Curcumin protects against acute renal injury by suppressing JAK2/STAT3 pathway in severe acute pancreatitis in rats

Abstract

Abstract. The aim of the present study was to investigate the effect of curcumin on acute renal injury in a rat model of severe acute pancreatitis (SAP). A SAP model with acute kidney injury was established in rats by retrograde injection of 5% sodium taurocholate into the pancreatic duct. The serum amylase, creatinine (Cr) and blood urea nitrogen (BUN) levels in rats were measured. Hematoxylin and eosin staining was used to assess pancreatic and renal histological changes. Serum tumor necrosis factor (TNF)-α and interleukin (IL)-6 levels were measured using ELISA kits. Renal protein levels of Janus kinase (JAK) 2/signal transducer and activator of transcription (STAT) 3 pathway components were determined by western blot assay. The results showed that curcumin significantly decreased serum amylase, Cr and BUN levels, and alleviated pancreatic and renal histological changes in SAP rats. Furthermore, curcumin markedly decreased serum TNF-α and IL-6 levels and downregulated renal protein levels of JAK2/STAT3 pathway components. These results proved that curcumin ameliorates acute renal injury in a rat model of SAP. The molecular mechanism of its effect may be associated with the suppression of the JAK2/STAT3 pathway to reduce TNF-α and IL-6 levels in SAP-induced acute renal injury. Therefore, the findings of the present study revealed the potential use of curcumin for the prevention and treatment of SAP and the associated renal injury. IntroductionSevere acute pancreatitis (SAP), an acute inflammatory condition of the pancreas, is considered to be a paradigm of sterile inflammation leading to systemic multiple organ dysfunction syndrome (MODS) and death. Acute renal injury (ARI) is one of the main complications of SAP and significantly increases the mortality rate of patients with AP (66.6 vs. 14.5%) (1). However, the underlying mechanisms of ARI occurring in patients with SAP have remained to be clarified. Increasing evidence has indicated that pro-inflammatory cytokines, including tumor necrosis factor-α (TNF-α) and interleukin (IL)-6, have an important role in the pathological mechanisms of SAP and SAP-associated organ failure (2-4). Therefore, inhibiting the transcription and translation of mediators to reduce the secretion of pro-inflammatory factors may ameliorate inflammation and renal failure in SAP.Signal transducers and activators of transcription (STATs), a protein family comprised of seven members (STAT1, -2, -3, -4, -5a, -5b and -6), generally transduce signals from activated receptors or intracellular kinases to the nucleus, thus activating and regulating gene transcription (5). The Janus kinase 2 (JAK2)/STAT3 pathway is well known to be involved in the immune response of numerous cytokines, including TNF-α and IL-6 (6). In addition, evidence derived from numerous clinical and experimental studies suggests the involvement of the JAK2/STAT3 pathway in pancreatitis (7-9) or renal diseases (10-12).Curcumin (diferuloylmethane), the active phytochemical component of turmeric (a spice used mostly in Asia) h...

Curcumin-Mediated Apoptotic Cell Death in Papillary Thyroid Cancer and Cancer Stem-Like Cells through Targeting of the JAK/STAT3 Signaling Pathway

“…Further, it is also involved in the modulation of aberrant epigenetics mechanisms and the expression of noncoding RNA [20]. Interestingly, a number of studies have shown that curcumin exerts its pharmacological action by targeting JAK/STAT3 signaling [22][23][24]. Anticancer drugs, such as cisplatin, that are used in chemotherapy (one of the therapeutic options used by clinicians) have been found to be associated with various critical complications, including drug resistance in papillary thyroid cancer (PTC) patients [11], and the available literature has shown that a number of natural products, including curcumin, have shown synergistic action with anticancer drugs [25][26][27][28].…”

Curcumin Attenuates Inflammation in a Severe Acute Pancreatitis Animal Model by Regulating TRAF1/ASK1 Signaling

“…It is believed that curcumin can reducing levels of proinflammatory cytokines, including interleukins (IL) and tumor necrosis factors (TNF) in several inflammation disorders such as bacterial infection and autoimmune arthritis [ 6 ]. Moreover, several previous studies suggested the protective effects of curcumin in animal models of SAP [ 7 ]. However, these studies did not describe the specific molecular mechanisms involved.…”

An integrated strategy for identifying new targets and inferring the mechanism of action: taking rhein as an example

“…Here, the enrichment analysis was innovatively used for the target identification since the enriched proteins often played similar and important biological roles in the biological process, and were likely to be the targets of the bioactive molecule. For example, the activation of JAK2 and STAT3 induced the expression of TNF-α and IL-6 in acute renal injury, while curcumin protected against the acute renal injury by distinctly inhibiting the activation of JAK2 and STAT3 in the JAK2/STAT3 pathway [ 47 ]. As shown in Fig.…”