Nat Prod Sci.  2019 Jun;25(2):165-171. 10.20307/nps.2019.25.2.165.

Identification of a Novel Function of Extract of Gingko biloba (EGb 761®) as a Regulator of PYY Secretion and FFA4 Activation

Affiliations
  • 1Research Group of Natural Material and Metabolism, Division of Functional Food Research, Korea Food Research Institute, 245 Nongsaengmyeong-ro, Iseo-myeon, Wanju-gun, Jeollabuk-do 55365, Korea. khyey@kfri.re.kr

Abstract

Although the functions of a standardized extract of Gingko biloba leaves (EGb 761®) has been reported with regard to neurobiological properties, no attention has been paid to the impact of EGb 761® on the neuronal regulation of energy homeostasis. To evaluate the hypothesis that EGb 761® affect the secretion of peptide tyrosine tyrosine (PYY) and the activation of free fatty acid receptor 4 (FFA4), which are involved in the neuronal circuitries that control energy homeostasis by inducing the transfer of information about the influx of energy to the brain, we examined whether EGb 761® can stimulate PYY secretion in the enteroendocrine NCI-H716 cells and if EGb 761® can activate FFA4 in FFA4-expressing cells. In NCI-H716 cells, EGb 761® stimulated PYY secretion and the EGb 761®-induced PYY secretion was involved in the increase in intracellular Ca2+ concentration and the activation of FFA4. Furthermore, in FFA4-expressing cells, EGb 761® activated FFA4. These results suggest that EGb 761® may affect the control of energy homeostasis via the regulation of PYY secretion and FFA4 activation.

Keyword

EGb 761®; Peptide tyrosine tyrosine; Free fatty acid receptor 4; NCI-H716 cells

MeSH Terms

Brain
Ginkgo biloba*
Homeostasis
Neurons
Tyrosine
Tyrosine

Figure

  • Fig. 1 EGb 761®-induced PYY secretion and [Ca2+]i increase in NCI-H716 cells. (A) EGb 761®-induced PYY secretion in NCI-H716 cells. (B) EGb 761®-induced [Ca2+]i increase in NCI-H716 cells. Values are expressed as mean ± SEM from three separate experiments performed in triplicate. Bars not sharing the same letters differ significantly (p < 0.05) by Tukey's test.

  • Fig. 2 FFA4-mediated PYY secretion and [Ca2+]i increase induced by EGb 761® in NCI-H716 cells. (A) Real-time RT-PCR analysis of FFA1, FFA2, FFA3, FFA4, and GPR119 mRNA expression in NCI-H716 cells. (B) FFA4 mRNA expression by transfection with 1, 10, and 100 nM FFA4-targeted siRNA in NCI-H716 cells. (C) Effect of transfection with 100 nM FFA4-targeted siRNA on EGb 761®-induced PYY secretion in NCI-H716 cells. (D) Effect of transfection with 100 nM FFA4-targeted siRNA on EGb 761®-induced [Ca2+]i increase in NCI-H716 cells. Values are mean ± SEM from three separate experiments performed in triplicate. Bars not sharing the same letters differ significantly (p < 0.05) by Tukey's test. *p < 0.05; **p < 0.01; ***p < 0.001 vs. groups treated with non-targeted (control) siRNA.

  • Fig. 3 [Ca2+]i response induced by (A) EGb 761® and (B) FFA4 agonist III in FFA4 cells (HEK 293 cells stably expressing FFA4 and G16). Values are expressed as mean ± SEM from three separate experiments performed in triplicate. ***p < 0.001 vs. groups treated with EGb 761® or FFA4 agonist III in HEK 293 cells. Bars not sharing the same letters differ significantly (p < 0.05) by Tukey's test.


