Laboratory of Molecular and Pharmacological Cell Biology, College of Pharmacy, Chung-Ang University, Seoul 06974, Republic of Korea.
Laboratory of Biomedical Mass Spectrometry, College of Pharmacy, Chung-Ang University, Seoul 06974, Republic of Korea.
Biomed Pharmacother. 2023 Dec;168:115746. doi: 10.1016/j.biopha.2023.115746. Epub 2023 Oct 19.
Mikania cordata (Burm. f.) B.L. Rob. has been traditionally used in tropical countries throughout Asia and Africa to treat gastric ulcers, dyspepsia, and dysentery. However, the mechanisms responsible for its anti-inflammatory and antioxidant activities are not fully understood. Therefore, this study sought to investigate the anti-inflammatory and antioxidant effects of methanol extracts of M. cordata (MMC) on inflammation and oxidative stress in lipopolysaccharide (LPS)-stimulated murine RAW 264.7 macrophages and elucidate its underlying regulatory mechanism. MMC significantly suppressed the production of nitric oxide (NO) and prostaglandin E (PGE) in LPS-stimulated RAW 264.7 macrophages by downregulating the expression of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) at both the mRNA and protein levels. Moreover, MMC effectively reduced the mRNA expression levels and production of pro-inflammatory cytokines, including interleukin-6 (IL-6), IL-1β, and tumor necrosis factor-α (TNF-α). These suppressive effects of MMC on pro-inflammatory mediators and cytokines were mediated through the inhibition of transforming growth factor beta-activated kinase 1 (TAK1), which subsequently blocked the activation of nuclear factor-κB (NF-κB) and mitogen-activated protein kinases (MAPKs). MMC also upregulated the nuclear factor erythroid-2-related factor 2 (Nrf2) by inducing the degradation of Kelch-like ECH-related protein 1 (Keap1), an Nrf2-specific E3 ligase. Accordingly, MMC enhanced Nrf2 target gene expression of anti-oxidative regulators such as heme oxygenase-1 (HO-1) and NAD(P)H quinone oxidoreductase 1 (NQO1). However, it had minimal effect on the DPPH radical scavenging capacity in vitro. Collectively, these findings demonstrate that MMC holds promise as a potential therapeutic agent for alleviating inflammation-related diseases and oxidative stress.
蔓泽兰（Burm. f.）B.L. Rob. 在整个亚洲和非洲的热带国家被传统用于治疗胃溃疡、消化不良和痢疾。然而，其抗炎和抗氧化活性的机制尚未完全阐明。因此，本研究旨在探讨蔓泽兰甲醇提取物（MMC）对脂多糖（LPS）刺激的小鼠 RAW 264.7 巨噬细胞炎症和氧化应激的抗炎和抗氧化作用，并阐明其潜在的调节机制。MMC 通过下调诱导型一氧化氮合酶（iNOS）和环氧化酶-2（COX-2）的 mRNA 和蛋白水平，显著抑制 LPS 刺激的 RAW 264.7 巨噬细胞中一氧化氮（NO）和前列腺素 E（PGE）的产生。此外，MMC 还能有效降低促炎细胞因子白细胞介素-6（IL-6）、IL-1β和肿瘤坏死因子-α（TNF-α）的 mRNA 表达水平和产生。MMC 对促炎介质和细胞因子的这些抑制作用是通过抑制转化生长因子β激活激酶 1（TAK1）介导的，从而阻断核因子-κB（NF-κB）和丝裂原活化蛋白激酶（MAPKs）的激活。MMC 还通过诱导 Kelch 样 ECH 相关蛋白 1（Keap1）的降解，上调核因子红细胞 2 相关因子 2（Nrf2），Keap1 是 Nrf2 特异性 E3 连接酶。因此，MMC 增强了血红素加氧酶-1（HO-1）和 NAD（P）H 醌氧化还原酶 1（NQO1）等抗氧化调节剂的 Nrf2 靶基因表达。然而，它对体外 DPPH 自由基清除能力的影响很小。综上所述，这些发现表明 MMC 有望成为缓解炎症相关疾病和氧化应激的潜在治疗剂。
