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Mini-Reviews in Medicinal Chemistry

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ISSN (Online): 1875-5607

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Review Article

Spinacia oleracea Linn Considered as One of the Most Perfect Foods: A Pharmacological and Phytochemical Review

Author(s): Rosa Martha Perez Gutierrez*, Elisa Gutierrez Velazquez and Silvia Patricia Paredes Carrera

Volume 19, Issue 20, 2019

Page: [1666 - 1680] Pages: 15

DOI: 10.2174/1389557519666190603090347

Price: $65

Abstract

Background: Leaves of Spinacia oleracea have been widely used as vegetarian foods. Some studies on the chemical composition of spinach have shown that it contains a high content of micronutrients (vitamins and minerals), and has an important economic value with some agronomic advantages. S. oleracea in traditional medicine is reported to cure more than one health problem.

Objective: This review focuses on the ethnopharmacological uses and pharmacological and phytochemical studies of Spinacia oleracea.

Methods: Information on S. oleracea was obtained via electronic search of scientific databases such as Scopus, PubMed, Google Scholar, Scirus, Science Direct, Scielo, Web of Science, Medline, Springerlink, BioMed Central (BMC), and SciFinder for publications on this plant. In addition, books on medicinal herbs were also consulted.

Results: Approximately 100 chemical compounds were isolated and characterized from S. oleracea. The major active components of the plant are flavones, flavanols, methylenedioxyflavonol glucuronides, glucuronides, and carotenoids, which were extensively investigated. This review revealed potential pharmacological properties of these isolated compounds such as anti-obesity, anti-α-amylase, bileacid binding capacity, anti-mutagenic, anti-oxidant, anticancer, anti-inflammatory, cognitive and mood effect, hypoglycemic, and anti-hypertriglyceridemia.

Conclusion: S. oleracea is an important edible plant also used for ethnomedical therapy of obesity, inflammation of lungs, lumbago, flatulence, and treatment of urinary calculi. Pharmacological and phytochemical studies of this plant including bioactives, which have been adequately studied, support its uses in traditional medicine. Additionally, prospects and future trends of this plant are proposed.

Keywords: Spinacia oleracea, edible plant, anti-obesity, flavonoids, carotenoids, thylakoids.

