Flavonoids Effects on Hepatocellular Carcinoma in Murine Models: A Systematic Review

The hepatocellular carcinoma (HCC) is the second most common cause of cancer deaths worldwide. It occurs primarily as manifestation of other pathological processes, such as viral hepatitis, cirrhosis, and toxin exposure that affect directly the cellular process. Studies were selected from PubMed and Scopus databases according to the PRISMA statement. The research filters were constructed using three parameters: flavonoids, hepatocellular carcinoma, and animal model. The bias analysis of the 34 selected works was done using the ARRIVE guidelines. The most widely used flavonoid in the studies was epigallocatechin gallate extracted from green tea. In general, the treatment with different flavonoids presented inhibition of tumor growth and antiangiogenic, antimetastatic, antioxidant, and anti-inflammatory activities. The bias analysis evidenced the absence of methodological processes in all studies, such as the age or weight of the animals, the method of flavonoids’ extraction, or the experimental designs, analytical methods, and outcome measures. It has been known that flavonoids have a protective effect against HCC. However, the absence or incomplete characterization of the animal models, treatment protocols, and phytochemical and toxicity analyses impaired the internal validity of the individual studies, making it difficult to determine the effectiveness of plant-derived products in the treatment of HCC

Hipercolesterolemic effect of phenolic extract of capim gordura’s inflorescence (Melinis minutiflora)

O consumo de alimentos com compostos fenólicos tem aumentado na redução de risco de doenças como câncer, diabetes, hipercolesterolemia. Na procura de novas fontes com potencial terapêutico, este trabalho teve como um dos objetivos quantificar os compostos fenólicos presentes no extrato da inflorescência de capim gordura mediante a quantificação de fenóis totais por Follin ciocalteu, antocianinas totais e determinação antioxidante pelo método ABTS•+. A capacidade para reduzir o nível de colesterol sérico foi feita por meio da avaliação do perfil lipídico no plasma sanguíneo e mediante a histomorfometria foi determinada sua capacidade hepatoprotetora nos coelhos de raça Nova Zelândia. No estudo foram utilizados 25 coelhos de raça Nova Zelândia que tiveram um período de adaptação de 5 dias e mantidos em condições controladas, e foram divididos em 5 grupos que receberam os seguintes tratamentos: Grupo 1 (R), 125g de ração e água a vontade; Grupo 2 (RCA), 125g de ração contendo 1% de colesterol, 0,1% ácido cólico e água a vontade; Grupo 3 (RE), 125g de ração, água a vontade e 2mL de extrato (0,88mg/2mL); Grupo 4 (RCAE1), 125g de ração contendo 1% de colesterol, 0,1% ácido cólico, água a vontade e 2mL de extrato de capim gordura (0,88mg/2mL); Grupo 5 (RCAE2), 125g de ração contendo 1% de colesterol, 0,1% ácido cólico, água a vontade e 1mL de extrato de capim gordura (0,44mg/1mL). Foram realizadas três coletas de sangue antes de iniciar o experimento (dia 0), nos dias 30 e 60, na última coleta foi feita a coleta do fígado dos animais. As analises sanguíneos foram realizadas mediante método colorimétrico e se avaliaram os parâmetros de colesterol total, colesterol de baixa densidade (LDL), colesterol de alta densidade (HDL), colesterol de muito baixa densidade (VLDL), triacilgliceróis, proteínas totais, albumina, creatinina, glicose, aspartato aminotransferase (AST), alanina transferase (ALT), gamma GT e fosfatasse alcalina. Na análise histológica foi realizada a histomorfometria do fígado. O extrato da inflorescência de capim gordura apresentou um teor de fenóis totais de 603 mg AGE.100g-1, para antocianinas foi de 99,4 mg.100g-1 cianidina 3 glicosídeos e a atividade antioxidante do extrato foi de 3672 μMTrolox. 100 g-1 de inflorescência sendo valore similares a frutos de consumo diário. Na avaliação do efeito hipocolesterolêmico se observou que os tratamentos que tiveram dieta com colesterol e adição do extrato fenólico da inflorescência de capim gordura, apresentaram diminuição do colesterol total e LDL de 59 e 60% aos 30 dias do experimento respectivamente. Além disso, se observou que os tratamentos com dieta rica em colesterol e extrato fenólico, tiveram efeito hepatoprotetor. Com estes resultados obtidos o extrato fenólico da inflorescência de capim gordura, pode se considerar uma nova fonte natural de antioxidante com aplicação industrial e clínica.The consumption of foods with phenolic compounds has increased in reducing risk of diseases like cancer, diabetes, hypercholesterolemia. The search for new sources with therapeutic potential, this work aimed to quantify the phenolic compounds present in the capim gordura’s inflorescence (Melinis minutiflora) by the total phenols quantification by Follin Ciocalteu, anthocyanin quantification and antioxidant determination by the ABTS•+. Was determined the ability to reduce serum cholesterol level by assessing the lipid profile in blood plasma and was determined its hepatoprotective capacity by histomorphometry in New Zealand white rabbits. Were used 25 male New Zealand rabbits, had an adaptation period of five days, under controlled conditions, and were divided into five groups to the following treatments: Group 1 (R), 125g of food and water; Group 2 (RCA), 125g diet containing 1% cholesterol, 0.1% cholic acid and water; Group 3 (SR), 125g of feed, 2 mL of extract and water (0.88mg/2mL); Group 4 (RCAE1) 125g diet containing 1% cholesterol, 0.1% cholic acid, 2ml of extract and water (0.88mg/2mL); Group 5 (RCAE2), 125g diet containing 1% cholesterol, 0.1% cholic acid, water and 1 mL of extract (0,44mg / 1mL). These were submit to three-blood samples collection; before to starting the experimental study (0 days), to 30 days and 60 days, on the last collection in addition the liver tissues was collect. Blood analyzes were performed by colorimetric method and evaluated the parameters of total cholesterol, low density cholesterol(LDL), high density lipoprotein cholesterol (HDL), very low density lipoprotein cholesterol (VLDL), triglycerides, total protein, albumin, creatinine, glucose, aspartate aminotransferase (AST), alanine transferase (ALT), gamma GT and alkaline phosphatase. The histological analysis was performed morphometric of the liver. The inflorescence extract presented a total phenol content of 603 mg AGE.100g-1 for anthocyanins was 99.4 mg.100g-1 cyanidin 3 glycosides and the antioxidant activity of the extract was γ67β μMTrolox. 100 g-1 inflorescence being value similar to fruit daily consumption. In assessing the hypocholesterolemic effect was observe that the treatments had high cholesterol diet and phenolic extract addition, showed a decrease in total and LDL cholesterol of 59 and 60% at 30 days of the experiment respectively. Furthermore, it was observe that the treatment with a high cholesterol diet and phenolic extract had hepatoprotective effect. With these results, the inflorescence extract, can be considered a new source of natural antioxidant that could have industrial and clinical application