, methemoglobin, glutathion peroxidase, glutathione reductase, and erythropoietin were measured. Two biofluids (plasma and urine) obtained from mice were analyzed with GC-MS. Distinct changes in metabolite patterns of the two biofluids after mice were induced by APH and CTX, and mice were intervened with ASs were analyzed using partial least squares-discriminant analysis. Potential biomarkers were found using a novel method including variable importance in the projection (VIP) >1.0, volcano plot analysis, and significance analysis of microarray.

Results: The results of hematological, biochemical parameters and the integrated metabolomics all showed the blood deficiency syndrome model was built successfully, ASs exhibited different degree of enriching-blood effect, and AS pached with alcohol (AAS) exhibited the best enriching-blood effect. 16 metabolites in the plasma and 8 metabolites in the urine were considered as the potential biomarkers. These metabolites were involved in 7 metabolic pathways which were concerned with the different enriching-blood effect mechanisms of ASs. The correlation analysis results confirmed L-Valine (plasma), Linoleic acid (urine), L-Aspartic acid (urine) and Cholesterol (urine) were strong positive or negative associated with biochemical indicators.

Conclusions: The enriching-blood effects of ASs are different. The pathological mechanisms of blood deficiency syndrome and the enriching-blood effect mechanism of ASs are involved in 7 metabolic pathways. L-Valine (plasma), Linoleic acid (urine), L-Aspartic acid (urine), Cholesterol (urine) are four important biomarkers being related to the enriching-blood effect of ASs. The combination of VIP, volcano plot analysis and significance analysis of microarray is suitable for screening biomarkers in metabolomics study. They can lay the foundation for clinical practice.
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http://dx.doi.org/10.1016/j.jep.2017.09.028DOI Listing
January 2018

Treatment effects and mechanisms of Yujin Powder on rat model of large intestine dampness-heat syndrome.

J Ethnopharmacol 2017 Apr 19;202:265-280. Epub 2017 Mar 19.

College of Veterinary Medicine, Gansu Agricultural University, Lanzhou 730070, PR China. Electronic address:

Ethnopharmacological Relevance: Yujin Powder (YJP), an old prescription, is one of the most classical prescription for treating the large intestine dampness-heat syndrome (LIDHS). However, its potential modern pharmacological mechanisms remain unclear.

Aim Of The Study: The present study was designed to explore the essence of LIDHS and treatment mechanisms of the YJP on the LIDHS.

Methods: The rat model of LIDHS was established by such complex factors as high-sugar and high-fat diet, improper diet, high temperature and humidity environment (HTHE), drinking and intraperitoneal injection of Escherichia coli., which imitated the inducing conditions of LIDHS. Then the clinical symptoms and signs, blood routine, blood biochemistry, whole blood viscosity (WBV), serum inflammatory cytokines levels and the histopathological changes of main organs were detected and observed, respectively.

Results: The results showed that the clinical symptoms and signs of the model rats were consistent with the diagnostic criteria of LIDHS, moreover, there were obvious systemic inflammatory response and extensive congestion. And after treatment with YJP in different dosages, the clinical symptoms and signs of the rats with LIDHS were improved; the indexes of blood routine and blood biochemistry and inflammatory cytokines levels tended to be normal; the WBV decreased and histopathological changes of major organs were alleviated or returned to normal. There was an obvious dose-effect relationship, and the high dose of YJP (HD-YJP) had the best treatment effects.

Conclusions: These results suggested that in LIDHS, diarrhea was the major clinical manifestation; the large intestine was the main lesion area; mucosa injury, inflammation and congestion of the large intestine with systemic inflammatory response and congestion were the most typical pathological characteristics. Meanwhile, YJP exhibited the comprehensive effects of anti-diarrhea, anti-inflammation, lowering blood lipid, relieving blood stasis, repairing intestinal mucosa and regulation and protection of multiple organs on LIDHS. These findings provided not only important information for understanding the essence of LIDHS but also the theoretical basis for developing new-drugs for treating dampness-heat type of diarrheal diseases.
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http://dx.doi.org/10.1016/j.jep.2017.03.030DOI Listing
April 2017

Integrated metabonomic-proteomic studies on blood enrichment effects of Angelica sinensis on a blood deficiency mice model.