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[1]
Osterholm, M.T.; Ostrowsky, J.; Farrar, J.A.; Gravani, R.B.; Tauxe, R.V.; Buchanan, R.L.; Hedberg, C.W. A novel approach to enhance food safety: industry-academia-government partnership for applied research. J. Food Prot., 2009, 72(7), 1509-1512.
[http://dx.doi.org/10.4315/0362-028X-72.7.1509] [PMID: 19681279]
[2]
Hu, J.; Mou, B.; Vick, B. Genetic diversity of 38 spinach (Spinacia oleracea L.) germplasm accessions and 10 commercial hybrids assessed by TRAP markers. Genet. Resour. Crop Evol., 2007, 54, 1667-1674.
[http://dx.doi.org/10.1007/s10722-006-9175-4]
[3]
Bunea, A.; Andjelkovic, M.; Socaciu, C.; Bobis, O.; Neacsu, M.; Verhe, R.; Camp, J.V. Total and individual carotenoids and phenolic acids content in fresh, refrigerated and processed spinach (Spinacia oleracea L.). Food Chem., 2008, 108(2), 649-656.
[http://dx.doi.org/10.1016/j. foodchem.2007.11]
[4]
Jebb, S.; Livingstone, B.; Lluch, A. Appetite control. Methodological aspects of the evaluation of foods. Obesity Reviews: An Official J. Intern. Association Study of Obesity., 2010, 11, 251-270.
[5]
2005.FAOSTAT data., http://www.fao-stat.fao.org/faostat/
[6]
Le Strange, M.; Koike, S.; Valencia, J.; Chaney, W. Spinach production in California. Publication 7212; Vegetable Research and Information Center, Division of Agriculture and Natural Resources, University of California: Davis, 2003.
[7]
Metha, D.; Belemkar, S. Pharmacological activity of Spinacia oleracea linn. - a complete overview. Asian J. Pharm. Res. Develop., 2014, 2(1), 32-42.
[8]
Maeda, N.; Kokai, Y.; Ohtani, S.; Sahara, H.; Kumamoto-Yonezawa, Y.; Kuriyama, I.; Hada, T.; Sato, N.; Yoshida, H.; Mizushina, Y. Anti-tumor effect of orally administered spinach glycolipid fraction on implanted cancer cells, colon-26, in mice. Lipids, 2008, 43(8), 741-748.
[http://dx.doi.org/10.1007/s11745-008-3202-5] [PMID: 18594894]
[9]
Grossman, S.; Bergman, M.; Varshavsky, L.; Gottlieb, H.E. The antioxidant activity of aqueous spinach. Asian J. Pharm. Res. Develop., 2014, 2(1), 43-48.
[10]
Gregor, M.F.; Hotamisligil, G.S. Inflammatory mechanisms in obesity. Annu. Rev. Immunol., 2011, 29, 415-445.
[http://dx.doi.org/10.1146/annurev-immunol-031210-101322] [PMID: 21219177]
[11]
Stenblom, E.L.; Egecioglu, E.; Landin-Olsson, M.; Erlanson-Albertsson, C. Consumption of thylakoid-rich spinach extract reduces hunger, increases satiety and reduces cravings for palatable food in overweight women. Appetite, 2015, 91, 209-219.http://www.anrcatalog.ucdavis.edu/pdf/7212.pdf
[http://dx.doi.org/10.1016/j.appet.2015.04.051] [PMID: 25895695]
[12]
Montelius, C.; Szwiec, K.; Kardas, M.; Lozinska, L.; Erlanson-Albertsson, C.; Pierzynowski, S.; Rehfeld, J.F.; Weström, B. Dietary thylakoids suppress blood glucose and modulate appetite-regulating hormones in pigs exposed to oral glucose tolerance test. Clin. Nutr., 2014, 33(6), 1122-1126.
[http://dx.doi.org/10.1016/j.clnu.2013.12.009] [PMID: 24411616]
[13]
Wolf, F.T.; Coniglio, J.G.; Davis, J.T. Fatty acids of spinach chloroplasts. Plant Physiol., 1962, 37(1), 83-85.
[http://dx.doi.org/10.1104/pp.37.1.83] [PMID: 16655613]
[14]
Singh, G.; Kawatra, A.; Sehgal, S. Nutritional composition of selected green leafy vegetables, herbs and carrots. Plant Foods Hum. Nutr., 2001, 56(4), 359-364.
[http://dx.doi.org/10.1023/A:1011873119620] [PMID: 11678441]
[15]
Kim, H.; Kim, G.; Jang, W.; Kim, S.Y.; Chang, N. Association between intake of B vitamins and cognitive function in elderly Koreans with cognitive impairment. Nutr. J., 2014, 13(1), 118-123.
