Abstract
Acrolein, known as one of the most common reactive carbonyl species, is a toxic small molecule affecting human health in daily life. This study is focused on the scavenging abilities and mechanism of ferulic acid and some other phenolic acids against acrolein. Among the 13 phenolic compounds investigated, ferulic acid was found to have the highest efficiency in scavenging acrolein under physiological conditions. Ferulic acid remained at (3.04±1.89)% and acrolein remained at (29.51±4.44)% after being incubated with each other for 24 h. The molecular mechanism of the detoxifying process was also studied. Detoxifying products, namely 2-methoxy-4-vinylphenol (product 21) and 5-(4-hydroxy-3-methoxyphenyl)pent-4-enal (product 22), were identified though nuclear magnetic resonance (NMR) and gas chromatography-mass spectrometry (GC-MS), after the scavenging process. Ferulic acid showed significant activity in scavenging acrolein under physiological conditions. This study indicates a new method for inhibiting damage from acrolein.
概要
目 的
寻找一种方便、 快捷且有效的清除丙烯醛的天然试剂并研究其反应机理。
创新点
发现了常见的天然酚酸阿魏酸具有有效清除丙烯醛的活性, 且其反应位点与其他具有丙烯醛清除活性的酚酸类化合物不同。 研究了该反应的过程, 推测了其反应机理, 并考察了该反应的构效关系。
方 法
(1) 通过相同时间内阿魏酸对丙烯醛、 谷胱甘肽的影响考察其清除活性; (2) 运用气相色谱-质谱联用技术(GC-MS)、 核磁共振技术 (NMR) 等技术鉴定产物结构; (3) 通过研究阿魏酸、 丙烯醛和反应产物之间的互相转化关系, 推断该反应的过程。
结 论
(1) 阿魏酸可以有效抑制丙烯醛对细胞抗氧化系统的破坏; (2)该反应的过程是由阿魏酸在丙烯醛作用下脱羧, 得到脱羧产物, 再与丙烯醛进行迈克尔加成, 得到最终加合产物; (3)苯环 4 号位的羟基对于脱羧过程是必需的; (4) 苯环 3 号位的甲氧基可以大幅度提高加合产物的产率; (5)阿魏酸及其类似物的酯与丙烯醛不发生反应。
Article PDF
Similar content being viewed by others
References
Ålin P, Danielson UH, Mannervik B, 1985. 4-Hydroxyalk-2-enals are substrates for glutathione transferase. FEBS Lett, 179(2):267–270. https://doi.org/10.1016/0014-5793(85)80532-9
Amro B, Aburjai T, Al-Khalil S, 2002. Antioxidative and radical scavenging effects of olive cake extract. Fitoterapia, 73(6):456–461. https://doi.org/10.1016/s0367-326x(02)00173-9
Balasubashini MS, Rukkumani R, Menon VP, 2003. Protective effects of ferulic acid on hyperlipidemic diabetic rats. Acta Diabetol, 40(3):118–122. https://doi.org/10.1007/s00592-003-0099-6
Barone E, Calabrese V, Mancuso C, 2009. Ferulic acid and its therapeutic potential as a hormetin for age-related diseases. Biogerontology, 10(2):97–108. https://doi.org/10.1007/s10522-008-9160-8
Baskaran X, Vigila AVG, Zhang S, et al., 2018. A review of the use of pteridophytes for treating human ailments. J Zhejiang Univ-Sci B (Biomed & Biotechnol), 19(2):85–119. https://doi.org/10.1631/jzus.B1600344
Calabrese V, Calafato S, Puleo E, et al., 2008. Redox regulation of cellular stress response by ferulic acid ethyl ester in human dermal fibroblasts: role of vitagenes. Clin Dermatol, 26(4):358–363. https://doi.org/10.1016/j.clindermatol.2008.01.005
Cassano R, Trombino S, Cilea A, et al., 2010. L-lysine pro-prodrug containing trans-ferulic acid for 5-amino salicylic acid colon delivery: synthesis, characterization and in vitro antioxidant activity evaluation. Chem Pharm Bull (Tokyo), 58(1):103–105. https://doi.org/10.1248/cpb.58.103
Catino S, Paciello F, Miceli F, et al., 2016. Ferulic acid regulates the Nrf2/heme oxygenase-1 system and counteracts trimethyltin-induced neuronal damage in the human neuroblastoma cell line SH-SY5Y. Front Pharmacol, 6:305. https://doi.org/10.3389/fphar.2015.00305
Cox PJ, 1979. Cyclophosphamide cystitis—Identification of acrolein as the causative agent. Biochem Pharmacol, 28(13):2045–2049. https://doi.org/10.1016/0006-2952(79)90222-3
DeJarnett N, Conklin DJ, Riggs DW, et al., 2014. Acrolein exposure is associated with increased cardiovascular disease risk. J Am Heart Assoc, 3(4):e000934. https://doi.org/10.1161/JAHA.114.000934
Doggui S, Belkacemi A, Paka GD, et al., 2013. Curcumin protects neuronal-like cells against acrolein by restoring Akt and redox signaling pathways. Mol Nutr Food Res, 57(9):1660–1670. https://doi.org/10.1002/mnfr.201300130
