Anti-renal fibrosis and anti-inflammation effect of urolithin B, ellagitannin-gut microbial-derived metabolites in unilateral ureteral obstruction rats

• Published in: Journal of functional foods 2020-02, Vol.65, p.103748, Article 103748
• Main Authors: Li, Qiaoling, Li, Kuangyu, Chen, Zhenzhen, Zhou, Benhong
• Format: Article
• Language: English
• Subjects: Fibrosis; HK-2 cells; Inflammation; TGF-β1; Unilateral ureteral obstruction (UUO); Urolithin B
• ISSN: 1756-4646; 2214-9414
• DOI: 10.1016/j.jff.2019.103748

[Display omitted] •Renal fibrosis model was established by unilateral ureteral obstruction (UUO) rats.•Urolithin B (UB) ameliorated renal function and pathological changes in UUO rats.•UB inhibited the proliferation of TGF-β1-induced fibrotic in HK-2 cells in vitro.•UB has anti-renal fibrosis effect via TGF-β/Smad and TLR4/NF-кB signaling.•UB exerts its anti-inflammatory effect in UUO-induced renal fibrosis. Urolithin B, gut microbiota metabolite of ellagitannins, contributes toward multiple health benefits attributed to ellagitannin-rich foods. The influence of urolithin B on unilateral ureteral obstruction (UUO) induced renal fibrosis and TGF-β1 induced HK-2 cells and the underlying mechanism was investigated. The results showed UUO-induced kidney injury was significantly ameliorated as shown by the improvement of renal function (BUN and Cr), kidney morphology and the suppression of renal tubular injury markers of TGF-β1, Ang II, alpha-SMA and Col IV mRNA levels. Meanwhile, the renal inflammatory induced by UUO were also strikingly attenuated in urolithin B-treated rats (TNF-α, IL-6 and MCP-1). In vitro, urolithin B treatment markedly inhibited TGF-β1-induced HK-2 cells fibrosis and proliferation, suppressed TGF-β1 and NF-κB activation. This works indicated that urolithin B contributes critically to renal inflammation in vivo and in vitro, involving the inhibition on TGF-β/Smad and TLR4/NF-кB signaling activation.