Pharm Biol 2017 Dec;55(1):853-863

a College of Veterinary Medicine , Gansu Agricultural University , Lanzhou , Gansu Province , People's Republic of China.

Context: Angelica sinensis (Oliv.) Diels (Umbelliferae) (AS) is a well-known Traditional Chinese Medicine (TCM) that enriches and regulates the blood.

Objective: An integrated metabonomic and proteomic method was developed and applied to study the blood enrichment effects and mechanisms of AS on blood deficiency (BD) mouse model.

Materials And Methods: Forty mice were randomly divided into the control, BD, High-dose of AS (ASH), Middle-dose of AS (ASM), and Low-dose of AS (ASL) groups. BD model mice were established by injecting N-acetylphenylhydrazine (APH) and cyclophosphamide (CTX) (ip). The aqueous extract of AS was administered at three dose of 20, 10, or 5 g/kg b. wt. orally for 7 consecutive days before/after APH and CTX administration. Gas chromatography-mass spectrometry (GC-MS) combined with pattern recognition method and 2D gel electrophoresis (2-DE) proteomics were performed in this study to discover the underlying hematopoietic regulation mechanisms of AS on BD mouse model.

Results: Unlike in the control group, the HSP90 and arginase levels increased significantly (p < 0.05) in the BD group, but the levels of carbonic anhydrase, GAPDH, catalase, fibrinogen, GSTP, carboxylesterase and hem binding protein in the BD group decreased significantly (p < 0.05). Unlike the levels in the BD group, the levels of these biomarkers were regulated to a normal state near the control group in the ASM group. Unlike in the control group, l-alanine, arachidonic acid, l-valine, octadecanoic acid, glycine, hexadecanoic acid, l-threonine, butanoic acid, malic acid, l-proline and propanoic acid levels increased significantly (p < 0.05) in the BD group, the levels of d-fructose in the BD group decreased significantly (p < 0.05). The relative concentrations of 12 endogenous metabolites were also significantly affected by the ASL, ASM, and ASH treatments. Notably, most of the altered BD-related metabolites were restored to normal state after ASM administration.

Conclusion: AS can promote hematopoietic activities, inhibit production of reactive oxygen species, regulate energy metabolism, increase antiapoptosis, and potentially contribute to the blood enrichment effects of AS against APH- and CTX-induced BD mice.
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http://dx.doi.org/10.1080/13880209.2017.1281969DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6130503PMC
December 2017

Integrin αvβ3 promotes infection by Japanese encephalitis virus.

Res Vet Sci 2017 Apr 28;111:67-74. Epub 2016 Dec 28.

State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, Hubei 430070, PR China; Laboratory of Animal Virology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei 430070, PR China. Electronic address:

Japanese encephalitis virus (JEV) is a mosquito-borne flavivirus that is one of the major causes of viral encephalitis diseases worldwide. The JEV envelope protein facilitates viral entry, and its domain III contains an Arg-Gly-Asp (RGD) motif, that may modulate JEV entry through the RGD-binding integrin. In this study, the roles of integrin αv and β3 on the infection of JEV were evaluated. Reduced expression of integrin αv/β3 by special shRNA confers 2 to 4-fold inhibition of JEV replication in BHK-21 cells. Meanwhile, antibodies specific for integrin αv/β3 displayed ~58% and ~33% inhibition of JEV infectivity and RGD-specific peptides produced ~36% of inhibition. Expression of E protein and JEV RNA loads were clearly increased in CHO cells transfected with cDNA encoding human integrin β3. Moreover, integrin αv mediates JEV infection in viral binding stage of life cycle. Therefore, our study suggested that integrin αv and β3 serve as a host factor associated with JEV entry into the target cells.
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http://dx.doi.org/10.1016/j.rvsc.2016.12.007DOI Listing
April 2017

Quantitative phosphoproteomic analysis identifies the critical role of JNK1 in neuroinflammation induced by Japanese encephalitis virus.

