Picroside II attenuates fatty acid accumulation in HepG2 cells via modulation of fatty acid uptake and synthesis
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Background/Aims: Hepatic steatosis is caused by an imbalance between free fatty acids (FFAs) uptake, utilization, storage, and disposal. Understanding the molecular mechanisms involved in FFAs accumulation and its modulation could drive the development of potential therapies for Nonalcoholic fatty liver disease. The aim of the current study was to explore the effects of picroside II, a phytoactive found in Picrorhiza kurroa, on fatty acid accumulation vis-à-vis silibinin, a known hepatoprotective phytoactive from Silybum marianum. Methods: HepG2 cells were loaded with FFAs (oleic acid:palmitic acid/2:1) for 20 hours to mimic hepatic steatosis. The FFAs concentration achieving maximum fat accumulation and minimal cytotoxicity (500 μM) was standardized. HepG2 cells were exposed to the standardized FFAs concentration with and without picroside II pretreatment. Results: Picroside II pretreatment inhibited FFAs-induced lipid accumulation by attenuating the expression of fatty acid transport protein 5, sterol regulatory element binding protein 1 and stearoyl CoA desaturase. Preatreatment with picroside II was also found to decrease the expression of forkhead box protein O1 and phosphoenolpyruvate carboxykinase. Conclusions: These findings suggest that picroside II effectively attenuated fatty acid accumulation by decreasing FFAs uptake and lipogenesis. Picroside II also decreased the expression of gluconeogenic genes.
Abstract
Background/Aims: Hepatic steatosis is caused by an imbalance between free fatty acids (FFAs) uptake, utilization, storage, and disposal. Understanding the molecular mechanisms involved in FFAs accumulation and its modulation could drive the development of potential therapies for Nonalcoholic fatty liver disease. The aim of the current study was to explore the effects of picroside II, a phytoactive found in Picrorhiza kurroa, on fatty acid accumulation vis-à-vis silibinin, a known hepatoprotective phytoactive from Silybum marianum. Methods: HepG2 cells were loaded with FFAs (oleic acid:palmitic acid/2:1) for 20 hours to mimic hepatic steatosis. The FFAs concentration achieving maximum fat accumulation and minimal cytotoxicity (500 μM) was standardized. HepG2 cells were exposed to the standardized FFAs concentration with and without picroside II pretreatment. Results: Picroside II pretreatment inhibited FFAs-induced lipid accumulation by attenuating the expression of fatty acid transport protein 5, sterol regulatory element binding protein 1 and stearoyl CoA desaturase. Preatreatment with picroside II was also found to decrease the expression of forkhead box protein O1 and phosphoenolpyruvate carboxykinase. Conclusions: These findings suggest that picroside II effectively attenuated fatty acid accumulation by decreasing FFAs uptake and lipogenesis. Picroside II also decreased the expression of gluconeogenic genes.
참고문헌 (36)
- Green CJ, "The influence of dietary fat on liver fat accumulation", Nutrients, 6, pp.5018~5033 (2014)[DOI]
- Schaffer JE, "Lipotoxicity: when tissues overeat", Curr Opin Lipidol, 14, pp.281~287 (2003)[DOI]
- Chalasani N, "The diagnosis and management of non-alcoholic fatty liver disease: practice guideline by the American Gastroenterological Association, American Association for the Study of Liver Diseases, and American College of Gastroenterology", Gastroenterology, 142, pp.1592~1609 (2012)[DOI]
- Sanyal AJ, "Mechanisms of disease: pathogenesis of nonalcoholic fatty liver disease", Nat Clin Pract Gastroenterol Hepatol, 2, pp.46~53 (2005)[DOI]
- Rui L, "Energy metabolism in the liver", Compr Physiol, 4, pp.177~197 (2014)
- Tolman KG, "Treatment of non-alcoholic fatty liver disease", Ther Clin Risk Manag, 3, pp.1153~1163 (2007)
- Gulabkunvarba Ayurvedic Society, "Charak-Samhita", pp.1600~1607 (1949)
- Pandey VN, "Effect of indigenous drug kutaki on bile after producing biliary fistula in dogs", Indian J Med Res, 5, pp.1~24 (1970)
- Antarkar DS, "A pilot phase II trial with arogya- wardhani and Punarnavadi-Kwath in viral hepatitis", Panminerva Med, 20, pp.157~163 (1978)
