Lemon basil seed-derived peptide: Hydrolysis, purification, and its role as a pancreatic lipase inhibitor that reduces adipogenesis by downregulating SREBP-1c and PPAR-γ in 3T3-L1 adipocytes.

Publisher: Public Library of Science Country of Publication: United States NLM ID: 101285081 Publication Model: eCollection Cited Medium: Internet ISSN: 1932-6203 (Electronic) Linking ISSN: 19326203 NLM ISO Abbreviation: PLoS One Subsets: MEDLINE

Original Publication: San Francisco, CA : Public Library of Science

Adipogenesis*/drug effects ; 3T3-L1 Cells* ; Seeds*/chemistry ; PPAR gamma*/metabolism ; Adipocytes*/drug effects ; Adipocytes*/metabolism ; Lipase*/antagonists & inhibitors ; Lipase*/metabolism ; Peptides*/pharmacology ; Peptides*/chemistry ; Peptides*/isolation & purification ; Sterol Regulatory Element Binding Protein 1*/metabolism ; Ocimum basilicum*/chemistry; Mice ; Animals ; Hydrolysis ; Down-Regulation/drug effects ; Molecular Docking Simulation

The purpose of this study is to assess the bioactive peptides derived from the defatted lemon basil seeds hydrolysate (DLSH) for their ability to inhibit pancreatic lipase, decrease intracellular lipid accumulation, and reduce adipogenesis. Response surface methodology (RSM) was employed to optimize trypsin hydrolysis conditions for maximizing lipase inhibitory activity (LI). A hydrolysis time of 387.06 min, a temperature of 49.03°C, and an enzyme concentration of 1.61% w/v, resulted in the highest LI with an IC50 of 368.07 μg/mL. The ultrafiltration of the protein hydrolysate revealed that the fraction below 0.65kDa exhibited the greatest LI potential. Further purification via RP-HPLC identified the Gly-Arg-Ser-Pro-Asp-Thr-His-Ser-Gly (GRSPDTHSG) peptide in the HPLC fraction F1 using mass spectrometry. The peptide was synthesized and demonstrated LI with an IC50 of 0.255 mM through a non-competitive mechanism, with a constant (Ki) of 0.61 mM. Docking studies revealed its binding site with the pancreatic lipase-colipase complex. Additionally, GRSPDTHSG inhibited lipid accumulation in 3T3-L1 cells in a dose-dependent manner without cytotoxic effects. Western blot analysis indicated downregulation of PPAR-γ and SREBP-1c levels under GRSPDTHSG treatment, while an increase in AMPK-α phosphorylation was observed, suggesting a role in regulating cellular lipid metabolism. Overall, GRSPDTHSG demonstrates potential in attenuating lipid absorption and adipogenesis, suggesting a prospective application in functional foods and nutraceuticals.
Competing Interests: The authors have declared that no competing interests exist.
(Copyright: © 2024 Kuptawach et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Int J Biol Macromol. 2020 Oct 1;160:623-631. (PMID: 32473219)
Anal Biochem. 1976 May 7;72:248-54. (PMID: 942051)
Food Chem. 2018 Sep 1;259:46-54. (PMID: 29680061)
Nat Rev Mol Cell Biol. 2011 Sep 28;12(11):722-34. (PMID: 21952300)
Obes Rev. 2000 Oct;1(2):127-39. (PMID: 12119986)
Eur J Pharmacol. 2011 Jan 10;650(1):479-85. (PMID: 20951125)
Int J Mol Sci. 2022 Feb 19;23(4):. (PMID: 35216415)
Front Endocrinol (Lausanne). 2021 Sep 06;12:706978. (PMID: 34552557)