Sci Signal 2016 10 4;9(448):ra98. Epub 2016 Oct 4.

State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, Hubei 430070, PR China. Laboratory of Animal Virology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei 430070, PR China. The Cooperative Innovation Center for Sustainable Pig Production, Huazhong Agricultural University, Wuhan, Hubei 430070, PR China.

Japanese encephalitis virus (JEV) is the leading cause of epidemic encephalitis worldwide. The pathogenesis of JEV is linked to a robust inflammatory response in the central nervous system (CNS). Glial cells are the resident immune cells in the CNS and represent critical effectors of CNS inflammation. To obtain a global overview of signaling events in glial cells during JEV infection, we conducted phosphoproteomics profiling of a JEV-infected glial cell line. We identified 1816 phosphopeptides, corresponding to 1264 proteins, that exhibited a change in phosphorylation status upon JEV infection. Bioinformatics analysis revealed that these proteins were predominantly related to transcription regulation, signal transduction, the cell cycle, and the cytoskeleton. Kinase substrate motif revealed that substrates for c-Jun N-terminal kinase 1 (JNK1) were the most overrepresented, along with evidence of increased AKT1 and protein kinase A (PKA) signaling. Pharmacological inhibition of JNK, AKT, or PKA reduced the inflammatory response of cultured glial cells infected with JEV, as did knockdown of JNK1 or its target JUN. JEV genomic RNA was sufficient to activate JNK1 signaling in cultured glial cells. Of potential clinical relevance, we showed that inhibition of JNK signaling significantly attenuated the production of inflammatory cytokines in the brain and reduced lethality in JEV-infected mice, thereby suggesting that JNK signaling is a potential therapeutic target for the management of Japanese encephalitis.
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http://dx.doi.org/10.1126/scisignal.aaf5132DOI Listing
October 2016

[Effects of Volatile Oils from Different Preparations of Angelica sinensis Root on Acute Inflammation Induced by LPS in Rats].

Zhong Yao Cai 2016 Aug;39(8):1757-62

Objective: To compare the intervention effects of volatile oils from different preparations of Angelica sinensis root on acute inflammation induced by lipopolysaccharide in rats.

Methods: Acute inflammation model was induced by intraperitoneal injection of lipopolysaccharide( 100 μg/kg) in rats. Blood and serum inflammatory mediators and cytokines were detected, combining with the pathological histological observation of lung and liver to evaluate the anti-inflammatory activities of volatile oils from parching Angelica sinensis root with wine( J-VOAS),volatile oils from charred Angelica sinensis root( C-VOAS) and Angelica sinensis root( S-VOAS).

Results: Compared with control group, the WBC count, the percentage of NE and PLT count in acute inflammation model group significantly increased ( P < 0. 05),and the percentage of LY significantly decreased( P < 0. 05); the content of IL-1β,IL-6,NO and TNF-α significantly increased( P < 0. 001) and content of IL-10 significantly decreased( P < 0. 05) in model group; after J-VOAS,C-VOAS and S-VOAS intervention, the blood routine index and serum inflammatory mediators and cytokines significantly reversed( P < 0. 05). The pathological histological study showed that expanded alveoli, massive inflammatory cells infiltration in alveoli and pulmonary interstitium, the liver leaflets diffuse necrosis, hepatic cord derangement, and some of the liver cells degeneration and edema in model group; after J-VOAS intervention, their pathological changes significantly reduced.

Conclusion: All volatile oils from different preparations of Angelica sinensis root had intervention on acute inflammation induced by LPS. And J-VOAS had the best effect, followed by C-VOAS and S-VOAS.
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August 2016

Semi-bionic extraction of compound turmeric protects against dextran sulfate sodium-induced acute enteritis in rats.

J Ethnopharmacol 2016 Aug 7;190:288-300. Epub 2016 Jun 7.

