Curcumin attenuates inflammation and cell apoptosis through regulating NF-κB and JAK2/STAT3 signaling pathway against acute kidney injury

Abstract

Curcumin alleviates septic acute kidney injury (SAKI); however, the underlying mechanism remained unclear. To explore this, SAKI cell model and mice model were conducted by using LPS and cecal ligation and puncture (CLP), respectively. Cell counting kit-8 (CCK-8) and enzyme-linked immunosorbent assay (ELISA) assays indicated that LPS reduced the viability, but upregulated the levels of tumor necrosis factor (TNF)-α and interleukin (IL)-6, whereas Curcumin pretreatment had no effect on viability, but reduced the levels of TNF-α and IL-6. Further assays showed that Curcumin partly attenuated the LPS-induced injury as the viability was enhanced, TNF-α and IL-6 expressions and cell apoptosis rates were reduced. Western blot analysis indicated that Janus kinase (JAK) 2/signal transducer and activator of transcription (STAT) 3, p-65-NF-κB and cell apoptosis pathways were activated by LPS but suppressed by Curcumin. Mice SAKI model further indicated that the serum Cystatin C (Cys-C), creatinine (Cr) and blood urea nitrogen (BUN) were increased within 24 h of model construction while those indicators were decreased at 48 h. Pretreated with Curcumin, NF-κB inhibitor (PDTC) or JAK2 inhibitor (AG-490) could weaken the renal histological injury and the increased serum Cys-C, Cr and BUN, IL-6 and TNF-α induced by CLP. Moreover, PDTC, AG-490 and Curcumin all significantly reversed the previously increased expressions of p-JAK2/STAT3, p-p65 and proapoptotic proteins in the mice with AKI. The present study revealed that Curcumin attenuated SAKI through inhibiting NF-κB and JAK2/STAT3 signaling pathways, and proposed that Curcumin could be a potential therapeutic agent for treating SAKI.

Isoquercitrin Ameliorates Cisplatin-Induced Nephrotoxicity Via the Inhibition of Apoptosis, Inflammation, and Oxidative Stress

“…As expected, our results elucidated that IQC normalized cisplatin-induced increase of inflammatory markers. A previous investigation demonstrated that p65 is involved in cisplatin mediated renal toxicity (Zhu et al, 2020). Here, we also observed that IQC decreased the upregulation of both p65 and P-p65.…”

Curcumin plays a protective role against septic acute kidney injury by regulating the TLR9 signaling pathway

“…The change in TLR9 expression is usually considered to be a sign of the development of various inflammation-related diseases, while Cur can reduce TLR9 expression in the rat liver and act as an antiinflammatory and immunomodulatory agent to treat liver inflammation (28). The most recent study has revealed that Cur could ameliorate the SAKI induced by CLP, but they only detected the kidney protective effect of the Cur (29). While in this paper, we have found that the Cur could significantly decrease the mortality caused by AKI, and we also determined that Cur could prevent multiple organs from dysfunction caused by AKI, meanwhile, our results were almost based on the in vivo data, which may be more coincidence with the pathogenesis of AKI in human.…”

Erythropoietin Attenuates Experimental Contrast-Induced Nephrology: A Role for the Janus Kinase 2/Signal Transducer and Activator of Transcription 3 Signaling Pathway

“…It was reported that the phosphorylated activation of JAK2/STAT3 played a part in the induction of apoptosis, autophagy, inflammation, and oxidative stress and that the activation of the JAK2-STAT3 signaling pathway protected tissue against acute injury in some studies (35)(36)(37). In contrast, the renoprotective effect of curcumin in AKI caused by lipopolysaccharide (LPS) or severe acute pancreatitis may be associated with inflammation reduction mediated by suppression of JAK2/STAT3 signaling pathway (38,39). In our study, increased phosphorylation of JAK2/STAT3 after EPO treatment alleviated CIN by ameliorating cell apoptosis and pyroptosis in vivo and in vitro.…”