Publications by authors named "Hongyue Ma"

28 Publications

  • Page 1 of 1

Pulmonary Edema in COVID-19 Patients: Mechanisms and Treatment Potential.

Front Pharmacol 2021 7;12:664349. Epub 2021 Jun 7.

Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, and Jiangsu Key Laboratory for High Technology Research of TCM Formulae, College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China.

COVID-19 mortality is primarily driven by abnormal alveolar fluid metabolism of the lung, leading to fluid accumulation in the alveolar airspace. This condition is generally referred to as pulmonary edema and is a direct consequence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. There are multiple potential mechanisms leading to pulmonary edema in severe Coronavirus Disease (COVID-19) patients and understanding of those mechanisms may enable proper management of this condition. Here, we provide a perspective on abnormal lung humoral metabolism of pulmonary edema in COVID-19 patients, review the mechanisms by which pulmonary edema may be induced in COVID-19 patients, and propose putative drug targets that may be of use in treating COVID-19. Among the currently pursued therapeutic strategies against COVID-19, little attention has been paid to abnormal lung humoral metabolism. Perplexingly, successful balance of lung humoral metabolism may lead to the reduction of the number of COVID-19 death limiting the possibility of healthcare services with insufficient capacity to provide ventilator-assisted respiration.
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http://dx.doi.org/10.3389/fphar.2021.664349DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8215379PMC
June 2021

Ultrafiltration strategy combined with nanoLC-MS/MS based proteomics for monitoring potential residual proteins in TCMIs.

J Chromatogr B Analyt Technol Biomed Life Sci 2021 May 30;1178:122818. Epub 2021 May 30.

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

Traditional Chinese medicine injections (TCMIs) containing complex constituents frequently cause unpredictable adverse reactions. The residual heterologous proteins in TCMIs may be one kind of the sensitized constituents. However, few methods were developed to identify and monitor the residual proteins of TCMIs in industry. Here, we described a method combining the advantages of ultrafiltration and mass spectrometry-based proteomics for monitoring the potential residual proteins in Re Du Ning injection (RDNI) intermediates and preparations. We identified and quantified both de novo peptides and the proteins matched against databases of three raw plants by using PEAKS software. Interesting, we found there was a significant decrease of peptides and proteins in No. 3-5 of RDNI intermediates and some even disappeared. Besides, we found this method could greatly reduce the interference of contaminants in proteomics experiments. The rapid and accurate method proposed in this paper could be used for monitoring potential residual proteins in TCMIs to guarantee their quality and safety.
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http://dx.doi.org/10.1016/j.jchromb.2021.122818DOI Listing
May 2021

Anti-inflammatory and analgesic actions of bufotenine through inhibiting lipid metabolism pathway.

Biomed Pharmacother 2021 Aug 28;140:111749. Epub 2021 May 28.

Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, and Jiangsu Key Laboratory for High Technology Research of TCM Formulae, College of Pharmacy, Nanjing University of Chinese Medicine, 138 Xianlin Road, Nanjing 210023, China.

Inflammation is a primary defense and immune response. However, under pathological conditions, the inflammation processes always become uncontrolled and lead to chronic diseases. Bufotenine, as a natural component from toad venom, showed great potential for development as a novel anti-inflammation and analgesia agent. This study aimed to investigate the therapeutic effects of bufotenine against inflammation and pain on animal models with a focus on lipid metabolism. In pharmacological studies, bufotenine significantly inhibited the swelling rates on formalin-induced paw edema model, and increased paw withdrawal mechanical thresholds (PWMTs) in von Frey test and thermal pain thresholds (TPTs) in hot-plate test. High-sensitivity lipidomics analysis revealed the effects might be related to the down-regulation of inflammatory mediators from cyclooxygenase (COX), lipoxygenase (LOX), cytochrome P450 (CYP450), linoleic acid (LA), docosahexaenoic acid (DHA) and other pathways. The activities might result from the binding of bufotenine and its receptors, including sigma-1 receptor and 5-Hydroxytryptamine receptor 3A, thus regulating lipid metabolism pathway. The research provided a systemic evidence for the actions and mechanism of bufotenine. It suggested that the natural compound might be a potential candidate for reducing inflammatory pain disorders.
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http://dx.doi.org/10.1016/j.biopha.2021.111749DOI Listing
August 2021

SHP2-mediated mitophagy boosted by lovastatin in neuronal cells alleviates parkinsonism in mice.

Signal Transduct Target Ther 2021 Jan 29;6(1):34. Epub 2021 Jan 29.

State Key Laboratory of Pharmaceutical Biotechnology, Department of Biotechnology and Pharmaceutical Sciences, School of Life Sciences, Nanjing University, Nanjing, China.

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http://dx.doi.org/10.1038/s41392-021-00474-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7846847PMC
January 2021

Evaluation of analgesic and anti-inflammatory actions of indolealkylamines from toad venom in mice using lipidomics and molecular docking.

J Ethnopharmacol 2021 Apr 13;269:113677. Epub 2020 Dec 13.

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

Ethnopharmacological Relevance: Toad venom is one of widely used traditional Chinese medicines due to its analgesic and anti-inflammatory activities. However, hydrophilic alkaloids from toad venom, which may have certain pharmacological activities, have not been systematic studied.

Aim Of The Study: The aim of the study was to identify the indolealkylamines (IAAs) from toad venom and investigate the analgesic and anti-inflammatory actions.

Materials And Methods: The alkaloids were extracted and identified by high-resolution mass spectrometry. The analgesic abilities were determined using hot-plate test, formalin test and von Frey test. High-sensitivity lipidomics was used to investigate the regulatory function of IAAs on inflammatory eicosanoids. Besides, network pharmacology and molecular docking were used to demonstrate the candidate targets of IAAs.

