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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

Light photomicrographs of liver sections stained with Masson are trichrome to demonstrate the fibrous tissue (scale bar 50 μm). (a) Control liver showing normal amount and distribution of fibrous tissue (arrow) mainly in the portal area. (b) Liver section from rat exposed to CCl4 showing increase of the fibrous tissue (arrow) which extends outside the portal area. (c) Liver from rat exposed to CCl4 and receiving 2 mL/kg of DPE showing mild decrease of the amount abnormal deposited fibrous tissue. Also (d) represents liver from rat exposed to CCl4 and 4 mL/kg of DPE and shows decrease of fibrous tissue but still abnormally deposited outside portal area. ((e), (f)) Liver sections from rat exposed to CCl4 and receiving doses of 6 and 8 mL/kg of DPE, respectively, show apparently normal amount and distribution of fibrous tissue if compared with the control group (a).
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fig2: Light photomicrographs of liver sections stained with Masson are trichrome to demonstrate the fibrous tissue (scale bar 50 μm). (a) Control liver showing normal amount and distribution of fibrous tissue (arrow) mainly in the portal area. (b) Liver section from rat exposed to CCl4 showing increase of the fibrous tissue (arrow) which extends outside the portal area. (c) Liver from rat exposed to CCl4 and receiving 2 mL/kg of DPE showing mild decrease of the amount abnormal deposited fibrous tissue. Also (d) represents liver from rat exposed to CCl4 and 4 mL/kg of DPE and shows decrease of fibrous tissue but still abnormally deposited outside portal area. ((e), (f)) Liver sections from rat exposed to CCl4 and receiving doses of 6 and 8 mL/kg of DPE, respectively, show apparently normal amount and distribution of fibrous tissue if compared with the control group (a).

Mentions: As indicated by Masson trichome staining (Figures 1 and 2), the dose 2 mL/kg of both DFE and DPE did not show prominent decrease in collagen deposition. Doses 4, 6, and 8 showed a prominent decrease in collagen content; however, the doses 6 and 8 mL/kg of DFE (Figure 1) and DPE (Figure 2) showed the best reduction in the amount of collagen deposition compared to dose 4 mL/kg and so supposed to exhibit the best protection from CCl4-induced liver fibrosis. As the effect of 6 and 8 mL/kg were almost the same and both showed apparently normal amount and distribution of fibrous tissue if compared with the normal control group so, we selected the dose 6 mL/kg as the most appropriate dose to complete the main study. Liver function was also assessed by determining ALT activity (data not shown) that revealed that doses 6 and 8 mL/kg have the best improvement in ALT activity 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)

Light photomicrographs of liver sections stained with Masson are trichrome to demonstrate the fibrous tissue (scale bar 50 μm). (a) Control liver showing normal amount and distribution of fibrous tissue (arrow) mainly in the portal area. (b) Liver section from rat exposed to CCl4 showing increase of the fibrous tissue (arrow) which extends outside the portal area. (c) Liver from rat exposed to CCl4 and receiving 2 mL/kg of DPE showing mild decrease of the amount abnormal deposited fibrous tissue. Also (d) represents liver from rat exposed to CCl4 and 4 mL/kg of DPE and shows decrease of fibrous tissue but still abnormally deposited outside portal area. ((e), (f)) Liver sections from rat exposed to CCl4 and receiving doses of 6 and 8 mL/kg of DPE, respectively, show apparently normal amount and distribution of fibrous tissue if compared with the control group (a).
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4402562&req=5

fig2: Light photomicrographs of liver sections stained with Masson are trichrome to demonstrate the fibrous tissue (scale bar 50 μm). (a) Control liver showing normal amount and distribution of fibrous tissue (arrow) mainly in the portal area. (b) Liver section from rat exposed to CCl4 showing increase of the fibrous tissue (arrow) which extends outside the portal area. (c) Liver from rat exposed to CCl4 and receiving 2 mL/kg of DPE showing mild decrease of the amount abnormal deposited fibrous tissue. Also (d) represents liver from rat exposed to CCl4 and 4 mL/kg of DPE and shows decrease of fibrous tissue but still abnormally deposited outside portal area. ((e), (f)) Liver sections from rat exposed to CCl4 and receiving doses of 6 and 8 mL/kg of DPE, respectively, show apparently normal amount and distribution of fibrous tissue if compared with the control group (a).
Mentions: As indicated by Masson trichome staining (Figures 1 and 2), the dose 2 mL/kg of both DFE and DPE did not show prominent decrease in collagen deposition. Doses 4, 6, and 8 showed a prominent decrease in collagen content; however, the doses 6 and 8 mL/kg of DFE (Figure 1) and DPE (Figure 2) showed the best reduction in the amount of collagen deposition compared to dose 4 mL/kg and so supposed to exhibit the best protection from CCl4-induced liver fibrosis. As the effect of 6 and 8 mL/kg were almost the same and both showed apparently normal amount and distribution of fibrous tissue if compared with the normal control group so, we selected the dose 6 mL/kg as the most appropriate dose to complete the main study. Liver function was also assessed by determining ALT activity (data not shown) that revealed that doses 6 and 8 mL/kg have the best improvement in ALT activity 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