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Article: Isolation and identification of anti-inflammatory constituents from Ligusticum chuanxiong and their underlying mechanisms of action on microglia

TitleIsolation and identification of anti-inflammatory constituents from Ligusticum chuanxiong and their underlying mechanisms of action on microglia
Authors
KeywordsBV-2
Human peripheral blood monocyte derived macrophages (PBMac)
Ligusticum chuanxiong (LCX)
Lipopolysaccharide (LPS)
Microglia
Mitogen-activated protein kinases (MAPK)
mRNA stability
Nitric oxide
Nuclear factor kappa B (NF-κB)
Senkyunolide A
Tumor necrosis factor-alpha (TNF-α)
Z-Ligustilide
Issue Date2011
PublisherPergamon. The Journal's web site is located at http://www.elsevier.com/locate/neuropharm
Citation
Neuropharmacology, 2011, v. 60 n. 6, p. 823-831 How to Cite?
AbstractStroke is the third most common cause of death worldwide. Recent findings showed that the severity of cerebrovascular diseases including ischemic stroke correlates with inflammation mediated responses in the neural cells. During ischemia, inflammatory mediators including tumor necrosis factor-alpha (TNF-α) and nitric oxide are produced by microglia, which play a central role in the pathogenesis of the disease. Ligusticum chuanxiong (LCX) is a commonly used traditional Chinese medicine (TCM) for empiric treatment of cerebrovascular and cardiovascular diseases for many centuries. By applying a bioactivity-guided fractionation scheme, two compounds with inhibition on neuroinflammation were isolated from LCX. Using chromatographic and spectrometric methods, they were identified to be senkyunolide A and Z-ligustilide. They could inhibit the production of proinflammatory mediators in lipopolysaccharide (LPS)-stimulated murine BV-2 microglial cells and human peripheral blood monocyte derived macrophages. In addition, both compounds protected Neuro-2a cells from neuroinflammatory toxicity induced by the conditioned culture media produced by LPS-stimulated BV-2 cells. The underlying mechanisms of action of senkyunolide A were further delineated. Its inhibitory effects were shown to be independent of the phosphorylation of mitogen-activated protein kinases (MAPK) and translocation of nuclear factor kappa B (NF-κB). However, senkyunolide A could increase the degradation of TNF-α mRNA and reduce its half life by 43%. In conclusion, bioactivity-guided fractionation is an effective way of isolating bioactive compounds from medicinal herbs. In addition, senkyunolide A and Z-ligustilide isolated from LCX may be considered as potential complementary drug candidates for treating inflammatory processes associated with cerebrovascular diseases. © 2010 Elsevier Ltd. All rights reserved.
Persistent Identifierhttp://hdl.handle.net/10722/136307
ISSN
2015 Impact Factor: 4.936
2015 SCImago Journal Rankings: 2.506
ISI Accession Number ID
Funding AgencyGrant Number
Prof. Francis SK Lau Research Fund
University of Hong Kong
Funding Information:

This project was supported in part by grants from Prof. Francis SK Lau Research Fund and Purapharm international awarded to Prof. A Lau. We thank Prof. E Choi from Laboratory of Cell Death and Human Diseases, Korea University for providing the BV-2 microglial cells. We also thank Gang Chen and Jian Zhou from Purapharm International (Hong Kong) Limited for their technical support. Terry C.T. Or received the "Award for Outstanding Research Postgraduate Student 2008-2009" from The University of Hong Kong.

References

 