- Dwivedi Y, "Hepatoprotective activity of picroliv against carbon tetrachloride induced liver damage in rats", Indian J Med Res, 92, pp.195~200 (1990)
- Dwivedi Y, "Prevention of paracetamolinduced hepatic damage in rats by picroliv, the standardized active fraction from Picrorhiza kurroa", Phytother Res, 5, pp.115~119 (1991)[DOI]
- Dwivedi Y, "Picroliv affords protection against thioacetamide-induced hepatic damage in rats", Planta Med, 57, pp.25~28 (1991)[DOI]
- Visen PK, "Prevention of galactosamine- induced hepatic damage by picroliv: study on bile flow and isolated hepatocytes (ex vivo)", Planta Med, 59, pp.37~41 (1993)[DOI]
- Varghese L, "Silibinin efficacy against human hepatocellular carcinoma", Clin Cancer Res, 11, pp.8441~8448 (2005)[DOI]
- Cousin SP, "Free fatty acid-induced inhibition of glucose and insulin-like growth factor 1-induced deoxyribonucleic acid synthesis in the pancreatic beta-cell line INS-1", Endocrinology, 142, pp.229~240 (2000)
- Zanoni I, "mRNA expression analysis by real-time PCR", Nature Protocol Exchange, pp.138~ (2009)[DOI]
- Mahmood T, "Western blot: technique, theory, and trouble shooting", N Am J Med Sci, 4, pp.429~434 (2012)[DOI]
- Malhi H, "Hepatocyte death: a clear and present danger", Physiol Rev, 90, pp.1165~1194 (2010)[DOI]
- Johnson NA, "Aerobic exercise training reduces hepatic and visceral lipids in obese individuals without weight loss", Hepatology, 50, pp.1105~1112 (2009)[DOI]
- Catalano D, "Bright liver, body composition and insulin resistance changes with nutritional intervention: a follow-up study", Liver Int, 28, pp.1280~1287 (2008)[DOI]
- Koutsari C, "Systemic free fatty acid disposal into very low-density lipoprotein triglycerides", Diabetes, 62, pp.2386~2395 (2013)[DOI]
- Yan C, "Punicalagin attenuates palmitate-induced lipotoxicity in HepG2 cells by activating the Keap1-Nrf2 antioxidant defense system", Mol Nutr Food Res, 60, pp.1139~1149 (2016)[DOI]
- Vaidya AD, "Reverse pharmacology-A paradigm shift for drug discovery and development", Curr Res Drug Discovery, 1, pp.39~44 (2014)[DOI]
- Shetty SN, "A study of standardized extracts of Picrorhiza kurroa Royle ex Benth in experimental nonalcoholic fatty liver disease", J Ayurveda Integr Med, 1, pp.203~210 (2010)[DOI]
- Feldstein AE, "Diet associated hepatic steatosis sensitizes to Fas mediated liver injury in mice", J Hepatol, 39, pp.978~983 (2003)[DOI]
- Gomez-Lechon MJ, "A human hepatocellular in vitro model to investigate steatosis", Chem Bio Interact, 165, pp.106~116 (2007)[DOI]
- Pohl J, "Role of FATP in parenchymal cell fatty acid uptake", Biochim Biophys Acta, 1686, pp.1~6 (2004)[DOI]
- Mitsuyoshi H, "Analysis of hepatic genes involved in the metabolism of fatty acids and iron in nonalcoholic fatty liver disease", Hepatol Res, 39, pp.366~373 (2009)[DOI]
- Doege H, "Silencing of hepatic fatty acid transporter protein 5 in vivo reverses dietinduced non-alcoholic fatty liver disease and improves hyperglycemia", J Bio Chem, 283, pp.22186~22192 (2008)[DOI]
- Lambert JE, "Increased de novo lipogenesis is a distinct characteristic of individuals with nonalcoholic fatty liver disease", Gasteroenterology, 146, pp.726~735 (2014)[DOI]
- Pettinelli P, "Molecular mechanisms of steatosis in nonalcoholic fatty liver disease", Nutr Hosp, 26, pp.441~450 (2011)
- Serviddio G, "Oxidation of hepatic carnitine palmitoyl transferase-I (CPT-I) impairs fatty acid beta-oxidation in rats fed a methionine-choline deficient diet", PloS One, 6, pp.e24084~ (2011)[DOI]
- Begriche K, "Mitochondrial adaptations and dysfunctions in nonalcoholic fatty liver disease", Hepatology, 58, pp.1497~1507 (2013)[DOI]
- Sunny NE, "Excessive hepatic mitochondrial TCA cycle and gluconeogenesis in humans with nonalcoholic fatty liver disease", Cell Metab, 14, pp.804~810 (2011)[DOI]
- Zhang W, "FoxO1 regulates multiple metabolic pathways in the liver: effects on gluconeogenic, glycolytic, and lipogenic gene expression", J Biol Chem, 281, pp.10105~10117 (2006)[DOI]
- Salamone F, "Silibinin modulates lipid homeostasis and inhibits nuclear factor kappa B activation in experimental nonalcoholic steatohepatitis", Transl Res, 159, pp.477~486 (2012)[DOI]
