Natural antioxidants’ effects on endoplasmic reticulum stress-related diseases

Reyes-Fermín, Laura María; Aparicio-Trejo, Omar Emiliano; Avila-Rojas, Sabino Hazael; Gómez-Sierra, Tania; Martínez-Klimova, Elena; Pedraza-Chaverri, José

doi:10.1016/j.fct.2020.111229

Cited by 50Endoplasmic Reticulum Stress and DiseaseGenomics, phytochemicals, and oxidative stressAntioxidant Activity and Oxidative Stress

Natural antioxidants’ effects on endoplasmic reticulum stress-related diseases

Reyes-Fermín, Laura María, Aparicio-Trejo, Omar Emiliano, Avila-Rojas, Sabino Hazael, Gómez-Sierra, Tania, Martínez-Klimova, Elena, Pedraza-Chaverri, José·2020·Food and Chemical Toxicology

DOI 10.1016/j.fct.2020.111229

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Abstract

Endoplasmic reticulum (ER) stress is a normal molecular process induced by the over-accumulation of misfolded or unfolded proteins. ER stress induces the unfolded protein response (UPR), which reduces global protein synthesis, increases ER capacity and protein degradation, to restart ER homeostasis, allowing cell survival. However, the over-induction of UPR can also trigger inflammatory processes, tissue damage and cell death. ER stress is involved in several pathologies, like endothelial dysfunction, diabetes and heart, liver, kidney or neurological diseases. Although the progression of these diseases is the result of several pathological mechanisms, oxidative stress has been widely related to these pathologies. Moreover, ER stress can establish a progressive pathological cycle with oxidative stress. Therefore, the use of natural antioxidants, able to modulate both oxidative and ER stress, can be a new strategy to mitigate these diseases. This review is focused on the effects of natural antioxidant compounds on ER stress in endothelial dysfunction, diabetes and heart, liver, kidney or neurological diseases.

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Various investigations have shown that nutraceuticals are capable of fulfilling neuroprotective functions on molecular mechanisms that trigger Alzheimer's disease, acting as antioxidants or anti-neuroinflammatory drugs, affecting aggregation of β amyloid peptides, hyperphosphorylation of Tau protein, and decrease of acetylcholine in cholinergic neurons.
“Various investigations have shown that nutraceuticals are capable of fulfilling neuroprotective functions on molecular mechanisms that trigger AD, acting as antioxidants or anti-neuroinflammatory drugs, taking effect on the aggregation of β amyloid peptides, the hyperphosphorylation of the Tau protein and the decrease of the neurotransmitter ACh in cholinergic neurons [70,71,72]”
From Multi-Target Mechanisms of Phytochemicals in Alzheimer’s Disease: Effects on Oxidative Stress, Neuroinflammation and Protein Aggregation (2022) · cites this paper as [71]

