Anti-inflammatory effects of saponins derived from the roots of Platycodon grandiflorus in lipopolysaccharide-stimulated BV2 microglial cells
Anti-inflammatory effects of saponins derived from the roots of Platycodon grandiflorus in lipopolysaccharide-stimulated BV2 microglial cells
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DOI：
10.3892/ijmm.2013.1330
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发表时间：
2013-06-01
影响因子：
5.4
通讯作者：
Choi, Yung Hyun
中科院分区：
文献类型：
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作者：
Jang, Kyung-Jun;Kim, Hong Ki;Choi, Yung Hyun
桔梗为桔梗的根，在传统东方医学中被广泛用作食品原料和治疗多种慢性炎症性疾病。本研究观察了桔梗总皂苷(PGS)对内毒素刺激的BV2小胶质细胞产生炎症介质和细胞因子的影响。我们还研究了PGS对内毒素诱导的核因子-kappaB(NF-kappa B)活化、磷脂酰肌醇3-激酶(PI3K)/AKT和丝裂原活化蛋白激酶(MAPK)信号通路的影响。经脂多糖刺激后，BV2小胶质细胞一氧化氮(NO)、前列腺素E-2(PGE(2))和促炎细胞因子产生增加。然而，PGS以浓度依赖的方式显著抑制NO2-PGE(2)和包括白介素1-β(IL-1β)和肿瘤坏死因子-α(TNF-α)在内的促炎细胞因子的过度产生，而不产生任何细胞毒性作用。此外，PGS还可抑制NF-kappa B转位，并抑制内毒素诱导的AKT和MAPKs的磷酸化。提示PGS抑制BV2小胶质细胞内毒素刺激的炎症反应与抑制NF-kappaB活化及PI3K/AKT和MAPK信号通路有关。因此，这些发现表明，PGS可能通过抑制激活的小胶质细胞的炎症反应而用于治疗神经退行性疾病。
Radix platycodi is the root of Platycodon grandiflorus A. DC, which has been widely used as a food material and for the treatment of a number of chronic inflammatory diseases in traditional oriental medicine. In this study, the anti-inflammatory effects of the saponins isolated from radix platycodi (PGS) on the production of inflammatory mediators and cytokines in lipopolysaccharide (LPS)-stimulated BV2 murine microglial cells were examined. We also investigated the effects of PGS on LPS-induced nuclear factor-kappa B (NF-kappa B) activation and phosphoinositide 3-kinase (PI3K)/AKT and mitogen-activated protein kinase (MAPK) signaling pathways. Following stimulation with LPS, elevated nitric oxide (NO), prostaglandin E-2 (PGE(2)) and pro-inflammatory cytokine production was detected in the BV2 microglial cells. However, PGS significantly inhibited the excessive production of NO2 PGE(2) and pro- inflammatory cytokines, including interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha) in a concentration-dependent manner without causing any cytotoxic effects. In addition, PGS suppressed NF-kappa B translocation and inhibited the LPS-induced phosphorylation of AKT and MAPKs. Our results indicate that the inhibitory effect of PGS on LPS-stimulated inflammatory response in BV2 microglial cells is associated with the suppression of NF-kappa B activation and the PI3K/AKT and MAPK signaling pathways. Therefore, these findings suggest that PGS may be useful in the treatment of neurodegenerative diseases by inhibiting inflammatory responses in activated microglial cells.