Reference

1. Clemmensen C, Müller TD, Woods SC, Berthoud HR, Seeley RJ, Tschöp MH. Cell. 2017; 168:758–774.
2. Brooks L, Viardot A, Tsakmaki A, Stolarczyk E, Howard JK, Cani PD, Everard A, Sleeth ML, Psichas A, Anastasovskaj J, Bell JD, Bell-Anderson K, Mackay CR, Ghatei MA, Bloom SR, Frost G, Bewick GA. Mol Metab. 2016; 6:48–60.
3. Lousie P, Herbert H. Kastin AJ, editor. Handbook of Biologically Active Peptides (Second Edition): PYY. United States of America: Academic press;2013. p. 1307–1313.
4. Depoortere I. Peptides. 2015; 66:9–12.
5. Im DS. Mol Aspects Med. 2018; 64:92–108.
6. Gribble FM, Diakogiannaki E, Reimann F. Handb Exp Pharmacol. 2017; 236:181–203.
7. Hansen SV, Ulven T. Handb Exp Pharmacol. 2017; 236:33–56.
8. Liu HD, Wang WB, Xu ZG, Liu CH, He DF, Du LP, Li MY, Yu X, Sun JP. Eur J Pharmacol. 2015; 763(Pt. B):160–168.
9. Auguste S, Fisette A, Fernandes MF, Hryhorczuk C, Poitout V, Alquier T, Fulton S. Int J Neuropsychopharmacol. 2016; 19:1–10.
10. Cintra DE, Ropelle ER, Moraes JC, Pauli JR, Morari J, Souza CT, Grimaldi R, Stahl M, Carvalheira JB, Saad MJ, Velloso LA. PLoS One. 2012; 7:e30571.
11. Moodaley R, Smith DM, Tough IR, Schindler M, Cox HM. Br J Pharmacol. 2017; 174:4508–4522.
12. Cox HM. Curr Opin Pharmacol. 2016; 31:50–56.
13. Moniri NH. Biochem Pharmacol. 2016; 110-111:1–15.
14. Song WY, Aihara Y, Hashimoto T, Kanazawa K, Mizuno M. J Clin Biochem Nutr. 2015; 57:164–169.
15. Kim MJ, Son HJ, Song SH, Jung M, Kim Y, Rhyu MR. PLoS One. 2013; 8:e71603.
16. Schiess S, Platz S, Kemper M, Schreiner M, Mewis I, Rohn S, Bumke-Vogt C, Pivovarova O, Pfeiffe AFH. Mol Nutr Food Res. 2017; 61:1600886.
17. Zanzer YC, Plaza M, Dougkas A, Turner C, Björck I, Östman E. J Funct Food. 2017; 35:574–583.
18. Hara T, Hirasawa A, Sun Q, Sadakane K, Itsubo C, Iga T, Adachi T, Koshimizu TA, Hashimoto T, Asakawa Y, Tsujimoto G. Naunyn-Schmiedeberg's Arch Pharmacol. 2009; 380:247–255.
19. Mahadevan S, Park Y. J Food Sci. 2008; 73:R14–R19.
20. Ramassamy C, Longpré F, Christen Y. Curr Alzheimer Res. 2007; 4:253–262.
21. Hsieh SK, Chung TY, Li YC, Lo YH, Lin NH, Kuo PC, Chen WY, Tzen JT. J Ethnopharmacol. 2016; 193:237–247.
22. Kim K, Park M, Lee YM, Rhyu MR, Kim HY. Arch Pharm Res. 2014; 37:1193–1200.
23. Reimer RA, Darimont C, Gremlich S, Nicolas-Méttral V, Rüegg UT, Macé K. J Endocrinology. 2001; 142:4522–4528.
24. Nakajima S, Hira T, Yahagi A, Nishiyama C, Yamashita T, Imagi J, Hara H. Mol Nutr Food Res. 2014; 58:1042–1051.
25. Hirasawa A, Tsumaya K, Awaji T, Katsuma S, Adachi T, Yamada M, Sugimoto Y, Miyazaki S, Tsujimoto G. Nat Med. 2005; 11:90–94.
26. Stewart JE, Feinle-Bisset C, Keast RS. Prog Lipid Res. 2011; 50:225–233.
Full Text Links
  • NPS
Actions
Cited
CITED
export Copy
Close
Share
  • Twitter
  • Facebook
Similar articles
Copyright © 2024 by Korean Association of Medical Journal Editors. All rights reserved.     E-mail: koreamed@kamje.or.kr