High Anti-oxidative and Lipid-lowering Activities of Flavonoid Glycosides-rich Extract from the Leaves of Zanthoxylum bungeanum in Multi-system

Limei Ma¹, Ke Li¹, Dandan Wei², Hengyi Xiao², Hai Niu^1, and Wen Huang^1,

¹Institute for Nanobiomedical Technology and Membrane Biology, and Laboratory of Ethnopharmacology, Regenerative Medicine Research Center, Lab for Aging Research, West China Hospital/West China Medical School, Sichuan University, Chengdu, China

²College of Light Industry, Textile and Food Engineering, Sichuan University, Chengdu, China

Cite this paper:
Limei Ma, Ke Li, Dandan Wei, Hengyi Xiao, Hai Niu and Wen Huang. High Anti-oxidative and Lipid-lowering Activities of Flavonoid Glycosides-rich Extract from the Leaves of Zanthoxylum bungeanum in Multi-system. Journal of Food and Nutrition Research. 2015; 3(1):62-68. doi: 10.12691/jfnr-3-1-11

Abstract

Epidemiological studies observed that Zanthoxylum bungeanum leaf, a popular vegetable in China, could interfere progression of cardiovascular diseases, especially hyperlipidemia. In the work, the pharmacological properties of Z.bungeanum leaves extract (ZLE) containing isovitexin, vitexin, hyperoside, rutin, isoquercitrin, foeniculin, trifolin, quercitrin, astragalin, and afzelin were investigated using multi-system such as mice organ tissue, HepG2 cell and apoE-/- mice. ZLE exhibited a stronger activity of scavenging free radicals. ZLE also appeared to inhibit lipid peroxidation of mice organ tissues including the heart, liver, spleen, lung, kidney, brain and pancreas. ZLE could lower lipid accumulation in HepG2 cells induced by free fatty acids (FFAs, an inducer of lipid peroxidation and free radicals production) in a dose-dependent manner. Compared with fenofibrate, a commercial product popularly used in clinical, the treatment of ZLE in apoE-/- mice had a stronger anti-hyperlipidemia without any detectable histopathological damage. This is the first report that ZLE containing high content of flavonoids with satisfying safety could significantly inhibit the development of hyperlipidemia by preventing the oxidative damage induced by free radicals and lipid peroxidation.

Keywords:
Zanthoxylum bungeanum Hyperlipidemia Flavonoid glycosides HepG2 apoE-/- deficient mice

This work is licensed under a Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

Figures

References:

