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Licensed Unlicensed Requires Authentication Published by De Gruyter December 25, 2020

10-gingerol induces oxidative stress through HTR1A in cumulus cells: in-vitro and in-silico studies

Kiptiyah Kiptiyah, Widodo Widodo, Gatot Ciptadi, Aulanni’am Aulanni’Am, Mohammad A. Widodo and Sutiman B. Sumitro

Abstract

Background

We investigated whether 10-gingerol is able to induce oxidative stress in cumulus cells.

Methods

For the in-vitro research, we used a cumulus cell culture in M199, containing 10-gingerol in various concentrations (0, 12, 16, and 20 µM), and detected oxidative stress through superoxide dismutase (SOD) activity and malondialdehyde (MDA) concentrations, with incubation periods of 24, 48, 72, and 96 h. The obtained results were confirmed by in-silico studies.

Results

The in-vitro data revealed that SOD activity and MDA concentration increased with increasing incubation periods: SOD activity at 0 µM (1.39 ± 0.24i), 12 µM (16.42 ± 0.35ab), 16 µM (17.28 ± 0.55ab), 20 µM (17.81 ± 0.12a), with a contribution of 71.1%. MDA concentration at 0 µM (17.82 ± 1.39 l), 12 µM (72.99 ± 0.31c), 16 µM (79.77 ± 4.19b), 20 µM (85.07 ± 2.57a), with a contribution of 73.1%. Based on this, the in-silico data uncovered that 10˗gingerol induces oxidative stress in cumulus cells by inhibiting HTR1A functions and inactivating GSK3B and AKT˗1.

Conclusions

10-gingerol induces oxidative stress in cumulus cells through enhancing SOD activity and MDA concentration by inhibiting HTR1A functions and inactivating GSK3B and AKT˗1.

Abbreviations

10-G

10-gingerol

CID

chem identity

ELISA

enzyme-linked immunoabsorbent assay

eNOS

endothelial nitric oxide synthase

FOXO

forkhead box

GSK3B

glycogen synthase kynase-3 β

h

hour

HTR1A

5-hydroxytryptamine receptor 1 A

ILK

integrin-linked kinase

M199

medium 199

MDA

malondialdehyde

MDM2

murine double minute clone 2

mTOR

mammalian target of rapamycin

NO

nitric oxide

NOS

nitric oxide synthase

NOS3

nitric oxide synthase 3

PDB

protein data bank

PI3K/AKT

phosphatidylinositol-3-OH kinase/AKT

PTEN

phosphatase and tensin homologue delete on chromosome ten

PUFA

polyunsaturated fatty acids

RICTOR

rapamycin-insensitive companion of mTOR

ROS

reactive oxygen species

SOD

superoxide dismutase.

Acknowledgments

We would like to thank the laboratories in the Maulana Malik Ibrahim Islamic State University of Malang, State Polytechnic of Malang, Brawijaya University of Malang, the abattoir in Malang City, and CV. Gamma Scientific Biolab of Malang, who collaborated with us and National Educational Ministry of Indonesian Republic Government which supplied fund No. 708/H10.14/AK/2010. The authors declare that no conflict of interest would prejudice the impartiality of this scientific work.

  1. Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

  2. Research funding: National Educational Ministry of Indonesian Republic Government, fund No. 708/H10.14/AK/2010.

  3. Employment or leadership: None declared.

  4. Honorarium: None declared.

  5. Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

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Received: 2019-03-01
Accepted: 2019-10-24
Published Online: 2020-12-25

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