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Lim, T.; Ryu, J.; Lee, K.; Park, S.Y.; Hwang, K.T. Effects of Black Raspberry Extract. Encyclopedia. Available online: https://encyclopedia.pub/entry/1726 (accessed on 18 April 2024).
Lim T, Ryu J, Lee K, Park SY, Hwang KT. Effects of Black Raspberry Extract. Encyclopedia. Available at: https://encyclopedia.pub/entry/1726. Accessed April 18, 2024.
Lim, Taehwan, Juhee Ryu, Kiuk Lee, Sun Young Park, Keum Taek Hwang. "Effects of Black Raspberry Extract" Encyclopedia, https://encyclopedia.pub/entry/1726 (accessed April 18, 2024).
Lim, T., Ryu, J., Lee, K., Park, S.Y., & Hwang, K.T. (2020, August 19). Effects of Black Raspberry Extract. In Encyclopedia. https://encyclopedia.pub/entry/1726
Lim, Taehwan, et al. "Effects of Black Raspberry Extract." Encyclopedia. Web. 19 August, 2020.
Effects of Black Raspberry Extract
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This entry is adapted from the peer-reviewed paper 10.3390/nu12082448

Consumption of fruits and vegetables has been widely known to be able to prevent incidence of chronic diseases, such as cardiovascular diseases and dyslipidemia. Black rasbperry (BR) polyphenols, especially anthocyanins, have a variety of biological functions. The aims of this study were to investigate the effect of excessive choline intake on serum lipid profile and inflammation in rats fed high-fat diet and to evaluate the protective effect of polyphenols including anthocyanins in BR.

black raspberry polyphenols anthocyanins diet-induced hypercholesterolemia inflammation choline TMA TMAO

1. Introduction

Choline, one of the components of phospholipids in cell membrane and neurotransmitter, is regarded as an essential nutrient [1]. However, choline is also a precursor of trimethylamine-N-oxide (TMAO), which has been reported to act as a putative promoter of chronic diseases in human [2][3][4][5][6]. A part of excessive dietary choline is metabolized by gut microbiota to produce trimethylamine (TMA). Once TMA is absorbed from intestine, it is transported to liver via portal circulation and further oxidized to TMAO by hepatic flavin monooxygenases [2].

Since various epidemiological studies revealed connection between TMAO and cardiovascular diseases (CVD) [5][7][8], studies on TMAO and its precursors, such as choline, lecithin, and L-carnitine, have focused on vascular inflammation, endothelial dysfunction, and cholesterol homeostasis [3][4][5][9][10][11][12]. In addition, the effects of TMAO and its precursors on glucose intolerance [6] and hepatotoxicity [9][12] have been investigated. Taken together, it would likely be possible that TMAO can act in various organs throughout the body. More recently, TMAO has been demonstrated to induce expressions of cytokines and adhesion molecules in primary human aortic endothelial cells and vascular smooth muscle cells [3]. These inflammatory responses were also reported to be mediated via activation of nuclear factor-κB (NF-κB) signaling pathway, which is pivotal in inflammation, immunity, and cell death of various cell types [3].

Both epidemiological and experimental studies have revealed positive correlation between TMAO and chronic diseases such as CVD, renal disease, and diabetes [5][6][7][8][13][14][15][16]. Besides, evidences that TMAO might be able to cause hepatotoxicity or inflammation in adipose tissue have been provided [6][9][12]. However, consumption of fruits and vegetables has been widely known to be able to prevent incidence of chronic diseases. Phytochemicals, bioactive compounds in plants, contribute to reduce risks of those diseases mostly by their anti-oxidant activity [17].

2. Black Raspberry (Rubus occidentalis; BR)

Black raspberry (Rubus occidentalis; BR) is relatively high in anthocyanins among Rubus fruits [18]. It has been found that the major bioactive compounds in BR were anthocyanins, mainly cyanidin-3-rutinoside (C3R), cyanidin-3-glucoside (C3G), and cyanidin-3-xylosylrutinoside (C3XR) [19][20]. BR has been known to possess anti-oxidative, anti-inflammatory, and anti-cancer activities [21]. Especially, C3R and C3G were demonstrated to have anti-inflammatory activity through down-regulating NF-κB expression and inhibiting inhibitory κB (I-κB) degradation in lipopolysaccharide (LPS)-treated murine macrophages [19]. However, to the best of our knowledge, protective effects of polyphenols in BR on inflammation induced by excessive choline intake have not been reported.

