大蒜有機硫化合物diallyl sulfide與diallyl disulfide對血管新生作用及其相關因子之影響

Effects of diallyl sulfide and diallyl disulfide on angiogenesis and angiogenesis-related factors

周歆倩(Sin-Chien Chou)

指導教授 ： 陳玉華

臺北醫學大學/公共衛生暨營養學院/保健營養學研究所/碩士(2007年)

https://doi.org/10.6831/TMU.2007.00114

摘要

本研究為利用細胞及動物模式探討大蒜有機硫化合物對血管新生作用及其相關因子之影響。細胞實驗方面，分別在有無10 ng/ml VEGF投予下，給予血管內皮EA hy 926細胞DAS (diallyl sulfide) 及DADS (diallyl disulfide) 後，分析有機硫化合物對細胞生長及血管新生相關因子之影響。結果顯示，大蒜萃取物DAS (2.5~7.5 μM) 及DADS (0.05~0.5 μM) 可抑制EA hy 926細胞之生長與增生，但可促進血管新生過程最後階段-類血管 (tube formation) 之生成，且此影響與促血管新生因子VEGF、IL-8及活化型MMP-2表現增加相關。在VEGF誘導血管新生下，DAS、DADS及二者合併使用皆可抑制因VEGF誘導之EA hy 926細胞增生及類血管生成，其影響與增加IL-8及降低活化型MMP-2表現相關。於動物實驗方面，以皮下注射含有無1 μg/ml bFGF (basic fibroblast growth factor) 之matrigel，以誘導C57BL/6小鼠病理性血管新生作用後，結果顯示，連續10天腹腔注射DAS (12.5 mg/kg)、DADS (50 mg/kg) 及合併使用組別，matrigel中之血紅素含量有低於bFGF組之傾向，但無顯著差異。總而言之，大蒜可促進細胞生理性血管新生，且抑制VEGF誘導之細胞血管新生作用，其作用與調節血管新生相關因子VEGF、IL-8及MMP-2表現相關，但動物實驗結果有待進一步確認之。

關鍵字: 大蒜有機硫化合物、血管新生、癌症、傷口癒合

關鍵字

大蒜有機硫化合物 ； 血管新生 ； 癌症 ； 傷口癒合

並列摘要

This study was aimed at studying the effects of diallyl sulfide (DAS) and diallyl disulfide (DADS), organosulfur compounds derived form garlic (Allium sativum L.), on the process of angiogenesis. In cultured cells, DAS (2.5~7.5 μM) and DADS (0.05~0.5 μM) enhanced tube formation of EA hy 926 cells, and which was associated with up-regulated expression of pro-angiogenic factors, including VEGF, IL-8 and activated MMP-2 (p<0.05). On the other hand, DAS, DADS, as well as combination of DAS and DADS (0.5+0.005 μM, 1+0.01 μM) inhibited VEGF-stimulated tube formation and activated MMP-2 expression, but increased IL-8 production in EA hy 926 cells (p<0.05). In animals, pathological angiogenesis were induced by subcutaneously injection of 1 μg/ml bFGF-contained matrigel followed by daily ip. injection of DAS (12.5 mg/kg), DADS (50 mg/kg) and DAS+DADS for 10 days. The results showed that DAS, DADS and DAS+DADS mixture did not significantly suppress bFGF-induced hemoglobin contents in matrigels. In summary, DAS and DADS enhanced tube formation under a basal state, but suppressed tube formation in VEGF-stimulated pathological condition, indicating the potential roles of garlic in promoting wound healing as well as in inhibiting carcinogenesis.

key words: garlic organosulfur compounds, angiogenesis, wound healing, carcinogenesis

並列關鍵字

garlic organosulfur compounds ； angiogenesis ； wound healing ； carcinogenesis

參考文獻

Amagase H, Petesch BL, Matsuura H, Kasuga S, Itakura Y (2001) Intake of garlic and its bioactive components. J Nutr. 131:955S-962S.

Antosiewicz J, Herman-Antosiewicz A, Marynowski SW, Singh SV. (2006) c-Jun NH(2)-terminal kinase signaling axis regulates diallyl trisulfide-induced generation of reactive oxygen species and cell cycle arrest in human prostate cancer cells.Cancer Res. 66:5379-5386.

Banerjee SK, Mukherjee PK, Maulik SK (2003) Garlic as an antioxidant: the good, the bad and the ugly. Phytother Res. 17:97-106.

Battersby S, Sales KJ, Williams AR, Anderson RA, Gardner S, Jabbour HN. (2007) Seminal plasma and prostaglandin E2 up-regulate fibroblast growth factor 2 expression in endometrial adenocarcinoma cells via E-series prostanoid-2 receptor-mediated transactivation of the epidermal growth factor receptor and extracellular signal-regulated kinase pathway. Human Reprod. 22:36-44.

Belloir C, Singh V, Daurat C, Siess MH, Le Bon AM. (2006) Protective effects of garlic sulfur compounds against DNA damage induced by direct- and indirect-acting genotoxic agents in HepG2 cells. Food Chem Toxicol. 44:827-834.