title: 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.
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.
authors.affiliation: Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11495, Saudi Arabia.
authors.forename: Nouf M
authors.initials: NM
authors.lastname: Al-Rasheed
authors.affiliation: Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11495, Saudi Arabia ; Biochemistry Department, College of Pharmacy, Mansoura University, Mansoura 35516, Egypt.
authors.forename: Hala A
authors.initials: HA
authors.lastname: Attia
authors.affiliation: Anatomy Department, Faculty of Medicine, King Saud University, Riyadh 11495, Saudi Arabia.
authors.forename: Raeesa A
authors.initials: RA
authors.lastname: Mohamad
authors.affiliation: Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11495, Saudi Arabia.
authors.forename: Nawal M
authors.initials: NM
authors.lastname: Al-Rasheed
authors.affiliation: Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11495, Saudi Arabia.
authors.forename: Maha A
authors.initials: MA
authors.lastname: Al-Amin
authors.affiliation: Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11495, Saudi Arabia.
authors.forename: Asma
authors.initials: A
authors.lastname: Al-Onazi