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Nano-oleanolic acid alleviates metabolic dysfunctions in rats with high fat and fructose diet
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Morin Exhibits Anti-Inflammatory Effects on IL-1β-Stimulated Human Osteoarthritis Chondrocytes by Activating the Nrf2 Signaling Pathway
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Ilexgenin A inhibits mitochondrial fission and promote Drp1 degradation by Nrf2‐induced PSMB5 in endothelial cells
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Pharmacokinetic, bioavailability, metabolism and plasma protein binding evaluation of NADPH-oxidase inhibitor apocynin using LC–MS/MS
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Curcumin inhibits endoplasmic reticulum stress induced by cerebral ischemia‑reperfusion injury in rats
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In Vitro and In Vivo Antioxidant Activity of Aged Ginseng (Panax ginseng)
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Curcumin attenuates palmitic acid-induced cell apoptosis by inhibiting endoplasmic reticulum stress in H9C2 cardiomyocytes
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Endothelium and Cardiovascular Diseases
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Grape seed proanthocyanidins protect against streptozotocin‑induced diabetic nephropathy by attenuating endoplasmic reticulum stress‑induced apoptosis
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Alpha-mangostin attenuates diabetic nephropathy in association with suppression of acid sphingomyelianse and endoplasmic reticulum stress
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Caspase-12, but Not Caspase-11, Inhibits Obesity and Insulin Resistance
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Stachydrine Mediates Rapid Vascular Relaxation: Activation of Endothelial Nitric Oxide Synthase Involving AMP-Activated Protein Kinase and Akt Phosphorylation in Vascular Endothelial Cells
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Oxidative Stress and the Kidney: Riding on the Curve of Hormesis
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Tournefolic acid B methyl ester attenuates glutamate‐induced toxicity by blockade of ROS accumulation and abrogating the activation of caspases and JNK in rat cortical neurons
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Theoretical and Experimental in vivo Study of Antioxidant Activity of Crocin in Order to Propose Novel Derivatives with Higher Antioxidant Activity and Their Delivery via Nanotubes and Nanocones
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A recent update on the multifaceted health benefits associated with ginger and its bioactive components
Ma, R., Ni, Z., Zhu, Y.-Y., Thakur, K., Zhang, F., Zhang, Y.-Y., Hu, F., Zhang, J., & Wei, Z. (2020) · Food & Function · doi:10.1039/d0fo02834g · Cited by 141 · see citing works
Multi-Target Mechanisms of Phytochemicals in Alzheimer’s Disease: Effects on Oxidative Stress, Neuroinflammation and Protein Aggregation
Sharifi-Rad, J., Rapposelli, S., Sestito, S., Herrera-Bravo, J., Arancibia-Diaz, A., Salazar, L. A., Yeskaliyeva, B., Beyatli, A., Leyva-Gómez, G., González-Contreras, C., et al. (2022) · Journal of Personalized Medicine · doi:10.3390/jpm12091515 · Cited by 125 · see citing works
Endoplasmic reticulum stress as the basis of obesity and metabolic diseases: focus on adipose tissue, liver, and pancreas
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Protective Effect of Natural Antioxidants on Reducing Cisplatin-Induced Nephrotoxicity
Zhou, J., Nie, R., Yin, Y., Cai, X., Xie, D., & Cai, M. (2022) · Disease Markers · doi:10.1155/2022/1612348 · Cited by 63 · see citing works
Melatonin inhibits oxalate-induced endoplasmic reticulum stress and apoptosis in HK-2 cells by activating the AMPK pathway
Song, Q., He, Z., Li, B., Liu, J., Liu, L., Liao, W., Xiong, Y., Song, C., Yang, S., & Liu, Y. (2020) · Cell Cycle · doi:10.1080/15384101.2020.1810401 · Cited by 40 · see citing works
6-Shogaol mediated ROS production and apoptosis via endoplasmic reticulum and mitochondrial pathways in human endometrial carcinoma Ishikawa cells
Ma, R., Ni, Z., Zhang, F., Zhang, Y., Liu, M., Thakur, K., Zhang, J., Wang, S., & Wei, Z. (2020) · Journal of Functional Foods · doi:10.1016/j.jff.2020.104178 · Cited by 36 · see citing works
Arctigenin alleviates cadmium-induced nephrotoxicity: Targeting endoplasmic reticulum stress, Nrf2 signaling, and the associated inflammatory response
Salama, S. A., Mohamadin, A. M., & Abdel‐Bakky, M. S. (2021) · Life Sciences · doi:10.1016/j.lfs.2021.120121 · Cited by 33 · see citing works
Dieckol, an algae-derived phenolic compound, suppresses airborne particulate matter-induced skin aging by inhibiting the expressions of pro-inflammatory cytokines and matrix metalloproteinases through regulating NF-κB, AP-1, and MAPKs signaling pathways
Wang, L., Lee, W., Jayawardena, T. U., Cha, S., & Jeon, Y. (2020) · Food and Chemical Toxicology · doi:10.1016/j.fct.2020.111823 · Cited by 32 · see citing works
Resolvin D1 Attenuates Doxorubicin-Induced Cardiotoxicity by Inhibiting Inflammation, Oxidative and Endoplasmic Reticulum Stress
Wang, M., Zhang, J., Zhao, M., Liu, J., Ye, J., Xu, Y. Q., Wang, Z., Ye, D., Li, D., & Wan, J. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.749899 · Cited by 29 · see citing works
Isoliquiritigenin Pretreatment Induces Endoplasmic Reticulum Stress-Mediated Hormesis and Attenuates Cisplatin-Induced Oxidative Stress and Damage in LLC-PK1 Cells
