Structural Characterization of Peripolin and Study of Antioxidant Activity of HMG Flavonoids from Bergamot Fruit

Overview

Journal Antioxidants (Basel)

Date 2022 Oct 27

PMID 36290571

Authors

Lucia Bartella

Fabio Mazzotti

Ines Rosita Talarico

Giuseppina De Luca

Ilaria Santoro

Mario Prejano

Costanza Riccioni

Tiziana Marino

Leonardo Di Donna

Affiliations

Soon will be listed here.

Abstract

The structural characterization of a new flavonoid from bergamot fruit (Citrus bergamia Risso) carrying the 3-hydroxy-3-methyl glutaryl (HMG) ester moiety has been accomplished, and its antioxidant ability was tested from a chemical point of view. The peculiarity of the new molecule, named peripolin, relies on the presence of the HMG chemical group linked to the sugar portion of neoeriocitrin; the structure was elucidated using both high-resolution mass spectrometry and nuclear magnetic resonance experiments performed on the purified molecule extracted from the fruit. The antioxidant ability of the new molecule was tested by classical chemical approaches, such as DPPH, ABTS and FRAP assays, and from a theoretical point of view. H and C NMR experiments and HR-ESI-MS/MS experiments show unequivocally that the HMG moiety is linked to the primary position of the glucose unit of neohesperidose, while the chemical tests and the computational results show that peripolin possesses strong antioxidant behavior, similar to that of neoeriocitrin and remarkably higher respect to the other flavonoids present in the fruit. Furthermore, the quantitative assays carried out by UPLC-MS/MS showed that its amount in the fruit is similar to that of the other main flavonoids. Furthermore, molecular dynamics simulations allowed us to investigate the possible conformations adopted by the antioxidants in the presence of water molecules. In particular, the switch of open-closed conformations of HMG-containing species was evidenced. As far as the reaction with DPPH, the calculation of ΔG supported the experimental outcomes regarding the peripolin and neoeriocitrin activity. In conclusion, bergamot fruit, already known for its potential to lower the level of blood cholesterol, has been proven to contain molecules such as neoeriocitrin and the newly characterized peripolin, which could have important in-vivo antioxidant characteristics.

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References

Mazzotti F, Bartella L, Talarico I, Napoli A, Di Donna L . High-throughput determination of flavanone-O-glycosides in citrus beverages by paper spray tandem mass spectrometry. Food Chem. 2021; 360:130060. DOI: 10.1016/j.foodchem.2021.130060. View

Salehi B, Cruz-Martins N, Butnariu M, Sarac I, Bagiu I, Ezzat S . Hesperetin's health potential: moving from preclinical to clinical evidence and bioavailability issues, to upcoming strategies to overcome current limitations. Crit Rev Food Sci Nutr. 2021; 62(16):4449-4464. DOI: 10.1080/10408398.2021.1875979. View

Cicero A, Fogacci F, Pantea Stoian A, Vrablik M, Al Rasadi K, Banach M . Nutraceuticals in the Management of Dyslipidemia: Which, When, and for Whom? Could Nutraceuticals Help Low-Risk Individuals with Non-optimal Lipid Levels?. Curr Atheroscler Rep. 2021; 23(10):57. PMC: 8332568. DOI: 10.1007/s11883-021-00955-y. View

Parise A, De Simone B, Marino T, Toscano M, Russo N . Quantum Mechanical Predictions of the Antioxidant Capability of Moracin C Isomers. Front Chem. 2021; 9:666647. PMC: 8097241. DOI: 10.3389/fchem.2021.666647. View

Montenegro-Landivar M, Tapia-Quiros P, Vecino X, Reig M, Valderrama C, Granados M . Polyphenols and their potential role to fight viral diseases: An overview. Sci Total Environ. 2021; 801:149719. PMC: 8373592. DOI: 10.1016/j.scitotenv.2021.149719. View

Grimme S, Ehrlich S, Goerigk L . Effect of the damping function in dispersion corrected density functional theory. J Comput Chem. 2011; 32(7):1456-65. DOI: 10.1002/jcc.21759. View

