RESUMO
Red rice bran extract (RRBE) is rich in phytonutrients and has been shown to have anti-diabetic, anti-inflammatory, and antioxidant properties. However, its anti-hepatic steatosis and anti-dyslipidemic properties have not been thoroughly investigated. This study examined the aforementioned properties of RRBE, the underlying mechanism by which it alleviated non-alcoholic fatty liver disease in high-fat diet (HFD)-fed mice, and its major bioactive constituents. The mice were divided into four groups based on their diet: (1) low-fat diet (LFD), (2) LFD with high-dose RRBE (1 g/kg/day), (3) HFD, and (4) HFD with three different doses of RRBE (0.25, 0.5, and 1 g/kg/day). The administration of RRBE, especially at medium and high doses, significantly mitigated HFD-induced hepatosteatosis and concomitantly improved the serum lipid profile. Further, RRBE modified the level of expression of lipid metabolism-related genes (adipose triglyceride lipase (ATGL), cluster of differentiation 36 (CD36), lipoprotein lipase (LPL), liver X receptor alpha (LXRα), sterol regulatory element-binding protein-1c (SREBP-1c), SREBP-2, 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), and carnitine palmitoyltransferase 1A (CPT1A)) in hepatic or adipose tissues and improved the expression of hepatic high-density lipoprotein cholesterol (HDL-C) cmetabolism-related genes (hepatic lipase (HL) and apolipoprotein A-Ç (ApoA-Ç)). RRBE also attenuated markers of liver injury, inflammation, and oxidative stress, accompanied by a modulated expression of inflammatory (nuclear factor-kappa B (NF-κB) and inducible nitric oxide synthase (iNOS)), pro-oxidant (p47phox), and apoptotic (B-cell lymphoma protein 2 (Bcl-2)-associated X and Bcl-2) genes in the liver. High-performance liquid chromatography analyses indicated the presence of protocatechuic acid, γ-oryzanol, vitamin E, and coenzyme Q10 in RRBE. Our data indicate that RRBE alleviates HFD-induced hepatosteatosis, dyslipidemia, and their pathologic complications in part by regulating the expression of key genes involved in lipid metabolism, inflammation, oxidative stress, and apoptosis.
Assuntos
Dislipidemias , Hepatopatia Gordurosa não Alcoólica , Oryza , Camundongos , Animais , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/metabolismo , Dieta Hiperlipídica/efeitos adversos , Fígado/metabolismo , Metabolismo dos Lipídeos , Inflamação/metabolismo , Dislipidemias/etiologia , Dislipidemias/complicações , Anti-Inflamatórios/metabolismo , Camundongos Endogâmicos C57BLRESUMO
Background: Tetrahydrocurcumin (THC) demonstrated an anti-cancer and anti-angiogenic effects in cervical cancer. Celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, have also shown anticancer effect. However, the combinational treatment effect of THC and celecoxib on tumor growth and tumor angiogenesis, especially, using cervical cancer (CaSki)-implanted nude mice has yet not been reported. Objective: To evaluate the combinational treatment effect of THC and celecoxib on tumor progression and tumor angiogenesis in cervical cancer (CaSki)-implanted nude mice. Material and Method: CaSki cells were inoculated in mice to establish subcutaneous tumors. One month after inoculation, vehicle, THC100 mg/kg, Celecoxib100 mg/kg, or THC50 + Celecoxib50 mg/kg was orally administered every day for 28 consecutive days. The tumor volume was measured every 3-4 days. The microvascular density (MVD) was evaluated using the CD31 expression. VEGF, COX-2, and EGFR expression were also detected by immunohistochemistry. Results: THC, celecoxib, and the combination treatments statistically retarded the tumor volume by 70.40, 65.11 and 77.04%, respectively. The MVD was significantly increased in CaSki + vehicle group, but THC, celecoxib, and the combination treatments markedly attenuated the MVD. VEGF, COX-2, and EGFR were up-regulated in CaSki + vehicle group; however, they were attenuated by THC, celecoxib, and the combination treatments. Conclusion: The combinational treatment effect of THC and celecoxib causing inhibition of tumor growth and tumor angiogenesis via down-regulation of VEGF, COX-2 and EGFR expression. However, this combined treatment did not show the synergistic effect on inhibiting the tumor growth and tumor angiogenesis in cervical cancer (CaSki)-implanted nude mice model.