[http://dx.doi.org/10.1186/1475-2891-13-118] [PMID: 25516359]
[16]
Aisen, P.S.; Schneider, L.S.; Sano, M.; Diaz-Arrastia, R.; van Dyck, C.H.; Weiner, M.F.; Bottiglieri, T.; Jin, S.; Stokes, K.T.; Thomas, R.G.; Thal, L.J. High-dose B vitamin supplementation and cognitive decline in Alzheimer disease: A randomized controlled trial. JAMA, 2008, 300(15), 1774-1783.
[http://dx.doi.org/10.1001/jama.300.15.1774] [PMID: 18854539]
[17]
Chopra, R.N.; Nayar, S.L.; Chopra, I.C. Glossary of Indian Medicinal Plants Including the Supplement; Council of Scientific and Industrial Researc: New Delhi, 1956.
[18]
Kirtikar, K.R.; Basu, B.D. Indian Medicinal plants. Dehradun. International Book Distributors., 2005, 8, 2078-2079.
[19]
Morelock, T.E.; Correll, J.C. Vegetables I: Handbook of Plant Breeding, 1st eds. J. Prohens-Tomás and F. Nuez, . Springer, New York., ; , 2008, pp. 189-218.
[20]
Sultana, B.; Anwar, F. Flavonols (kaempeferol, quercetin, myricetin) contents of selected fruits, vegetables and medicinal plants. Food Chem., 2008, 108(3), 879-884.
[http://dx.doi.org/10.1016/j.foodchem.2007.11.053] [PMID: 26065748]
[21]
Ferreres, F.; Castaner, M.; Tomas-Barberan, F.A. Acylated flavonol glycoside from spinach leaves (Spinacia oleracea). Phytochemistry, 1997, 45(8), 1701-1705.
[http://dx.doi.org/10.1016/S0031-9422(97)00244-6]
[22]
Annonymus. The wealth of India. . New Delhi: National Institute of Science, Communication & Information Resources (CSIR).,, 2004, 5, 146-147.
[23]
Morishita, Y.; Saito, E.; Takemura, E.; Fujikawa, R.; Yamamoto, R.; Kuroyanagi, M.; Shirota, N.; Muto, O. Flavonoid glucuronides isolated from spinach inhibit IgE mediated degranulation in basophilic leukemia RBL-2H3 cells and passive cutaneous anaphylaxis reaction in mice. Integr. Mol. Med., 2015, 2, 99-100.
[http://dx.doi.org/10.15761/IMM.1000119]
[24]
Roberts, J.L.; Moreau, R. Functional properties of spinach (Spinacia oleracea L.) phytochemicals and bioactives. Food Funct., 2016, 7(8), 3337-3353.
[http://dx.doi.org/10.1039/C6FO00051G] [PMID: 27353735]
[25]
Edenharder, R.; Keller, G.; Platt, K.L.; Unger, K.K. Isolation and characterization of structurally novel antimutagenic flavonoids from spinach (Spinacia oleracea). J. Agric. Food Chem., 2001, 49(6), 2767-2773.
[http://dx.doi.org/10.1021/jf0013712] [PMID: 11409964]
[26]
Singh, J.G.K.; Bhimanagouda, J.; Patil, S. An optimized solvent extraction and rapid identification of unidentified flavonoid glucuronide derivatives from spinach by UHPLC-HR-QTOF-MS. Talanta, 2018.
[http://dx.doi.org/10.1016/j.talanta.2018.06.025]
[27]
Sözgen Başkan, K.; Tütem, E.; Özer, N.; Apak, R. Spectrophotometric and chromatographic assessment of contributions of carotenoids and chlorophylls to the total antioxidant capacities of plant foods. J. Agric. Food Chem., 2013, 61(47), 11371-11381.
[http://dx.doi.org/10.1021/jf403356h] [PMID: 24168293]
[28]
Kuriyama, I.; Musumi, K.; Yonezawa, Y.; Takemura, M.; Maeda, N.; Iijima, H.; Hada, T.; Yoshida, H.; Mizushina, Y. Inhibitory effects of glycolipids fraction from spinach on mammalian DNA polymerase activity and human cancer cell proliferation. J. Nutr. Biochem., 2005, 16(10), 594-601.
[http://dx.doi.org/10.1016/j.jnutbio.2005.02.007] [PMID: 16081275]
[29]
Hafez Hetta, M.; Moawad, A.S.; Abdel-Aziz Hamed, M.; Sabri, A.I. In-vitro and in-vivo hypolipidemic activity of spinach roots and flowers. Iran. J. Pharm. Res., 2017, 16(4), 1509-1519.
[PMID: 29552059]
[30]