RSC Adv. 2021 May 25;11(31):18915-18929. (PMID: 35478653)
J Endocrinol. 2016 Dec;231(3):R77-R99. (PMID: 27935822)
Medicine (Baltimore). 2022 Jun 10;101(23):e29240. (PMID: 35687773)
Foods. 2022 Oct 21;11(20):. (PMID: 37431052)
Peptides. 2007 Nov;28(11):2098-103. (PMID: 17935831)
Int J Environ Res Public Health. 2010 Mar;7(3):765-83. (PMID: 20617002)
Molecules. 2022 Dec 26;28(1):. (PMID: 36615405)
Molecules. 2018 Nov 27;23(12):. (PMID: 30486380)
J Mol Graph Model. 1999 Feb;17(1):57-61. (PMID: 10660911)
J Biol Chem. 2001 Apr 20;276(16):12505-12. (PMID: 11278590)
J Hepatol. 2019 Mar;70(3):531-544. (PMID: 30414863)
J Physiol. 2006 Jul 1;574(Pt 1):55-62. (PMID: 16709632)
Bioorg Med Chem. 2007 Jul 15;15(14):4674-99. (PMID: 17521912)
Curr Opin Endocrinol Diabetes Obes. 2011 Apr;18(2):139-43. (PMID: 21297467)
J Comput Chem. 2004 Oct;25(13):1605-12. (PMID: 15264254)
Phytochemistry. 2010 Oct;71(14-15):1625-41. (PMID: 20732701)
Bioanalysis. 2012 May;4(8):937-59. (PMID: 22533568)
Heliyon. 2022 Oct 13;8(10):e11067. (PMID: 36303910)
Biophys Chem. 2020 Sep;264:106409. (PMID: 32534374)
PLoS One. 2021 Sep 2;16(9):e0256595. (PMID: 34473745)
Sci Rep. 2022 Mar 18;12(1):4659. (PMID: 35304505)
Clin Sci (Lond). 2019 Oct 30;133(20):2107-2119. (PMID: 31654064)
Cell. 2015 Mar 26;161(1):161-172. (PMID: 25815993)
J Lipid Res. 2012 Dec;53(12):2490-514. (PMID: 22798688)
Int J Mol Sci. 2013 Feb 01;14(2):3124-39. (PMID: 23377020)
Food Funct. 2020 Sep 23;11(9):8161-8178. (PMID: 32966470)
Int J Mol Med. 2015 May;35(5):1362-8. (PMID: 25761066)
Protein Sci. 2021 Jan;30(1):70-82. (PMID: 32881101)
Pharmaceuticals (Basel). 2023 Mar 15;16(3):. (PMID: 36986539)
J Biol Chem. 1996 Jul 26;271(30):18007-16. (PMID: 8663362)
Food Funct. 2020 Jun 24;11(6):4994-5003. (PMID: 32515459)
J Comput Chem. 2010 Jan 30;31(2):455-61. (PMID: 19499576)
Physiol Rev. 1998 Jul;78(3):783-809. (PMID: 9674695)
Int J Mol Sci. 2020 Jan 10;21(2):. (PMID: 31936890)
Biochim Biophys Acta. 2014 Mar;1842(3):352-7. (PMID: 23735215)
Future Med Chem. 2019 Jan;11(1):5-19. (PMID: 30526045)
Front Endocrinol (Lausanne). 2020 Jun 24;11:412. (PMID: 32670197)
J Sci Food Agric. 2010 Nov;90(14):2512-8. (PMID: 20690111)
Biomed Pharmacother. 2020 Aug;128:110314. (PMID: 32485574)
Cancers (Basel). 2023 Jan 12;15(2):. (PMID: 36672434)
Food Chem. 2023 Feb 15;402:134192. (PMID: 36179519)
Molecules. 2019 Sep 29;24(19):. (PMID: 31569521)
J Lipid Res. 2012 Jul;53(7):1277-86. (PMID: 22493094)
Drug Saf. 2014 Aug;37(8):597-608. (PMID: 25064699)
Biopolymers. 2009;92(6):573-95. (PMID: 19795449)
Genes Dev. 2002 Jan 1;16(1):22-6. (PMID: 11782441)
Eur J Pharmacol. 2002 Apr 12;440(2-3):109-17. (PMID: 12007529)
Molecules. 2016 Jan 12;21(1):72. (PMID: 26771594)
Diabetes Metab Syndr Obes. 2021 Jan 08;14:67-83. (PMID: 33447066)
Sci Rep. 2020 Jul 2;10(1):10873. (PMID: 32616827)
J Biol Chem. 1997 Jan 3;272(1):9-12. (PMID: 8995215)
Organogenesis. 2008 Oct;4(4):228-35. (PMID: 19337402)
Eur J Nutr. 2009 Apr;48(3):162-9. (PMID: 19165521)

0 (PPAR gamma)
EC 3.1.1.3 (Lipase)
0 (Peptides)
0 (Sterol Regulatory Element Binding Protein 1)

Date Created: 20240522 Date Completed: 20240522 Latest Revision: 20240529

20240529

PMC11111035

10.1371/journal.pone.0301966

38776280