Results: 22 constituents have been characterized by high performance liquid chromatography (HPLC)-Triple TOF 5600, including six specific IAAs (serotonin, N-methyl serotonin, bufotenine, bufotenidine, bufothionine and dehydrobufotenine). Pharmacological studies showed that the IAAs from toad venom exerted significant analgesic activities at doses of 5, 15 and 45 mg/kg in vivo. Moreover, lipids analysis revealed IAAs might down-regulate inflammatory mediators from COX, LOX, DHA and LA pathways in formalin models, thus showing anti-inflammatory effect. The potent pharmacological function might because of the binding of IAAs and protein targets, such as sigma-1 receptor.

Conclusion: The studies provided a systemic evidence for the analgesic and anti-inflammatory activities of IAAs from toad venom. It suggested that IAAs might be a potential candidate to reduce inflammatory pain disorders.
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http://dx.doi.org/10.1016/j.jep.2020.113677DOI Listing
April 2021

Chip-based serum proteomics approach to reveal the potential protein markers in the sub-acute stroke patients receiving the treatment of Ginkgo Diterpene Lactone Meglumine Injection.

J Ethnopharmacol 2020 Oct 13;260:112964. Epub 2020 May 13.

State Key Laboratory of New-tech for Chinese Medicine Pharmaceutical Process, Lianyungang, 222000, China.

Ethnopharmacological Relevance: Ginkgo biloba L. is a kind of traditional Chinese medicinal material with a long history. Its main active ingredients, ginkgolides, can be used for the treatment of stroke and other cardio-cerebrovascular diseases. Ginkgo Diterpene Lactone Meglumine Injection (GDLI), a modernized TCM, has attracted much attention because of its neuroprotective and anti-inflammatory properties.

Aim Of The Study: To uncover the effects of GDLI on ischemic stroke patients, as well as the underlying biomarkers involved in sub-acute stroke.

Materials And Methods: We used a state-of-the-art targeted proteomics chip to investigate the association between numerous serum proteins (1101 proteins) and the sub-acute phase post-ischemic stroke. Then, the relative proteins of anti-apoptosis, anticoagulant, and neuroprotection of GDLI were verified in animal models.

Results: Compared with the serum from healthy volunteers, we identified 15 up-regulated proteins and 26 down-regulated proteins (FC ≥ 1.5) involved in inflammatory response, immune response, and nervous system development in the sub-acute ischemic stroke. The pro-inflammatory proteins, such as IL17, MSP-R, G-CSF-R, TLR3, MIP-3β, TNFRSF19, and TNFRSF12, were significantly increased in serum, illustrating that the chronic inflammatory state was evident in the sub-acute stage of ischemic stroke. However, the common pro-inflammatory proteins, such as IL-1β, IL-6, IL-8, TNF-α, IFN-γ, and IL-10, known to be up-regulated in acute stroke, had close or lightly lower levels than healthy humans (FC ≥ 1.5, P > 0.05). And some cytokines (IL3, CCL13, TNFRSF3, IL10 R beta, HLA-A, IL-1 F8/FIL1 eta, TNFRSF8, CCL18) were also markedly down-regulated in the sub-acute phase of stroke. These proteins are highly associated with the onset of stroke-induced immunosuppression and post-stroke infection. Moreover, we noticed that Ginkgo Diterpene Lactone Meglumine Injection (GDLI) treatment for 14 days was helpful to the recovery of patients in the subacute period. After the treatment of GDLI, it was observed that several inflammatory cytokines (i.e. IL-17 and IL-28A), chemokine (i.e. CCL14), and Coagulation Factor III were reduced. Meanwhile, the anti-inflammatory cytokines (IL-10 R alpha, GREMLIN, and Activin C) and neurotrophic factors (Neurturin and IGFBP2) were found to be up-regulated in stroke patients through self-control observation. Finally, we identified the IGFBP2 as a novel marker in the animal models.

Conclusions: In summary, the potential markers in sub-acute stroke patients were highly different from known protein markers in the acute phase of ischemic stroke. The serum protein IGFBP2 could be novel biomarkers for the treatment of GDLI in sub-acute stroke patients. Our present findings provide an innovative insight into the novel treatment of GDLI in ischemic stroke therapy.
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http://dx.doi.org/10.1016/j.jep.2020.112964DOI Listing
October 2020

Target lipidomics approach to reveal the resolution of inflammation induced by Chinese medicine combination in Liu-Shen-Wan against realgar overexposure to rats.

J Ethnopharmacol 2020 Mar 20;249:112171. Epub 2019 Aug 20.

Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Jiangsu Key Laboratory for High Technology Research of TCM Formulae, Jiangsu Key Laboratory of Efficacy and Safety Evaluation of TCM, Nanjing University of Chinese Medicine, Nanjing, China.

Ethnopharmacological Relevance: Liu-Shen-Wan (LSW) is one of the popular over-the-counter drugs in Asia, which contains realgar (AsS), used for the treatment of upper respiratory tract inflammation and skin infections. However, the safety and potential risk of this arsenic remain unknown.

Aim Of The Study: The aim of this study was to determine total arsenic in tissue and investigate effects of regular dose and overdose LSW exposure on rat liver.

Materials And Methods: We used a target lipidomics approach to quantify inflammatory eicosanoids and employed ICP-MS to determine total arsenic in tissue.

Results: The results showed that oral administration of 8 and 40 mg/kg LSW (1 and 5 fold human-equivalent dose) induced light changes of liver lipidomic profile in rats, which was associated with anti-inflammatory function of LSW. In our recent report, we observed that 41 and 134 mg/kg realgar (40 and 132 fold human-equivalent dose) stimulated rat liver inflammation through up-regulation of pro-inflammatory LOX-derived, CYP-derived HETEs and COX-derived PGs. However, we found that LSW in the form of drug combination, containing 41 and 134 mg/kg realger, could not stimulate these similar inflammatory responses in rats, although the liver total arsenic levels of the realger and LSW groups were same.

Conclusion: The downregulation of pro-inflammatory response showed that the LSW containing realger is safer than realger alone administrated to rats. These results suggested that Chinese medicines combination could reduce realgar-derived arsenic toxicity in rats.
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http://dx.doi.org/10.1016/j.jep.2019.112171DOI Listing
March 2020

High Resolution Mass Profile of Bufadienolides and Peptides Combing with Anti-Tumor Cell Screening and Multivariate Analysis for the Quality Evaluation of Bufonis Venenum.

