Inhibitory effects of several spices on the AGEs formation and AGEs-induced inflammatory cytokines production

• Main Authors: Pin-Yuan Yu, 余品淵
• Other Authors: Su-Chen Ho
• Format: Others
• Language: zh-TW
• Online Access: http://ndltd.ncl.edu.tw/handle/gujdyf

碩士 === 元培科技大學 === 食品科學研究所 === 100 === Non-enzymatic glycosylation catalyzed the formation of AGEs can lead to protein irreversible modification and cause the protein structure and function abnormalities. Interaction of AGEs and RAGE induces inflammatory reaction which was associated with the development of diabetes complications and degenerative diseases. In eastern traditional medicine, spices often used as medicine for prevention of chronic diseases and diabetes. In this study, an in vitro BSA/glucose system and an AGEs-induced inflammation in BV2 microglia culture system were adopted to evaluate the capacity of spices to attenuate the fluorescent AGEs formation and to inhibit the proinflammatory cytokines production, respectively. The anti-diabetic complication activity of spices was further evaluated by the combined results of their anti-glycating and anti-inflammatory capacities. We used an in vitro BSA/glucose glycation system to examine the antiglycating abilities of the spices. The results showed that cinnamon in concentrations ranging from 6.6 mg/ml to 1.6 mg/ml had an inhibitory effect of about 50% on the early glycation product (fructosamine) formation. Only oregano at a concentration of 6.6 mg/ml had an inhibitory effect of 58% on intermediate glycating product (carbonyl compound) formation. All of the tested spices showed a good inhibitory effect on the late glycating products (fluorescent AGEs) formation. At a concentration of 6.6 mg/ml, green pepper, white pepper, oregano, cinnamon and turmeric inhibited more than 70% of fluorescent AGEs formation. Among the tested spices, green pepper had the best antiglycating capacity. Additionally, the inhibitory capacity of spices on the fluorescent AGEs formation in a methylglyoxal/BSA glycating system was accordant with their inhibitory capacity on the fluorescent AGEs formation in a glucose/BSA glycation system. A significant correlation (p<0.01) was existed between results of methylglyoxal/BSA and glucose/BSA glycation systems. It implies spices exert their antiglycating effect mainly through inhibiting the late stage of glycation. The anti-inflammatory capacity of spices was evaluated based on their inhibitory effect on the production of the inflammatory substances, such as NO, IL-6 and TNF-α and on the mRNA expression of the inflammatory molecules, such as iNOS、IL-6、TNF-α、IL-1βand RAGE in AGEs-stimulated BV2 microglia. All of the 11 tested spices dose-dependently suppressed the production of NO in the AGEs-stimulated BV2 microglia. The inhibitory capacities of the spice extracts on NO, given by IC50 declined in the order; rosemary (0.15 mg/ml), ginger (0.40 mg/ml), paprika (0.65 mg/ml), oregano (0.68 mg/ml), cinnamon (0.74 mg/ml), thyme (4.82 mg/ml), pink pepper（1.49 mg/ml）, green pepper (1.81 mg/ml), white pepper (3.31 mg/ml), jamaica pepper (4.00 mg/ml) and turmeric (4.82 mg/ml). Rosemary and oregano almost complete inhibited the IL-6 production in the AGEs-stimulated BV2 microglia. Additionally, oregano also showed the most potent inhibition on AGEs-stimulated TNF-α production. The amounts of NO secreted by different spice-treated cells were highly correlated with the amounts of IL-6 and TNF-α secreted. Secretion of IL-6 and TNF-α were highly correlated with the IL-6 and TNF-α mRNA levels. Rosemary and oregon also had the strongest inhibitory effect on the mRNA expression of IL-1β. In the other hand, only cinnamon and jamaica pepper significantly attenuated RAGE expression in the AGEs-stimulated BV2 cells. Rosemary and oregano exhibited the strongest inhibitory capacities on the AGEs-induced inflammation, but cinnamon and jamaica pepper were good at attenuating RAGE expression. Rosemary, oregano, cinnamon and Jamaica pepper might have potential to develop as health foods for prevention of diabetes complications and neurodegenerative diseases.