Abstract
This study aimed to investigate the effects of ethanol extract of astringent persimmon on antioxidant activity, cholesterol, 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase activity, and mRNA expression of cholesterol metabolism-related genes in human hepatoma cell line (HepG2 cells). In the results, DPPH and ABTS radical scavenging activity showed that the different types cultivars of astringent persimmon was similar to Vitamin C as positive control. However, there are not significant differences among samples. In addition, our results showed that cholesterol amounts and HMG-CoA reductase activity were inhibited by astringent persimmon in HepG2 cells. Further, treatment with astringent persimmon upregulated the expression of LDL receptor and SREBP-2, and also increased the level of HDL-associated ABCA1. Taken together, our results indicate that astringent persimmon regulate cholesterol accumulation by inhibiting the oxidative stress and controlling the levels of LDL & HDLassociated gene.
Keywords: astringent persimmon, anti-oxidants activity, 3-hydroxy-3-methylglutaryl-CoA reductase, low-density lipoprotein, high-density lipoprotein
References
- 1.Badimon L, Vilahur G, Padro T. Lipoproteins, platelets and atherothrombosis. Rev. Esp. Cardiol. 2009;62:1161–1178. doi: 10.1016/S0300-8932(09)72385-1. [DOI] [PubMed] [Google Scholar]
- 2.Badimon L, Storey RF, Vilahur G. Update on lipids, inflammation and atherothrombosis. Thromb. Haemostasis. 2011;105:S34–S42. doi: 10.1160/THS10-11-0717. [DOI] [PubMed] [Google Scholar]
- 3.Sekalska B. Aortic expression of monocyte chemotactic protein-1(MCP-1) gene in rabbits with experimental atherosclerosis. Ann. Acad. Med. Stetin. 2003;49:79–90. [PubMed] [Google Scholar]
- 4.Vogiatzi G, Tousoulis D, Stefanadis C. The role of oxidative stress in atherosclerosis. Hell. J. Cardiol. 2009;50:402–409. [PubMed] [Google Scholar]
- 5.Halliwell B, Gutteridge JM, Cross CE. Free radicals, antioxidants, and human disease: where are we now? J. Lab. Clin. Med. 1992;119:598–620. [PubMed] [Google Scholar]
- 6.Loke WM, Proudfoot JM, Hodgson JM, McKinley AJ, Hime N, Magat M, Stocker R, Croft KD. Specific dietary polyphenols attenuate atherosclerosis in apolipoprotein E-knockout mice by alleviating inflammation and endothelial dysfunction. Arterioscl. Throm. Vas. 2010;30:749–757. doi: 10.1161/ATVBAHA.109.199687. [DOI] [PubMed] [Google Scholar]
- 7.Wedworth SM, Lynch S. Dietary flavonoids in atherosclerosis prevention. Ann. Pharmacother. 1995;29:627–628. doi: 10.1177/106002809502900614. [DOI] [PubMed] [Google Scholar]
- 8.Kang WW, Kim JK, Oh SL, Kim JH, Han JH, Yang JM, Choi JU. Physicochemical characteristics of Sang ju traditional dried persimmons during drying process. J. Korean Soc. Food Sci. Nutr. 2004;33:386–391. doi: 10.3746/jkfn.2004.33.2.386. [DOI] [Google Scholar]
- 9.Lee MH, No HK. Quality changes during storage of persimmon vinegar clarified by chitosan treatment. J. Korean Soc. Food Sci. Nutr. 2001;30:283–287. [Google Scholar]
- 10.Ohguchi K, Nakajima C, Oyama M, Iinuma M, Itoh T, Akao Y, Nozawa Y, Ito M. Inhibitory effects of flavonoid glycosides isolated from the peel of Japanese persimmon (Diospyros kaki 'Fuyu') on melanin biosynthesis. Biol. Pharm. Bull. 2010;33:122–124. doi: 10.1248/bpb.33.122. [DOI] [PubMed] [Google Scholar]