Molecules 2019 May 20;24(10). Epub 2019 May 20.

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

In order to evaluate the quality of Bufonis Venenum commercial herbs, a three-step qualitative and quantitative research study was performed. Firstly, we tried to identify small molecules and peptides in Bufonis Venenum using pre-fractionation chromatography and high-resolution mass spectrometry. The database search of the small molecules and peptides of Bufonis Venenum revealed that the dried venom consisted of free/conjugated-type bufadienolides and peptides with a mass range of 0.4-2 kDa. Secondly, we used partial least squares (PLS) multivariate statistical analysis to screen bufadienolides markers (VIP > 1.5) responsible for the anti-tumor cell activity of Bufonis Venenum, including 21 identified bufadienolides and 7 unknown compounds. It is noticeable that these bufadienolide markers could not be recognized by traditional HPLC-UV based spectrum-effect relationship analysis (correlation coefficient ranging from -0.24 to 0.40). Finally, we proposed a weight coefficient-based corrected total contents of 9 bufadienolides as a quality evaluation indicator, which had good correlation with inhibitory effects on tumor cells of commercial Bufonis Venenum. The correlation coefficient increased from 0.4 to 0.6. Thus, our pre-fractionation chromatography and mass spectrometry strategy had significant advancement over the traditional spectrum-effect relationship method for chemical marker identification. These results could be crucial and helpful in the development of a quality evaluation method that could reflect the pharmacological activity of Bufonis Venenum.
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http://dx.doi.org/10.3390/molecules24101943DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6572007PMC
May 2019

Lipidomic profiling of subchronic AsS exposure identifies inflammatory mediators as sensitive biomarkers in rats.

Metallomics 2019 03;11(3):576-585

Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, and Jiangsu Key Laboratory for High Technology Research of TCM Formulae, College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China.

Arsenic sulfide compounds provide nearly all of the world's supply of arsenic. However, the risk of arsenic trisulfide exposure is still not fully investigated. Here, we systemically assessed the toxicology of As4S4 in rats by combining arsenic metabolite detection, routine testing and lipidomic profiling. It was revealed that the oral administration of As4S4 for two months increased the total arsenic content in the liver reaching a saturation level. Further analysis by anion exchange chromatography coupled with inductively coupled plasma mass spectrometry (ICP-MS) technology showed no trace of inorganic arsenic, but there was significant presence of dimethylarsinic acid (DMA), in the livers of rats. This arsenic metabolite was less toxic to rats and did not induce overt liver pathology and functional injury. In contrast, lipidomic profiling provided a comprehensive map of lipids and uncovered a more complex inflammatory response, exhibiting more sensitive change to arsenic exposure. We observed that metabolites of cyclooxygenase, including PGF2α, dhk PGF2α, 15k PGF2α, 8-iso-PGF2a, PGE2, dhk PGE2, PGD2, 15d-PGD2, and PGJ2, were significantly elevated. But mediators from lipoxygenase, cytochrome P450, docosahexaenoic acid, and eicosapentaenoic acid pathways were not markedly affected. In summary, we identified DMA as the predominant arsenic species in the livers of rats, and found cyclooxygenase-derived lipids as the inflammatory mediators before the development of overt liver injury for subchronic As4S4 exposure. These mediators could translate into potential metabolic biomarkers in early arsenic risk assessment and as targets for therapeutic intervention.
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http://dx.doi.org/10.1039/c8mt00181bDOI Listing
March 2019

A strategy for the metabolomics-based screening of active constituents and quality consistency control for natural medicinal substance toad venom.

Anal Chim Acta 2018 Nov 22;1031:108-118. Epub 2018 May 22.

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

Natural medicinal substances (NMS) have great inconsistency due to chemical variability, seriously limiting their development as therapeutics. Here, we chose toad venom with anti-tumor activities as a model and developed a pipeline of metabolomics-based screening and quality consistency control (MSQCC) as one potential solution to this long-standing problem. Our study firstly exemplified the power of the co-correlation screen of metabolomic and biological profiles of 180 fractions prepared from natural heterogeneous venom samples, to identify a series of bufadinolides as quality control markers for cancer cell inhibition. The next quantitative monitoring of these markers revealed great batch-to-batch variation of toad venoms. Finally, we developed a marker-based blending program (Markers-NMBT) to normalize heterogeneity of NMS. It created the blends for the conversion of the unqualified venoms with high variation in the contents of bufadienolides, into qualified products consistent with the reference. Thus, this work provides a strategy for rapid, large-scale discovery, quantification and application of quality control markers to ensure batch-to-batch consistency, and can be a crucial technology in the development of modern NMS preparations.
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http://dx.doi.org/10.1016/j.aca.2018.05.054DOI Listing
November 2018

Identification of <10 KD peptides in the water extraction of Venenum Bufonis from Bufo gargarizans using Nano LC-MS/MS and De novo sequencing.

J Pharm Biomed Anal 2018 Aug 19;157:156-164. Epub 2018 May 19.

Natural Drug Discovery Group, School of Pharmacy, Queen's University, Belfast BT9 7BL, Northern Ireland, UK.