The aims of this study were to investigate the effect of excessive choline intake on serum lipid profile and inflammation in rats fed high-fat diet and to evaluate the protective effect of polyphenols including anthocyanins in BR.

3. Conclusions

Excessive choline can cause hypercholesterolemia and induce hepatic inflammation via, in part, NF-κB signaling pathway in rats fed high-fat diet. It might be due to elevated levels of cecal TMA and serum TMAO. Consistent intake of BR extract could lower the levels of cecal TMA and serum TMAO, which might result in the improvement of serum lipid profile in diet-induced hypercholesterolemia in rats. The result that BR could alter cecal TMA level suggests that BR polyphenols may act as a prebiotic in human gut as well. It could also alleviate hepatic inflammation via down-regulating the mRNA and protein expressions of genes related to inflammation. Further study, such as microbiome analysis, may be needed to elucidate the role of BR polyphenols, which seem to have a potent activity in reduction of cecal TMA level via modulation of gut bacteria.

References

  1. Zeisel, S.H.; Da Costa, K.A. Choline: An essential nutrient for public health. Nutr. Rev. 2009, 67, 615–623.
  2. Zeisel, S.H.; Warrier, M. Trimethylamine N-oxide, the microbiome, and heart and kidney disease. Annu. Rev. Nutr. 2017, 37, 157–181.
  3. Seldin, M.M.; Meng, Y.; Qi, H.; Zhu, W.; Wang, Z.; Hazen, S.L.; Lusis, A.J.; Shih, D.M. Trimethylamine N-oxide promotes vascular inflammation through signaling of mitogen-activated protein kinase and nuclear factor-κB. J. Am. Heart Assoc. 2016, 5, e002767.
  4. Chen, M.L.; Yi, L.; Zhang, Y.; Zhou, X.; Ran, L.; Yang, J.; Zhu, J.D.; Zhang, Q.Y.; Mi, M.T. Resveratrol attenuates trimethylamine-N-oxide (TMAO)-induced atherosclerosis by regulating TMAO synthesis and bile acid metabolism via remodeling of the gut microbiota. MBio 2016, 7, e02210–e02215.
  5. Wang, Z.; Klipfell, E.; Bennett, B.J.; Koeth, R.; Levison, B.S.; Dugar, B.; Feldstein, A.E.; Britt, E.B.; Fu, X.; Chung, Y.M.; et al. Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease. Nature 2011, 472, 57–63.
  6. Gao, X.; Xu, J.; Jiang, C.; Zhang, Y.; Xue, Y.; Li, Z.; Wang, J.; Xue, C.; Wang, Y. Fish oil ameliorates trimethylamine N-oxide-exacerbated glucose intolerance in high-fat diet-fed mice. Food Funct. 2015, 6, 1117–1125.
  7. Wang, Z.; Tang, W.H.; Buffa, J.A.; Fu, X.; Britt, E.B.; Koeth, R.A.; Levison, B.S.; Fan, Y.; Wu, Y.; Hazen, S.L. Prognostic value of choline and betaine depends on intestinal microbiota-generated metabolite trimethylamine-N-oxide. Eur. Heart J. 2014, 35, 904–910.
  8. Tang, W.H.; Wang, Z.; Levison, B.S.; Koeth, R.A.; Britt, E.B.; Fu, X.; Wu, Y.; Hazen, S.L. Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk. N. Engl. J. Med. 2013, 368, 1575–1584.
  9. Jia, M.; Ren, D.; Nie, Y.; Yang, X. Beneficial effects of apple peel polyphenols on vascular endothelial dysfunction and liver injury in high choline-fed mice. Food Funct. 2017, 8, 1282–1292.
  10. He, Z.; Lei, L.; Kwek, E.; Zhao, Y.; Liu, J.; Hao, W.; Zhu, H.; Liang, N.; Ma, K.Y.; Ho, H.M.; et al. Ginger attenuates trimethylamine-N-oxide (TMAO)-exacerbated disturbance in cholesterol metabolism and vascular inflammation. J. Funct. Foods 2019, 52, 25–33.