- 11.Briand CH. The common persimmon (Diospyros virginiana L.): The history of an underutilized fruit tree (16th-19th centuries) Huntia. 2005;12:71–89. [Google Scholar]
- 12.Kawase M, Motohashi N, Satoh K, Sakagami H, Nakashima H, Tani S, Shirataki Y, Kurihara T, Spengler G, Wolfard K M J. Biological activity of persimmon (Diospyros kaki) peel extracts. Phytother. Res. 2003;17:495–500. doi: 10.1002/ptr.1183. [DOI] [PubMed] [Google Scholar]
- 13.Kotani M, Matsumoto M, Fujita A, Higa S, Wang W, Suemura M, Kishimoto T, Tanaka T. Persimmon leaf extract and astragalin inhibit development of dermatitis and IgE elevation in NC/Nga mice. J. Allergy Clin. Immun. 2000;106:159–166. doi: 10.1067/mai.2000.107194. [DOI] [PubMed] [Google Scholar]
- 14.Im CY, Jeong ST, Choi HS, Choi JH, Yeo SH, Kang WW. Characteristics of Gammakgeolli added with processed forms of persimmon. Korean J. Food Preserv. 2012;19:159–166. doi: 10.11002/kjfp.2012.19.1.159. [DOI] [Google Scholar]
- 15.Shin DS, Park HY, Kim MH, Han GW. Quality characteristics of bread with persimmon peel powder. Korean J. Food Cook. Sci. 2011;27:589–597. doi: 10.9724/kfcs.2011.27.5.589. [DOI] [Google Scholar]
- 16.Yoo KH, Kim SJ, Jeong JM. Effects of persimmon (Diospyros kaki Thunb.) syrup extracted from persimmon and persimmon by-products on blood glucose level. J. Korean Soc. Food Sci. Nutr. 2011;40:682–688. doi: 10.3746/jkfn.2011.40.5.682. [DOI] [Google Scholar]
- 17.Singleton VL, Rossi JA. A colorimetry of totalphenolics with phosphomolybdicphosphotungstic acid reagents. Am. J. Enol. Viticult. 1965;16:144–158. [Google Scholar]
- 18.Bubba MD, Giordani E, Pippucci L, Cincinelli A, Checchini L, Galvan P. Changes in tannins, ascorbic acid, and sugar content in astringent persimmons during on-tree growth and ripening and in response to different postharvest treatments. J. Food Compos. Anal. 2009;22:668–677. doi: 10.1016/j.jfca.2009.02.015. [DOI] [Google Scholar]
- 19.Mensor LL, Menezes FS, Leitao GG, Reis AS, dos Santos TC, Coube CS, Leitao SG. Screening of brazilian plant extracts for antioxidant activity by the use of DPPH free radical method. Phytother. Res. 2001;15:127–130. doi: 10.1002/ptr.687. [DOI] [PubMed] [Google Scholar]
- 20.Re R, Pellegrini N, Pannala A, Yang M, Rice-evans C. Antioxidant activity applying an improved ABTS radical cation decolorization assay. Free Radical Bio. Med. 1999;26:1231–1237. doi: 10.1016/S0891-5849(98)00315-3. [DOI] [PubMed] [Google Scholar]
- 21.Denev P, Yordanov A. Total polyphenol, proanthocyanidin and flavonoid content, carbohydrate composition and antioxidant activity of persimmon (Diospyros kaki L.) fruit in relation to cultivar and maturity stage. Bulg. J. Agric. Sci. 2013;19:981–988. [Google Scholar]
- 22.Koh YJ, Cha DS, Choi HD, Park YK, Choi IW. Hot water extraction optimization of dandelion leaves to increase antioxidant activity. Korean J. Food Sci. Technol. 2008;40:283–289. [Google Scholar]
- 23.Gesquière L, Loreau N, Minnich A, Davignon J, Blache D. Oxidative stress leads to cholesterol accumulation in vascular smooth muscle cells. Free Radical Bio. Med. 1999;27:134–145. doi: 10.1016/S0891-5849(99)00055-6. [DOI] [PubMed] [Google Scholar]