DC FieldValueLanguage
dc.contributor.authorOr, TCTen_HK
dc.contributor.authorYang, CLHen_HK
dc.contributor.authorLaw, AHYen_HK
dc.contributor.authorLi, JCBen_HK
dc.contributor.authorLau, ASYen_HK
dc.date.accessioned2011-07-27T02:12:55Z-
dc.date.available2011-07-27T02:12:55Z-
dc.date.issued2011en_HK
dc.identifier.citationNeuropharmacology, 2011, v. 60 n. 6, p. 823-831en_HK
dc.identifier.issn0028-3908en_HK
dc.identifier.urihttp://hdl.handle.net/10722/136307-
dc.description.abstractStroke is the third most common cause of death worldwide. Recent findings showed that the severity of cerebrovascular diseases including ischemic stroke correlates with inflammation mediated responses in the neural cells. During ischemia, inflammatory mediators including tumor necrosis factor-alpha (TNF-α) and nitric oxide are produced by microglia, which play a central role in the pathogenesis of the disease. Ligusticum chuanxiong (LCX) is a commonly used traditional Chinese medicine (TCM) for empiric treatment of cerebrovascular and cardiovascular diseases for many centuries. By applying a bioactivity-guided fractionation scheme, two compounds with inhibition on neuroinflammation were isolated from LCX. Using chromatographic and spectrometric methods, they were identified to be senkyunolide A and Z-ligustilide. They could inhibit the production of proinflammatory mediators in lipopolysaccharide (LPS)-stimulated murine BV-2 microglial cells and human peripheral blood monocyte derived macrophages. In addition, both compounds protected Neuro-2a cells from neuroinflammatory toxicity induced by the conditioned culture media produced by LPS-stimulated BV-2 cells. The underlying mechanisms of action of senkyunolide A were further delineated. Its inhibitory effects were shown to be independent of the phosphorylation of mitogen-activated protein kinases (MAPK) and translocation of nuclear factor kappa B (NF-κB). However, senkyunolide A could increase the degradation of TNF-α mRNA and reduce its half life by 43%. In conclusion, bioactivity-guided fractionation is an effective way of isolating bioactive compounds from medicinal herbs. In addition, senkyunolide A and Z-ligustilide isolated from LCX may be considered as potential complementary drug candidates for treating inflammatory processes associated with cerebrovascular diseases. © 2010 Elsevier Ltd. All rights reserved.en_HK
dc.languageengen_US
dc.publisherPergamon. The Journal's web site is located at http://www.elsevier.com/locate/neuropharmen_HK
dc.relation.ispartofNeuropharmacologyen_HK
dc.subjectBV-2en_HK
dc.subjectHuman peripheral blood monocyte derived macrophages (PBMac)en_HK
dc.subjectLigusticum chuanxiong (LCX)en_HK
dc.subjectLipopolysaccharide (LPS)en_HK
dc.subjectMicrogliaen_HK
dc.subjectMitogen-activated protein kinases (MAPK)en_HK
dc.subjectmRNA stabilityen_HK
dc.subjectNitric oxideen_HK
dc.subjectNuclear factor kappa B (NF-κB)en_HK
dc.subjectSenkyunolide Aen_HK
dc.subjectTumor necrosis factor-alpha (TNF-α)en_HK
dc.subjectZ-Ligustilideen_HK
dc.subject.mesh4-Butyrolactone - analogs and derivatives - pharmacology-
dc.subject.meshAnti-Inflammatory Agents, Non-Steroidal - pharmacology-
dc.subject.meshBenzofurans - pharmacology-
dc.subject.meshDrugs, Chinese Herbal - chemistry-
dc.subject.meshMicroglia - drug effects - metabolism - physiology-
dc.titleIsolation and identification of anti-inflammatory constituents from Ligusticum chuanxiong and their underlying mechanisms of action on microgliaen_HK
dc.typeArticleen_HK
dc.identifier.emailLi, JCB: jamesli@hku.hken_HK
dc.identifier.emailLau, ASY: asylau@hku.hken_HK
dc.identifier.authorityLi, JCB=rp00496en_HK
dc.identifier.authorityLau, ASY=rp00474en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1016/j.neuropharm.2010.12.002en_HK
dc.identifier.pmid21146552-
dc.identifier.scopuseid_2-s2.0-79952447872en_HK
dc.identifier.hkuros187955en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-79952447872&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume60en_HK
dc.identifier.issue6en_HK
dc.identifier.spage823en_HK
dc.identifier.epage831en_HK
dc.identifier.isiWOS:000289133200001-
dc.publisher.placeUnited Kingdomen_HK
dc.identifier.scopusauthoridOr, TCT=36806520700en_HK
dc.identifier.scopusauthoridYang, CLH=26668171500en_HK
dc.identifier.scopusauthoridLaw, AHY=8692488400en_HK
dc.identifier.scopusauthoridLi, JCB=23103447500en_HK
dc.identifier.scopusauthoridLau, ASY=7202626202en_HK
dc.identifier.citeulike8452653-

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