College of Veterinary Medicine, Gansu Agricultural University, Lanzhou, Gansu 730070, PR China. Electronic address:

Ethnopharmacological Relevance: Compound turmeric has been widely used as a remedy for infectious diseases in China. It is a classic multi-herb prescription in traditional Chinese medicine, commonly used in the treatment of enteritis, pneumonia, and abdominal pain for hundreds of years. However, throughout this history, the powder of multi-herbs was directly swallowed, which is currently difficult to administer to patients. The extract of Chinese herbal medicine is made by semi-bionic extraction technology, which is great progress in the modernization of powders of traditional Chinese medicine. The aim of this work is to investigate the protective effects of semi-bionic extraction of compound turmeric (SET) on acute enteritis (AE) induced by dextran sulfate sodium (DSS) in rats.

Materials And Methods: SET was extracted in artificial gastric juice or artificial intestinal juice and mixed. After vacuum drying, the SET powder was dissolved in distilled water. Adult male Sprague-Dawley rats were randomly divided into six groups. Rats were given salazosulfapyridine (SASP, 175.0mg/kg) or SET (0.42 or 0.21g/kg) before intragastric administration of 5% DSS solutions (0.75g/kg). The treatments lasted 7 days. The food intake in 24h, disease activity index (DAI), and wet/dry (W/D) weight ratios and histological changes in colon tissue were measured. The tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), IL-1β, IL-8, and IL-10 in serum were determined at 1, 4, or 7 d after DSS challenge. Myeloperoxidase (MPO), malonaldehyde (MDA), diamine oxidase (DAO), and glutathione peroxidase (GSH-Px) activities in colon tissue were determined at 7 d. In addition, the nuclear factor-kappa (NF-κ B) and intercellular cell adhesion molecule-1 (ICAM-1) activations in colon tissue were analyzed by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot.

Results: In rats with AE, SET significantly reduced DAI at 7 d after DSS treatment, increased the body weight of rats and the food intake in 24h at 3 or 6 d after DSS challenge, and reduced the colon W/D ratio. SET also reduced the TNF-α, IL-6, IL-1β, and IL-8 in serum and increased IL-10 in serum at 4 and 7 d. In addition, SET decreased MPO, MDA, DAO, and GSH-Px activities in colon and attenuated histological changes in the colon at 7 d after DSS treatment. Further studies demonstrated that SET significantly inhibited NF-κB and ICAM-1 activations in colon tissue.

Conclusions: The current study demonstrated that SET has potent protective effects on DSS-induced AE in rats through its anti-inflammatory and anti-oxidant activities.
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http://dx.doi.org/10.1016/j.jep.2016.05.054DOI Listing
August 2016

[EXPERIMENTAL STUDIES ON EFFECTS OF SALIDROSIDE/COLLAGEN/ POLYCAPROLACTONE NERVE GUIDE CONDUITS FOR REPAIRING SCIATIC NERVE DEFECT IN RATS].

Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi 2016 May;30(5):634-640

College of Life Sciences and Technology, Gansu Agricultural University, Lanzhou Gansu, 730070, P. R. China.

Objective: To fabricate salidroside/collagen/polycaprolactone (PCL) nerve conduit composite and to investigate the effect of composite nerve conduits for repairing sciatic nerve defect.

Methods: The salidroside microspheres were prepared by W/O/W method, and the sustained release rate of microspheres was detected. The microspheres containing 10, 20, and 40 μg salidroside were mixed with collagen to prepare the nerve conduit core layer by freeze-drying method. The shell layer of collagen/PCL scaffold material was fabricated by electrospinning technology. The genipin cross-linked salidroside/collagen/PCL nerve conduit composite was prepared. The structure of nerve conduit was observed before and after cross-linked by scanning electron microscope. Thirty-eight Wistar rats were used to make the right sciatic nerve defect model of 15 mm in length, and randomly divided into groups A, B, C, D (=9), and group E (=2), then defect was repaired with the collagen/PCL conduit in group A, autologous nerve in group E, the 10, 20, and 40 μg/mL salidroside/collagen/PCL conduit in groups B, C, and D, respectively. The survival of rats was observed. The sciatic functional index (SFI) was evaluated at 1, 3, and 6 months after operation. At 6 months, the tissue of defect area was harvested for the general, electrophysiology, histological, and immunohistochemical[S-100 and peripheral myelin protein 0(P0)] staining observations.