Skins of anurans (frogs and toads) are rich sources of bioactive peptides. However, the peptides secreted by the skin glands of Bufo gargarizans, the most common toad in China, remained unexplored to date. Here, a strategy combines LC-MS/MS, RNA sequencing and bioinformation analysis was applied to unravel the peptides in the Bufo gargarizans secretions. Data-dependent LC-MS/MS acquisitions of intact peptides followed by automated chromatographic alignment, De novo analysis, database and homology searches with manual validations showed that the venom is composed by 939 features, with masses ranging from 0.7-4 kDa. These peptides derived from 85 proteins were identified using the PEAKS software with acquired MS and MS/MS spectra of Venenum Bufonis against the house-built protein database using De novo RNA sequencing, while only 23 peptides from 8 proteins were found when searching known amphibian database. Moreover, it was found that many peptides with high abundance in Venenum Bufonis derived from proteolytic processing of a larger precursor protein, named as CL4590. Molecular cloning was applied to validate a short domain of CL4590 to evident the accuracy of these obtained sequences. Although the bioactivities of peptides identified by MS/MS are unknown, the next function annotation showed that they may involve in the cell killing, immune and metabolic process, antioxidant activity and antimicrobial actions. Therefore, the peptidomics analysis on Bufo gargarizans discover abundant novel toad peptides which broaden our horizons on the secretion multiplicity and supplied an assortment of pharmacological candidates.
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http://dx.doi.org/10.1016/j.jpba.2018.05.027DOI Listing
August 2018

Metabolomics method based on ultra high performance liquid chromatography with time-of-flight mass spectrometry to analyze toxins in fresh and dried toad venom.

J Sep Sci 2016 Dec 25;39(24):4681-4687. Epub 2016 Nov 25.

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

Drying is a critical step to prolong the storage time in natural medicine processing but it changes the chemical characteristics of the product. In this study, research was performed to characterize the metabolomic changes in toad venom induced by vacuum-drying at 60°C and air-drying at room temperature by ultra high performance liquid chromatography coupled with pattern recognition approaches. In total 52 metabolites, down-regulated or up-regulated, were identified as potential chemical markers. Compared with fresh toad venom, vacuum-drying at 60°C succeeded in raising the conjugated-type bufadienolide content significantly, while the content of free-type bufadienolides were slightly reduced. On the other hand, toad venom air-dried at room temperature presented a relatively low amount of bufadienolides compared with fresh venom. For example, the content of several known anti-tumor components (gamabufotalin, bufotalin, cinobufagin, etc.) were significantly reduced. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide bioassay further showed that venom air-dried at room temperature had weaker anti-tumor activity on human hepatocellular carcinoma SMMC-7721 proliferation in vitro than samples vacuum-dried at 60°C. These results showed that the great metabolomic changes of toad venom occurred during the drying process, suggesting that a proper drying procedure is important for sustaining the chemical quality of natural medicines.
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http://dx.doi.org/10.1002/jssc.201600827DOI Listing
December 2016

An in vitro metabolomics approach to identify hepatotoxicity biomarkers in human L02 liver cells treated with pekinenal, a natural compound.

Anal Bioanal Chem 2016 Feb 29;408(5):1413-24. Epub 2015 Dec 29.

Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Pharmacy College, Nanjing University of Chinese Medicine, 138 Xianlin Road, Nanjing, 210023, China.

An in vitro cell metabolomics study was performed on human L02 liver cells to investigate the toxic biomarkers of pekinenal from the herb Euphorbia pekinensis Rupr. Pekinenal significantly induced L02 cell damage, which was characterised by necrosis and apoptosis. Metabolomics combined with data pattern recognition showed that pekinenal significantly altered the profiles of more than 1299 endogenous metabolites with variable importance in the projection (VIP) > 1. Further, screening correlation coefficients between the intensities of all metabolites and the extent of L02 cell damage (MTT) identified 12 biomarker hits: ten were downregulated and two were upregulated. Among these hits, LysoPC(18:1(9Z)/(11Z)), PC(22:0/15:0) and PC(20:1(11Z)/14:1(9Z)) were disordered, implying the initiation of inflammation and cell damage. Several fatty acids (FAs) (3-hydroxytetradecanedioic acid, pivaloylcarnitine and eicosapentaenoyl ethanolamide) decreased due to fatty acid oxidation. Dihydroceramide and Cer(d18:0/14:0) were also altered and are associated with apoptosis. Additional examination of the levels of intracellular reactive oxygen species (ROS) and two eicosanoids (PGE2, PGF2α) in the cell supernatant confirmed the fatty acid oxidation and arachidonic acid metabolism pathways, respectively. In summary, cell metabolomics is a highly efficient approach for identifying toxic biomarkers and helping understand toxicity mechanisms and predict herb-induced liver injury.
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http://dx.doi.org/10.1007/s00216-015-9202-4DOI Listing
February 2016

Phosphoproteomic network analysis in the sea urchin Strongylocentrotus purpuratus reveals new candidates in egg activation.

Proteomics 2015 Dec 7;15(23-24):4080-95. Epub 2015 Sep 7.

Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON, Canada.

Fertilization triggers a dynamic symphony of molecular transformations induced by a rapid rise in intracellular calcium. Most prominent are surface alterations, metabolic activation, cytoskeletal reorganization, and cell-cycle reentry. While the activation process appears to be broadly evolutionarily conserved, and protein phosphorylation is known to play a key role, the signaling networks mediating the response to fertilization are not well described. To address this gap, we performed a time course phosphoproteomic analysis of egg activation in the sea urchin Strongylocentrotus purpuratus, a system that offers biochemical tractability coupled with exquisite synchronicity. By coupling large-scale phosphopeptide enrichment with unbiased quantitative MS, we identified striking changes in global phosphoprotein patterns at 2- and 5-min postfertilization as compared to unfertilized eggs. Overall, we mapped 8796 distinct phosphosite modifications on 2833 phosphoproteins, of which 15% were differentially regulated in early egg activation. Activated kinases were identified by phosphosite mapping, while enrichment analyses revealed conserved signaling cascades not previously associated with egg activation. This work represents the most comprehensive study of signaling associated with egg activation to date, suggesting novel mechanisms that can be experimentally tested and providing a valuable resource for the broader research community. All MS data have been deposited in the ProteomeXchange with identifier PXD002239 (http://proteomecentral.proteomexchange.org/dataset/PXD002239).
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http://dx.doi.org/10.1002/pmic.201500159DOI Listing
December 2015

Effect of drying methods on the free and conjugated bufadienolide content in toad venom determined by ultra-performance liquid chromatography-triple quadrupole mass spectrometry coupled with a pattern recognition approach.

J Pharm Biomed Anal 2015 Oct 15;114:482-7. Epub 2015 Jul 15.