  11. Ma, G.; Pan, B.; Chen, Y.; Guo, C.; Zhao, M.; Zheng, L.; Chen, B. Trimethylamine N-oxide in atherogenesis: Impairing endothelial self-repair capacity and enhancing monocyte adhesion. Biosci. Rep. 2017, 37, BSR20160244.
  12. Ren, D.; Liu, Y.; Zhao, Y.; Yang, X. Hepatotoxicity and endothelial dysfunction induced by high choline diet and the protective effects of phloretin in mice. Food Chem. Toxicol. 2016, 94, 203–212.
  13. Organ, C.L.; Otsuka, H.; Bhushan, S.; Wang, Z.; Bradley, J.; Trivedi, R.; Polhemus, D.J.; Tang, W.H.; Wu, Y.; Hazen, S.L.; et al. Choline diet and its gut microbe–derived metabolite, trimethylamine N-oxide, exacerbate pressure overload–induced heart failure. Circ. Heart Fail. 2016, 9, e002314.
  14. Tang, W.H.; Wang, Z.; Kennedy, D.J.; Wu, Y.; Buffa, J.A.; Agatisa-Boyle, B.; Li, X.S.; Levison, B.S.; Hazen, S.L. Gut microbiota-dependent trimethylamine N-oxide (TMAO) pathway contributes to both development of renal insufficiency and mortality risk in chronic kidney disease. Circ. Res. 2015, 116, 448–455.
  15. Missailidis, C.; Hällqvist, J.; Qureshi, A.R.; Barany, P.; Heimbürger, O.; Lindholm, B.; Stenvinkel, P.; Bergman, P. Serum trimethylamine-N-oxide is strongly related to renal function and predicts outcome in chronic kidney disease. PLoS ONE 2016, 11, e0141738.
  16. Koeth, R.A.; Wang, Z.; Levison, B.S.; Buffa, J.A.; Org, E.; Sheehy, B.T.; Britt, E.B.; Fu, X.; Wu, Y.; Li, L.; et al. Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis. Nat. Med. 2013, 19, 576.
  17. Liu, R.H. Health benefits of fruit and vegetables are from additive and synergistic combinations of phytochemicals. Am. J. Clin. Nutr. 2003, 78, 517S–520S.
  18. Torre, L.C.; Barritt, B.H. Quantitative evaluation of Rubus fruit anthocyanin pigments. J. Food Sci. 1977, 42, 488–490.
  19. Jung, H.; Kwak, H.K.; Hwang, K.T. Antioxidant and antiinflammatory activities of cyanidin-3-glucoside and cyanidin-3-rutinoside in hydrogen peroxide and lipopolysaccharide-treated RAW264.7 cells. Food Sci. Biotechnol. 2014, 23, 2053–2062.
  20. Paudel, L.; Wyzgoski, F.J.; Scheerens, J.C.; Chanon, A.M.; Reese, R.N.; Smiljanic, D.; Wesdemiotis, C.; Blakeslee, J.J.; Riedl, K.M.; Rinaldi, P. Nonanthocyanin secondary metabolites of black raspberry (Rubus occidentalis L.) fruits: Identification by HPLC-DAD, NMR, HPLC-ESI-MS, and ESI-MS/MS analyses. J. Agric. Food Chem. 2013, 61, 12032–12043.
  21. Kula, M.; Krauze-Baranowska, M. Rubus occidentalis: The black raspberry—Its potential in the prevention of cancer. Nutr. Cancer 2016, 68, 18–28.
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Subjects: Nutrition & Dietetics
Contributors MDPI registered users' name will be linked to their SciProfiles pages. To register with us, please refer to https://encyclopedia.pub/register :
Taehwan Lim
,
Juhee Ryu
,
Kiuk Lee
,
Sun Young Park
,
Keum Taek Hwang
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Revisions: 2 times (View History)
Update Date: 24 Aug 2020
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