Gómez‐Sierra, T., Medina‐Campos, O. N., Solano, J. D., Ibarra‐Rubio, M. E., & Pedraza‐Chaverrí, J. (2020) · Molecules · doi:10.3390/molecules25194442 · Cited by 26 · see citing works
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Artepillin C, a major component of Brazilian green propolis, inhibits endoplasmic reticulum stress and protein aggregation
Hirata, Y., Motoyama, M., Kimura, S., Takashima, M., Ikawa, T., Oh‐hashi, K., & Kamatari, Y. O. (2021) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2021.174572 · Cited by 21 · see citing works
Impact of Air-Drying Temperatures on Drying Kinetics, Physicochemical Properties, and Bioactive Profile of Ginger
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Manganese-induced neuronal apoptosis: new insights into the role of endoplasmic reticulum stress in regulating autophagy-related proteins
Liu, C., & Ju, R. (2022) · Toxicological Sciences · doi:10.1093/toxsci/kfac130 · Cited by 18 · see citing works
Syringic acid ameliorates ischemia/reperfusion-induced testicular injury in rats via suppressing of HMGB1/NF-κB axis and endoplasmic reticulum stress
Demir, E. A., Demir, S., Kazaz, İ. O., Küçük, H., Alemdar, N. T., Gecici, O. F., Menteşe, A., & Aliyazıcıoğlu, Y. (2023) · European Journal of Trauma and Emergency Surgery · doi:10.1007/s00068-023-02227-7 · Cited by 18 · see citing works
Sigma-1 receptor exerts protective effects on ameliorating nephrolithiasis by modulating endoplasmic reticulum-mitochondrion association and inhibiting endoplasmic reticulum stress-induced apoptosis in renal tubular epithelial cells
Hu, K., Su, X., Dong, C., He, Z., Song, Q., Song, C., Zhou, J., Liao, W., Wang, C., Yang, S., et al. (2024) · Redox Report · doi:10.1080/13510002.2024.2391139 · Cited by 17 · see citing works
Berberine-Albumin Nanoparticles: Preparation, Thermodynamic Study and Evaluation Their Protective Effects Against Oxidative Stress in Primary Neuronal Cells as a Model of Alzheimer’s Disease
Zhang, Y., Wang, L., Li, G., & Gao, J. (2021) · Journal of Biomedical Nanotechnology · doi:10.1166/jbn.2021.2995 · Cited by 17 · see citing works
Natural Compounds Play Therapeutic Roles in Various Human Pathologies via Regulating Endoplasmic Reticulum Pathway
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Sedum takesimense Protects PC12 Cells against Corticosterone-Induced Neurotoxicity by Inhibiting Neural Apoptosis
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Multi‐Targeting Phytochemicals for Alzheimer's Disease
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Advances in Alzheimer’s disease therapeutics: biochemistry, exploring bioactive compounds and novel approaches
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SIK2 protects against renal tubular injury and the progression of diabetic kidney disease
Liu, B., Zhang, L., Yang, H., Chen, X., Zheng, H., & Liao, X. (2022) · Translational research · doi:10.1016/j.trsl.2022.08.012 · Cited by 14 · see citing works
Regulation of endoplasmic reticulum stress in models of kidney disease
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Protective roles of thrombomodulin in cisplatin-induced nephrotoxicity through the inhibition of oxidative and endoplasmic reticulum stress
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The detrimental role of galectin‐3 and endoplasmic reticulum stress in the cardiac consequences of myocardial ischemia in the context of obesity
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Oxidative stress modulation in alcohol-related liver disease: From chinese botanical drugs to exercise-based interventions
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Nutritional composition, antioxidant activity and anticancer potential of Syzygium cumini (L.) and Syzygium malaccense (L.) fruits
Gibbert, L., Sereno, A. B., Piltz, M. T., da Silva, M. A. B., Miguel, M. D., Montrucchio, D. P., Messias-Reason, I., Dantas, A. M., Borges, G. D. S. C., Miguel, O. G., et al. (2021) · Research Society and Development · doi:10.33448/rsd-v10i4.13743 · Cited by 12 · see citing works
Antioxidants targeting mitochondria function in kidney diseases
Aranda‐Rivera, A. K., Cruz‐Gregorio, A., Amador‐Martínez, I., Cruz, E. Y. H., Tapia, E., & Pedraza‐Chaverrí, J. (2024) · Mitochondrial Communications · doi:10.1016/j.mitoco.2024.03.002 · Cited by 11 · see citing works
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Chemical and biological antioxidant activity evaluation of extracts from berries pomaces
Vergara‐Castro, M., Soto‐Maldonado, C., Zúñiga‐Hansen, M. E., Arancibia‐Díaz, A., Fuentes, P., & Altamirano, C. (2025) · Applied Food Research · doi:10.1016/j.afres.2025.100781 · Cited by 11 · see citing works
Antioxidant and Anti-Diabetic Effects of Agastache rugosa Extract
Ji, Y., Lee, E. Y., Lee, J. Y., Lee, Y. J., Lee, S. E., Seo, K. H., & Kim, H. D. (2020) · Journal of the East Asian Society of Dietary Life · doi:10.17495/easdl.2020.8.30.4.297 · Cited by 10 · see citing works
Gentisic acid attenuates 5-fluorouracil-induced ovotoxicity in rats via modulating Nrf2 signalling: An experimental approach
Menteşe, A., Demir, S., Yuluğ, E., Küçük, H., Alemdar, N. T., Demir, E. A., & Aliyazıcıoğlu, Y. (2024) · Reproductive Toxicology · doi:10.1016/j.reprotox.2024.108661 · Cited by 8 · see citing works
BEER AS A SOURCE OF HOP PRENYLATED FLAVONOIDS, COMPOUNDS WITH ANTIOXIDANT, CHEMOPROTECTIVE AND PHYTOESTROGEN ACTIVITY
Urminská, D., & Jedináková, N. (2021) · Journal of Microbiology Biotechnology and Food Sciences · doi:10.15414/jmbfs.4426 · Cited by 7 · see citing works