[1]	Anderson, K. M., Wilson, P. W. F., Garrison R. J., Castelli, W. P., “Longitudinal and secular trends in lipoprotein cholesterol measurements in a general population sample, The Framingham offspring study”. Atherosclerosis 68. 59-66. 1987.
[2]	Gordon, T., Kannel, W. B., “Predisposition to atherosclerosis in the head, heart, and legs”. The Journal of the American Medical Association 221. 661-666.1972.
[3]	Alikhani, N., Ferguson, R. D., Novosyadlyy, R.,Gallagher, E. J., Scheinman, E. J., Yakar, S., et al. “Mammary tumor growth and pulmonary metastasis are enhanced in a hyperlipidemic mouse model”. Oncogene 32. 961-967. 2012.
[4]	Sabatine, M. S., Wiviott, S. D., Morrow, D. A., “TIMI study group High-dose atorvastatin associated with worse glycemic control a PROVE-IT TIMI 22 substudy (abstr)”. Circulation. 110. 2004.
[5]	Negi, P., “Extent and pattern of use of statins and ezetimibe as lipid lowering agents and their influence on marketing strategies”. 2010.
[6]	Kardum, N., Takić, M., Šavikin, K., Zec, M., Zdunić, G., Zdunićb, G., “Effects of polyphenol rich chokeberry juice on cellular antioxidant enzymes and membrane lipid status in healthy women”. Journal of Functional Foods 9. 89-97. 2014.
[7]	Monagas, M., Bartolomè, B., Gómez-Cordovès, C., “Evolution of the phenolic content of red wines from Vitis vinifera L during ageing in bottle”. Food Chemistry 95. 405-412. 2006.
[8]	Athukorala, Y., Lee, K.-W., Kim, S.-K., Jeon, Y. J., “Anticoagulant activity of marine green and brown algae collected from Jeju Island in Korea”. Bioresour. Technol 98. 1711-1716. 2007.
[9]	Xiong, Q., Shi, D., Mizuno, M., “Flavonol glucosides in pericarps of Zanthoxylum bungeanum”. Phytochemistry 39. 723-725. 1995.
[10]	Zhong, K., Li, X. J., Gou, A. N., Huang, Y. N., Bu, Q., & Gao, H., “Antioxidant and Cytoprotective Activities of Flavonoid Glycosides-rich Extract from the Leaves of Zanthoxylum bungeanum”. Journal of Food and Nutrition Research 2(7). 349-356. 2014.
[11]	Ružić, I., Škerget, M., Knez, Ž., and Runje, M., “Phenolic content and antioxidant potential of macerated white wines”. Europe Food Research Technol 233. 465-472. 2011.
[12]	Woldegiorgis, A.Z., Abate, D., Haki, G.D., and Ziegler, G.R., “Antioxidant property of edible mushrooms collected from Ethiopia”. Food Chemistry 157. 30-36. 2014.
[13]	Brand-Williams,W., Cuvelier, M. E., Berset, C., “Use of a free radical method to evaluate antioxidant activity”. LWT-Food Science and Technology 28. 25-30.1995.
[14]	Dasgupta, N., Bratati, D., “Antioxidant activity of Piper betle L. leaf extract in vitro”. Food Chemistry 88. 219-224. 2004.
[15]	Wu, X., Zhang, L., Gurley, E., Studer, E., Shang, J., Wang, T., “Prevention of free fatty acid-induced hepatic lipotoxicity by 18 beta-glycyrrhetinic acid through lysosomal and mitochondrial pathways”. Hepatology 47. 1905-1915. 2008.
[16]	Wangcharoen, W., Gomolanee, S., “Antioxidant Capacity and Total Phenolic Content of Moringa oleifera Grown in Chiang Mai, Thailand”. Thai Journal of Agricultural Science 44(5). 118-124. 2011.
[17]	D’Archivio, M., Filesi, C., Di Benedetto, R., Gargiulo, R., Giovannini, C., Masella, R., “Polyphenols, dietary sources and bioavailability”. Ann Ist Super Sanità. 348-361. 2007.
[18]	Cook, N.C., Samman, S., “Flavonoids-Chemistry, metabolism, cardioprotective effects, and dietary sources”. Nutritional Biochemistry7. 66-76. 1996.
[19]	Choi, Y., Jeong, H.S., and Lee, J., “Antioxidant activity of methanolic extracts from some grains consumed in Korea”. Food Chemistry 103. 130-138. 2007.
[20]	Sukito, A., Tachibana, S., “Isolation of Hyperoside and Isoquercitrin from Camellia sasanqua as Antioxidant Agents”. Pakistan Journal of Biological Sciences 17. 999-1006. 2014.
[21]	Mahmoud, A. M., Soliman, A. S., “Rutin attenuates Hyperlipidemia and Cardiac Oxidative Stress in Diabetic Rats”. Egypt Journal of Medical Science 34. 287-302. 2013.
