Curcumin ameliorates streptozotocin-induced liver damage through modulation of endoplasmic reticulum stress-mediated apoptosis in diabetic rats

Abstract

We investigated the effect of curcumin on liver injury in diabetic rats induced by streptozotocin (STZ) through modulation of endoplasmic reticulum stress (ERS) and unfolded protein response (UPR). Experimental diabetes was induced by a single intraperitoneal injection of STZ (55 mg/kg), and curcumin was given at 100 mg/kg by gavage for 56 days. We observed that curcumin improved the morphological and histopathological changes, significantly decreased hepatic ERS marker protein: glucose-regulated protein 78, and improved liver function in diabetic rats. Moreover, treatment with curcumin markedly decreased the sub-arm of the UPR signaling protein such as phospho–double-stranded RNA-dependent protein kinase-like ER kinase, CCAAT/enhancer-binding protein homologous protein, tumor necrosis factor receptor-associated factor 2, and inositol-requiring enzyme1α; and inhibited tumor necrosis factor α, interleukin 1β, phospho-p38 mitogen-activated protein kinase, and apoptosis signal-regulating kinase 1 in liver tissues of diabetic rats. Apoptotic and anti-apoptotic signaling proteins, such as cleaved caspase-3 and B-cell lymphoma 2, were significantly increased and decreased, respectively in diabetic rats; curcumin treatment prevented all of these alterations. In summary, our results indicate that curcumin has the potential to protect the diabetic liver by modulating hepatic ERS-mediated apoptosis, and provides a novel therapeutic strategy for the diabetic liver damage.

RETRACTED: Curcumin Improves Palmitate-Induced Insulin Resistance in Human Umbilical Vein Endothelial Cells by Maintaining Proteostasis in Endoplasmic Reticulum

“…In addition, curcumin displays a specific ability to ameliorate ER stress (Afrin et al, 2015; Rashid and Sil, 2015; Wang et al, 2016). In the present study, we found that curcumin supplementation significantly mitigated palmitate-induced insulin resistance ( Figures 1C–E ) and suppressed palmitate-stimulated ER stress/JNK/IRS-1 signaling in HUVECs ( Figure 4 ), suggesting that curcumin reverted palmitate-induced insulin resistance of HUVECs by inhibiting ER stress.…”

TCM Formula Xiaoyaosan Decoction Improves Depressive-Like Behaviors in Rats with Type 2 Diabetes

“…As a traditional Chinese formula consisting of multiple compounds, Xiaoyaosan targets both depression and diabetes. The constituent chemical compounds, such as paeoniflorin, liquiritin, curcumin, and saikosaponins A and C, are active ingredients as antidepressants [ 22 – 26 ], while curcumin and paeoniflorins have antidiabetic effects [ 27 – 30 ]. The HPLC-LTQ-Orbitrap-MS chromatogram results showed that the eight compounds, including paeoniflorin, liquiritin, glycyrrhizic acid, ferulic acid, saikosaponins A and C, curcumin, and Poria cocos alcohol derived from Radix Paeoniae Alba, liquorice, Angelica sinensis , Radix Bupleuri, fresh ginger, and Poria cocos , respectively, could match corresponding peaks of reference standards by the same HPLC-LTQ-Orbitrap-MS eluted system.…”

Bioactivity, Health Benefits, and Related Molecular Mechanisms of Curcumin: Current Progress, Challenges, and Perspectives

“…The intake of overdose drugs may cause severe side-effects, like hepatoxicity. Curcumin has been reported to ameliorate streptozotocin-induced liver injury of diabetic rats by decreasing hepatic endoplasmic reticulum stress marker protein and the sub-arm of unfolded protein response signaling protein, and inhibiting TNF-α, IL1β, phospho-p38 MAPK, and ASK1 in liver [ 116 ]. Paracetamol-induced mitochondrial dysfunction in hepatocytes is also attenuated by curcumin.…”