Grape King Biotechnology Center, Chung-Li City, Taiwan.
J Agric Food Chem. 2010 Nov 24;58(22):12006-13. doi: 10.1021/jf103070m. Epub 2010 Oct 19.
Hypercholesterolemia initiates the atherogenic process; however, chronic inflammation promotes atherogenesis. Monascus spp. fermented products are recognized for their anti-hypercholesterolemic effect, but their anti-inflammatory activity is not as significant as that of many plant-derived foods. To enhance the anti-inflammatory function of Monascus pilosus fermented products, ginger was added to the PDB medium at a ratio of 20% (v/v). The mycelia and broth were collected, freeze-dried, and extracted by ethanol for assays. Macrophage RAW264.7 was challenged with lipopolysaccharide (LPS) and coincubated with the extracts of fermented product cultured in ginger-supplemented medium (MPG) or extracts of fermented product cultured in regular PDB medium (MP) for 18 h. Human umbilical vein endothelial cell HUVEC was challenged with tumor necrosis factor (TNF)-α and coincubated with the extracts of either MPG or MP for 6 h. The results showed that MPG significantly (p<0.05) lowered the production of macrophage pro-inflammatory cytokines TNF-α, nitric oxide (NO), interleukin (IL)-1, IL-6, and prostaglandin E2 (PGE2) by 68.53%, 84.29%, 32.55%, 84.49%, and 69.49%, respectively; however, MP had no inhibitory effect. MPG significantly downregulated the expression of p-IκB, cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS) in macrophage by 42.16%, 50.87%, and 51.35%, respectively, while MP had no inhibition on COX-2 expression and only 16.64% and 19.22% downregulatory effect on iNOS and phosphorylated-IκB (p-IκB), respectively. Moreover, MPG significantly suppressed the expression of vessel cell adhesion molecule-1 (VCAM-1) and p-IκB in endothelial cell by 63.48% and 63.41%, respectively. LC/MS/MS analysis indicated that 6-gingerdiol was formed in the ginger-modified medium during fermentation. The results of this study will facilitate the development of Monascus spp. fermented products as antiatherosclerotic nutraceuticals.
高胆固醇血症会引发动脉粥样硬化过程；然而，慢性炎症会促进动脉粥样硬化的发生。红曲菌发酵产品因其抗高胆固醇血症的作用而被认可，但它们的抗炎活性不如许多植物源性食品显著。为了增强红曲毛霉发酵产品的抗炎功能，在 PDB 培养基中加入 20%（体积/体积）的生姜。收集菌丝体和发酵液，经冷冻干燥后用乙醇提取进行测定。用脂多糖（LPS）刺激巨噬细胞 RAW264.7，并与在添加生姜的培养基中培养的发酵产物提取物（MPG）或在常规 PDB 培养基中培养的发酵产物提取物（MP）共孵育 18 小时。用肿瘤坏死因子（TNF）-α刺激人脐静脉内皮细胞 HUVEC，并与 MPG 或 MP 的提取物共孵育 6 小时。结果表明，MPG 显著（p<0.05）降低了巨噬细胞促炎细胞因子 TNF-α、一氧化氮（NO）、白细胞介素（IL）-1、IL-6 和前列腺素 E2（PGE2）的产生，分别降低了 68.53%、84.29%、32.55%、84.49%和 69.49%；然而，MP 没有抑制作用。MPG 显著下调了巨噬细胞中 p-IκB、环氧化酶-2（COX-2）和诱导型一氧化氮合酶（iNOS）的表达，分别降低了 42.16%、50.87%和 51.35%，而 MP 对 COX-2 的表达没有抑制作用，仅对 iNOS 和磷酸化-IκB（p-IκB）有 16.64%和 19.22%的下调作用。此外，MPG 显著抑制了内皮细胞中血管细胞黏附分子-1（VCAM-1）和 p-IκB 的表达，分别降低了 63.48%和 63.41%。LC/MS/MS 分析表明，在发酵过程中，生姜改良培养基中形成了 6-姜二醇。本研究结果将有助于开发红曲菌发酵产品作为抗动脉粥样硬化的营养保健品。