Results: Salidroside microspheres showed burst release at 3 days, and then it tended to be stable at 13 days and lasted for 16 days, with a cumulative release rate of 76.59%. SEM showed that the disordered fiber of nerve conduit shell layer after crosslinking became conglutination, shrinkage, and density, and had void. The channels of core layer were clearly visible before and after crosslinking. The rats had no infection or death after operation. The SFI of group E was significantly higher than that of groups A, B, C, and D at 1, 3, and 6 months (<0.05); it was significantly higher in groups B, C, and D than group A (<0.05), but no significant difference was found among groups B, C, and D at 1 month (>0.05); there was no significant difference in SFI among groups A, B, C, and D at 3 months (>0.05); SFI was significantly higher in group C than groups A, B, and D and in groups A and B than group D (<0.05), but no significant difference between groups A and B (>0.05) at 6 months. In addition, no significant difference was shown among different time points in the other groups (>0.05) except groups C and E at 1, 3, and 6 months (<0.05). The general observation showed that good connection with the thick nerve in groups B and C, and connection with the fine nerves in groups A and D. The conduit materials obviously degraded. Nerve electrophysiological examination showed that the latency/conduction velocity of groups C and E were significantly lower than those of groups A, B, and D (<0.05), but difference was not significant between groups C and E, and among groups A, B, and D (>0.05). The histological observation showed that the nerve fiber tissue of groups B, C, and E was obviously more than that of groups A and D, and group C was similar to group E in the nerve fiber arrangement, and the core layer material of each group was completely degraded. Immunohistochemical staining showed that S-100 and P0 proteins expressed in all groups; and the expression level of groups B, C, and E was significantly higher than that of groups A and D, and gradually increased (<0.05); difference in S-100 expression level was not significant between groups A and D (>0.05), and P0 expression level of group A was significantly lower than that of group D (<0.05).

Conclusions: Salidroside/collagen/PCL nerve conduit can promote sciatic nerve defect repair.
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http://dx.doi.org/10.7507/1002-1892.20160127DOI Listing
May 2016

Effects of volatile oils of Angelica sinensis on an acute inflammation rat model.

Pharm Biol 2016 Sep 6;54(9):1881-90. Epub 2016 Feb 6.

a College of Veterinary Medicine, Gansu Agricultural University , Lanzhou , Gansu Province , People's Republic of China.

Context Despite several pharmacological studies of volatile oils of Angelica sinensis (Oliv.) Diels (Umbelliferae) (VOAS), its anti-inflammatory mechanism remains unknown. Objective The study investigates the effects of VOAS on the lipopolysaccharide (LPS)-induced acute inflammation rat model and analyzes its possible anti-inflammatory mechanisms. Materials and methods Fourty rats were randomly divided into the control, model, VOAS and dexamethasone (Dex) groups. The VOAS and Dex groups were given VOAS (0.176 mL/kg) and Dex (40 μg/kg), respectively. Rats in all groups except the control group were intraperitoneally injected with LPS (100 μg/kg), their exterior behaviour and liver pathological changes were observed, and the level of white blood cell (WBC), the number of neutrophils (NE)%, glutamic oxalacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), alkaline phosphatase (ALP), tumour necrosis factor (TNF-α), interleukin (IL)-1β, IL-6, IL-10, histamine (HIS), 5-hydroxytryptamine (5-HT), nitric oxide (NO), prostaglandin E2 (PGE2), inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX-2) were detected. Results Compared with the model group, VOAS and Dex significantly accelerated the recovery of the exterior behaviour, the liver pathological changes of rats, and increased the level of IL-10, but decreased the level of WBC, NE%, GOT, GPT, ALP, TNF-α, IL-1β, IL-6, HIS, 5-HT, NO, PGE2, iNOS and COX-2 (p < 0.05). Conclusion VOAS exhibits anti-inflammatory and liver protection effects by inhibiting the secretion of the pro-inflammatory cytokines (TNF-α, IL-1β and IL-6), the inflammatory mediators (HIS, 5-HT, PGE2 and NO), the inflammation-related enzymes (iNOS and COX-2), as well as promoting the production of the anti-inflammatory cytokines IL-10.
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http://dx.doi.org/10.3109/13880209.2015.1133660DOI Listing
September 2016

