Department of Microbiology, College of Natural Sciences, Pusan National University, Busan 609-735, Republic of Korea.
Int Immunopharmacol. 2010 Dec;10(12):1580-6. doi: 10.1016/j.intimp.2010.09.011. Epub 2010 Oct 14.
Cordyceps militaris, a traditional medicinal mushroom, produces the bioactive compound cordycepin (3'-deoxyadenosine). Although cordycepin has been shown to have pharmacological, immunological stimulating, anti-cancer, and anti-inflammatory activities, its activities and cellular mechanisms during microglial activation have yet to be elucidated. Thus, we evaluated the anti-inflammatory effect of cordycepin on the production of inflammatory mediators in lipopolysaccharide (LPS)-stimulated murine BV2 microglia. We also investigated the effects of cordycepin on LPS-induced nuclear factor-kappaB (NF-κB) activation and on phosphorylation of mitogen-activated protein kinases (MAPKs). After LPS stimulation, nitric oxide (NO), prostaglandin E₂ (PGE₂), and pro-inflammatory cytokine production was detected in BV2 microglia. However, we found that cordycepin significantly inhibited the excessive production of NO, PGE₂, and pro-inflammatory cytokines in a concentration-dependent manner without causing cytotoxicity. In addition, cordycepin suppressed NF-κB translocation by blocking IkappaB-α (IκB-α) degradation and inhibited the phosphorylation of Akt, ERK-1/2, JNK, and p38 kinase. Our results indicate that the inhibitory effect of cordycepin on LPS-stimulated inflammatory mediator production in BV2 microglia is associated with the suppression of the NF-κB, Akt, and MAPK signaling pathways. Therefore, cordycepin may be useful in treating neurodegenerative diseases by inhibiting inflammatory mediator production in activated microglia.
蛹虫草，一种传统的药用蘑菇，产生生物活性化合物蛹虫草素（3'-脱氧腺苷）。虽然已经证明蛹虫草素具有药理学、免疫刺激、抗癌和抗炎活性，但它在小胶质细胞激活过程中的活性和细胞机制尚未阐明。因此，我们评估了蛹虫草素对脂多糖（LPS）刺激的鼠 BV2 小胶质细胞中炎症介质产生的抗炎作用。我们还研究了蛹虫草素对 LPS 诱导的核因子-kappaB（NF-κB）激活和丝裂原激活蛋白激酶（MAPKs）磷酸化的影响。在 LPS 刺激后，BV2 小胶质细胞中检测到一氧化氮（NO）、前列腺素 E₂（PGE₂）和促炎细胞因子的产生。然而，我们发现蛹虫草素以浓度依赖的方式显著抑制了过量的 NO、PGE₂和促炎细胞因子的产生，而没有引起细胞毒性。此外，蛹虫草素通过阻止 IkappaB-α（IκB-α）降解抑制 NF-κB 易位，并抑制 Akt、ERK-1/2、JNK 和 p38 激酶的磷酸化。我们的结果表明，蛹虫草素对 LPS 刺激的 BV2 小胶质细胞中炎症介质产生的抑制作用与抑制 NF-κB、Akt 和 MAPK 信号通路有关。因此，蛹虫草素通过抑制激活的小胶质细胞中炎症介质的产生，可能对治疗神经退行性疾病有用。
