ABSTRACT
OBJECTIVE: Inflammation is crucial to limiting vascular disease. Previously we reported that acrolein, a known toxin in tobacco smoke, might play an important role in the progression of atherosclerosis via an inflammatory response involving cyclooxygenase-2 (COX-2) and prostaglandin production in human umbilical vein endothelial cells (HUVECs). Curcumin has been known to improve vascular function and have anti-inflammatory properties. In this study, we investigated whether curcumin prevents the induction of inflammatory response caused by acrolein.METHODS: Anti-inflammatory effects of curcumin were examined in acrolein-stimulated HUVECs. Induction of proteins, mRNA, prostaglandin and reactive oxygen species (ROS) were measured using immunoblot analysis, real-time reverse-transcription polymerase chain reaction, enzyme-linked immunosorbent assay and flow cytometry, respectively.RESULTS: Curcumin attenuates inflammatory response via inhibition of COX-2 expression and prostaglandin production in acrolein-induced human endothelial cells. This inhibition by curcumin results in the abolition of phosphorylation of protein kinase C, p38 mitogen-activated protein kinase, and cAMP response element-binding protein. Furthermore, curcumin suppresses the production of ROS and endoplasmic reticulum stress via phosphorylation of eukaryotic initiation factor-2α caused by acrolein.CONCLUSION: These results suggest that curcumin might be a useful agent against endothelial dysfunction caused by acrolein-induced inflammatory response.
Subject(s)
Humans , Acrolein , Atherosclerosis , Curcumin , Cyclic AMP Response Element-Binding Protein , Cyclooxygenase 2 , Endoplasmic Reticulum Stress , Endothelial Cells , Enzyme-Linked Immunosorbent Assay , Flow Cytometry , Human Umbilical Vein Endothelial Cells , Inflammation , Phosphorylation , Polymerase Chain Reaction , Protein Kinase C , Protein Kinases , Reactive Oxygen Species , RNA, Messenger , Smoke , Tobacco , Vascular DiseasesABSTRACT
Nausea and emesis are a major side effect and obstacle for chemotherapy in cancer patients. Employ of antiemetic drugs help to suppress chemotherapy-induced emesis in some patients but not all patients. Ginger, an herbal medicine, has been traditionally used to treat various kinds of diseases including gastrointestinal symptoms. Ginger is effective in alleviating nausea and emesis, particularly, for cytotoxic chemotherapy drug-induced emesis. Ginger-mediated antiemetic effect has been attributed to its pungent constituents-mediated inhibition of serotonin (5-HT) receptor activity but its cellular mechanism of action is still unclear. Emetogenic chemotherapy drugs increase 5-HT concentration and activate visceral vagal afferent nerve activity. Thus, 5-HT mediated vagal afferent activation is essential to provoke emesis during chemotherapy. In this experiment, water extract of ginger and its three major pungent constituent's effect on 5-HT-evoked responses were tested on acutely dispersed visceral afferent neurons with patch-clamp methods. The ginger extract has similar effects to antiemetic drug ondansetron by blocking 5-HT-evoked responses. Pungent constituents of the ginger, [6]-shogaol, [6]-gingerol, and zingerone inhibited 5-HT responses in a dose dependent manner. The order of inhibitory potency for these compounds were [6]-shogaol>[6]-gingerol>zingerone. Unlike well-known competitive 5-HT3 receptor antagonist ondansetron, all tested ginger constituents acted as non-competitive antagonist. Our results imply that ginger and its pungent constituents exert antiemetic effects by blocking 5-HT-induced emetic signal transmission in vagal afferent neurons.