Eugenol protects cells against oxidative stress via Nrf2

Ma,Leina; Liu,Jia; Lin,Qian; Gu,Yuchao; Yu,Wengong

doi:10.3892/etm.2020.9539

Eugenol protects cells against oxidative stress via Nrf2

Authors:
- Leina Ma
- Jia Liu
- Qian Lin
- Yuchao Gu
- Wengong Yu
View Affiliations

Affiliations: Key Laboratory of Marine Drugs (Ministry of Education), Shandong Provincial Key Laboratory of Glycoscience and Glycoengineering, School of Medicine and Pharmacy, Ocean University of China, Qingdao, Shandong 266003, P.R. China, Qingdao Cancer Institute, College of Medicine, Qingdao University, Qingdao, Shandong 266021, P.R. China
Published online on: November 27, 2020 https://doi.org/10.3892/etm.2020.9539
Article Number: 107
Copyright: © Ma et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Eugenol is a naturally occurring compound that is present in a variety of plants and has previous been demonstrated to exert a number of bioactivities. However, the potential effects of Eugenol on cellular protection against oxidative stress remain poorly understood. In the present study, HEK‑293 cells and the mouse fibroblast cell line NIH‑3T3 cells were used as models to explore the effects of eugenol on H₂O₂‑induced damage. Among the three natural compounds tested, namely eugenol, methyleugenol and acetyleugenol, eugenol was found to increase the transcriptional activity and expression level of nuclear factor erythroid 2‑related factor 2 (Nrf2), a central regulator of cellular responses to oxidative stress, in a dose‑dependent manner. The mRNA levels of Nrf2 target genes glutamate‑cysteine ligase modifier regulatory subunit and glutathione S‑transferase A1, were also found to be upregulated following eugenol treatment. Further study revealed that eugenol enhanced the stabilization and nuclear translocation of Nrf2. Additionally, treatment with eugenol was found to reduce intracellular ROS levels while increasing cellular resistance to H₂O₂, in a manner that was dependent on Nrf2. In conclusion, data from the present study suggest that eugenol is a protective agent against oxidative stress that exerts its effects through a Nrf2‑dependent pathway, rendering eugenol and its derivatives to be promising candidates for the future development of antioxidants.

View Figures

View References

1	Kamatou GP, Vermaak I and Viljoen AM: Eugenol--from the remote Maluku Islands to the international market place: A review of a remarkable and versatile molecule. Molecules. 17:6953–6981. 2012.PubMed/NCBI View Article : Google Scholar
2	Srinivasan K: Antioxidant potential of spices and their active constituents. Crit Rev Food Sci Nutr. 54:352–372. 2014.PubMed/NCBI View Article : Google Scholar
3	Nagashima K: Inhibitory effect of eugenol on Cu2+-catalyzed lipid peroxidation in human erythrocyte membranes. Int J Biochem. 21:745–749. 1989.PubMed/NCBI View Article : Google Scholar
4	Nagababu E and Lakshmaiah N: Inhibition of microsomal lipid peroxidation and monooxygenase activities by eugenol. Free Radic Res. 20:253–266. 1994.PubMed/NCBI View Article : Google Scholar
5	Joe B and Lokesh BR: Role of capsaicin, curcumin and dietary n-3 fatty acids in lowering the generation of reactive oxygen species in rat peritoneal macrophages. Biochim Biophys Acta. 1224:255–263. 1994.PubMed/NCBI View Article : Google Scholar
6	Jaganathan SK and Supriyanto E: Antiproliferative and molecular mechanism of eugenol-induced apoptosis in cancer cells. Molecules. 17:6290–6304. 2012.PubMed/NCBI View Article : Google Scholar
7	Kim SS, Oh OJ, Min HY, Park EJ, Kim Y, Park HJ, Nam Han Y and Lee SK: Eugenol suppresses cyclooxygenase-2 expression in lipopolysaccharide-stimulated mouse macrophage RAW264.7 cells. Life Sci. 73:337–348. 2003.PubMed/NCBI View Article : Google Scholar
8	Ogata M, Kaneya D, Shin-Ya K, Li L, Abe Y, Katoh H, Seki S, Seki Y, Gonda R, Urano S, et al: Trapping effect of eugenol on hydroxyl radicals induced by L-DOPA in vitro. Chem Pharm Bull (Tokyo). 53:1167–1170. 2005.PubMed/NCBI View Article : Google Scholar
9	Huang MZ, Yang YJ, Liu XW, Qin Z and Li JY: Aspirin eugenol ester attenuates oxidative injury of vascular endothelial cells by regulating NOS and Nrf2 signalling pathways. Br J Pharmacol. 176:906–918. 2019.PubMed/NCBI View Article : Google Scholar
10	Gold R, Kappos L, Arnold DL, Bar-Or A, Giovannoni G, Selmaj K, Tornatore C, Sweetser MT, Yang M, Sheikh SI, et al: DEFINE Study Investigators: Placebo-controlled phase 3 study of oral BG-12 for relapsing multiple sclerosis. N Engl J Med. 367:1098–1107. 2012.PubMed/NCBI View Article : Google Scholar
11	Niture SK, Khatri R and Jaiswal AK: Regulation of Nrf2-an update. Free Radic Biol Med. 66:36–44. 2014.PubMed/NCBI View Article : Google Scholar
12	Kumar H, Kim IS, More SV, Kim BW and Choi DK: Natural product-derived pharmacological modulators of Nrf2/ARE pathway for chronic diseases. Nat Prod Rep. 31:109–139. 2014.PubMed/NCBI View Article : Google Scholar
13	Xie Y, Zhao QY, Li HY, Zhou X, Liu Y and Zhang H: Curcumin ameliorates cognitive deficits heavy ion irradiation-induced learning and memory deficits through enhancing of Nrf2 antioxidant signaling pathways. Pharmacol Biochem Behav. 126:181–186. 2014.PubMed/NCBI View Article : Google Scholar
14	Lu YF, Liu J, Wu KC and Klaassen CD: Protection against phalloidin-induced liver injury by oleanolic acid involves Nrf2 activation and suppression of Oatp1b2. Toxicol Lett. 232:326–332. 2015.PubMed/NCBI View Article : Google Scholar
15	Zhou J, Ma X, Cui Y, Song Y, Yao L, Liu Y and Li S: Methyleugenol protects against t-BHP-triggered oxidative injury by induction of Nrf2 dependent on AMPK/GSK3β and ERK activation. J Pharmacol Sci. 135:55–63. 2017.PubMed/NCBI View Article : Google Scholar
16	Miltenberger RJ, Cortner J and Farnham PJ: An inhibitory Raf-1 mutant suppresses expression of a subset of v-raf-activated genes. J Biol Chem. 268:15674–15680. 1993.PubMed/NCBI
17	Wasserman WW and Fahl WE: Functional antioxidant responsive elements. Proc Natl Acad Sci USA. 94:5361–5366. 1997.PubMed/NCBI View Article : Google Scholar
18	Jaramillo MC and Zhang DD: The emerging role of the Nrf2-Keap1 signaling pathway in cancer. Genes Dev. 27:2179–2191. 2013.PubMed/NCBI View Article : Google Scholar
19	Liu J, Shaik S, Dai X, Wu Q, Zhou X, Wang Z and Wei W: Targeting the ubiquitin pathway for cancer treatment. Biochim Biophys Acta. 1855:50–60. 2015.PubMed/NCBI View Article : Google Scholar