Gattuso G, Barreca D, Caristi C, Gargiulli C, Leuzzi U . Distribution of flavonoids and furocoumarins in juices from cultivars of Citrus bergamia Risso. J Agric Food Chem. 2007; 55(24):9921-7. DOI: 10.1021/jf072065s. View

Spiegel M, Marino T, Prejano M, Russo N . On the Scavenging Ability of Scutellarein against the OOH Radical in Water and Lipid-like Environments: A Theoretical Study. Antioxidants (Basel). 2022; 11(2). PMC: 8868326. DOI: 10.3390/antiox11020224. View

Nogata Y, Sakamoto K, Shiratsuchi H, Ishii T, Yano M, Ohta H . Flavonoid composition of fruit tissues of citrus species. Biosci Biotechnol Biochem. 2006; 70(1):178-92. DOI: 10.1271/bbb.70.178. View

10.

Formagio A, Volobuff C, Santiago M, Cardoso C, do Carmo Vieira M, Pereira Z . Evaluation of Antioxidant Activity, Total Flavonoids, Tannins and Phenolic Compounds in Psychotria Leaf Extracts. Antioxidants (Basel). 2016; 3(4):745-57. PMC: 4665508. DOI: 10.3390/antiox3040745. View

11.

Di Donna L, De Luca G, Mazzotti F, Napoli A, Salerno R, Taverna D . Statin-like principles of bergamot fruit (Citrus bergamia): isolation of 3-hydroxymethylglutaryl flavonoid glycosides. J Nat Prod. 2009; 72(7):1352-4. DOI: 10.1021/np900096w. View

12.

Gattuso G, Caristi C, Gargiulli C, Bellocco E, Toscano G, Leuzzi U . Flavonoid glycosides in bergamot juice (Citrus bergamia Risso). J Agric Food Chem. 2006; 54(11):3929-35. DOI: 10.1021/jf060348z. View

13.

Prejano M, Romeo I, Russo N, Marino T . On the Catalytic Activity of the Engineered Coiled-Coil Heptamer Mimicking the Hydrolase Enzymes: Insights from a Computational Study. Int J Mol Sci. 2020; 21(12). PMC: 7352413. DOI: 10.3390/ijms21124551. View

14.

Wang J, Wolf R, Caldwell J, Kollman P, Case D . Development and testing of a general amber force field. J Comput Chem. 2004; 25(9):1157-74. DOI: 10.1002/jcc.20035. View

15.

Giuffre A . Bergamot (, Risso): The Effects of Cultivar and Harvest Date on Functional Properties of Juice and Cloudy Juice. Antioxidants (Basel). 2019; 8(7). PMC: 6680538. DOI: 10.3390/antiox8070221. View

16.

Benzie I, Strain J . The ferric reducing ability of plasma (FRAP) as a measure of "antioxidant power": the FRAP assay. Anal Biochem. 1996; 239(1):70-6. DOI: 10.1006/abio.1996.0292. View

17.

Perez-Gonzalez A, Prejano M, Russo N, Marino T, Galano A . Capsaicin, a Powerful OH-Inactivating Ligand. Antioxidants (Basel). 2020; 9(12). PMC: 7763808. DOI: 10.3390/antiox9121247. View

18.

Prejano M, Romeo I, Sgrizzi L, Russo N, Marino T . Why hydroxy-proline improves the catalytic power of the peptidoglycan N-deacetylase enzyme: insight from theory. Phys Chem Chem Phys. 2019; 21(42):23338-23345. DOI: 10.1039/c9cp03804c. View

19.

Shen N, Wang T, Gan Q, Liu S, Wang L, Jin B . Plant flavonoids: Classification, distribution, biosynthesis, and antioxidant activity. Food Chem. 2022; 383:132531. DOI: 10.1016/j.foodchem.2022.132531. View

20.

Lee , Yang , PARR . Development of the Colle-Salvetti correlation-energy formula into a functional of the electron density. Phys Rev B Condens Matter. 1988; 37(2):785-789. DOI: 10.1103/physrevb.37.785. View