Usnic acid alleviates testicular ischemia/reperfusion injury in rats by modulating endoplasmic reticulum stress
Demir, S., Kazaz, İ. O., Mungan, S. A., Alemdar, N. T., Perolli, N., Demir, E. A., & Menteşe, A. (2024) · Reproductive Toxicology · doi:10.1016/j.reprotox.2024.108654 · Cited by 7 · see citing works
From peel to health: jaboticaba’s phenolics counteract oxidative stress and liver fat buildup
Viana, K. W. C., Borges, L. L. R., Nascimento, A. L. A. A., Rigolon, T. C. B., Neves, N. D. A., da Matta, S. L. P., Wischral, D., Martins, E., Campelo, P. H., & Stringheta, P. C. (2025) · Food, Nutrition and Health. · doi:10.1007/s44403-025-00015-2 · Cited by 6 · see citing works
Isoliquiritigenin pretreatment regulates ER stress and attenuates cisplatin‐induced nephrotoxicity in male Wistar rats
Gómez‐Sierra, T., Ortega-Lozano, A. J., Rojas‐Morales, P., Medina‐Reyes, E. I., Barrera‐Oviedo, D., & Pedraza‐Chaverrí, J. (2023) · Journal of Biochemical and Molecular Toxicology · doi:10.1002/jbt.23492 · Cited by 6 · see citing works
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Dietary conjugated linoleic acid downregulates the AlCl3-induced hyperactivation of compensatory and maladaptive signalling in the mouse brain cortex
Cuciniello, R., Luongo, D., Maurano, F., Crispi, S., & Bergamo, P. (2024) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2024.01.006 · Cited by 6 · see citing works
The protective role of selenium against high-fructose corn syrup–induced kidney damage: a histopathological and molecular analysis
Tepebaşı, M. Y., Savran, M., Coşan, S., Taştan, Ş. A., & Aydın, B. (2024) · Naunyn-Schmiedeberg s Archives of Pharmacology · doi:10.1007/s00210-024-03149-w · Cited by 4 · see citing works
Neuroprotective Effects of Lilium Lancifolium Thunberg Extract Against Corticosterone-Induced Dysfunctions in PC12 Cells
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Octanoic Acid and Decanoic Acid Inhibit Tunicamycin‐Induced ER Stress in Rat Aortic Smooth Muscle Cells
Sukketsiri, W., Tipmanee, V., Rungruang, P., Higashihara, M., Sumi, T., Moriyama, T., & Zaima, N. (2024) · Advances in Pharmacological and Pharmaceutical Sciences · doi:10.1155/adpp/9076988 · Cited by 3 · see citing works
Punicalagin relieves lipotoxic injuries on pancreatic β-cells via regulating the oxidative stress and endoplasmic reticulum stress-mediated apoptosis
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Antioxidants affect endoplasmic reticulum stress-related diseases
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Antitumor effects of Dadas Cress (Lepidium sativum var. sativum) on Ehrlich Ascites tumor cells: an in vitro and in vivo study
Ünalmiş, D., Ülger, H., Doğanyiğit, Z., Karatoprak, G. Ş., Pandır, D., Uçar, S., Kaymak, E., Okan, A., & Yılmaz, S. (2025) · Journal of Molecular Histology · doi:10.1007/s10735-025-10575-4 · Cited by 3 · see citing works
Quinoa Polyphenols Alleviate Glucose Deprivation‐Induced Endoplasmic Reticulum Stress by Enhancing Hepatic Cellular Autophagy and Antioxidant Capacity
Gao, Q., Fan, M., Qian, H., Li, Y., & Wang, L. (2025) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.70279 · Cited by 2 · see citing works
A review on endoplasmic reticulum-dependent anti-breast cancer activity of herbal drugs: possible challenges and opportunities
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Nanocapsule-based vitamin B12 as a novel strategy against vancomycin-induced nephrotoxicity: Targeting oxidative stress, ER stress, inflammation, and fibrosis in rats
El-Emam, M. M. A., Kilany, M. S., Ibrahim, M. F., Qelliny, M. R., Mostafa, M., Sayed, M. M. E., Khamis, T., Agaga, R., Eltaweel, A. M., & Mansour, M. F. (2025) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2025.117662 · Cited by 1 · see citing works
Soy isoflavone alleviates high-fat diet-induced liver injury in rice field eel (Monopterus albus) by ameliorating lipid metabolic disorders, oxidative and endoplasmic reticulum stress, and inflammation
Li, Q., Hu, W., Zhou, T., Xie, K., Hu, Y., & Zhang, J. (2025) · Aquaculture International · doi:10.1007/s10499-025-02391-0 · Cited by 1 · see citing works
Development of Neem Based Instant Herbal Soup Mix
Hema Prabha., P. (2022) · International Journal for Research in Applied Science and Engineering Technology · doi:10.22214/ijraset.2022.42524
Avaliação das propriedades físicas e estabilidade oxidativa de oleogéis como alternativa aos óleos parcialmente hidrogenados
de Faria, E. C. (2022) · doi:10.11606/d.9.2022.tde-26072022-183749
Renoprotective effect of Limonium duriusculum (de Girard) Kuntze via modulation of oxidative stress/ UPR markers and inflammation during cyclosporine-induced nephrotoxicity in rats.
Redouane-Salah, A., Ameddah, S., Kerkatou, W., Wojnicki, K., Ramos, A. M., Ortíz, A., Kaminska, B., & Menad, A. (2024) · PubMed Central · doi:10.22038/ijbms.2024.77052.16661
Protective Effects of Myricetin Against Valproic Acid-Induced Endoplasmic Reticulum Stress, Apoptosis and Inflammation in Rats: Molecular Docking Analysis of PERK and IRE1Preprint
İskender, H., Dokumacıoğlu, E., Kapakin, A. K. T., Kılıçlıoğlu, M., Dereli, E., Sarıyer, E., Sarıyer, A. S., & Yıldırım, O. G. (2026) · Research Square · doi:10.21203/rs.3.rs-10945962/v1
Pea protein–starch conjugates as plant-based interfacial materials for stabilizing double emulsions loaded with ginger extract
Shaukat, M. N., Niroula, A., Zia, R., Arafat, M., Fallico, B., & Nazir, A. (2026) · Next Materials · doi:10.1016/j.nxmate.2026.103792