[22]	Borza, C., Muntean, D., Dehelean, C., Săvoiu, G., SERBAN, C., Simu, G., & Drăgan, S., “Oxidative stress and lipid peroxidation-a lipid metabolism dysfunction”. Lipid metabolism. 2013.
[23]	Bertrand, Y., “Oxygen-free radicals and lipid peroxidation in adult respiratory distress syndrome”. Intensive care medicine 11. 56-60. 1985.
[24]	Liang, T., Yue, W., Li, Q., “Comparison of the phenolic content and antioxidant activities of Apocynum venetum L. (Luo-Bu-Ma) and two of its alternative species”. International journal of molecular sciences 11. 4452-4464. 2010.
[25]	Choi, J. H., Kim, D. W., Yun, N., Choi, J. S., Islam, M. N., Kim, Y. S., & Lee, S. M., “Protective effects of hyperoside against carbon tetrachloride-induced liver damage in mice”. Journal of natural products 74. 1055-1060. 2011.
[26]	Zhang, Z., Chang, Q., Zhu, M., Huang. Y., Ho, WK., Chen, Z., “Characterization of antioxidants present in hawthorn fruits”. Journal of Nutrition Biochemistry 12. 144-152. 2001.
[27]	Terasawa, Y., Ladha, Z., Leonard. S.W., Morrow, J. D., Newland, D., Sanan, D., Packeri, L., Traber, M. G., and Farese, Jr. R. V., “Increased atherosclerosis in hyperlipidemic mice deficient in a-tocopherol transfer protein and vitamin E”. PNAS 97. 13830-13834. 2000.
[28]	Nguyen, P., Leray, V., Diez, M., Serisier, S., Le, B., Siliart, B., Dumon, H., “Liver lipid metabolism”. Jounal of animal physiology and animal nutrition's (Berl) 92. 272-83. 2008.
[29]	Yao, H. R., Liu, J., Plumeri, D., Cao, Y. B., He, T., Lin, L., Li, Y., Jiang, Y. Y., Li, J., Shang, J., “Lipotoxicity in HepG2 cells triggered by free fatty acids”. American Journal of Translational Research 15. 284-91. 2011.
[30]	Brown, J.P., “A review of the genetic effects of naturally occurring flavonoids anthraquinone and related compounds”. Mutation. Research 75. 243-277. 1980.
[31]	Hertog, M.G.L., Feskens, E.J.M., Hollman, P.C.H., Katan, M.B., Kromhout, D., “Dietary antioxidant flavonoids and risk of coronary heart disease”. The Zutphen Elderly Study Lancet 342. 1007-1011. 1993.
[32]	Li, J. F., Chen, H. Y., Ke, J. Y., Jian, H., Xiao, Y. D., “Hypolipidemic and antioxidant effects of total flavonoids of Perilla Frutescens leaves in hyperlipidemia rats induced by high-fat diet”. Food Research International 44. 404-409. 2011.
[33]	Fazio, S., Linton, M. F., “Mouse models of hyperlipidemia and atherosclerosis”. Frontiers in Bioscience 6. D515-525. 2001.
[34]	Ma, J. Y., Shi, Y. K., Fang, D. Z., “Antiatherogenic effect of Huajiao volatile oil on experimental atherosclerosis in guinea pigs”. Sichuan Da Xue Xue Bao 36. 696. 2005.
[35]	Mertz, D. P., “Atherosclerosis-index (LDL/HDL): risk indicator in lipid metabolism disorders”. Medizinische Klinik 75. 159-161. 1980.
[36]	Yang, X. Z., Liu, Y., Mi, J., Tang, C. S., Du, J. B., “Pre-clinical atherosclerosis evaluated by carotid artery intima-media thickness and the risk factors in children”. Chinese Medical Journal 120. 359-362. 2007.
[37]	Fernanda, B., Arauj, D. S., Barbos, C. Y., Hsi, R. C., Maranh, Z., Dulcineia, S. P. A. “Evaluation of oxidative stress in patients with hyperlipidemia”. Atherosclerosis117. 61-71. 1995.
[38]	Zang, M. W., Zuccollo, A., Hou, X. Y., Nagata, D., Walsh, K., Herscovitz, H., Brecher, P., Ruderman, N. B., Cohen, R. A., “AMP-activated protein kinase is required for the lipid-lowering effect of metformin in insulin-resistant human HepG2 cells”. Journal of Biology Chemistry 279. 47898-47905. 2004.
[39]	Zang, M.W., Xu, S.Q., Maitland-Toolan, K.A., Zuccollo, A., Hou, X.Y., Jiang, B.B., Wierzbicki, M., Verbeuren, T. J., and Cohen, R. A., “Polyphenols stimulate AMP-activated protein kinase, lower lipids, and inhibit accelerated atherosclerosis in diabetic LDL receptor-deficient mice”. Diabetes 55. 2180-2191. 2006.