The investigation of anti-inflammatory activity of volatile oil of Angelica sinensis by plasma metabolomics approach.

Int Immunopharmacol 2015 Dec 11;29(2):269-277. Epub 2015 Nov 11.

Institute of Traditional Chinese Veterinary Medicine, College of Veterinary Medicine, Gansu Agricultural University, Lanzhou 730070, PR China. Electronic address:

Angelica sinensis (AS) is an important medicinal plant, and volatile oil is the main pharmacologically active ingredient. This study was aimed to investigate the anti-inflammatory activity of the volatile oil of A. sinensis (VOAS) and explore its potential anti-inflammatory mechanism by plasma metabolomics approach. Rat acute inflammation was induced by subcutaneous injection of carrageenan in hind paws. Paw edema, histamine (HIS) and 5-hydroxytryptamine (5-HT) were detected. Then, we analyzed plasma metabolic profiling of acute inflammation and performed pathway analysis on the metabolite markers reversed after VOAS administration and further integration of metabolic networks. The results showed that VOAS could alleviate the paw edema and decrease plasma HIS and 5-HT levels. Fourteen metabolite markers of acute inflammation were screened, and the levels were all reversed to different degrees after VOAS administration. These metabolite markers mainly related to linoleic acid metabolism, ascorbate and aldarate metabolism, arachidonic acid metabolism, glyoxylate and dicarboxylate metabolism, and glycine, serine and threonine metabolism. In metabolic networks, glycine and arachidonic acid were node molecules. It indicated that VOAS could significantly inhibit systemic inflammatory response triggered by acute local stimulation and it exerted anti-inflammatory activity mainly through regulating the disturbed metabolic networks centered on glycine and arachidonic acid.
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http://dx.doi.org/10.1016/j.intimp.2015.11.006DOI Listing
December 2015

Quantitative Label-Free Phosphoproteomics Reveals Differentially Regulated Protein Phosphorylation Involved in West Nile Virus-Induced Host Inflammatory Response.

J Proteome Res 2015 Dec 4;14(12):5157-68. Epub 2015 Nov 4.

Department of Pathology, University of Georgia , Athens, Georgia 30602, United States.

West Nile virus (WNV) can cause neuro-invasive and febrile illness that may be fatal to humans. The production of inflammatory cytokines is key to mediating WNV-induced immunopathology in the central nervous system. Elucidating the host factors utilized by WNV for productive infection would provide valuable insights into the evasion strategies used by this virus. Although attempts have been made to determine these host factors, proteomic data depicting WNV-host protein interactions are limited. We applied liquid chromatography-tandem mass spectrometry for label-free, quantitative phosphoproteomics to systematically investigate the global phosphorylation events induced by WNV infection. Quantifiable changes to 1,657 phosphoproteins were found; of these, 626 were significantly upregulated and 227 were downregulated at 12 h postinfection. The phosphoproteomic data were subjected to gene ontology enrichment analysis, which returned the inflammation-related spliceosome, ErbB, mitogen-activated protein kinase, nuclear factor kappa B, and mechanistic target of rapamycin signaling pathways. We used short interfering RNAs to decrease the levels of glycogen synthase kinase-3 beta, bifunctional polynucleotide phosphatase/kinase, and retinoblastoma 1 and found that the activity of nuclear factor kappa B (p65) is significantly decreased in WNV-infected U251 cells, which in turn led to markedly reduced inflammatory cytokine production. Our results provide a better understanding of the host response to WNV infection and highlight multiple targets for the development of antiviral and anti-inflammatory therapies.
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http://dx.doi.org/10.1021/acs.jproteome.5b00424DOI Listing
December 2015

Metabolomics study of hematopoietic function of Angelica sinensis on blood deficiency mice model.

