探討七層塔水萃物對LPS所誘發上皮細胞發炎之抗發炎機制

脂多醣體是存在於格蘭氏陰性菌細胞壁上的成分，主要會造成急性肺傷害、呼吸失調以及慢性呼吸道發炎，且進一步可能會增加癌症罹患的風險。因此，藉由抑制脂多醣體所誘導的慢性呼吸道疾病和肺傷害就可以有效抑止發炎反應。七層塔是目前市面上的食物香料和傳統的草本植物，過去文獻有指出在七層塔油萃物中具有一些治療的功效，而對於七層塔水萃物的功效仍然不清楚。在本篇研究中發現在七層塔水萃物中分別以100 和200 μg/ml處理正常的肺上皮BEAS-2B細胞四小時後，以脂多醣體(1 μg/ml)下去刺激，可以明顯降低脂多醣體所誘導的IL-8和IL-6 mRNA的產生，而先前文獻指出說當脂多醣體刺激細胞產生IL-8和IL-6主要是跟MAPKs和PI3K/AKT路徑有關，由此，我們進一步探討七層塔水萃物抑制脂多醣體所造成的發炎反應是否是透過MAPKs和PI3K/AKT路徑。由結果可以明顯看到當以七層塔水萃物刺激下，確實可以降低脂多醣體所誘導的磷酸化MAPK家族和Akt，其中MAPK家族包含了ERK、JNK、P38。此外，我們也發現七層塔水萃物刺激下，可以透過抑制IκBα的降解，使細胞質中的NF-κB無法被送進細胞核內。綜合以上的結果，我們可以得到在七層塔水萃物刺激下，明顯降低脂多醣體所誘導的前發炎因子IL-8和IL-6 mRNA，是透過抑制MAPK家族和Akt這兩條路徑使NF-κB無法轉入到細胞核內，使下游的發炎基因無法開啟，且在最後我們也探討了另外也會造成發炎的途徑ROS，由結果得知七層塔水萃物也會抑制ROS的產生，也間接證明了七層塔水萃物具有抗氧化的能力。

關鍵字

七層塔；脂多醣體

並列摘要

Lipopolysaccharide (LPS), a main composition of Gram-negative bacteria cell wall, is a major cause of acute lung injury, respiratory distress and chronic pulmonary inflammation, which further increases the risk of lung carcionogensis. Therefore, inhibition of LPS-induced lung injury and the following chronic inflammation may play important roles in prevention or alleviation of sever lung disorder. Ocimum gratissimum (OG) is widely used as food spice and traditional herb. Oil extract of OG has shown several therapeutic properties, but the effect of aqueous extract of OG (OGE) is still unclear. In the present study, we found that LPS (1 ug/ml) significantly induced the mRNA expression of proinflammatory cytokines IL-8 and IL-6 of epithelial cell BEAS-2B, which was effectively decreased by OGE pretreatment (100 and 200 ug/ml 4 h). Previous studies have shown that mitogen-activated protein kinases (MAPKs) and Akt pathway involved in the mRNA expression of IL-8 and IL-6 induced by LPS. Accordingly, we further investigated the effect of OGE on LPS-induced MAPKs and Akt cascades. Our results revealed that OGE significantly inhibited the LPS-induced phosphorylation of MAPKs and Akt, including extracellular signal-regulated kinase1/2 (ERK1/2), p38 MAPK (p38), c-jun NH2-terminal kinase (JNK) and Akt . Additionally, we also found that OGE inhibited the translocation of p65/NF-kB into nucleus which may result from the suppression of IkBa degradation. Taken together, our finings indicated that OGE significantly diminished the LPS-induced mRNA expression of proinflammatory cytokines IL-8 and IL-6 in BEAS-2B cells, which may result from inhibition of MAPKs and Akt activation and suppressing ROS production, and the following reduced translocation of NF-kB into nucleus.

並列關鍵字

Ocimum gratissmum ； Lipopolysaccharide

參考文獻

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探討七層塔水萃物對LPS所誘發上皮細胞發炎之抗發炎機制

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