Aqueous Date Flesh or Pits Extract Attenuates Liver Fibrosis via Suppression of Hepatic Stellate Cell Activation and Reduction of Inflammatory Cytokines, Transforming Growth Factor-β1 and Angiogenic Markers in Carbon Tetrachloride-Intoxicated Rats

Abstract

Previous data indicated the protective effect of date fruit extract on oxidative damage in rat liver. However, the hepatoprotective effects via other mechanisms have not been investigated. This study was performed to evaluate the antifibrotic effect of date flesh extract (DFE) or date pits extract (DPE) via inactivation of hepatic stellate cells (HSCs), reducing the levels of inflammatory, fibrotic and angiogenic markers. Coffee was used as reference hepatoprotective agent. Liver fibrosis was induced by injection of CCl4 (0.4 mL/kg) three times weekly for 8 weeks. DFE, DPE (6 mL/kg), coffee (300 mg/kg), and combination of coffee + DFE and coffee + DPE were given to CCl4-intoxicated rats daily for 8 weeks. DFE, DPE, and their combination with coffee attenuated the elevated levels of inflammatory cytokines including tumor necrosis factor-α, interleukin-6, and interleukin-1β. The increased levels of transforming growth factor-β1 and collagen deposition in injured liver were alleviated by both extracts. CCl4-induced expression of α-smooth muscle actin was suppressed indicating HSCs inactivation. Increased angiogenesis was ameliorated as revealed by reduced levels and expression of vascular endothelial growth factor and CD31. We concluded that DFE or DPE could protect liver via different mechanisms. The combination of coffee with DFE or DPE may enhance its antifibrotic effects.

Gallic Acid and Dodecyl Gallate Prevents Carbon Tetrachloride-Induced Acute and Chronic Hepatotoxicity by Enhancing Hepatic Antioxidant Status and Increasing p53 Expression

“…2,34,35) The increase in serum level of these markers indicates a loss of liver cell membrane integrity, which might be directly related to an increase in ROS CCl 4 -induced. 36,37) In our study, we observed an obvious increase in the levels of TG about 63 and 113% in acute and chronic model respectively and TC about 38% in chronic model, which is in accordance with previous reports. 19,38) Lipids are a heterogeneous group containing active metabolic substances that play an important role in the pathogenesis of liver disease.…”

The antioxidant activity of date seed: preliminary results of a preclinical in vivo study

“…Because the elevation of urea and creatinine is an indicator of renal disease, this indicates that DSP does not interfere with renal function. Additionally, intracellular enzymes, including ALT, AST, ALP, GGT and LDH, which are indicators of tissue injury, especially the liver for ALT, AST and ALP, (Al-Rasheed et al, 2015;Drent et al, 1996) were considered. An increase of these parameters has been related to hepatic, pancreatic and skeletal muscle diseases (Gowda et al, 2009).…”

Treatment Efficiency of Different Routes of Bone Marrow-Derived Mesenchymal Stem Cell Injection in Rat Liver Fibrosis Model

“…Following liver injury, HSCs, which are dormant with low mitotic activity under basal conditions, are activated and change to myofibroblast-like cells, the chief producer of ECM protein in the liver, and increase their expression of α-SMA, which is a hallmark of activated HSCs [3]. Activated HSCs secrete TGF-β1 and CTGF to achieve their auto-activation [18].…”

“…In contrast, Xi et al [28] suggested that inflammation-associated angiogenesis could contribute to progressive liver fibrosis. Furthermore, Al-Rasheed et al [3] proposed that an immature vascular plexus appeared around regenerating hepatocytes, impeded the exchange of oxygen and nutrients between sinusoids and hepatocytes, decreased parenchymal perfusion, and finally induced the progression of fibrosis.…”