- 24.Tian Y, Li CM, Yang J, Xu SF, Hagerman AE. High molecular weight persimmon tannin is a potent antioxidant both ex vivo and in vivo. Food Res. Int. 2012;45:26–30. doi: 10.1016/j.foodres.2011.10.005. [DOI] [Google Scholar]
- 25.Gato N, Kadowaki A, Hashimoto N, Yokoyama S, Matsumoto K. Persimmon fruit tannin-rich fiber reduces cholesterol levels in humans. Ann. Nutr. Metab. 2013;62:1–6. doi: 10.1159/000343787. [DOI] [PubMed] [Google Scholar]
- 26.Schneider WJ, Goldstein JL, Brown MS. Partial purification and characterization of the low density lipoprotein receptor from bovine adrenal cortex. J. Biol. Chem. 1980;255:11442–11447. [PubMed] [Google Scholar]
- 27.Brown MS, Goldstein JL. The SREBP pathway: Regulation of cholesterol metabolism by proteolysis of a membrane-bound transcription factor. Cell. 1997;89:331–340. doi: 10.1016/S0092-8674(00)80213-5. [DOI] [PubMed] [Google Scholar]
- 28.Briggs MR, Yokoyama C, Wang X, Brown MS, Goldstein JJ. Nuclear protein that binds sterol regulatory element of LDL receptor promoter. I. Identification of the protein and delineation of its target nucleotide sequence. J. Biol. Chem. 1993;268:14490–14496. [PubMed] [Google Scholar]
- 29.Edwards PA, Ericsson J. Sterols and isoprenoids: Signaling molecules derived from the cholesterol biosynthetic pathway. Annu. Rev. Biochem. 1999;68:157–185. doi: 10.1146/annurev.biochem.68.1.157. [DOI] [PubMed] [Google Scholar]
- 30.Quazi F, Molday RS. Lipid transport by mammalian ABC proteins. Essays Biochem. 2011;50:265–290. doi: 10.1042/bse0500265. [DOI] [PubMed] [Google Scholar]
- 31.Zhao Y, Pennings M, Hildebrand RB, Ye D, Calpe-Berdiel L, Out R, Kjerrulf M, Hurt-Camejo E, Groen AK, Hoekstra M, Jessup W, Chimini G, Van Berkel TJ, Van Eck M. Enhanced foam cell formation, atherosclerotic lesion development, and inflammation by combined deletion of ABCA1 and SR-BI in Bone marrowderived cells in LDL receptor knockout mice on western-type diet. Circ. Res. 2010;107:e20–e31. doi: 10.1161/CIRCRESAHA.110.226282. [DOI] [PubMed] [Google Scholar]
- 32.Rigotti A, Trigatti B, Penman M, Rayburn H, Herz J, Krieger M. A targeted mutation in the murine gene encoding the high density lipoprotein(HDL) receptor scavenger class B type I reveals its key role in HDL metabolism. P. Natl. Acad. Sci. USA. 1997;94:12610–12615. doi: 10.1073/pnas.94.23.12610. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 33.Krause BR, Auerbach BJ. Reverse cholesterol transport and future pharmacological approaches to the treatment of atherosclerosis. Curr. Opin. Investig. D. 2001;2:375–381. [PubMed] [Google Scholar]
- 34.Matsumoto K, Yokoyama S, Gato N. Hypolipidemic effect of young persimmon fruit in C57BL/6.KOR-ApoEshl mice. Biosci. Biotech. Bioch. 2008;72:2651–2659. doi: 10.1271/bbb.80319. [DOI] [PubMed] [Google Scholar]
- 35.Dávalos A, Fernández-Hernando C, Cerrato F, Martínez-Botas J, Gómez-Coronado D, Gómez-Cordovés C, Lasunción MA. Red grape juice polyphenols alter cholesterol homeostasis and increase LDL-receptor activity in human cells in vitro. J. Nutr. 2006;136:1766–1773. doi: 10.1093/jn/136.7.1766. [DOI] [PubMed] [Google Scholar]
- 36.Mullen E, Brown RM, Osborne TF, Shay NF. Soy isoflavones affect sterol regulatory element binding proteins (SREBPs) and SREBP-regulated genes in HepG2 cells. J. Nutr. 2004;134:2942–2947. doi: 10.1093/jn/134.11.2942. [DOI] [PubMed] [Google Scholar]