Bhatia, D.; Bejarano, T.; Novo, M. Current interventions in the management of knee osteoarthritis. J. Pharm. Bioallied Sci., 2013, 5(1), 30-38.
[http://dx.doi.org/10.4103/0975-7406.106561] [PMID: 23559821]
[31]
Zhang, W.; Ouyang, H.; Dass, C.R.; Xu, J. Current research on pharmacologic and regenerative therapies for osteoarthritis. Bone Res., 2016, 4, 15040-15044.
[http://dx.doi.org/10.1038/boneres.2015.40] [PMID: 26962464]
[32]
Sharma, A.R.; Jagga, S.; Lee, S.S.; Nam, J.S. Interplay between cartilage and subchondral bone contributing to pathogenesis of osteoarthritis. Int. J. Mol. Sci., 2013, 14(10), 19805-19830.
[http://dx.doi.org/10.3390/ijms141019805] [PMID: 24084727]
[33]
Kim, W.K.; Chung, H.J.; Pyee, Y.; Choi, T.J.; Park, H.J.; Hong, J.Y.; Shin, J.S.; Lee, J.H.; Ha, I.H.; Lee, S.K. Effects of intra-articular SHINBARO treatment on monosodium iodoacetate-induced osteoarthritis in rats. Chin. Med., 2016, 11, 17.
[http://dx.doi.org/10.1186/s13020-016-0089-6] [PMID: 27069504]
[34]
Choudhary, D.; Kothari, P.; Tripathi, A-K.; Singh, S.; Adhikary, S.; Ahmad, N.; Kumar, S.; Dev, K.; Mishra, V.K.; Shukla, S.; Maurya, R.; Mishra, P.R.; Trivedi, R. Spinacia oleracea extract attenuates disease progression and sub-chondral bone changes in monosodium iodoacetate-induced osteoarthritis in rats. BMC Complement. Altern. Med., 2018, 18(1), 69.
[http://dx.doi.org/10.1186/s12906-018-2117-9] [PMID: 29463254]
[35]
Panda, V.; Shinde, P. Appetite suppressing effect of Spinacia oleracea in rats: Involvement of the short term satiety signal cholecystokinin. Appetite, 2017, 113, 224-230.https://Doi.org/10.1016/j.appet.2017.02.030
[http://dx.doi.org/10.1016/j.appet.2017.02.030] [PMID: 28238891]
[36]
Liao, M.C.; Arakak, H.; Li, Y.; Takamiyagi, A.; Tawata, S.; Aniya, Y.; Sakurai, H. Liao, M.C.; Arakaki, H.; Li, Y.; Takamiyagi, A.; Tawata, S.; Aniya, Y.; Sakurai, H.; Nonaka, S. Inhibitory effects of Alpinia speciosa K. SCHUM on the porphyrin photooxidative reaction. J. Dermatol., 2000, 27(5), 312-317.
[http://dx.doi.org/10.1111/j.1346-8138.2000.tb02173.x] [PMID: 10875197]
[37]
Bergman, M.; Perelman, A.; Dubinsky, Z.; Grossman, S. Scavenging of reactive oxygen species by a novel glucurinated flavonoid antioxidant isolated and purified from spinach. Phytochemistry, 2003, 62(5), 753-762.
[http://dx.doi.org/10.1016/S0031-9422(02)00537-X] [PMID: 12620328]
[38]
Vutharadhi, S.; Jolapuram, U.; Kodidhela, L.D. Nutraceutical inherent of Spinacia oleracea Linn. methanolic leaf extract ameliorates isoproterenol induced myocardial necrosis in male albino Wistar rats via mitigating inflammation. Biomed. Pharmacother., 2017, 85, 239-247.
[http://dx.doi.org/10.1016/j.biopha.2016.10.103] [PMID: 27914824]
[39]
Barkat, N.; Singh, J.; Jayaprakasha, G.K.; Patil, B.S. Effect of harvest time on the levels of phytochemicals, free radical scavenging activity, α-amylase inhibition, and bile acid binding capacity of spinach (Spinacia oleracea). J. Sci. Food Agric., 2017, 28.
[http://dx.doi.org/10.1002/jsfa.8862] [PMID: 29282747]
[40]
Launer, L.J. Demonstrating the case that AD is a vascular disease: epidemiologic evidence. Ageing Res. Rev., 2002, 1(1), 61-77.
[http://dx.doi.org/10.1016/S0047-6374(01)00364-5] [PMID: 12039449]
[41]
Loke, W.M.; Hodgson, J.M.; Proudfoot, J.M.; McKinley, A.J.; Puddey, I.B.; Croft, K.D. Pure dietary flavonoids quercetin and (-)-epicatechin augment nitric oxide products and reduce endothelin-1 acutely in healthy men. Am. J. Clin. Nutr., 2008, 88(4), 1018-1025.
[http://dx.doi.org/10.1093/ajcn/88.4.1018] [PMID: 18842789]
