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Cholesterol-lowering activity of adzuki bean (Vigna angularis) polyphenols

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Abstract

Background

Adzuki beans (ABs; Vigna angularis) were reported to show potential for prevention of cholesterol absorption and lowering of the blood cholesterol level. However, the main active compounds and some cellular effects remain unknown. In this study, we evaluated the potential cholesterol-lowering effects of (+)-catechin 7-O-β-d-glucopyranoside (C7G) and (+)-epicatechin 7-O-β-d-glucopyranoside (E7G), identified as abundant polyphenols in ABs.

Methods and results

To investigate the cholesterol-lowering activity in vitro, cholesterol micelles, bile acids, and Caco-2 cells as an intestinal model were used in the study. C7G and E7G each inhibited micellar solubility in a dose-dependent manner, and their inhibitory activity was as strong as that of (+)-catechin (IC50 values: C7G, 0.23 ± 0.03 mg/ml; E7G, 0.22 ± 0.02 mg/ml; (+)-catechin, 0.26 ± 0.11 mg/ml). The AB polyphenols showed binding activity toward bile acids and changed them into an insoluble form. When Caco-2 cells were treated with C7G or E7G, the amount of incorporated cholesterol was significantly decreased compared with vehicle-treated control cells, and no cytotoxicity was observed under the experimental conditions used. Meanwhile, quantitative real-time PCR revealed that the mRNA level of the cholesterol transporter NPC1L1 remained unchanged in the treated cells.

Conclusions

Taken together, the present findings suggest that C7G and E7G are the main active compounds in ABs, and have the ability to inhibit micellar solubility, bind to bile acids, and suppress cholesterol absorption. The present study supports the health benefits of ABs as a medicinal food and the application of AB polyphenols as medicinal supplements to suppress cholesterol elevation.

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References

  1. National Cholesterol Education Program Expert Panel on Detection Evaluation and Treatment of High Blood Cholesterol in Adults (2002) Third Report of the National Cholesterol Education Program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III) final report. Circulation 106:3143–3421

    Article  Google Scholar 

  2. Jacobson TA, Miller M, Schaefer EJ (2007) Hypertriglyceridemia and cardiovascular risk reduction. Clin Ther 29:763–777

    Article  CAS  PubMed  Google Scholar 

  3. Hui DY, Howles PN (2005) Molecular mechanisms of cholesterol absorption and transport in the intestine. Semin Cell Dev Biol 16:183–192

    Article  CAS  PubMed  Google Scholar 

  4. Turley SD (2008) The role of Niemann-Pick C1—Like 1 (NPC1L1) in intestinal sterol absorption. J Clin Lipidol 2:S20–S28

    Article  PubMed  PubMed Central  Google Scholar 

  5. Jia L, Betters JL, Yu L (2011) Niemann-pick C1-like 1 (NPC1L1) protein in intestinal and hepatic cholesterol transport. Annu Rev Physiol 73:239–259

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Itoh T, Kobayashi M, Horio F et al (2009) Hypoglycemic effect of hot-water extract of adzuki (Vigna angularis) in spontaneously diabetic KK-A(y) mice. Nutrition 25:134–141

    Article  PubMed  Google Scholar 

  7. Kojima M, Yamashita S, Nishi S et al (2006) Antioxidative effect and liver protective action of adzuki polyphenol. Nippon Shokuhin Kagaku Kogaku Kaishi 53:386–392

    Article  CAS  Google Scholar 

  8. Hori Y, Murakoso T, Fukumura M et al (2009) Constituents and antioxidative activity of a hot-water extract of adzuki (Vigna angularis) beans. Nippon Eiyo Shokuryo Gakkaishi 62:3–11

    Article  CAS  Google Scholar 

  9. Itoh T, Nakamura M, Nakamichi H et al (2014) Regulation of the differentiation of osteoblasts and osteoclasts by a hot-water extract of adzuki beans (Vigna angularis). Biosci Biotechnol Biochem 78:92–99

    Article  CAS  PubMed  Google Scholar 

  10. Kita-Tomihara T, Sato S, Yamasaki S et al (2019) Polyphenol-enriched azuki bean (Vina angularis) extract reduces the oxidative stress and prevents DNA oxidation in the hearts of streptozotocin-induced early diabetic rats. Int J Food Sci Nutr 70:845–855

    Article  CAS  PubMed  Google Scholar 

  11. Kuriya K, Nishio M, Ono N et al (2019) Isolation and characterization of antihyperglycemic compounds from Vigna angularis extracts. J Food Sci 84:3172–3178

    Article  CAS  PubMed  Google Scholar 

  12. Adisakwattana S, Chanathong B (2011) Alpha-glucosidase inhibitory activity and lipid-lowering mechanisms of Moringa oleifera leaf extract. Eur Rev Med Pharmacol Sci 15:803–808

