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Inhibition of Hydrogen Sulfide-induced Angiogenesis and Inflammation in Vascular Endothelial Cells: Potential Mechanisms of Gastric Cancer Prevention by Korean Red Ginseng
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  • Inhibition of Hydrogen Sulfide-induced Angiogenesis and Inflammation in Vascular Endothelial Cells: Potential Mechanisms of Gastric Cancer Prevention by Korean Red Ginseng
  • Inhibition of Hydrogen Sulfide-induced Angiogenesis and Inflammation in Vascular Endothelial Cells: Potential Mechanisms of Gastric Cancer Prevention by Korean Red Ginseng
저자명
Choi. Ki-Seok,Song. Heup,Kim. Eun-Hee,Choi. Jae-Hyung,Hong. Hua,Han. Young-Min,Hahm. Ki-Baik
간행물명
Journal of ginseng research
권/호정보
2012년|36권 2호|pp.135-145 (11 pages)
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고려인삼학회
파일정보
정기간행물|ENG|
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이 논문은 한국과학기술정보연구원과 논문 연계를 통해 무료로 제공되는 원문입니다.
서지반출

기타언어초록

Previously, we reported that Helicobacter pylori-associated gastritis and gastric cancer are closely associated with increased levels of hydrogen sulfide ($H_2S$) and that Korean red ginseng significantly reduced the severity of H. pylori-associated gastric diseases by attenuating $H_2S$ generation. Because the incubation of endothelial cells with $H_2S$ has been known to enhance their angiogenic activities, we hypothesized that the amelioration of $H_2S$-induced gastric inflammation or angiogenesis in human umbilical vascular endothelial cells (HUVECs) might explain the preventive effect of Korean red ginseng on H. pylori-associated carcinogenesis. The expression of inflammatory mediators, angiogenic growth factors, and angiogenic activities in the absence or presence of Korean red ginseng extracts (KRGE) were evaluated in HUVECs stimulated with the $H_2S$ generator sodium hydrogen sulfide (NaHS). KRGE efficiently decreased the expression of cystathionine ${eta}$-synthase and cystathionine ${gamma}$-lyase, enzymes that are essential for $H_2S$ synthesis. Concomitantly, a significant decrease in the expression of inflammatory mediators, including cyclooxygenase-2 and inducible nitric oxide synthase, and several angiogenic factors, including interleukin (IL)-8, hypoxia inducible factor-1a, vascular endothelial growth factor, IL-6, and matrix metalloproteinases, was observed; all of these factors are normally induced after NaHS. An in vitro angiogenesis assay demonstrated that NaHS significantly increased tube formation in endothelial cells, whereas KRGE pretreatment significantly attenuated tube formation. NaHS activated p38 and Akt, increasing the expression of angiogenic factors and the proliferation of HUVECs, whereas KRGE effectively abrogated this $H_2S$-activated angiogenesis and the increase in inflammatory mediators in vascular endothelial cells. In conclusion, KRGE was able to mitigate $H_2S$-induced angiogenesis, implying that antagonistic action against $H_2S$-induced angiogenesis may be the mechanism underlying the gastric cancer preventive effects of KRGE in H. pylori infection.