School of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, China.
State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
FASEB J. 2021 Nov;35(11):e21985. doi: 10.1096/fj.202100981RR.
Inflammation is broadly recognized as an important factor in the pathogenesis of acute kidney injury (AKI), but pharmacological approaches to alleviate inflammation in AKI have not been proved successful in clinical trials. Macrophage infiltration into renal tissue promotes inflammatory responses that contribute to the pathogenesis of AKI. Suppression of renal tissue inflammatory responses is postulated to improve renal injury of patients and animals. Rhodomeroterpene (RMT) is a novel meroterpenoid isolated from the Rhododendron genus that was shown to exert anti-inflammatory action in vivo or in vitro in this study. We investigated the treatment effects of RMT on LPS-induced sepsis and two different AKI models. The results showed that pretreatment with RMT (30 mg kg d , ip, for 3 days) significantly inhibited acute inflammatory responses in LPS-induced septic mice. In both renal ischemia-reperfusion injury (I/R) and sepsis-induced AKI models, RMT (30 mg kg d , ip, for 3 days) ameliorated renal function and injury and alleviated inflammation by reducing the infiltration of immune cells, including macrophages and neutrophils. Furthermore, our study demonstrated that RMT inhibits inflammatory responses in macrophages. The anti-inflammatory effects of RMT may be due to the inactivation of the IKK/NF-κB and PI3K/PDK1/Akt inflammatory signaling pathways in macrophages. Collectively, our findings indicate that RMT ameliorates renal injury and alleviates the renal inflammatory state in different AKI models, suggesting that RMT may be a potential agent for the treatment of AKI.
炎症被广泛认为是急性肾损伤 (AKI) 发病机制中的一个重要因素，但在 AKI 中减轻炎症的药物治疗方法在临床试验中并未被证明是成功的。巨噬细胞浸润到肾组织中会促进炎症反应，从而导致 AKI 的发病机制。抑制肾组织炎症反应被认为可以改善患者和动物的肾损伤。Rhodomeroterpene (RMT) 是一种从杜鹃花属植物中分离出来的新型倍半萜类化合物，本研究表明它在体内或体外具有抗炎作用。我们研究了 RMT 对 LPS 诱导的败血症和两种不同 AKI 模型的治疗效果。结果表明，RMT（30mgkg -1 d -1 ，ip，预处理 3 天）显著抑制了 LPS 诱导的败血症小鼠的急性炎症反应。在肾缺血再灌注损伤 (I/R) 和败血症诱导的 AKI 模型中，RMT（30mgkg -1 d -1 ，ip，预处理 3 天）通过减少免疫细胞（包括巨噬细胞和中性粒细胞）的浸润，改善了肾功能和损伤，并缓解了炎症。此外，我们的研究表明，RMT 抑制了巨噬细胞中的炎症反应。RMT 的抗炎作用可能是由于其在巨噬细胞中抑制了 IKK/NF-κB 和 PI3K/PDK1/Akt 炎症信号通路。综上所述，我们的研究结果表明，RMT 可改善不同 AKI 模型中的肾损伤并减轻肾炎症状态，表明 RMT 可能是治疗 AKI 的一种潜在药物。