Esterbauer H, Schaur RJ, Zollner H, 1991. Chemistry and biochemistry of 4-hydroxynonenal, malonaldehyde and related aldehydes. Free Radic Biol Med, 11(1):81–128. https://doi.org/10.1016/0891-5849(91)90192-6
Fetoni AR, Mancuso C, Eramo SLM, et al., 2010. In vivo protective effect of ferulic acid against noise-induced hearing loss in the guinea-pig. Neuroscience, 169(4):1575–1588. https://doi.org/10.1016/j.neuroscience.2010.06.022
He S, Jiang LY, Wu B, et al., 2009. Pallidol, a resveratrol dimer from red wine, is a selective singlet oxygen quencher. Biochem Biophys Res Commun, 379(2):283–287. https://doi.org/10.1016/j.bbrc.2008.12.039
Huang RT, Huang Q, Wu GL, et al., 2017. Evaluation of the antioxidant property and effects in Caenorhabditis elegans of Xiangxi flavor vinegar, a Hunan local traditional vinegar. J Zhejiang Univ-Sci B (Biomed & Biotechnol), 18(4):324–333. https://doi.org/10.1631/jzus.B1600088
Joshi G, Perluigi M, Sultana R, et al., 2006. In vivo protection of synaptosomes by ferulic acid ethyl ester (FAEE) from oxidative stress mediated by 2,2-azobis(2-amidinopropane) dihydrochloride (AAPH) or Fe2+/H2O2: insight into mechanisms of neuroprotection and relevance to oxidative stress-related neurodegenerative disorders. Neurochem Int, 48(4):318–327. https://doi.org/10.1016/j.neuint.2005.11.006
Jung SH, Kim JH, 2002. Efficient method for β-conjugate addition of α,β-unsaturated lactones and esters. Bull Korean Chem Soc, 23(3):365–366. https://doi.org/10.5012/bkcs.2002.23.3.365
Kovalev IP, Kolmogorov YN, Yinogradov MG, et al., 1990. The linear dimerization of vinyl ketones catalyzed by the [RhCl(C2H4)2]2-GeCl2 system. Russ Chem Bull, 39(5):1070–1071. https://doi.org/10.1007/bf00961723
Kumar N, Pruthi V, 2014. Potential applications of ferulic acid from natural sources. Biotechnol Rep, 4:86–93. https://doi.org/10.1016/j.btre.2014.09.002
Li C, Xu XF, Tao ZH, et al., 2015. Resveratrol dimers, nutritional components in grape wine, are selective ROS scavengers and weak Nrf2 activators. Food Chem, 173:218–223. https://doi.org/10.1016/j.foodchem.2014.09.165
Liu F, Li XL, Lin T, et al., 2012. The cyclophosphamide metabolite, acrolein, induces cytoskeletal changes and oxidative stress in Sertoli cells. Mol Biol Rep, 39(1):493–500. https://doi.org/10.1007/s11033-011-0763-9
Lovell MA, Xie CS, Markesbery WR, 2001. Acrolein is increased in Alzheimer’s disease brain and is toxic to primary hippocampal cultures. Neurobiol Aging, 22(2):187–194. https://doi.org/10.1016/s0197-4580(00)00235-9
Luo J, Shi RY, 2005. Acrolein induces oxidative stress in brain mitochondria. Neurochem Int, 46(3):243–252. https://doi.org/10.1016/j.neuint.2004.09.001
Mancuso C, Santangelo R, 2014. Ferulic acid: pharmacological and toxicological aspects. Food Chem Toxicol, 65:185–195. https://doi.org/10.1016/j.fct.2013.12.024
Mano J, 2012. Reactive carbonyl species: their production from lipid peroxides, action in environmental stress, and the detoxification mechanism. Plant Physiol Biochem, 59:90–97. https://doi.org/10.1016/j.plaphy.2012.03.010
Mano J, Miyatake F, Hiraoka E, et al., 2009. Evaluation of the toxicity of stress-related aldehydes to photosynthesis in chloroplasts. Planta, 230(4):639–648. https://doi.org/10.1007/s00425-009-0964-9
Martirosyan A, Leonard S, Shi XL, et al., 2006. Actions of a histone deacetylase inhibitor NSC3852 (5-nitroso-8-quinolinol) link reactive oxygen species to cell differentiation and apoptosis in MCF-7 human mammary tumor cells. J Pharmacol Exp Ther, 317(2):546–552. https://doi.org/10.1124/jpet.105.096891
Mhillaj E, Catino S, Miceli FM, et al., 2018. Ferulic acid improves cognitive skills through the activation of the heme oxygenase system in the rat. Mol Neurobiol, 55(2):905–916. https://doi.org/10.1007/s12035-017-0381-1
Picone P, Bondi ML, Montana G, et al., 2009. Ferulic acid inhibits oxidative stress and cell death induced by Ab oligomers: improved delivery by solid lipid nanoparticles. Free Radic Res, 43(11):1133–1145. https://doi.org/10.1080/10715760903214454
