Skip to main content

Hypocholesterolemic effect of sericin-derived oligopeptides in high-cholesterol fed rats

Abstract

The beneficial effect of cholesterol-lowering proteins and/or peptides derived from various dietary sources is continuously reported. A non-dietary protein from silk cocoon, sericin, has also demonstrated cholesterol-lowering activity. A sericin hydrolysate prepared by enzymatic hydrolysis was also expected to posses this effect. The present study was aimed at investigating the cholesterol-lowering effect of sericin peptides, so called “sericin-derived oligopeptides” (SDO) both in vivo and in vitro. The results showed that SDO at all three doses tested (10 mg kg−1 day−1, 50 mg kg−1 day−1, and 200 mg kg−1 day−1) suppressed serum total and non-HDL cholesterol levels in rats fed a high-cholesterol diet. Triglyceride and HDL-cholesterol levels were not significantly changed among all groups. The fecal contents of bile acids and cholesterol did not differ among high-cholesterol fed rats. SDO dose-dependently reduced cholesterol solubility in lipid micelles, and inhibited cholesterol uptake in monolayer Caco-2 cells. SDO also effectively bound to all three types of bile salts including taurocholate, deoxytaurocholate, and glycodeoxycholate. Direct interaction with bile acids of SDO may disrupt micellar cholesterol solubility, and subsequently reduce the absorption of dietary cholesterol in intestines. Taking all data together, SDO or sericin peptides exhibit a beneficial effect on blood cholesterol levels and could be potentially used as a health-promoting dietary supplement or nutraceutical product.

This is a preview of subscription content, access via your institution.

Fig. 1
Fig. 2
Fig. 3
Fig. 4a–c

References

  1. 1.

    Nagaoka S, Futamura Y, Miwa K, Awano T, Yamauchi K, Kanamaru Y, Tadashi K, Kuwata T (2001) Identification of novel hypocholesterolemic peptides derived from bovine milk beta-lactoglobulin. Biochem Biophys Res Commun 281:11–17

    CAS  Article  PubMed  Google Scholar 

  2. 2.

    Nagaoka S, Miwa K, Eto M, Kuzuya Y, Hori G, Yamamoto K (1999) Soy protein peptic hydrolysate with bound phospholipids decreases micellar solubility and cholesterol absorption in rats and caco-2 cells. J Nutr 129:1725–1730

    CAS  Article  PubMed  Google Scholar 

  3. 3.

    Sugano M, Goto S, Yamada Y, Yoshida K, Hashimoto Y, Matsuo T, Kimoto M (1990) Cholesterol-lowering activity of various undigested fractions of soybean protein in rats. J Nutr 120:977–985

    CAS  Article  PubMed  Google Scholar 

  4. 4.

    Wergedahl H, Liaset B, Gudbrandsen OA, Lied E, Espe M, Muna Z, Mork S, Berge RK (2004) Fish protein hydrolysate reduces plasma total cholesterol, increases the proportion of HDL cholesterol, and lowers acyl-CoA:cholesterol acyltransferase activity in liver of Zucker rats. J Nutr 134:1320–1327

    CAS  Article  PubMed  Google Scholar 

  5. 5.

    Ruiz Ruiz JC, Betancur Ancona DA, Segura Campos MR (2014) Bioactive vegetable proteins and peptides in lipid-lowering; nutraceutical potential. Nutr Hosp 29:776–784

    PubMed  Google Scholar 

  6. 6.

    Limpeanchob N, Trisat K, Duangjai A, Tiyaboonchai W, Pongcharoen S, Sutheerawattananonda M (2010) Sericin reduces serum cholesterol in rats and cholesterol uptake into Caco-2 cells. J Agric Food Chem 58:12519–12522

    CAS  Article  PubMed  Google Scholar 

  7. 7.

    Okazaki Y, Kakehi S, Xu Y, Tsujimoto K, Sasaki M, Ogawa H, Kato N (2010) Consumption of sericin reduces serum lipids, ameliorates glucose tolerance and elevates serum adiponectin in rats fed a high-fat diet. Biosci Biotechnol Biochem 74:1534–1538

    CAS  Article  PubMed  Google Scholar 

  8. 8.

    Seo CW, Um IC, Rico CW, Kang MY (2011) Antihyperlipidemic and body fat-lowering effects of silk proteins with different fibroin/sericin compositions in mice fed with high fat diet. J Agric Food Chem 59:4192–4197

    CAS  Article  PubMed  Google Scholar 

  9. 9.

