Trans-cinnamaldehyde attenuates renal ischemia/reperfusion injury through suppressing inflammation via JNK/p38 MAPK signaling pathway.

Inflammation is the major contributor to the mechanisms of acute kidney injury due to renal ischemia-reperfusion injury (IRI). Trans-cinnamaldehyde (TCA) is a main bioactive component extracted from the bark of cinnamon and has been proved to have good anti-inflammatory properties. The current study was to demonstrate the effect of TCA on renal IRI and explore its specific mechanism. C57BL/6J mice were injected prophylactically intraperitoneally for TCA 3 days, and IRI for 24 h. In parallel, Human Kidney-2 (HK-2) cells were prophylactically treated with TCA, and then exposed to oxygen glucose deprivation/reperfusion (OGD/R) and cobalt chloride (CoCl2). TCA was found to significantly attenuate renal pathological changes and renal dysfunction, and inhibit gene and protein expression of kidney injury molecule-1 (Kim-1) and neutrophil gelatinase-associated lipocalin (NGAL). Furthermore, TCA significantly suppressed the expression of TNF-α, IL-6, IL-1β, COX-2, iNOS, and MCP-1. Mechanistically, the activation of the JNK/p38 MAPK signaling pathway was inhibited by TCA in renal IRI as well as in OGD/R and CoCl2-stimulated cells. However, following pretreatment with anisomycin before OGD/R treatment, we found that the activation of the JNK/p38 MAPK signaling pathway was significantly enhanced, and concomitant abrogation of the TCA inhibitory effect on the JNK/p38 MAPK signaling pathway, which was followed by a worsening of cell injury that was characterized by an increased number of cell necrosis and an increase in the expression of Kim-1, NGAL as well as proinflammatory factors (IL-6, IL-1β, iNOS). In summary, TCA inhibited renal inflammation via the JNK/p38 MAPK signaling pathway and attenuated renal IRI.

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