Limits...
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

(a) Effect of date flesh extract (DFE), date pits extract (DPE), coffee, and the combination groups on hepatic levels of vascular endothelial growth factor (VEGF) 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. (b) Light microscopic photomicrographs of liver tissue immunostained with primary anti-VGEF antibody (scale bar = 50 μm). (A) Control liver showing negative immune reactivity of hepatocytes, while (B) represents liver section of rat receiving CCl4 showing strong abnormal irregularly distributed immune reactivity, especially between degenerated hepatocytes' cytoplasm and nuclei. Panels (C), (D), (E), (F), and (G) that represent liver sections from rat receiving coffee, DFE, DPE, coffee + DFE, and coffee + DPE, respectively, showed marked decrease in the intensity of the immune reactivity of hepatocytes surrounding portal areas especially in rats treated with the DFE and the combination of coffee + DFE. (c) Light microscopic photomicrographs of liver tissue immunostained with anti-VEGFR-1 primary antibody (scale bar = 100 μm). (A) Control liver showing normal few weak immune positive cellular and nuclear receptors. (B) represents liver section of rat receiving CCl4 in which there are focal strong abnormal immune reactivity of most of hepatocytes' cell membrane and nuclei. Panels (C), (D), (E), (F), and (G) that represent liver sections from rat receiving coffee, DFE, DPE, coffee + DFE, and coffee + DPE, respectively, revealed a decrease in the number of immunostained hepatocytes with marked depletion of immune positivity observed in rats treated with coffee + DPE and then with coffee + DFE and DFE alone-treated groups. (d) Light microscopic photomicrographs of liver tissue immunostained with primary anti-PECAM (CD31) antibody (scale bar = 50 μm). (A) Control liver showing normal positive immune reactivity of endothelial cells cell membranes of the blood vessels of the portal area and blood sinusoids, while (B) represents liver section of rat receiving CCl4 in which strong abnormal irregularly distributed immune reactivity, especially around degenerated hepatocytes, is prominent. Panels (C), (D), (E), (F), and (G) that represent liver sections from rat treated with coffee, DFE, DPE, coffee + DFE, and coffee + DPE, respectively, showed marked decrease of the immune reactivity outside portal areas especially in groups receiving DFE and combination.
© Copyright Policy - open-access
Related In: Results  -  Collection


getmorefigures.php?uid=PMC4402562&req=5

fig7: (a) Effect of date flesh extract (DFE), date pits extract (DPE), coffee, and the combination groups on hepatic levels of vascular endothelial growth factor (VEGF) 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. (b) Light microscopic photomicrographs of liver tissue immunostained with primary anti-VGEF antibody (scale bar = 50 μm). (A) Control liver showing negative immune reactivity of hepatocytes, while (B) represents liver section of rat receiving CCl4 showing strong abnormal irregularly distributed immune reactivity, especially between degenerated hepatocytes' cytoplasm and nuclei. Panels (C), (D), (E), (F), and (G) that represent liver sections from rat receiving coffee, DFE, DPE, coffee + DFE, and coffee + DPE, respectively, showed marked decrease in the intensity of the immune reactivity of hepatocytes surrounding portal areas especially in rats treated with the DFE and the combination of coffee + DFE. (c) Light microscopic photomicrographs of liver tissue immunostained with anti-VEGFR-1 primary antibody (scale bar = 100 μm). (A) Control liver showing normal few weak immune positive cellular and nuclear receptors. (B) represents liver section of rat receiving CCl4 in which there are focal strong abnormal immune reactivity of most of hepatocytes' cell membrane and nuclei. Panels (C), (D), (E), (F), and (G) that represent liver sections from rat receiving coffee, DFE, DPE, coffee + DFE, and coffee + DPE, respectively, revealed a decrease in the number of immunostained hepatocytes with marked depletion of immune positivity observed in rats treated with coffee + DPE and then with coffee + DFE and DFE alone-treated groups. (d) Light microscopic photomicrographs of liver tissue immunostained with primary anti-PECAM (CD31) antibody (scale bar = 50 μm). (A) Control liver showing normal positive immune reactivity of endothelial cells cell membranes of the blood vessels of the portal area and blood sinusoids, while (B) represents liver section of rat receiving CCl4 in which strong abnormal irregularly distributed immune reactivity, especially around degenerated hepatocytes, is prominent. Panels (C), (D), (E), (F), and (G) that represent liver sections from rat treated with coffee, DFE, DPE, coffee + DFE, and coffee + DPE, respectively, showed marked decrease of the immune reactivity outside portal areas especially in groups receiving DFE and combination.

Mentions: Immunostained section of liver tissues for detection of α-SMA fibers (Figure 6(e)) showed strong and massive immunopositivity especially around degenerated hepatocytes in CCl4-treated group only, while rats receiving coffee, DFE, DPE, and the combination treatment showed marked decrease of immune reactivity specially in those receiving DFE and the combination of coffee + DFE or coffee + DPE in which the immune reactivity is restricted to the vessels of the portal areas similar to that of control group. The improvement was prominent with DFE and combination groups.