    Cao TT, Zhang YQ (2016) Processing and characterization of silk sericin from Bombyx mori and its application in biomaterials and biomedicines. Mater Sci Eng C Mater Biol Appl 61:940–952

    CAS  Article  PubMed  Google Scholar 

  10. 10.

    van der Wulp MY, Verkade HJ, Groen AK (2013) Regulation of cholesterol homeostasis. Mol Cell Endocrinol 368:1–16

    Article  PubMed  Google Scholar 

  11. 11.

    Woollett LA, Wang Y, Buckley DD, Yao L, Chin S, Granholm N, Jones PJ, Setchell KD, Tso P, Heubi JE (2006) Micellar solubilisation of cholesterol is essential for absorption in humans. Gut 55:197–204

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  12. 12.

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

    CAS  Article  PubMed  Google Scholar 

  13. 13.

    Korhonen H, Pihlanto A (2006) Bioactive peptides: production and functionality. Int Dairy J 16:945–960

    CAS  Article  Google Scholar 

  14. 14.

    Zhang H, Bartley GE, Mitchell CR, Zhang H, Yokoyama W (2011) Lower weight gain and hepatic lipid content in hamsters fed high fat diets supplemented with white rice protein, brown rice protein, soy protein, and their hydrolysates. J Agric Food Chem 59:10927–10933

    CAS  Article  PubMed  Google Scholar 

  15. 15.

    Hosomi R, Fukao M, Fukunaga K, Okuno M, Yagita R, Kanda S, Nishiyama T, Yoshida M (2010) Effect of fish protein and peptides on lipid absorption in rats. Trace Nutr Res 27:21–27

    Google Scholar 

  16. 16.

    Duangjai A, Ingkaninan K, Praputbut S, Limpeanchob N (2013) Black pepper and piperine reduce cholesterol uptake and enhance translocation of cholesterol transporter proteins. J Nat Med 67:303–310

    CAS  Article  PubMed  Google Scholar 

  17. 17.

    Gudbrandsen OA, Wergedahl H, Liaset B, Espe M, Berge RK (2005) Dietary proteins with high isoflavone content or low methionine-glycine and lysine-arginine ratios are hypocholesterolaemic and lower the plasma homocysteine level in male Zucker fa/fa rats. Br J Nutr 94:321–330

    CAS  Article  PubMed  Google Scholar 

  18. 18.

    Morita T, Oh-hashi A, Takei K, Ikai M, Kasaoka S, Kiriyama S (1997) Cholesterol-lowering effects of soybean, potato and rice proteins depend on their low methionine contents in rats fed a cholesterol-free purified diet. J Nutr 127:470–477

    CAS  Article  PubMed  Google Scholar 

  19. 19.

    Hidalgo IJ, Raub TJ, Borchardt RT (1989) Characterization of the human colon carcinoma cell line (Caco-2) as a model system for intestinal epithelial permeability. Gastroenterology 96:736–749

    CAS  Article  PubMed  Google Scholar 

  20. 20.

    Metzger BT, Barnes DM, Reed JD (2007) Insoluble fraction of buckwheat (Fagopyrum esculentum Moench) protein possessing cholesterol-binding properties that reduce micelle cholesterol solubility and uptake by Caco-2 cells. J Agric Food Chem 55:6032–6038

    CAS  Article  PubMed  Google Scholar 

  21. 21.

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

  22. 22.

    Porter JL, Fordtran JS, Santa Ana CA, Emmett M, Hagey LR, Macdonald EA, Hofmann AF (2003) Accurate enzymatic measurement of fecal bile acids in patients with malabsorption. J Lab Clin Med 141:411–418

Download references

Acknowledgments

The authors thank Dr. Norman Scholfield for manuscript preparation. This research project was supported by Agricultural Research Development Agency (ARDA), and the Center of Excellence for Innovation in Chemistry (PERCH-CIC).

Author information

Affiliations

Authors

Corresponding author

Correspondence to Nanteetip Limpeanchob.

Ethics declarations

Conflict of interest

Phakhamon Lapphanichayakool declares no conflict of interest. The sponsor (ARDA), Manote Sutheerawattananonda, and Nanteetip Limpeanchob hold a patent WO2013/032411A1 in title silk-based bioactive oligopeptide compositions and manufacturing process thereof.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Lapphanichayakool, P., Sutheerawattananonda, M. & Limpeanchob, N. Hypocholesterolemic effect of sericin-derived oligopeptides in high-cholesterol fed rats. J Nat Med 71, 208–215 (2017). https://doi.org/10.1007/s11418-016-1050-9

Download citation

Keywords

  • Sericin
  • Hypocholesterolemic effect
  • Cholesterol
  • Protein hydrolysate
  • Bile acid binding
  • Micellar solubility