[42]
Bondonno, C.P.; Yang, X.; Croft, K.D.; Considine, M.J.; Ward, N.C.; Rich, L.; Puddey, I.B.; Swinny, E.; Mubarak, A.; Hodgson, J.M. Flavonoid-rich apples and nitrate-rich spinach augment nitric oxide status and improve endothelial function in healthy men and women: A randomized controlled trial. Free Radic. Biol. Med., 2012, 52(1), 95-102.
[http://dx.doi.org/10.1016/j.freeradbiomed.2011.09.028] [PMID: 22019438]
[43]
Bondonno, C.P.; Downey, L.A.; Croft, K.D.; Scholey, A.; Stough, C.; Yang, X.; Considine, M.J.; Ward, N.C.; Puddey, I.B.; Swinny, E.; Mubarak, A.; Hodgson, J.M. The acute effect of flavonoid-rich apples and nitrate-rich spinach on cognitive performance and mood in healthy men and women. Food Funct., 2014, 5(5), 849-858.
[http://dx.doi.org/10.1039/C3FO60590F] [PMID: 24676365]
[44]
Joseph, J.A.; Shukitt-Hale, B.; Denisova, N.A.; Bielinski, D.; Martin, A.; McEwen, J.J.; Bickford, P.C. Reversals of age-related declines in neuronal signal transduction, cognitive, and motor behavioral deficits with blueberry, spinach, or strawberry dietary supplementation. J. Neurosci., 1999, 19(18), 8114-8121.
[http://dx.doi.org/10.1523/JNEUROSCI.19-18-08114.1999] [PMID: 10479711]
[45]
Stahl, W.; Sies, H. Antioxidant activity of carotenoids. Mol. Aspects Med., 2003, 24(6), 345-351.
[http://dx.doi.org/10.1016/S0098-2997(03)00030-X] [PMID: 14585305]
[46]
Ferruzzi, M.G.; Bohm, V.; Courtney, P.D.; Schwartz, S.J. Antioxidant and antimutagenic activity of dietary chlorophyll derivatives determined by radical scavenging and bacterial reverse mutagenesis assays. J. Food Sci., 2002, 67(7), 2589-2595.
[http://dx.doi.org/10.1111/j.1365-2621.2002.tb08782.x]
[47]
Martin, H.D.; Ruck, C.; Schmidt, M.; Sell, S.; Beutner, S.; Mayer, B.; Walsh, R. Chemistry of carotenoid oxidation and free radical reactions. Pure Appl. Chem., 1999, 71(12), 2253-2262.
[http://dx.doi.org/10.1351/pac199971122253]
[48]
Di Mascio, P.; Kaiser, S.; Sies, H. Lycopene as the most efficient biological carotenoid singlet oxygen quencher. Arch. Biochem. Biophys., 1989, 274(2), 532-538.
[http://dx.doi.org/10.1016/0003-9861(89)90467-0] [PMID: 2802626]
[49]
Kim, J.H.; Na, H.J.; Kim, C.K.; Kim, J.Y.; Ha, K.S.; Lee, H.; Chung, H.T.; Kwon, H.J.; Kwon, Y.G.; Kim, Y.M. The non-provitamin A carotenoid, lutein, inhibits NF-kappaB-dependent gene expression through redox-based regulation of the phosphatidylinositol 3-kinase/PTEN/Akt and NF-kappaB-inducing kinase pathways: role of H2O2 in NF-kappaB activation. Free Radic. Biol. Med., 2008, 45(6), 885-896.
[http://dx.doi.org/10.1016/j.freeradbiomed.2008.06.019] [PMID: 18620044]
[50]
Kim, Y.; Seo, J.H.; Kim, H.; Kim, J.; Ha, K.; Lee, H.; Chung, H.; Jeong Kwon, H.; Kwon, Y.; Kim, Y.; Seo, J.H.; Ki, H. β-Carotene and lutein inhibit hydrogen peroxide-induced activation of NF-κB and IL-8 expression in gastric epithelial AGS cells. J. Nutr. Sci. Vitaminol. (Tokyo), 2011, 57(3), 216-223.
[http://dx.doi.org/10.3177/jnsv.57.216] [PMID: 21908944]
[51]
Havir, E.A.; Lorraine, S.; Richard, T.; Peterson, B. Purification and properties of violaxanthin de-epoxidase from spinach. Plant Sci., 1997, 123(1-2), 57-66.
[http://dx.doi.org/10.1016/S0168-9452(97)04579-2]
[52]
Soontornchaiboon, W.; Joo, S.S.; Kim, S.M. Anti-inflammatory effects of violaxanthin isolated from microalga Chlorella ellipsoidea in RAW 264.7 macrophages. Biol. Pharm. Bull., 2012, 35(7), 1137-1144.
[http://dx.doi.org/10.1248/bpb.b12-00187] [PMID: 22791163]
[53]