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

Drying is a useful technique for extending the shelf-life of biological products and enabling long-term storage; however, improper drying can reduce the chemical quality of the products. In this study, we used ultra-performance liquid chromatography-triple quadrupole/mass spectrometry (LC-MS/MS) and multivariate statistical analysis to investigate the effects of four drying methods (V: vacuum-drying at 60°C, F: freeze-drying, H: air-drying at 60°C and R: air-drying at room temperature) on the levels of 36 bufadienolides in toad venom. Vacuum-drying at 60°C produced the highest quality dried toad venom in terms of total bufadienolide content, whereas traditional air-drying at room temperature (RT) to dehydrate the toad venom led to a dramatic loss in free and conjugated bufadienolides, reaching up to 60% and 70%, respectively. Assaying for free bufadienolides ranked the drying methods as V≈F>H>R, whereas assaying for conjugated bufadienolides slightly changed the order to V>F≈H>R. Furthermore, we identified 21 bufadienolides as biomarkers responsible for the decline in the quality of dried toad venom, whose loss varied from 1.5-fold to 100-fold. Of these biomarkers, group I bufadienolides that contain 16-OAc (e.g., cinobufagin and its hydroxyl or arginine ester derivatives) were characteristic components and were reduced to trace levels (loss of more than 10-fold) following traditional air-drying at RT. This might be attributed to the fact that most enzyme-sensitive bufadienolides were biotransformed or degraded at room temperature but were retained using other drying methods.
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http://dx.doi.org/10.1016/j.jpba.2015.05.032DOI Listing
October 2015

Molecular structure-affinity relationship of bufadienolides and human serum albumin in vitro and molecular docking analysis.

PLoS One 2015 6;10(5):e0126669. Epub 2015 May 6.

Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, PR China.

The development of bufadienolides as anti-tumor agents is limited due to poor pharmacokinetic properties regarding drug half-lives and toxicity in vivo. These serious factors might be improved by increasing the drug/albumin-binding ratio. This study therefore investigated the relationship between the structural properties of nine bufadienolides and their affinities for human serum albumin (HSA) by a fluorescence spectroscopy-based analysis and molecular docking. Fluorescence quenching data showed that the interaction of each bufadienolide with HSA formed a non-fluorescent complex, while thermodynamic parameters revealed negative ΔS and ΔH values, corresponding to changes in enthalpy and entropy, respectively. The structural differences between the various bufadienolides markedly influenced their binding affinity for HSA. With the exception of a C = O bond at the C12 position that decreased the binding affinity for HSA, other polar groups tended to increase the affinity, especially a hydroxyl (OH) group at assorted bufadienolide sites. The rank order of binding affinities for drugs with tri-hydroxyl groups was as follows: 11-OH > 5-OH > 16-OH; in addition, 16-acetoxy (OAc), 10-aldehyde and 14-epoxy constituents notably enhanced the binding affinity. Among these groups, 11-OH and 16-acetyl were especially important for a seamless interaction between the bufadienolides and HSA. Furthermore, molecular docking analysis revealed that either an 11-OH or a 16-OAc group spatially close to a five-membered lactone ring significantly facilitated the anchoring of these compounds within site I of the HSA pocket via hydrogen bonding (H-bonding) with Tyr150 or Lys199, respectively. In summary, bufadienolide structure strongly affects binding with HSA, and 11-OH or 16-OAc groups improve the drug association with key amino acid residues. This information is valuable for the prospective development of bufadienolides with improved pharmacological profiles as novel anti-tumor drugs.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0126669PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4422520PMC
April 2016

Altered cytokine gene expression in peripheral blood monocytes across the menstrual cycle in primary dysmenorrhea: a case-control study.

PLoS One 2013 4;8(2):e55200. Epub 2013 Feb 4.

Jiangsu Key Laboratory for TCM Formulae Research, Nanjing University of Chinese Medicine, Nanjing, China.

Primary dysmenorrhea is one of the most common gynecological complaints in young women, but potential peripheral immunologic features underlying this condition remain undefined. In this paper, we compared 84 common cytokine gene expression profiles of peripheral blood mononuclear cells (PBMCs) from six primary dysmenorrheic young women and three unaffected controls on the seventh day before (secretory phase), and the first (menstrual phase) and the fifth (regenerative phase) days of menstruation, using a real-time PCR array assay combined with pattern recognition and gene function annotation methods. Comparisons between dysmenorrhea and normal control groups identified 11 (nine increased and two decreased), 14 (five increased and nine decreased), and 15 (seven increased and eight decreased) genes with ≥ 2-fold difference in expression (P<0.05) in the three phases of menstruation, respectively. In the menstrual phase, genes encoding pro-inflammatory cytokines (IL1B, TNF, IL6, and IL8) were up-regulated, and genes encoding TGF-β superfamily members (BMP4, BMP6, GDF5, GDF11, LEFTY2, NODAL, and MSTN) were down-regulated. Functional annotation revealed an excessive inflammatory response and insufficient TGF-β superfamily member signals with anti-inflammatory consequences, which may directly contribute to menstrual pain. In the secretory and regenerative phases, increased expression of pro-inflammatory cytokines and decreased expression of growth factors were also observed. These factors may be involved in the regulation of decidualization, endometrium breakdown and repair, and indirectly exacerbate primary dysmenorrhea. This first study of cytokine gene expression profiles in PBMCs from young primary dysmenorrheic women demonstrates a shift in the balance between expression patterns of pro-inflammatory cytokines and TGF-β superfamily members across the whole menstrual cycle, underlying the peripheral immunologic features of primary dysmenorrhea.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0055200PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3563666PMC
July 2013

Interactions between bufadienolides derived from toad venom and verapamil in langendorff-perfused guinea-pig hearts.

Toxicol In Vitro 2013 Feb 16;27(1):396-401. Epub 2012 Aug 16.

Jiangsu Key Laboratory for TCM Formulae Research, Pharmacy College, Nanjing University of Chinese Medicine, No 138 Xianlin Road, Nanjing 210046, China.

