Lee Junho, Uddin Salah, Jeong Chohee, Han Sang Beom, Cho Sayeon
Laboratory of Molecular and Pharmacological Cell Biology, College of Pharmacy, Chung-Ang University, Seoul 06974, Republic of Korea.
Botanika, Botanical Research Centre, Tejgaon, Dhaka 1208, Bangladesh.
Biomed Pharmacother. 2025 Jul 18;190:118372. doi: 10.1016/j.biopha.2025.118372.
Euphorbia cotinifolia L. (E. cotinifolia L.) is distributed in temperate and tropical regions. It exhibits various biological activities, including antioxidant, antimicrobial, and antiviral properties. Although its antioxidant properties have been described, its regulatory molecular mechanisms remain poorly understood and its anti-inflammatory effects have not been studied yet. This study investigated the effects of methanol extract of E. cotinifolia L. (MECL) on inflammation and oxidative stress in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. MECL significantly suppressed the production of inflammatory mediators, including nitric oxide (NO) and prostaglandin E (PGE), by downregulating inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). In addition, MECL inhibited the production of key pro-inflammatory cytokines, including interleukin-6 (IL-6), IL-1β, and tumor necrosis factor-α (TNF-α), by suppressing of nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways. It suppressed TAK1 phosphorylation, thereby inhibiting IKKα/β. Consequently, IκBα was stabilized, preventing its degradation and thereby suppressing NF-κB p65 phosphorylation and nuclear translocation. Additionally, MECL attenuated the activation of JNK, ERK, and p38 MAPK signaling. It also activated nuclear factor erythroid 2-related factor 2 (Nrf2), which is a key antioxidant transcription factor, upregulating its target genes, heme oxygenase-1 and NAD(P)H quinone dehydrogenase 1, which are essential for oxidative stress defense. These findings suggested that MECL mitigated inflammation and oxidative stress by regulating TAK1-mediated NF-κB/MAPK signaling and Nrf2 activation. Therefore, it showed potential as a natural therapeutic candidate for inflammatory diseases.
紫锦木（Euphorbia cotinifolia L.）分布于温带和热带地区。它具有多种生物活性，包括抗氧化、抗菌和抗病毒特性。尽管其抗氧化特性已有描述，但其调控分子机制仍知之甚少，且其抗炎作用尚未得到研究。本研究调查了紫锦木甲醇提取物（MECL）对脂多糖（LPS）刺激的RAW 264.7巨噬细胞炎症和氧化应激的影响。MECL通过下调诱导型一氧化氮合酶（iNOS）和环氧化酶-2（COX-2），显著抑制了包括一氧化氮（NO）和前列腺素E（PGE）在内的炎症介质的产生。此外，MECL通过抑制核因子κB（NF-κB）和丝裂原活化蛋白激酶（MAPK）信号通路，抑制了关键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）的产生。它抑制TAK1磷酸化，从而抑制IKKα/β。因此，IκBα得以稳定，防止其降解，从而抑制NF-κB p65磷酸化和核转位。此外，MECL减弱了JNK、ERK和p38 MAPK信号的激活。它还激活了关键的抗氧化转录因子核因子红细胞2相关因子2（Nrf2），上调了其靶基因血红素加氧酶-1和NAD（P）H醌脱氢酶1，这两种基因对氧化应激防御至关重要。这些发现表明，MECL通过调节TAK1介导的NF-κB/MAPK信号和Nrf2激活减轻了炎症和氧化应激。因此，它显示出作为炎症性疾病天然治疗候选药物的潜力。