Antioxidants affect endoplasmic reticulum stress-related diseases
Gómez‐Sierra, T., Jiménez‐Uribe, A. P., Ortega-Lozano, A. J., Ramírez-Magaña, K. J., & Pedraza‐Chaverrí, J. (2022) · Vitamins and hormones · doi:10.1016/bs.vh.2022.10.006 · Cited by 3 · see citing works
Self-citation
Impact of endoplasmic reticulum (ER) stress on cellular functions and role of natural products as modulators
Abd‐Elmawla, M. A., Ghaiad, H. R., Elbaqy, Y. M. A., Zaki, M. B., Abdelhamid, R., El‐Shiekh, R. A., & Gad, E. S. (2026) · Beni-Suef University Journal of Basic and Applied Sciences · doi:10.1186/s43088-026-00736-z · Cited by 6 · see citing works
Roles and Therapeutic Implications of Endoplasmic Reticulum Stress and Oxidative Stress in Cardiovascular Diseases
Zhou, Y., Murugan, D., Khan, H., Huang, Y., & Wai, S.-C.-A. (2021) · Antioxidants · doi:10.3390/antiox10081167 · Cited by 69 · see citing works
Natural Compounds Play Therapeutic Roles in Various Human Pathologies via Regulating Endoplasmic Reticulum Pathway
Ma, R.-H., Ni, Z.-J., Thakur, K., Zhang, F., Zhang, Y.-Y., Zhang, J.-G., & Wei, Z.-J. (2020) · Medicine in Drug Discovery · doi:10.1016/j.medidd.2020.100065 · Cited by 16 · see citing works
Targeting the Endoplasmic Reticulum Unfolded Protein Response to Counteract the Oxidative Stress‐Induced Endothelial Dysfunction
Amodio, G., Moltedo, O., Faraonio, R., & Remondelli, P. (2018) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2018/4946289 · Cited by 56 · see citing works