Drug toxicity may occur due to dangerous drug combination. We aimed to investigate the influence of verapamil (a P-gp inhibitor)--bufadienolides interaction on cardiotoxicity and bufadienolide uptake by the isolated heart. The study was performed in Langendorff isolated perfused guinea-pig hearts by bufadienolides infusion in the absence and presence of verapamil (250, 500ng/ml). Arrhythmia parameters were evaluated by ECG and the content of bufadienolides in heart were measured by ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS). In the present of verapamil, the wide QRS duration and lightly rapid heart rate (HR) were markedly reduced in the early stage of bufadienolide intoxication. However, the ECG changes characterized by prolonged P-R interval, and slow heart rate and low QRS amplitude in the late stage of bufadienolide intoxication were significantly enhanced. Furthermore, the contents of a variety of bufadienolide compounds in the verapamil+bufadienolide group were significantly higher when cardiac arrest occurred. Although verapamil reduced the bufadienolide-induced ventricular arrhythmias, verapamil worsened heart block and lethal bradycardia of bufadienolides partly via increasing the uptake of bufadienolides in heart tissue, which could compromise the protective effects of verapamil against bufadienolide intoxication. These results suggested that the verapamil may produce dangerous interactions with drugs containing bufadienolides.
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http://dx.doi.org/10.1016/j.tiv.2012.08.011DOI Listing
February 2013

Protective effect of taurine on cardiotoxicity of the bufadienolides derived from toad (Bufo bufo gargarizans Canto) venom in guinea-pigs in vivo and in vitro.

Toxicol Mech Methods 2012 Jan;22(1):1-8

Jiangsu Key laboratory for TCM formulae research, Nanjing University of Chinese Medicine, Nanjing, China.

In China, toad venom is an anti-inflammatory agent used in small doses for the treatment of various types of inflammation. Bufadienolides are cardioactive steroids responsible for the anti-inflammatory actions of toad venom. We studied the protective effect of taurine on the cardiotoxicity of bufadienolides in guinea-pigs. Bufadienolides (8 mg/kg) caused arrhythmias, cardiac dysfunction and death in guinea-pigs. Pretreatment with taurine (150, 300 mg/kg) significantly prevented bufadienolide-induced cardiotoxicity and reduced the mortality in vivo. Taurine markedly increased the cumulative doses of bufadienolides and resibufogenin required for lethal arrhythmia in ex vivo isolated guinea-pig heart. Taurine did not compromise the anti-inflammatory activity of the bufadienolides on concanavalin-A-stimulated proliferation of guinea-pig splenocytes in vitro. These data indicate that taurine can prevent bufadienolide-induced cardiotoxicity and could be a novel antidote in combination with bufadienolide therapy.
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http://dx.doi.org/10.3109/15376516.2011.583295DOI Listing
January 2012

Discovery of estrogen receptor α modulators from natural compounds in Si-Wu-Tang series decoctions using estrogen-responsive MCF-7 breast cancer cells.

Bioorg Med Chem Lett 2012 Jan 18;22(1):154-63. Epub 2011 Nov 18.

Jiangsu Key Laboratory for TCM Formulae Research, Nanjing University of Chinese Medicine, Xianlin Road 138(#), Nanjing 210046, China.

The binding between the estrogen receptor α (ER-α) and a variety of compounds in traditional Chinese formulae, Si-Wu-Tang (SWT) series decoctions, was studied using a stably-transfected human breast cancer cell line (MVLN). In 38 compounds tested from SWT series decoctions, the estrogen-like activity of 22 compounds was above 60% in 20 μg mL(-1). Furthermore, theoretical affinity of these compounds was certificated using the functional virtual screen of ER-α modulators by FlexX-Pharm. The accuracy of functional virtual screening of ER-α modulators could reach to 77.27%. The results showed that some compounds, such as organic acids and flavones in SWT series decoctions could be used as selective estrogen receptor modulators (SERMs) and could be selected for further development as potential agents for estrogen related diseases.
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http://dx.doi.org/10.1016/j.bmcl.2011.11.041DOI Listing
January 2012

Bilirubin attenuates bufadienolide-induced ventricular arrhythmias and cardiac dysfunction in guinea-pigs by reducing elevated intracellular Na(+) levels.

Cardiovasc Toxicol 2012 Mar;12(1):83-9

Jiangsu Key Laboratory for TCM Formulae Research, College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China.

Bufadienolides, known ligands of the sodium pump, have been shown to inhibit the proliferation of several cancer cell types. However, their development to date as anticancer agents has been impaired by a narrow therapeutic margin resulting from their potential to induce cardiotoxicity. In the present study, we examined the effects of bilirubin, an endogenous antioxidant, on the cardiotoxicity of bufadienolides (derived from toad venom) in guinea-pigs. The results showed that bufadienolides (8 mg/kg) caused ventricular arrhythmias, conduction block, cardiac dysfunction and death in guinea-pigs. Pretreatment with bilirubin (75 and 150 mg/kg) significantly prevented bufadienolide-induced premature ventricular complexes, ventricular tachycardia, ventricular fibrillation and death. Bilirubin also markedly improved the inhibition of cardiac contraction in bufadienolide-treated guinea-pigs as evidenced by increases in left ventricular systolic pressure and decreases in left ventricular diastolic pressure in vivo. Furthermore, bilirubin significantly reduced the intracellular sodium content ([Na(+)]( i )) in ex vivo bufadienolide-stimulated guinea-pig ventricular myocytes loaded with the sodium indicator Sodium Green. An antitumor study showed that bilirubin did not compromise the ability of bufadienolides to inhibit gastric cancer cell MGC-803 proliferation. These results suggested that bilirubin can attenuate bufadienolide-induced arrhythmias and cardiac dysfunction in guinea-pigs by reducing elevated [Na(+)]( i ) and may improve bufadienolide therapeutic index in cancer treatment.
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http://dx.doi.org/10.1007/s12012-011-9142-yDOI Listing
March 2012

Taoren-Honghua herb pair and its main components promoting blood circulation through influencing on hemorheology, plasma coagulation and platelet aggregation.

