A novel indole compound MA-35 attenuates renal fibrosis by inhibiting both TNF-α and TGF-β₁ pathways.

ABSTRACT: Renal fibrosis is closely related to chronic inflammation and is under the control of epigenetic regulations. Because the signaling of transforming growth factor-β₁ (TGF-β₁) and tumor necrosis factor-α (TNF-α) play key roles in progression of renal fibrosis, dual blockade of TGF-β₁ and TNF-α is desired as its therapeutic approach. Here we screened small molecules showing anti-TNF-α activity in the compound library of indole derivatives. 11 out of 41 indole derivatives inhibited the TNF-α effect. Among them, Mitochonic Acid 35 (MA-35), 5-(3, 5-dimethoxybenzyloxy)-3-indoleacetic acid, showed the potent effect. The anti-TNF-α activity was mediated by inhibiting IκB kinase phosphorylation, which attenuated the LPS/GaIN-induced hepatic inflammation in the mice.

SUBMITTER: Shima H 

PROVIDER: S-EPMC5432497 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature