Basic Medical College, Guizhou University of Traditional Chinese Medicine, Guian District, Guiyang 550025, China.
Guangdong Provincial Hospital of Chinese Medicine, Guangdong Provincial Academy of Chinese Medical Sciences, State Key Laboratory of Dampness Syndrome of Chinese Medicine, Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong-Hong Kong-Macau Joint Lab on Chinese Medcine and Immune Disease Research, Guangzhou 510006, China.
Molecules. 2022 Sep 22;27(19):6236. doi: 10.3390/molecules27196236.
Akebia saponin D (ASD) is derived from the Wall. ex Henry, which is a traditional Chinese medicine commonly used to treat rheumatic arthritis (RA). However, the in-depth mechanism of the anti-inflammatory effect of ASD is still unclear. This study aimed to preliminarily explore the anti-inflammatory effect of ASD and the underlying mechanisms from the perspective of DNA methylation and inflammation-related pathways. We found that ASD significantly reduced the production of multiple inflammatory mediators, including nitric oxide (NO) and prostaglandin E (PGE), in LPS-induced RAW264.7 cells. The expression of DNA methyltransferase (DNMT) 3b and inducible nitric oxide synthase (iNOS) was also obviously inhibited by the ASD treatment. The protein and mRNA levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were also significantly inhibited by ASD. ASD inhibited the macrophage M1 phenotype, inhibited the high level of DNMT3b, and downregulated the signal transducer and activator of the transcription 3 (STAT3) pathway to exert its anti-inflammatory activity. Furthermore, DNMT3b siRNA and Nrf2 siRNA significantly promoted the anti-inflammatory effect of ASD. Our study demonstrates for the first time that ASD inhibits the IL-6-STAT3-DNMT3b axis and activates the nuclear factor-E2-related factor 2 (Nrf2) signaling pathway to achieve its inhibitory effect on inflammatory reactions.
三叶木通皂苷 D（ASD）来源于木通科木通属三叶木通，是一种传统中药，常用于治疗风湿性关节炎（RA）。然而，ASD 抗炎作用的深入机制尚不清楚。本研究旨在从 DNA 甲基化和炎症相关途径的角度初步探讨 ASD 的抗炎作用及其潜在机制。我们发现 ASD 可显著降低 LPS 诱导的 RAW264.7 细胞中多种炎症介质的产生，包括一氧化氮（NO）和前列腺素 E（PGE）。ASD 处理还明显抑制 DNA 甲基转移酶（DNMT）3b 和诱导型一氧化氮合酶（iNOS）的表达。ASD 还显著抑制白细胞介素-6（IL-6）和肿瘤坏死因子-α（TNF-α）的蛋白和 mRNA 水平。ASD 抑制巨噬细胞 M1 表型，抑制高水平的 DNMT3b，并下调信号转导和转录激活因子 3（STAT3）通路，从而发挥其抗炎活性。此外，DNMT3b siRNA 和 Nrf2 siRNA 显著促进了 ASD 的抗炎作用。本研究首次证明，ASD 抑制了 IL-6-STAT3-DNMT3b 轴，并激活了核因子-E2 相关因子 2（Nrf2）信号通路，从而抑制炎症反应。