Authors: Reyes-Fermín, L. M., Aparicio-Trejo, O. E., Avila-Rojas, S. H., Gómez-Sierra, T., Martínez-Klimova, E., & Pedraza-Chaverri, J.
Affiliations: Universidad Nacional Autónoma de México (MX)
ORCID: Reyes-Fermín, Laura María
Avila-Rojas, Sabino Hazael
Venue: Food and Chemical Toxicology
Publisher: Elsevier BV
Published: 2020-04
Volume: 138
Pages: 111229
ISSN: 0278-6915 (ISSN-L)
DOI: 10.1016/j.fct.2020.111229
OpenAlex: W3006755228
Cited by: 50
References: 193
Citations by year: 2026: 2 · 2025: 9 · 2024: 12 · 2023: 4 · 2022: 8 · 2021: 7 · 2020: 8
FWCI: 0.78
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
Locations: Food and Chemical Toxicology (publishedVersion)
PubMed (publishedVersion)
Funders: Dirección General de Asuntos del Personal Académico, Universidad Nacional Autónoma de México
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Endoplasmic Reticulum Stress and Disease
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics, phytochemicals, and oxidative stress
Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
Keywords: endoplasmic reticulum stress, unfolded protein response, natural antioxidants, oxidative stress, endothelial dysfunction, diabetes mellitus, cardiovascular disease, liver disease, kidney disease, neurological disorders
MeSH terms: Animals, Antioxidants, Endoplasmic Reticulum, Homeostasis, Humans, Signal Transduction, Apoptosis, Unfolded Protein Response, Endoplasmic Reticulum Stress

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Natural antioxidants’ effects on endoplasmic reticulum stress-related diseases

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