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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 date flesh extract (DFE), date pits extract (DPE), coffee, and the combination groups on hepatic levels of proinflammatory mediators. (a) Tumor necrosis factor α (TNF-α), (b) interleukin-6 (IL-6), and (c) interleukin-1β (IL-1β) 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; d: significantly different from DFE-treated group. ∗∗∗P < 0.001, ∗∗P < 0.01, ∗P < 0.05.
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fig5: Effect of date flesh extract (DFE), date pits extract (DPE), coffee, and the combination groups on hepatic levels of proinflammatory mediators. (a) Tumor necrosis factor α (TNF-α), (b) interleukin-6 (IL-6), and (c) interleukin-1β (IL-1β) 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; d: significantly different from DFE-treated group. ∗∗∗P < 0.001, ∗∗P < 0.01, ∗P < 0.05.

Mentions: CCl4-intoxicated rats expressed significantly higher hepatic levels of proinflammatory cytokines (P < 0.001) including TNF-α, IL-1β, and IL-6, which have been shown to play important roles in the development of the fibrosis. However, remarkable decreases in the levels of all those three parameters were observed by the simultaneous administration of DFE and the combination of coffee + DFE and coffee + DPE (P < 0.001) and by DPE and coffee (P < 0.01) compared to CCl4-intoxicated rats. It was noted that DFE alone and the combination of coffee + DFE and coffee + DPE significantly improved the hepatic levels of TNF-α and IL-1β levels compared to coffee alone (Figures 5(a) and 5(c)); however, no significant differences were observed in the case of IL-6 (Figure 5(b)). In addition, the levels of TNF-α and IL-1β were significantly lowered by DFE alone compared to DPE alone (P < 0.001 and P < 0.01, resp.).


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 date flesh extract (DFE), date pits extract (DPE), coffee, and the combination groups on hepatic levels of proinflammatory mediators. (a) Tumor necrosis factor α (TNF-α), (b) interleukin-6 (IL-6), and (c) interleukin-1β (IL-1β) 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; d: significantly different from DFE-treated group. ∗∗∗P < 0.001, ∗∗P < 0.01, ∗P < 0.05.
© Copyright Policy - open-access
Related In: Results  -  Collection

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fig5: Effect of date flesh extract (DFE), date pits extract (DPE), coffee, and the combination groups on hepatic levels of proinflammatory mediators. (a) Tumor necrosis factor α (TNF-α), (b) interleukin-6 (IL-6), and (c) interleukin-1β (IL-1β) 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; d: significantly different from DFE-treated group. ∗∗∗P < 0.001, ∗∗P < 0.01, ∗P < 0.05.
Mentions: CCl4-intoxicated rats expressed significantly higher hepatic levels of proinflammatory cytokines (P < 0.001) including TNF-α, IL-1β, and IL-6, which have been shown to play important roles in the development of the fibrosis. However, remarkable decreases in the levels of all those three parameters were observed by the simultaneous administration of DFE and the combination of coffee + DFE and coffee + DPE (P < 0.001) and by DPE and coffee (P < 0.01) compared to CCl4-intoxicated rats. It was noted that DFE alone and the combination of coffee + DFE and coffee + DPE significantly improved the hepatic levels of TNF-α and IL-1β levels compared to coffee alone (Figures 5(a) and 5(c)); however, no significant differences were observed in the case of IL-6 (Figure 5(b)). In addition, the levels of TNF-α and IL-1β were significantly lowered by DFE alone compared to DPE alone (P < 0.001 and P < 0.01, resp.).

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