4.6 Article

Akebia Saponin D Inhibits the Inflammatory Reaction by Inhibiting the IL-6-STAT3-DNMT3b Axis and Activating the Nrf2 Pathway

期刊

MOLECULES
卷 27, 期 19, 页码 -

出版社

MDPI
DOI: 10.3390/molecules27196236

关键词

Dipsacus asper Wall; ex Henry; Akbia saponin D; DNMT3b; p-STAT3; Nrf2

资金

  1. Young Scientific and Technological Talent Growth Project of Guizhou Provincial Department of Education [[2021]194]
  2. Special Research Project on Science and Technology of Traditional Chinese Medicine and Ethnic Medicine in Guizhou Province [QZYY-2021-012]

向作者/读者索取更多资源

This study revealed the anti-inflammatory mechanisms of Akebia saponin D, including the inhibition of various inflammatory mediators, reduction of DNA methyltransferase and inducible nitric oxide synthase expression, as well as suppression of IL-6 and TNF-α levels. Additionally, ASD inhibited the IL-6-STAT3-DNMT3b axis and activated the Nrf2 signaling pathway to achieve its anti-inflammatory effects.
Akebia saponin D (ASD) is derived from the Dipsacus asper 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-2 (PGE(2)), 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-alpha (TNF-alpha) 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.

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