Nguyen Thuy-Duong, Nguyen Thi-Hong-Anh, Do Thi-Ha, Tran Van Thi-Hong, Nguyen Hoang-Anh, Pham Duc-Vinh
Hanoi University of Pharmacy, Hanoi, Viet Nam.
Vietnam National Institute of Medicinal Materials, Hanoi, Viet Nam.
Heliyon. 2022 Mar 5;8(3):e09070. doi: 10.1016/j.heliyon.2022.e09070. eCollection 2022 Mar.
, a medicinal plant traditionally used to treat fever, pain, and inflammation in Vietnam, has been reported to possess prominent anti-inflammatory activity. This study examined the active constituents and molecular mechanisms underlying these anti-inflammatory effects using bioactivity-guided isolation in combination with cell-based assays and animal models of inflammation. Among the isolated compounds, the triterpenoid (21α)-22-hydroxyhopan-3-one () showed the most potent inhibitory effect on COX-2 expression in LPS-stimulated Raw 264.7 macrophages. Furthermore, suppressed the expression of the inflammatory mediators iNOS, IL-1β, INFβ, and TNFα in activated Raw 264.7 macrophages and alleviated the inflammatory response in carrageenan-induced paw oedema and a cotton pellet-induced granuloma model. Mechanistically, the anti-inflammatory effects of were mediated decreasing cellular reactive oxygen species (ROS) levels by inhibiting NADPH oxidases (NOXs) and free radical scavenging activities. By downregulating ROS signalling, reduced the activation of MAPK signalling pathways, leading to decreased AP-1-dependent transcription of inflammatory mediators. These findings shed light on the chemical constituents that contribute to the anti-inflammatory actions of . and suggest that is a promising candidate for treating inflammation-related diseases.
一种传统上用于治疗越南发热、疼痛和炎症的药用植物,据报道具有显著的抗炎活性。本研究结合基于细胞的试验和炎症动物模型,采用生物活性导向分离法研究了这些抗炎作用的活性成分和分子机制。在分离出的化合物中,三萜类化合物(21α)-22-羟基何帕-3-酮()对脂多糖刺激的Raw 264.7巨噬细胞中COX-2的表达显示出最有效的抑制作用。此外,在活化的Raw 264.7巨噬细胞中抑制了炎症介质iNOS、IL-1β、INFβ和TNFα的表达,并减轻了角叉菜胶诱导的爪肿胀和棉球诱导的肉芽肿模型中的炎症反应。从机制上讲,的抗炎作用是通过抑制NADPH氧化酶(NOXs)和自由基清除活性来降低细胞活性氧(ROS)水平介导的。通过下调ROS信号,减少了MAPK信号通路的激活,导致炎症介质的AP-1依赖性转录减少。这些发现揭示了有助于发挥抗炎作用的化学成分,并表明是治疗炎症相关疾病的有希望的候选药物。