    CAS  PubMed  Google Scholar 

  13. Ngamukote S, Mäkynen K, Thilawech T et al (2011) Cholesterol-lowering activity of the major polyphenols in grape seed. Molecules (Basel Switz) 16:5054–5061

    Article  CAS  Google Scholar 

  14. Adisakwattana S, Intrawangso J, Hemrid A et al (2012) Extracts of edible plants inhibit pancreatic lipase, cholesterol esterase and cholesterol micellization, and bind bile acids. Food Technol Biotechnol 50:11–16

    CAS  Google Scholar 

  15. Yoshie-Stark Y (2004) In vitro binding of bile acids by lupin protein isolates and their hydrolysates. Food Chem 88:179–184

    Article  CAS  Google Scholar 

  16. Lin T, O’keefe S, Duncan S et al (2020) Manipulation of the dry bean (Phaseolus vulgaris L.) matrix by hydrothermal and high-pressure treatments: impact on in vitro bile salt-binding ability. Food Chem 310:125699

  17. Peng Y, Yadava P, Heikkinen AT et al (2014) Applications of a 7-day Caco-2 cell model in drug discovery and development. Eur J Pharm Sci 56:120–130

    Article  CAS  PubMed  Google Scholar 

  18. Sparrow CP, Patel S, Baffic J et al (1999) A fluorescent cholesterol analog traces cholesterol absorption in hamsters and is esterified in vivo and in vitro. J Lipid Res 40:1747–1757

    Article  CAS  PubMed  Google Scholar 

  19. Leifert WR, Abeywardena MY (2008) Grape seed and red wine polyphenol extracts inhibit cellular cholesterol uptake, cell proliferation, and 5-lipoxygenase activity. Nutr Res 28:842–850

    Article  CAS  PubMed  Google Scholar 

  20. Cai TQ, Guo Q, Wong B et al (2002) Protein-disulfide isomerase is a component of an NBD-cholesterol monomerizing protein complex from hamster small intestine. Biochim Biophys Acta 1581:100–108

    Article  CAS  PubMed  Google Scholar 

  21. Portioli Silva EP, Peres CM, Roberto Mendonça J et al (2004) NBD-cholesterol incorporation by rat macrophages and lymphocytes: a process dependent on the activation state of the cells. Cell Biochem Funct 22:23–28

    Article  PubMed  Google Scholar 

  22. Le B, Yang SH (2019) Identification of a novel potential probiotic Lactobacillus plantarum FB003 isolated from salted-fermented shrimp and its effect on cholesterol absorption by regulation of NPC1L1 and PPARα. Probiotics Antimicrob Proteins 11:785–793

    Article  CAS  PubMed  Google Scholar 

  23. Ge Z, Nie R, Maimaiti T et al (2016) Comparison of the inhibition on cellular 22-NBD-cholesterol accumulation and transportation of monomeric catechins and their corresponding A-type dimers in Caco-2 cell monolayers. J Funct Foods 27:343–351

    Article  CAS  Google Scholar 

  24. Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods 25:402–408

    Article  CAS  PubMed  Google Scholar 

  25. Kirana C, Rogers PF, Bennett LE et al (2005) Naturally derived micelles for rapid in vitro screening of potential cholesterol-lowering bioactives. J Agric Food Chem 53:4623–4627

    Article  CAS  PubMed  Google Scholar 

  26. Insull W Jr (2006) Clinical utility of bile acid sequestrants in the treatment of dyslipidemia: a scientific review. South Med J 99:257–273

    Article  PubMed  Google Scholar 

  27. Kojima M, Nishi S, Yamashita S et al (2006) Smaller increase in serum cholesterol level in Rats fed an ethanol extract of adzuki bean seeds. Nippon Shokuhin Kagaku Kogaku Kaishi 53:380–385

    Article  CAS  Google Scholar 

  28. Raederstorff DG, Schlachter MF, Elste V et al (2003) Effect of EGCG on lipid absorption and plasma lipid levels in rats. J Nutr Biochem 14:326–332

    Article  CAS  PubMed  Google Scholar 

  29. Kobayashi M, Nishizawa M, Inoue N et al (2014) Epigallocatechin gallate decreases the micellar solubility of cholesterol via specific interaction with phosphatidylcholine. J Agric Food Chem 62:2881–2890

    Article  CAS  PubMed  Google Scholar 

  30. Feng D, Ohlsson L, Duan RD (2010) Curcumin inhibits cholesterol uptake in Caco-2 cells by down-regulation of NPC1L1 expression. Lipids Health Dis 9:40