J Ethnopharmacol 2012 Jan 20;139(2):381-7. Epub 2011 Nov 20.

Jiangsu Key Laboratory for TCM Formulae Research, Nanjing University of Chinese Medicine, Nanjing, China.

Ethnopharmacological Relevance: Persicae Semen (Taoren) and Carthami Flos (Honghua) used in pair which is named as Taoren-Honghua (TH) herb pair has been used in traditional Chinese medicine (TCM) for promoting blood circulation to dissipate blood stasis for many years in China.

Aim Of The Study: This paper investigated the effects of TH and its main components amygdalin and hydroxysafflor yellow A (HSYA) on hemorheological disorders of blood stasis in rats.

Materials And Methods: Rats were randomly divided into seven groups (control group, model group, TH group, amygdalin group, HSYA group, amygdalin+HSYA group, and aspirin group) with eight animals in each, whose gender was equally distributed throughout groups. All treatments were performed by gavage and administered seven times with an interval of 12h. After the fifth administration, the model rats except those in control group with blood stasis were established by being placed in ice-cold water during the interval between two injections of adrenaline hydrochloride (Adr); and blood samples were collected 30min after the last administration on the following day.

Results: TH could significantly decrease whole blood viscosity (WBV), plasma viscosity (PV) and packed cell volume (PCV). It also significantly prolonged thrombin time (TT) and thromboplastin time (APTT), increased prothrombin time (PT) and lowered fibrinogen content (FIB). HSYA which significantly decreased WBV and PV had no effect on plasma coagulation parameters. Amygdalin could significantly decrease PV, prolong APTT and decrease FIB, showing few effects on WBV. TH and its main components amygdalin and HSYA could significantly reduce platelet aggregation and protect vascular endothelial cells. Based on the above results, amygdalin and HSYA were responsible for the main curative effects of TH and usually had synergetic effects, such as decreasing PV and platelet aggregation percentage.

Conclusions: The study may provide scientific information to further understanding of the mechanism(s) of TH and its main components in activating blood circulation to dissipate blood. It may also create valuable insight into the possible effects and utilization of TH and its components as a feasible alternative therapeutic agent for patients with hemorheological disorders.
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http://dx.doi.org/10.1016/j.jep.2011.11.016DOI Listing
January 2012

[Study on antioxidant effect and chemical constituents of taohong siwu decoction].

Zhongguo Zhong Yao Za Zhi 2011 Jun;36(12):1591-5

Jiangsu Key Laboratory for Traditional Chinese Medicine Formulae Research, Nanjing University of Chinese Medicine, Nanjing 210046, China.

Objective: To evaluate the antioxidant effects of Taohong Siwu decoction and to exploit the bioactive constituents.

Method: The samples were prepared by macroporous adsorptive resins (TH-1-TH-15). Three antioxidant models were adopted to evaluate the antioxidant activities of Taohong Siwu decoction and its different separated fractions in vitro. It was found that fractions (TH-2, TH-4, TH-7, TH-8, TH-9), separated from Taohong Siwu decoction, mainly contributed to the antioxidant effects. The chemical constituents in the most active fraction TH-8 were identified and determined by HPLC.

Result: TH-8 showed significant antioxidant activities in the antioxidant experiments. Six compounds in the fraction were determined which were amygdalin, albiflorin, paeoniflorin, benzoic acid, coumaric acid and ferulic acid. The contents were 75.70, 31.26, 60.79, 1.196, 1.108, 4.861 mg L(-1), respectively.

Conclusion: Glycosides and aromatic acids may be the principle effective constituents in the active fraction.
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June 2011

[Cell continuous extraction-HPLC determination biological affinity of 8 bufadienolides on MGC-803 cells and their correlation with anti-tumor activities].

Zhongguo Zhong Yao Za Zhi 2011 Jan;36(2):205-8

Jiangsu Key Laboratory for Traditional Chinese Medicine Formulae Research, Nanjing University of Traditional Chinese Medicine, Nanjing 210046, China.

Objective: To study the bioaffinity between 8 bufadienolides(Bu) and tumor cells and analyze the correlation between the bioaffinity and the anti-tumor activities of Bu.

Method: Mix and cultivate the chloroform extract of Chansu and MGC-803. Measure the content of 8 Bu in supernatant and cells using HPLC and calculate their affinity rate.

Result: The coefficient correlation between the decrease of Bu in cell supernatant after affinity and its MGC-803 restrictive activities, and between the cotent percentage of the free Bu in free cells with its MGC-803 restrictive activities, and between the difference between the decrease and the percentage and its MGC-803 restrictive activities is r = 0.82 (P < 0.05), r = -0.04 and r = 0.83 (P < 0.05) respectively.

Conclusion: Eight Bu have different levels of affinity with MGC-803 which correlate with their anti-tumor activities.
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January 2011

The novel antidote Bezoar Bovis prevents the cardiotoxicity of Toad (Bufo bufo gargarizans Canto) Venom in mice.

Exp Toxicol Pathol 2012 Jul 16;64(5):417-23. Epub 2010 Nov 16.

Jiangsu Key Laboratory for TCM Formulae Research, Nanjing University of Chinese Medicine, Nanjing 210046, PR China.

