The First School of Clinical Medicine, Guangzhou University of Chinese Medicine, Guangzhou, 510405, Guangdong, China.
Postdoctoral Research Station, Guangzhou University of Chinese Medicine, Guangzhou, 510405, Guangdong, China.
J Nat Med. 2023 Sep;77(4):898-915. doi: 10.1007/s11418-023-01741-7. Epub 2023 Aug 19.
In diabetic patients, diabetic cardiomyopathy (DCM) is one of the most common causes of death. The inflammatory response is essential in the pathogenesis of DCM. Rhein, an anthraquinone compound, is extracted from the herb rhubarb, demonstrating various biological activities. However, it is unclear whether rhein has an anti-inflammatory effect in treating DCM. In our research, we investigated the anti-inflammatory properties as well as its possible mechanism. According to the findings in vitro, rhein could to exert an anti-inflammatory effect by reducing the production of NO, TNF-α, PGE, iNOS, and COX-2 in RAW264.7 cells that had been stimulated with advanced glycosylation end products (AGEs). In addition, rhein alleviated H9C2 cells inflammation injury stimulated by AGEs/macrophage conditioned medium (CM). In vivo have depicted that continuous gavage of rhein could improve cardiac function and pathological changes. Moreover, it could inhibit the accumulation of AGEs and infiltration of inflammatory factors inside the heart of rats having DCM. Mechanism study showed rhein could suppress IKKβ and IκB phosphorylation via down-regulating TRAF6 expression to inhibit NF-κB pathway in AGEs/CM-induced H9C2 cells. Moreover, the anti-inflammation effect of rhein was realized through down-regulation phosphorylation of JNK MAPK. Furthermore, we found JNK MAPK could crosstalk with NF-κB pathway by regulating IκB phosphorylation without affecting IKKβ activity. And hence, the protective mechanism of rhein may involve the inhibiting of the TRAF6-NF/κB pathway, the JNK MAPK pathway, and the crosstalk between the two pathways. These results suggested that rhein may be a promising drug candidate in anti-inflammation and inflammation-related DCM therapy.
在糖尿病患者中，糖尿病心肌病 (DCM) 是最常见的死亡原因之一。炎症反应是 DCM 发病机制中的关键因素。大黄素是一种蒽醌类化合物，从大黄植物中提取，具有多种生物活性。然而，目前尚不清楚大黄素在治疗 DCM 中是否具有抗炎作用。在我们的研究中，我们研究了其抗炎特性及其可能的机制。根据体外研究结果，大黄素可通过降低 AGEs 刺激的 RAW264.7 细胞中 NO、TNF-α、PGE、iNOS 和 COX-2 的产生来发挥抗炎作用。此外，大黄素可减轻 AGEs/巨噬细胞条件培养基 (CM) 刺激的 H9C2 细胞炎症损伤。体内研究表明，连续灌胃大黄素可改善 DCM 大鼠的心功能和病理变化。此外，它可以抑制 AGEs 在心脏中的积累和炎症因子的浸润。机制研究表明，大黄素通过下调 TRAF6 表达抑制 IKKβ 和 IκB 磷酸化，从而抑制 AGEs/CM 诱导的 H9C2 细胞中 NF-κB 通路。此外，大黄素通过下调 JNK MAPK 的磷酸化来实现其抗炎作用。此外，我们发现 JNK MAPK 可以通过调节 IκB 磷酸化而不影响 IKKβ 活性来与 NF-κB 通路发生交联。因此，大黄素的保护机制可能涉及抑制 TRAF6-NF/κB 通路、JNK MAPK 通路以及两条通路之间的交联。这些结果表明，大黄素可能是一种有前途的抗炎和炎症相关 DCM 治疗药物。
