National R & D Center for Edible Fungus Processing Technology, Henan University, Kaifeng 475004, China.
Joint International Research Laboratory of Food & Medicine Resource Function of Henan Province, Kaifeng 475004, China.
Acta Biochim Biophys Sin (Shanghai). 2021 Feb 4;53(2):229-237. doi: 10.1093/abbs/gmaa160.
The dry bulbs of Fritillaria cirrhosa species can help resolve phlegm, soothe cough, clear heat, and moisten the lung, and the main active components responsible for these effect are its alkaloids. However, it is unclear whether or how edpetiline in Fritillaria can inhibit the excessive inflammatory response and oxidative stress. In this research, we aimed to examine this aspect using lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages as an inflammatory model. The quantitative real-time polymerase chain reaction and western blot analysis results showed that edpetiline significantly inhibited the content and mRNA expression levels of proinflammatory cytokines (TNF-α and IL-6) in LPS-induced RAW264.7 cells, significantly increased the mRNA expression of IL-4 (anti-inflammatory cytokine), and markedly downregulated the inflammatory mediators inductible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) mRNA and protein expression levels. The oxidative stress induced by LPS was also inhibited by edpetiline, as the level of intracellular reactive oxygen species decreased notably. Edpetiline may exert anti-inflammatory and antioxidant effects through inhibiting the phosphorylation of IκB and the nuclear transcription of nuclear transcription factor-κB p65 and decreasing the phosphorylation of p38 and ERK in the mitogen-activated protein kinase signaling pathway, without activating the JNK/mitogen-activated protein kinase signaling pathway. These findings suggest that edpetiline may be a potential therapeutic agent for the prevention or treatment of inflammation- and oxidative stress-related pathophysiological processes and diseases.
百合科贝母属植物的干鳞茎具有化痰止咳、清热润肺的功效，其主要活性成分生物碱对此类功效的发挥起着重要作用。然而，贝母属植物中的紫堇灵（edpetiline）是否以及如何抑制过度的炎症反应和氧化应激尚不清楚。本研究旨在采用脂多糖（lipopolysaccharide，LPS）刺激的 RAW264.7 巨噬细胞作为炎症模型对此进行研究。实时定量聚合酶链式反应和 Western blot 分析结果表明，紫堇灵可显著抑制 LPS 诱导的 RAW264.7 细胞中促炎细胞因子（TNF-α 和 IL-6）的含量和 mRNA 表达水平，显著增加抗炎细胞因子（IL-4）的 mRNA 表达，并显著下调炎症介质诱导型一氧化氮合酶（inducible nitric oxide synthase，iNOS）和环氧化酶-2（cyclooxygenase-2，COX-2）mRNA 和蛋白表达水平。LPS 诱导的氧化应激也被紫堇灵抑制，因为细胞内活性氧水平明显降低。紫堇灵可能通过抑制 IκB 磷酸化和核转录因子-κB p65 的核转录，以及降低丝裂原活化蛋白激酶信号通路中 p38 和 ERK 的磷酸化，而不激活 JNK/丝裂原活化蛋白激酶信号通路，发挥抗炎和抗氧化作用。这些发现表明，紫堇灵可能是预防或治疗炎症和氧化应激相关病理生理过程和疾病的潜在治疗药物。