Jaime, L.; Vázquez, E.; Fornari, T.; López-Hazas, M. del C.; García-Risco, M.R.; Santoyo, S.; Reglero, G. Extraction of functional ingredients from spinach (Spinacia oleracea L.) using liquid solvent and supercritical CO2 extraction. J. Sci. Food Agric., 2015, 95(4), 722-729.
[http://dx.doi.org/10.1002/jsfa.6788] [PMID: 24930815]
[54]
de Vogel, J.; Jonker-Termont, D.S.; van Lieshout, E.M.; Katan, M.B.; van der Meer, R. Green vegetables, red meat and colon cancer: Chlorophyll prevents the cytotoxic and hyperproliferative effects of haem in rat colon. Carcinogenesis, 2005, 26(2), 387-393.
[http://dx.doi.org/10.1093/carcin/bgh331] [PMID: 15550456]
[55]
Andersson, L.; Bratt, C.; Arnoldsson, K.C.; Herslöf, B.; Olsson, N.U.; Sternby, B.; Nilsson, A. Hydrolysis of galactolipids by human pancreatic lipolytic enzymes and duodenal contents. J. Lipid Res., 1995, 36(6), 1392-1400.
[PMID: 7666015]
[56]
Albertsson, P.A.; Köhnke, R.; Emek, S.C.; Mei, J.; Rehfeld, J.F.; Akerlund, H.E.; Erlanson-Albertsson, C. Chloroplast membranes retard fat digestion and induce satiety: Effect of biological membranes on pancreatic lipase/co-lipase. Biochem. J., 2007, 401(3), 727-733.
[http://dx.doi.org/10.1042/BJ20061463] [PMID: 17044813]
[57]
Goedecke, J.H.; Barsdorf, M.; Beglinger, C.; Levitt, N.S.; Lambert, E.V. Effects of a lipase inhibitor (Orlistat) on cholecystokinin and appetite in response to a high-fat meal. Int. J. Obes. Relat. Metab. Disord., 2003, 27(12), 1479-1485.
[http://dx.doi.org/10.1038/sj.ijo.0802436] [PMID: 14634678]
[58]
Köhnke, R.; Lindqvist, A.; Göransson, N.; Emek, S.C.; Albertsson, P.A.; Rehfeld, J.F.; Hultgårdh-Nilsson, A.; Erlanson-Albertsson, C. Thylakoids suppress appetite by increasing cholecystokinin resulting in lower food intake and body weight in high-fat fed mice. Phytother. Res., 2009, 23(12), 1778-1783.
[http://dx.doi.org/10.1002/ptr.2855] [PMID: 19548286]
[59]
Stenblom, E.L.; Montelius, C.; Östbring, K.; Håkansson, M.; Nilsson, S.; Rehfeld, J.F.; Erlanson-Albertsson, C. Supplementation by thylakoids to a high carbohydrate meal decreases feelings of hunger, elevates CCK levels and prevents postprandial hypoglycaemia in overweight women. Appetite, 2013, 68, 118-123.
[http://dx.doi.org/10.1016/j.appet.2013.04.022] [PMID: 23632035]
[60]
Rebello, C.J.; Chu, J.; Beyl, R.; Edwall, D.; Erlanson-Albertsson, C.; Greenway, F.L. Acute effects of a spinach extract rich in thylakoids on satiety: A randomized controlled crossover trial. J. Am. Coll. Nutr., 2015, 34(6), 470-477.
[http://dx.doi.org/10.1080/07315724.2014.1003999] [PMID: 26029978]
[61]
Montelius, C.; Osman, N.; Weström, B.; Ahrné, S.; Molin, G.; Albertsson, P.A.; Erlanson-Albertsson, C. Feeding spinach thylakoids to rats modulates the gut microbiota, decreases food intake and affects the insulin response. J. Nutr. Sci., 2013.2e20.
[http://dx.doi.org/10.1017/jns.2012.29] [PMID: 25191569]
[62]
Chandler, R.F.; Hooper, S.N.; Ismail, H.A. Antihypercholesterolemic studies with sterols: β-sitosterol and stigmasterol. J. Pharm. Sci., 1979, 68(2), 245-247.
[http://dx.doi.org/10.1002/jps.2600680235] [PMID: 423101]
[63]
Davidson, M.H.; Stein, E.A.; Bays, H.E.; Maki, K.C.; Doyle, R.T.; Shalwitz, R.A.; Ballantyne, C.M.; Ginsberg, H.N. Efficacy and tolerability of adding prescription omega-3 fatty acids 4 g/d to simvastatin 40 mg/d in hypertriglyceridemic patients: An 8-week, randomized, double-blind, placebo-controlled study. Clin. Ther., 2007, 29(7), 1354-1367.
[http://dx.doi.org/10.1016/j.clinthera.2007.07.018] [PMID: 17825687]

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