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Aqueous Date Flesh or Pits Extract Attenuates Liver Fibrosis via Suppression of Hepatic Stellate Cell Activation and Reduction of Inflammatory Cytokines, Transforming Growth Factor- β 1 and Angiogenic Markers in Carbon Tetrachloride-Intoxicated Rats.

Al-Rasheed NM, Attia HA, Mohamad RA, Al-Rasheed NM, Al-Amin MA, Al-Onazi A - Evid Based Complement Alternat Med (2015)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11495, Saudi Arabia.

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.

No MeSH data available.


Related in: MedlinePlus

Effect of coffee, date flesh extract (DFE), date pits extract (DPE), and the combination groups on hepatic levels of MDA, a marker of lipid peroxidation in CCl4-intoxicated rats. Values are expressed as mean ± SEM. a: significantly different from normal control group, b: significantly different from CCl4-treated group; c: significantly different from coffee-treated group, ∗∗∗P < 0.001, ∗∗P < 0.01, ∗P < 0.05.
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fig3: Effect of coffee, date flesh extract (DFE), date pits extract (DPE), and the combination groups on hepatic levels of MDA, a marker of lipid peroxidation in CCl4-intoxicated rats. Values are expressed as mean ± SEM. a: significantly different from normal control group, b: significantly different from CCl4-treated group; c: significantly different from coffee-treated group, ∗∗∗P < 0.001, ∗∗P < 0.01, ∗P < 0.05.

Mentions: CCl4 induced excessive lipid peroxidation in hepatic tissues as revealed by the drastically elevated hepatic levels of MDA, an end product of lipid peroxidation (P < 0.001) compared to normal control rats (Figures 3 and 4). The levels of GSH, a nonenzymatic antioxidant, and the activities of SOD and GPx, the enzymatic antioxidant, were significantly reduced with CCl4 treatment (P < 0.001) compared to normal control. On the other hand, the activity of GR was significantly higher in CCl4-intoxicated rats (P < 0.001). Coffee, DFE, DPE, and the combination groups significantly ameliorated the CCl4-induced oxidative stress in hepatic tissue as revealed by the significantly lowered levels of MDA and GR (P < 0.001) together with the significant increase in hepatic levels of GSH (P < 0.001), GPx (P < 0.001), and SOD. SOD activities were increased significantly by coffee, DPE (P < 0.01), and more effectively DFE alone and by the combination groups (P < 0.001) compared to CCl4-intoxicated rats.


Aqueous Date Flesh or Pits Extract Attenuates Liver Fibrosis via Suppression of Hepatic Stellate Cell Activation and Reduction of Inflammatory Cytokines, Transforming Growth Factor- β 1 and Angiogenic Markers in Carbon Tetrachloride-Intoxicated Rats.

Al-Rasheed NM, Attia HA, Mohamad RA, Al-Rasheed NM, Al-Amin MA, Al-Onazi A - Evid Based Complement Alternat Med (2015)

Effect of coffee, date flesh extract (DFE), date pits extract (DPE), and the combination groups on hepatic levels of MDA, a marker of lipid peroxidation in CCl4-intoxicated rats. Values are expressed as mean ± SEM. a: significantly different from normal control group, b: significantly different from CCl4-treated group; c: significantly different from coffee-treated group, ∗∗∗P < 0.001, ∗∗P < 0.01, ∗P < 0.05.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4402562&req=5

fig3: Effect of coffee, date flesh extract (DFE), date pits extract (DPE), and the combination groups on hepatic levels of MDA, a marker of lipid peroxidation in CCl4-intoxicated rats. Values are expressed as mean ± SEM. a: significantly different from normal control group, b: significantly different from CCl4-treated group; c: significantly different from coffee-treated group, ∗∗∗P < 0.001, ∗∗P < 0.01, ∗P < 0.05.
Mentions: CCl4 induced excessive lipid peroxidation in hepatic tissues as revealed by the drastically elevated hepatic levels of MDA, an end product of lipid peroxidation (P < 0.001) compared to normal control rats (Figures 3 and 4). The levels of GSH, a nonenzymatic antioxidant, and the activities of SOD and GPx, the enzymatic antioxidant, were significantly reduced with CCl4 treatment (P < 0.001) compared to normal control. On the other hand, the activity of GR was significantly higher in CCl4-intoxicated rats (P < 0.001). Coffee, DFE, DPE, and the combination groups significantly ameliorated the CCl4-induced oxidative stress in hepatic tissue as revealed by the significantly lowered levels of MDA and GR (P < 0.001) together with the significant increase in hepatic levels of GSH (P < 0.001), GPx (P < 0.001), and SOD. SOD activities were increased significantly by coffee, DPE (P < 0.01), and more effectively DFE alone and by the combination groups (P < 0.001) compared to CCl4-intoxicated rats.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11495, Saudi Arabia.

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.

No MeSH data available.


Related in: MedlinePlus