Toad Venom, called chansu (CS) in China, is an anti-inflammatory drug used in small doses for the treatment of various types of inflammation in China. Its use is hampered by the cardiotoxicity of bufadienolides derived from Toad Venom. Bezoar Bovis is another frequently used drug in Toad Venom preparations for the treatment of inflammatory or cardiovascular diseases in Asia. We explored whether Bezoar Bovis could protect against CS-induced acute toxicity in mice. Toxicity was assessed by the general features of poisoning, electrocardiography (ECG), and levels of creatine kinase (CK), lactate dehydrogenase (LDH) and calcium ions (Ca(2+)) in cardiac tissues. Toad Venom (90 mg/kg) caused opisthotonus, ventricular arrhythmias, and increases in cardiac levels of Ca(2+), CK and LDH. Pretreatment with Bezoar Bovis (120, 240 and 480 mg/kg) significantly reduced the prevalence of opisthotonus and mortality, and prevented cardiotoxicity in CS-treated mice as evidenced by decreases in the scores of arrhythmias and cardiac levels of CK, LDH and Ca(2+). Furthermore, the bilirubin, and taurine derived from Bezoar Bovis offered marked protection against the arrhythmias induced by CS or bufalin in vivo and in vitro. An anti-inflammatory study showed that Bezoar Bovis did not compromise the anti-inflammatory activity of Toad Venom on concanavalin-A (ConA)-stimulated proliferation of human peripheral blood mononuclear cells. These results suggested that Bezoar Bovis elicited protective and anti-arrhythmic effects against Toad Venom intoxication in mice, and is a novel antidote in combination with Toad Venom therapy.
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http://dx.doi.org/10.1016/j.etp.2010.10.007DOI Listing
July 2012

Evaluation of the analgesic activities of the crude aqueous extract and fractions of Shao Fu Zhu Yu decoction.

Pharm Biol 2011 Feb 13;49(2):137-45. Epub 2010 Oct 13.

Jiangsu Key Laboratory for TCM Formulae Research, Nanjing University of Chinese Medicine, Nanjing, China.

Context: Shao Fu Zhu Yu decoction (SFD), a well-known Chinese medicine, has been used for the treatment of primary dysmenorrhea in China for more than 200 years.

Objective: A crude water extract and four fractions from SFD were evaluated for their analgesic activities for the purpose of validating the ethnomedical use of SFD.

Material And Method: The analgesic activities were studied by measuring nociception using acetic acid-induced abdominal contractions, the hot-plate test, formalin-induced licking and oxytocin-induced writhing in estrogen-treated mouse models. Prostaglandin E(2) and nitric oxide production in cultured lipopolysaccharide (LPS)-treated macrophage cells were determined. Chemical components were separated and identified in the SFD analgesic fractions using ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS).

Results: Oral SFD exerted significant analgesic activities in all nociceptive models except the hot-plate test. The activity-guided fractionation demonstrated that the SFD-40% fraction was the most potent with marked inhibition of pain responses at a dose of 54 mg/kg in vivo, and significantly inhibited prostaglandin E(2) and nitric oxide production in LPS-treated mouse peritoneal macrophages in vitro. Further UPLC-MS analysis showed the presence of several chemical components in the SFD-40% fraction, including ferulic acid, paeoniflorin, typhaneoside, and isorhamnetin-3-O-neohesperidoside.

Discussion And Conclusion: These results demonstrated that SFD has significant peripheral analgesic activities, mainly attributed to the SFD-40% fraction, and supports the use of SFD in traditional Chinese medicine.
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http://dx.doi.org/10.3109/13880209.2010.504965DOI Listing
February 2011

A series of natural flavonoids as thrombin inhibitors: structure-activity relationships.

Thromb Res 2010 Nov 15;126(5):e365-78. Epub 2010 Sep 15.

Jiangsu Key Laboratory for TCM Formulae Research, Nanjing University of Chinese Medicine, Nanjing 210046, China.

A series of natural flavonoids has been evaluated as potential inhibitors of thrombin using the optimized method of thrombin time. Myricetin and quercetin have shown to be the best thrombin inhibitors tested. In order to investigate the thrombin recognition of the most active and selective compounds, a molecular modeling study has been performed using available Protein Data Bank (PDB) structures as receptor models for docking experiments. Structure-activity relationships of flavonoids (SARs) on thrombin would facilitate the design of chemical compounds with higher potency to serve as potential thrombin inhibitors, and provide information for the exploitation and utilization of flavonoids as thrombin inhibitors for thrombotic disease treatment.
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http://dx.doi.org/10.1016/j.thromres.2010.08.006DOI Listing
November 2010

Liu-Shen-Wan, a traditional Chinese medicine, improves survival in sepsis induced by cecal ligation and puncture via reducing TNF-alpha levels, MDA content and enhancing macrophage phagocytosis.

Int Immunopharmacol 2006 Aug 5;6(8):1355-62. Epub 2006 Apr 5.

Department of Traditional Chinese Prescription, China Pharmaceutical University, 1 Shennong Road, Nanjing 210038, PR China.

Sepsis in humans is a difficult condition to treat and is often associated with a high mortality rate. Here, we investigated putative protective effects of Liu-Shen-Wan (LSW), a well-known Chinese formula used in treating infectious diseases, against polymicrobial sepsis induced by cecal ligation and puncture (CLP). The oral administration of LSW, at the first dose of 60 mg/kg and then 30 mg/kg every 12 h, significantly improved the survival of CLP mice during a 4-day observation period. The effects of LSW on the inflammatory response (circulating tumor necrosis factor-alpha (TNF-alpha), interleukin-1 (IL-1) levels and malondialdehyde (MDA) content-an index of lipid peroxidation), infectious degree (peritoneal bacteria counts), and innate immunity function (leukocyte counts, macrophage phagocytosis and neutrophil respiratory burst) were further examined in rats. We demonstrated that treatment of LSW significantly decreased elevated levels of circulating TNF-alpha at 4 h and further reduced plasma MDA levels at 24 h after CLP, at first doses of 15 and 30 mg/kg and then 7.5 and 15 mg/kg every 12 h. Moreover, LSW markedly enhanced clearance of intraperitoneal bacteria associated with the increasing count of peritoneal leukocytes and enhancing phagocytic activity of macrophages partly impaired at 24 h after CLP. In contrast, LSW lightly reduced IL-1 levels at 4 h and failed to improve deactivated respiratory burst activity of neutrophils at 24 h after CLP. Thus, LSW exerts protective effects against sepsis induced by CLP, mainly by reducing plasma TNF-alpha and MDA levels and enhancing peritoneal macrophage phagocytosis, suggesting that it is a potential agent in the prevention and treatment of sepsis.
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http://dx.doi.org/10.1016/j.intimp.2006.03.003DOI Listing
August 2006
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