Rom O, Korach- Rechtman H, Hayek T, et al., 2017. Acrolein increases macrophage atherogenicity in association with gut microbiota remodeling in atherosclerotic mice: protective role for the polyphenol-rich pomegranate juice. Arch Toxicol, 91(4):1709–1725. https://doi.org/10.1007/s00204-016-1859-8
Shamoto-Nagai M, Maruyama W, Hashizume Y, et al., 2007. In parkinsonian substantia nigra, α-synuclein is modified by acrolein, a lipid-peroxidation product, and accumulates in the dopamine neurons with inhibition of proteasome activity. J Neural Transm (Vienna), 114(12):1559–1567. https://doi.org/10.1007/s00702-007-0789-2
Sheu SJ, Ho YS, Chen YP, et al., 1987. Analysis and processing of Chinese herbal drugs; VI. The study of Angelicae radix. Planta Med, 53(4):377–378. https://doi.org/10.1055/s-2006-962742
Srinivasan M, Sudheer AR, Menon VP, 2007. Ferulic acid: therapeutic potential through its antioxidant property. J Clin Biochem Nutr, 40(2):92–100. https://doi.org/10.3164/jcbn.40.92
Stevens JF, Maier CS, 2008. Acrolein: sources, metabolism, and biomolecular interactions relevant to human health and disease. Mol Nutr Food Res, 52(1):7–25. https://doi.org/10.1002/mnfr.200700412
Suzuki D, Miyata T, 1999. Carbonyl stress in the pathogenesis of diabetic nephropathy. Intern Med, 38(4):309–314. https://doi.org/10.2169/internalmedicine.38.309
Trombino S, Cassano R, Ferrarelli T, et al., 2013. Trans-ferulic acid-based solid lipid nanoparticles and their antioxidant effect in rat brain microsomes. Colloids Surf B Biointerfaces, 109:273–279. https://doi.org/10.1016/j.colsurfb.2013.04.005
Vandeputte C, Guizon I, Genestie- Denis I, et al., 1994. A microtiter plate assay for total glutathione and glutathione disulfide contents in cultured/isolated cells: performance study of a new miniaturized protocol. Cell Biol Toxicol, 10(5-6):415–421. https://doi.org/10.1007/bf00755791
Wang WX, Qi YJ, Rocca JR, et al., 2015. Scavenging of toxic acrolein by resveratrol and hesperetin and identification of adducts. J Agric Food Chem, 63(43):9488–9495. https://doi.org/10.1021/acs.jafc.5b03949
Wang Y, Cui P, 2015. Reactive carbonyl species derived from omega-3 and omega-6 fatty acids. J Agric Food Chem, 63(28):6293–6296. https://doi.org/10.1021/acs.jafc.5b02376
Yaylayan VA, Keyhani A, 2000. Origin of carbohydrate degradation products in L-alanine/D-[13C]glucose model systems. J Agric Food Chem, 48(6):2415–2419. https://doi.org/10.1021/jf000004n
Zamora R, Aguilar I, Granvogl M, et al., 2016. Toxicologically relevant aldehydes produced during the frying process are trapped by food phenolics. J Agric Food Chem, 64(27):5583–5589. https://doi.org/10.1021/acs.jafc.6b02165
Author information
Authors and Affiliations
Contributions
Zhi-hao TAO performed the experimental research and data analysis, wrote and edited the manuscript. Chang LI contributed to the study design, data analysis, writing and editing of the manuscript. Xiao-fei XU contributed to the study design and data analysis of the manuscript. Yuan-jiang PAN contributed to the study design, writing and editing of the manuscript. All authors read and approved the final manuscript and, therefore, had full access to all the data in the study and take responsibility for the integrity and security of the data.
Corresponding authors
Ethics declarations
Zhi-hao TAO, Chang LI, Xiao-fei XU, and Yuan-jiang PAN declare that they have no conflict of interest.
This article does not contain any studies with human or animal subjects performed by any of the authors.
Additional information
Project supported by the National Natural Science Foundation of China (Nos. 21327010 and 21372199)
Electronic supplementary material
Rights and permissions
About this article
Cite this article
Tao, Zh., Li, C., Xu, Xf. et al. Scavenging activity and mechanism study of ferulic acid against reactive carbonyl species acrolein. J. Zhejiang Univ. Sci. B 20, 868–876 (2019). https://doi.org/10.1631/jzus.B1900211
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1631/jzus.B1900211