METHODS: The phenolic compounds of PKC were obtained by solvent extraction and the product rich in phenolic compounds was labeled as phenolic-enriched fraction (PEF). This fraction was evaluated for its phenolic compounds composition. The antioxidant activity of PEF was determined by using 1,1-diphenyl-2-picryl-hydrazil scavenging activity, ferric reducing antioxidant power, inhibition of ß-carotene bleaching, and thiobarbituric acid reactive substances assays. The cytotoxicity assay and molecular biomarkers analyses were performed to evaluate the cytoprotective effects of PEF towards aflatoxin B1 (AFB1)-induced cell damage.
RESULTS: The results showed that PEF contained gallic acid, pyrogallol, vanillic acid, caffeic acid, syringic acid, epicatechin, catechin and ferulic acid. The PEF exhibited free radical scavenging activity, ferric reducing antioxidant power, ß-carotene bleaching inhibition and thiobarbituric acid reactive substances inhibition. The PEF demonstrated cytoprotective effects in AFB1-treated chicken hepatocytes by reducing the cellular lipid peroxidation and enhancing antioxidant enzymes production. The viability of AFB1-treated hepatocytes was improved by PEF through up-regulation of oxidative stress tolerance genes and down-regulation of pro-inflammatory and apoptosis associated genes.
CONCLUSIONS: The present findings supported the proposition that the phenolic compounds present in PKC could be a potential cytoprotective agent towards AFB1 cytotoxicity.
AIMS: In the present study, we used a newly established model of fructose-induced metabolic syndrome in male Wistar rats in order to investigate the ultrastructural changes in hepatic mitochondria that occur with fructose consumption and their association with NAFLD pathogenesis.
METHODS: The concentration of fructose-drinking water (FDW) used in this study was 20%. Six male Wistar rats were supplemented with FDW 20% for eight weeks. Body composition and metabolic parameters were measured before and after 8 weeks of FDW 20%. Histomorphology of the liver was evaluated and ultrastructural changes of mitochondria were assessed with transmission electron micrograph.
RESULTS: After 8 weeks of fructose consumption, the animals developed several features of the metabolic syndrome. Moreover, fructose consumption led to the development of macrovesicular hepatic steatosis and mitochondrial ultrastructural changes, such as increase in mitochondrial size, disruption of the cristae, and reduction of matrix density.
CONCLUSION: We conclude that in male Wistar rat 8-week consumption of FDW 20% leads to NAFLD likely via mitochondrial structural alteration.
MATERIAL AND METHOD: The purity of mitragynine in a Mitragyna speciosa alkaloid extract (MSAE) was determined using Ultra-Fast Liquid Chromatography (UFLC). In vitro high throughput ADMETox studies such as aqueous solubility, plasma protein binding, metabolic stability, permeability and cytotoxicity tests were carried out to analyze the physicochemical properties of MSAE and mitragynine. The UFLC quantification revealed that the purity of mitragynine in the MSAE was 40.9%.
RESULTS: MSAE and mitragynine are highly soluble in aqueous solution at pH 4.0 but less soluble at pH 7.4. A parallel artificial membrane permeability assay demonstrated that it is extensively absorbed through the semi-permeable membrane at pH 7.4 but very poorly at pH 4.0. Both are relatively highly bound to plasma proteins (> 85 % bound) and are metabolically stable to liver microsomes (> 84 % remained unchanged). In comparison to MSAE, mitragynine showed higher cytotoxicity against WRL 68, HepG2 and Clone 9 hepatocytes after 72 h treatment.
CONCLUSION: The obtained ADME and cytotoxicity data demonstrated that both MSAE and mitragynine have poor bioavailability and have the potential to be significantly cytotoxic.
MATERIALS AND METHODS: Sprague-Dawley rats were randomly divided into 5 groups, namely: normal control (NC), diabetic control (DC), diabetic on 300 mg/kg b.w. MP, diabetic on 300 mg/kg b.w. metformin, and diabetic on MP and metformin combined therapy. Treatment was done orally for 4 weeks, and NC and DC groups received distilled water as vehicle.
KEY FINDINGS: Results showed increased fasting blood glucose and serum markers of hepatic lesion (aspartate aminotransferase, alkaline phosphatase, alanine aminotransferase and gamma-glutamyl transferase), increased hepatic lactate dehydrogenase activity, decreased hepatic superoxide dismutase, catalase, glutathione peroxidase, glutathione-S-transferase and glutathione reductase activities, increased immunoexpressions of nuclear factor kappa B, tumor necrosis factor-α, interleukin(IL)-1β and caspase-3, and decreased immunoexpressions of IL-10 and proliferating cell nuclear antigen in the liver of DC group. Histopathology of the liver revealed numerous hepatocytes with pyknotic nuclei and inflammatory infiltration, while periodic acid-schiff staining decreased in the liver of DC group. Treatment with MP attenuated these negative effects and was comparable to metformin. Furthermore, these effects were better attenuated in the combined therapy-treated diabetic rats.
SIGNIFICANCE: Malaysian propolis attenuates hepatic lesion in DM and exerts a synergistic protective effect with the anti-hyperglycemic medication, metformin.