J Ethnopharmacol 2015 May 20;166:261-9. Epub 2015 Mar 20.

College of Veterinary Medicine, Gansu Agricultural University, Lanzhou, Gansu Province 730070, China. Electronic address:

Ethnopharmacological Relevance: Angelica sinensis (AS) has been used in traditional Chinese medicine for thousands of years to enrich and invigorate blood. In this study, the aim is to investigate the influence of AS on metabolism of blood deficiency mice model and to explore its anti-blood deficiency mechanism.

Materials And Methods: The blood deficiency mice model was induced by being hypodermically injected with N-acetyl phenylhydrazine (APH) and being intraperitoneally injected with cyclophosphamide (CTX). Gas chromatography-mass spectrometry (GC-MS), principle component analysis (PCA) and partial least squares-discriminant analysis (PLS-DA) were used to identify potential biomarkers in plasma and splenic tissue.

Results: The levels of white blood cell (WBC), red blood cell (RBC), hemoglobin (HGB) and platelet (PLT) showed a trend to return to control group after administrating with AS, while the dose of 10g/kg showed the best effect. Potential metabolite biomarkers (nine in the plasma and nine in the spleen homogenates) were identified in this study. These biomarkers were mainly related to five metabolic pathways, such as arachidonic acid metabolism, valine, leucine and isoleucine biosynthesis, glycine, serine and threonine metabolism, arginine and proline metabolism and TCA cycle.

Conclusion: Metabolomics was used to reflect an organism׳s physiological and metabolic state comprehensively, indicating that metabolomics was a potentially powerful tool to reveal the anti-blood deficiency mechanism of AS.
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http://dx.doi.org/10.1016/j.jep.2015.03.010DOI Listing
May 2015

Metabolomics research on the hepatoprotective effect of Angelica sinensis polysaccharides through gas chromatography-mass spectrometry.

J Chromatogr B Analyt Technol Biomed Life Sci 2014 12 18;973C:45-54. Epub 2014 Oct 18.

Institute of Traditional Chinese Veterinary Medicine, College of Veterinary Medicine, Gansu Agricultural University, Lanzhou 730070, PR China.

Angelica sinensis polysaccharides (ASP) have an established hepatoprotective effect, but the mechanism for this effect remains unclear. A novel approach using biochemical parameters coupled with metabolomics based on gas chromatography-mass spectrometry (GC-MS) and chemometrics was established in this study to explain the hepatoprotective effect mechanism of ASP. The superoxide dismutase activity, malonaldehyde content, alanine aminotransferase, aspartate aminotransferase, and γ-glutamyl transpeptidase in plasma were measured. Pathological changes in the liver were observed. Plasma and liver homogenate obtained from mice were analyzed using GC-MS. Distinct changes in metabolite patterns in the plasma and liver homogenate after being induced by carbon tetrachloride and drug intervention were observed using principal component analysis (PCA) and partial least squares-discriminate analysis (PLS-DA). Potential biomarkers were found using PLS-DA and T-test. The results of the pathological changes observed in the liver, the biochemical parameters in plasma, and the metabolomics of the plasma and liver homogenate all showed that liver injury was successfully reproduced, ASP exhibited hepatoprotective effect, and the medium dose of ASP exhibited the best. Nine endogenous metabolites in the liver homogenate and ten endogenous metabolites in the plasma were all considered as potential biomarkers. They were considered to be in response to hepatoprotective effects of ASP involved in the amino acids metabolism, energy metabolism, and lipids metabolism. Therefore metabolomics is a valuable tool in measuring the efficacy and mechanisms of action of traditional Chinese medicines.
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http://dx.doi.org/10.1016/j.jchromb.2014.10.009DOI Listing
December 2014
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