    Article  PubMed  PubMed Central  Google Scholar 

  31. Nekohashi M, Ogawa M, Ogihara T et al (2014) Luteolin and quercetin affect the cholesterol absorption mediated by epithelial cholesterol transporter niemann-pick c1-like 1 in caco-2 cells and rats. PLoS ONE 9:e97901

    Article  PubMed  PubMed Central  Google Scholar 

  32. Zeng J, Liu W, Liang B et al (2022) Inhibitory effect of isoliquiritigenin in Niemann-Pick C1-Like 1-mediated cholesterol uptake. Molecules 27:7494. https://doi.org/10.3390/molecules27217494

  33. Chen R, Wang JB, Zhang XQ et al (2011) Green tea polyphenol epigallocatechin-3-gallate (EGCG) induced intermolecular cross-linking of membrane proteins. Arch Biochem Biophys 507:343–349

    Article  CAS  PubMed  Google Scholar 

  34. Davis HR Jr, Altmann SW (2009) Niemann-Pick C1 Like 1 (NPC1L1) an intestinal sterol transporter. Biochim Biophys Acta 1791:679–683

    Article  CAS  PubMed  Google Scholar 

  35. Itoh T, Furuichi Y (2009) Lowering serum cholesterol level by feeding a 40% ethanol-eluted fraction from HP-20 resin treated with hot water extract of adzuki beans (Vigna angularis) to rats fed a high-fat cholesterol diet. Nutrition 25:318–321

    Article  CAS  PubMed  Google Scholar 

  36. Nishi S, Saito Y, Souma C et al (2008) Suppression of serum cholesterol levels in Mice by adzuki bean polyphenols. Food Sci Technol Res 14:217–220

    Article  CAS  Google Scholar 

  37. Liu R, Zheng Y, Cai Z et al (2017) Saponins and flavonoids from adzuki bean (Vigna angularis L.) ameliorate high-fat diet-induced obesity in ICR Mice. Front Pharmacol 8:687–687

    Article  PubMed  PubMed Central  Google Scholar 

  38. Milgate J, Roberts DCK (1995) The nutritional & biological significance of saponins. Nutr Res 15:1223–1249

    Article  CAS  Google Scholar 

  39. Han KH, Fukushima M, Shimizu K et al (2003) Resistant starches of beans reduce the serum cholesterol concentration in rats. J Nutr Sci Vitaminol 49:281–286

    Article  CAS  PubMed  Google Scholar 

  40. Han KH, Iijuka M, Shimada K et al (2005) Adzuki resistant starch lowered serum cholesterol and hepatic 3-hydroxy-3-methylglutaryl-CoA mRNA levels and increased hepatic LDL-receptor and cholesterol 7alpha-hydroxylase mRNA levels in rats fed a cholesterol diet. Br J Nutr 94:902–908

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

We thank H. Ishikawa (Mie University) for technical contributions to the study.

Funding

This research did not receive any specific grants from funding agencies in the public, commercial, or not-for-profit sectors.

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Contributions

KK, MN, and HU conceived and designed the study. SG and EK carried out the experiments. KK, SG, and EK performed the data analysis. MN and MN prepared the facilities and instruments. KK and HU wrote the manuscript. All authors read and approved the final manuscript.

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Correspondence to Kenji Kuriya.

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Supplementary Information

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11033_2023_8481_MOESM1_ESM.tif

Supplementary file1 (TIF 2096 kb) Supplementary Fig. 1 HPLC chromatogram of ABE. ABE (50 μg) was analyzed by HPLC using a C18 column and ultraviolet detection at 210 nm. The mobile phases were ultrapure water and methanol (0–15 min, 100% ultrapure water; 15–45 min, 100% ultrapure water to 100% methanol), and the flow rate was 1 ml/min. The identified compounds were as follows: peak I, C7G; peak II, (+)-catechin; peak III, E7G

11033_2023_8481_MOESM2_ESM.tif

Supplementary file2 (TIF 2270 kb) Supplementary Fig. 2 Effects of prolonged treatment with C7G or E7G on NPC1L1 mRNA expression. RNA was extracted from Caco-2 cells treated with C7G or E7G at a final concentration of 100 µg/ml for 72 h. The relative expression of NPC1L1 mRNA was calculated as a percentage relative to the vehicle control (CNT) and normalized by β-actin mRNA. Data are shown as mean ± SE of triplicate determinations in three independent experiments. No significant differences were found compared with CNT

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Kuriya, K., Goto, S., Kobayashi, E. et al. Cholesterol-lowering activity of adzuki bean (Vigna angularis) polyphenols. Mol Biol Rep 50, 5575–5584 (2023). https://doi.org/10.1007/s11033-023-08481-7

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