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Conference Paper: Gallic acid-L-leucine (GAL) conjugate protects mice against endotoxic shock via suppressing the production of pro-inflammatory lipid mediators and nitric oxide (NO) in macrophages
Title | Gallic acid-L-leucine (GAL) conjugate protects mice against endotoxic shock via suppressing the production of pro-inflammatory lipid mediators and nitric oxide (NO) in macrophages |
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Authors | |
Issue Date | 2016 |
Citation | The 15th Meeting of the Consortium for Globalization of Chinese Medicine (CGCM 2016), Academia Sinica, Taipei, Taiwan, 23-25 August 2016. How to Cite? |
Abstract | Aberrant production of pro-inflammatory lipid mediators and nitric oxide (NO) is implicated in the pathology of LPS-induced inflammation and sepsis. We recently synthesized a novel gallic acid-L-leucine (GAL) conjugate and discovered that GAL conjugate could promote macrophage phagocytosis via inducing LTB4DH (Cheng YY et al Mol Immunol. 2016 May 2;74:39-46). The aim of present study was to discover the anti-inflammatory potential of GAL conjugate in the treatment of endotoxic shock. We focused on the effects of GAL conjugate on the generation of the key pro-inflammatory lipid mediators and NO. We not only examined whether GAL could antagonize the effects of liposaccharide (LPS) on the expression of cyclooxygenase-2 (COX-2), 5-lipoxygenase (5-LOX) and inducible NO synthase (iNOS) but also determined the products of these pro-inflammatory enzymes in RAW264.7 cells, primary peritoneal macrophages and mice. Based on Western blot analysis, GAL attenuated LPS-induced expression of COX-2, 5-LOX and iNOS in a concentration-dependent manner. Consistently, the results of ESI-MS based lipidomics profiling verified that GAL suppressed LPS-induced overproduction of prostaglandin E2, prostaglandin F2, leukotriene B4 and thromboxane B2. We further discovered that GAL exhibited anti-inflammatory activities by targeting the following mechanisms: 1) suppressing LPS-induced phosphorylation of MAP kinases such as p38, JNK and ERK1/2; 2) reducing the production of reactive oxygen species and NO; and 3) preventing LPS-induced nuclear translocation of transcription factors NF-κB and AP-1. On the other hand, GAL significantly decreased the plasma levels of pro-inflammatory lipid mediators and the enzyme levels of COX-2 and iNOS expression in LPS-treated mice. Importantly, GAL pretreatment enhanced the survival of mice against LPS-induced endotoxic shock. Collectively, these results suggest that GAL may be a potential anti-inflammatory drug for the treatment of endotoxemia and sepsis. |
Persistent Identifier | http://hdl.handle.net/10722/232240 |
DC Field | Value | Language |
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dc.contributor.author | Cheng, Y | - |
dc.contributor.author | Li, XC | - |
dc.contributor.author | Tse, HF | - |
dc.contributor.author | Han, Y | - |
dc.contributor.author | Rong, J | - |
dc.date.accessioned | 2016-09-20T05:28:40Z | - |
dc.date.available | 2016-09-20T05:28:40Z | - |
dc.date.issued | 2016 | - |
dc.identifier.citation | The 15th Meeting of the Consortium for Globalization of Chinese Medicine (CGCM 2016), Academia Sinica, Taipei, Taiwan, 23-25 August 2016. | - |
dc.identifier.uri | http://hdl.handle.net/10722/232240 | - |
dc.description.abstract | Aberrant production of pro-inflammatory lipid mediators and nitric oxide (NO) is implicated in the pathology of LPS-induced inflammation and sepsis. We recently synthesized a novel gallic acid-L-leucine (GAL) conjugate and discovered that GAL conjugate could promote macrophage phagocytosis via inducing LTB4DH (Cheng YY et al Mol Immunol. 2016 May 2;74:39-46). The aim of present study was to discover the anti-inflammatory potential of GAL conjugate in the treatment of endotoxic shock. We focused on the effects of GAL conjugate on the generation of the key pro-inflammatory lipid mediators and NO. We not only examined whether GAL could antagonize the effects of liposaccharide (LPS) on the expression of cyclooxygenase-2 (COX-2), 5-lipoxygenase (5-LOX) and inducible NO synthase (iNOS) but also determined the products of these pro-inflammatory enzymes in RAW264.7 cells, primary peritoneal macrophages and mice. Based on Western blot analysis, GAL attenuated LPS-induced expression of COX-2, 5-LOX and iNOS in a concentration-dependent manner. Consistently, the results of ESI-MS based lipidomics profiling verified that GAL suppressed LPS-induced overproduction of prostaglandin E2, prostaglandin F2, leukotriene B4 and thromboxane B2. We further discovered that GAL exhibited anti-inflammatory activities by targeting the following mechanisms: 1) suppressing LPS-induced phosphorylation of MAP kinases such as p38, JNK and ERK1/2; 2) reducing the production of reactive oxygen species and NO; and 3) preventing LPS-induced nuclear translocation of transcription factors NF-κB and AP-1. On the other hand, GAL significantly decreased the plasma levels of pro-inflammatory lipid mediators and the enzyme levels of COX-2 and iNOS expression in LPS-treated mice. Importantly, GAL pretreatment enhanced the survival of mice against LPS-induced endotoxic shock. Collectively, these results suggest that GAL may be a potential anti-inflammatory drug for the treatment of endotoxemia and sepsis. | - |
dc.language | eng | - |
dc.relation.ispartof | Meeting of Consortium for Globalization of Chinese Medicine, CGCM 2016 | - |
dc.relation.ispartof | 第15屆中藥全球化聯盟會議 | - |
dc.title | Gallic acid-L-leucine (GAL) conjugate protects mice against endotoxic shock via suppressing the production of pro-inflammatory lipid mediators and nitric oxide (NO) in macrophages | - |
dc.type | Conference_Paper | - |
dc.identifier.email | Li, XC: xuechenl@hku.hk | - |
dc.identifier.email | Tse, HF: hftse@hkucc.hku.hk | - |
dc.identifier.email | Rong, J: jrong@hku.hk | - |
dc.identifier.authority | Li, XC=rp00742 | - |
dc.identifier.authority | Tse, HF=rp00428 | - |
dc.identifier.authority | Rong, J=rp00515 | - |
dc.identifier.hkuros | 264420 | - |