Standardized Material Bank for New Botanical Drugs; College of Pharmacy, Wonkwang University, Iksan, Republic of Korea.
Eur J Pharmacol. 2012 Jan 15;674(2-3):153-62. doi: 10.1016/j.ejphar.2011.11.016. Epub 2011 Nov 16.
6,4'-Dihydroxy-7-methoxyflavanone (DMF), a biologically active compound, was isolated from the heartwood of Dalbergia odorifera T. Chen (Leguminosae). The present study proposed to examine the role of DMF as an anti-oxidative and anti-inflammatory heme oxygenase-1 (HO-1) inducer in mouse hippocampal HT22 cells and BV2 microglia cells. The effect of DMF on cell viability was determined by MTT assay and the effects of DMF on pro-inflammatory enzymes and cytokines were analyzed by western blot and ELISA. Parameters such as DMF induced HO-1 protein immunocontents, HO activity and mitogen-activated protein kinases (MAPK) activation were also measured. DMF increased cellular resistance to oxidative injury caused by glutamate-induced cytotoxicity in HT22 cells, via JUN N-terminal kinase (JNK) pathway dependent HO-1 expression. Furthermore, DMF suppressed the lipopolysaccharide (LPS)-induced expression of pro-inflammatory enzymes and inflammatory mediators in BV2 microglia. DMF suppressed production of nitric oxide (NO), prostaglandin E2 (PGE(2)), tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β), through extracellular signal-regulated kinase (ERK) pathway dependent HO-1 expression. This study indicates that DMF effectively modulates the regulation of anti-oxidative and anti-inflammatory action, via up-regulation of HO-1 in HT22 cells and BV2 microglia. These results suggest that DMF possesses therapeutic potentials against neurodegenerative diseases that are induced by oxidative stress and neuroinflammation.
6,4'-二羟基-7-甲氧基二氢黄酮（DMF），一种具有生物活性的化合物，从黄檀心材（豆科）中分离得到。本研究旨在探讨 DMF 作为抗氧化和抗炎血红素加氧酶-1（HO-1）诱导剂在小鼠海马 HT22 细胞和 BV2 小胶质细胞中的作用。通过 MTT 法测定 DMF 对细胞活力的影响，通过 Western blot 和 ELISA 分析 DMF 对促炎酶和细胞因子的影响。还测量了 DMF 诱导的 HO-1 蛋白免疫含量、HO 活性和丝裂原活化蛋白激酶（MAPK）激活等参数。DMF 通过 JNK 途径依赖性 HO-1 表达增加 HT22 细胞对谷氨酸诱导的细胞毒性引起的氧化损伤的细胞抵抗力。此外，DMF 抑制 LPS 诱导的 BV2 小胶质细胞中促炎酶和炎症介质的表达。DMF 通过 ERK 途径依赖性 HO-1 表达抑制一氧化氮（NO）、前列腺素 E2（PGE2）、肿瘤坏死因子-α（TNF-α）和白细胞介素-1β（IL-1β）的产生。这项研究表明，DMF 通过上调 HT22 细胞和 BV2 小胶质细胞中的 HO-1，有效调节抗氧化和抗炎作用的调节。这些结果表明，DMF 具有针对氧化应激和神经炎症引起的神经退行性疾病的治疗潜力。