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)

(a) Effect of date flesh extract (DFE), date pits extract (DPE), coffee, and the combination groups on hepatic levels of vascular endothelial growth factor (VEGF) 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. (b) Light microscopic photomicrographs of liver tissue immunostained with primary anti-VGEF antibody (scale bar = 50 μm). (A) Control liver showing negative immune reactivity of hepatocytes, while (B) represents liver section of rat receiving CCl4 showing strong abnormal irregularly distributed immune reactivity, especially between degenerated hepatocytes' cytoplasm and nuclei. Panels (C), (D), (E), (F), and (G) that represent liver sections from rat receiving coffee, DFE, DPE, coffee + DFE, and coffee + DPE, respectively, showed marked decrease in the intensity of the immune reactivity of hepatocytes surrounding portal areas especially in rats treated with the DFE and the combination of coffee + DFE. (c) Light microscopic photomicrographs of liver tissue immunostained with anti-VEGFR-1 primary antibody (scale bar = 100 μm). (A) Control liver showing normal few weak immune positive cellular and nuclear receptors. (B) represents liver section of rat receiving CCl4 in which there are focal strong abnormal immune reactivity of most of hepatocytes' cell membrane and nuclei. Panels (C), (D), (E), (F), and (G) that represent liver sections from rat receiving coffee, DFE, DPE, coffee + DFE, and coffee + DPE, respectively, revealed a decrease in the number of immunostained hepatocytes with marked depletion of immune positivity observed in rats treated with coffee + DPE and then with coffee + DFE and DFE alone-treated groups. (d) Light microscopic photomicrographs of liver tissue immunostained with primary anti-PECAM (CD31) antibody (scale bar = 50 μm). (A) Control liver showing normal positive immune reactivity of endothelial cells cell membranes of the blood vessels of the portal area and blood sinusoids, while (B) represents liver section of rat receiving CCl4 in which strong abnormal irregularly distributed immune reactivity, especially around degenerated hepatocytes, is prominent. Panels (C), (D), (E), (F), and (G) that represent liver sections from rat treated with coffee, DFE, DPE, coffee + DFE, and coffee + DPE, respectively, showed marked decrease of the immune reactivity outside portal areas especially in groups receiving DFE and combination.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig7: (a) Effect of date flesh extract (DFE), date pits extract (DPE), coffee, and the combination groups on hepatic levels of vascular endothelial growth factor (VEGF) 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. (b) Light microscopic photomicrographs of liver tissue immunostained with primary anti-VGEF antibody (scale bar = 50 μm). (A) Control liver showing negative immune reactivity of hepatocytes, while (B) represents liver section of rat receiving CCl4 showing strong abnormal irregularly distributed immune reactivity, especially between degenerated hepatocytes' cytoplasm and nuclei. Panels (C), (D), (E), (F), and (G) that represent liver sections from rat receiving coffee, DFE, DPE, coffee + DFE, and coffee + DPE, respectively, showed marked decrease in the intensity of the immune reactivity of hepatocytes surrounding portal areas especially in rats treated with the DFE and the combination of coffee + DFE. (c) Light microscopic photomicrographs of liver tissue immunostained with anti-VEGFR-1 primary antibody (scale bar = 100 μm). (A) Control liver showing normal few weak immune positive cellular and nuclear receptors. (B) represents liver section of rat receiving CCl4 in which there are focal strong abnormal immune reactivity of most of hepatocytes' cell membrane and nuclei. Panels (C), (D), (E), (F), and (G) that represent liver sections from rat receiving coffee, DFE, DPE, coffee + DFE, and coffee + DPE, respectively, revealed a decrease in the number of immunostained hepatocytes with marked depletion of immune positivity observed in rats treated with coffee + DPE and then with coffee + DFE and DFE alone-treated groups. (d) Light microscopic photomicrographs of liver tissue immunostained with primary anti-PECAM (CD31) antibody (scale bar = 50 μm). (A) Control liver showing normal positive immune reactivity of endothelial cells cell membranes of the blood vessels of the portal area and blood sinusoids, while (B) represents liver section of rat receiving CCl4 in which strong abnormal irregularly distributed immune reactivity, especially around degenerated hepatocytes, is prominent. Panels (C), (D), (E), (F), and (G) that represent liver sections from rat treated with coffee, DFE, DPE, coffee + DFE, and coffee + DPE, respectively, showed marked decrease of the immune reactivity outside portal areas especially in groups receiving DFE and combination.
Mentions: Immunostained section of liver tissues for detection of α-SMA fibers (Figure 6(e)) showed strong and massive immunopositivity especially around degenerated hepatocytes in CCl4-treated group only, while rats receiving coffee, DFE, DPE, and the combination treatment showed marked decrease of immune reactivity specially in those receiving DFE and the combination of coffee + DFE or coffee + DPE in which the immune reactivity is restricted to the vessels of the portal areas similar to that of control group. The improvement was prominent with DFE and combination groups.

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