Mechanism of the Inhibitory Effects ofEucommia ulmoidesOliv. Cortex Extracts (EUCE) in the CCl₄-Induced Acute Liver Lipid Accumulation in Rats

Abstract

Eucommia ulmoides Oliv. (EU) has been used for treatment of liver diseases. The protective effects of Eucommia Ulmoides Oliv. cortex extracts (EUCE) on the carbon tetrachloride- (CCl4-) induced hepatic lipid accumulation were examined in this study. Rats were orally treated with EUCE in different doses prior to an intraperitoneal injection of 1 mg/kg CCl4. Acute injection of CCl4 decreased plasma triglyceride but increased hepatic triglyceride and cholesterol as compared to control rats. On the other hand, the pretreatment with EUCE diminished these effects at a dose-dependent manner. CCl4 treatment decreased glutathione (GSH) and increased malondialdehyde (MDA) accompanied by activated P450 2E1. The pretreatment with EUCE significantly improved these deleterious effects of CCl4. CCl4 treatment increased P450 2E1 activation and ApoB accumulation. Pretreatment with EUCE reversed these effects. ER stress response was significantly increased by CCl4, which was inhibited by EUCE. One of the possible ER stress regulatory mechanisms, lysosomal activity, was examined. CCl4 reduced lysosomal enzymes that were reversed with the EUCE. The results indicate that oral pretreatment with EUCE may protect liver against CCl4-induced hepatic lipid accumulation. ER stress and its related ROS regulation are suggested as a possible mechanism in the antidyslipidemic effect of EUCE.

Inhibition of soluble epoxide hydrolase attenuates hepatic fibrosis and endoplasmic reticulum stress induced by carbon tetrachloride in mice

“…In this study we investigated whether exposure to CCl 4 induces hepatic ER stress in vivo and evaluated the effects of sEH pharmacological inhibition on CCl 4 -induced hepatic ER stress. In line with published studies exposure to CCl 4 induced ER stress (Lewis and Roberts, 2005; Lee et al , 2011; Jin et al , 2013), as evidenced by increased PERK (Thr 980 ), eIF2α (Ser 51 ) and IRE1α (Ser 724 ) phosphorylation and increased sXBP1 expression in liver lysates (Figure 5A). Importantly, pharmacological inhibition of sEH attenuated hepatic ER stress in CCl 4 -treated mice as evidenced by decreased PERK (Thr 980 ), eIF2α (Ser 51 ) and IRE1α (Ser 724 ) phosphorylation and decreased sXBP1 expression (Figure 5A).…”

“…Directly relevant to this study, recent reports have demonstrated an increase in ER stress in rodents injected with CCl 4 (Ji et al , 2011; Lee et al , 2011; Jin et al , 2013). However, the link between the development of hepatic fibrosis and ER stress is still poorly understood.…”

“…Recent studies provided evidence that ER stress can affect production of the extracellular matrix and consequently the progression of fibrotic diseases (Mollica et al , 2011; Lenna and Trojanowska, 2012; Tanjore et al , 2012), including hepatic fibrosis that results from the injection of CCl 4 (Ji et al , 2011; Lee et al , 2011; Jin et al , 2013). In a nonalcoholic steatohepatitis methionine-choline-deficient diet-induced model, liver fibrosis correlated with the increased expression of BiP and activation of caspases 12 and 7 (Mu et al , 2009).…”

Iron deposition causes oxidative stress, inflammation and fibrosis in carbon tetrachloride-induced liver dysfunction in rats

“…Additionally, histopathological assessment in liver tissues of CCl4 treated rats also revealed typical hepatotoxic effects, as described previously in the literature (Nabeshima et al, 2006;Jin et al, 2013). Inflammatory cells have been accumulated in the necrotized region and alongside the bile ducts and blood vessels in liver of CCl4 treated rats.…”

Health‐Promoting Properties of Eucommia ulmoides: A Review

“…EU enhances lysosomal enzyme activity relieving protein folding requirement which turns into attenuation of ER stress. ApoB secretion was improved by effects of ER stress; along this, it regulates biotransformation of CCl 4 and its resultant inhibition of ROS accumulation [ 88 ].…”