Title
Author
DOI
Article Type
Special Issue
Volume
Issue
Curcumin exerts anti-inflammatory, antioxidant and anti-ferroptotic effects through the Nrf2/HO-1 pathway to protect cardiomyocytes against sepsis
1Department of Pediatrics, Key Laboratory for Molecular Diagnosis of Hubei Province, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, 430014 Wuhan, Hubei, China
2Department of Ophthalmology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430022 Wuhan, Hubei, China
3Department of Neonatology, Key Laboratory for Molecular Diagnosis of Hubei Province, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, 430014 Wuhan, Hubei, China
DOI: 10.22514/sv.2024.057 Vol.20,Issue 5,May 2024 pp.46-53
Submitted: 09 November 2023 Accepted: 15 December 2023
Published: 08 May 2024
*Corresponding Author(s): Xiaobo Yang E-mail: yxb02441981@163.com
This study explores the therapeutic effect of curcumin on H9c2 rat cardiac myoblasts in vitro sepsis model and its potential mechanisms. At first, Cell viability was measured using Cell Counting Kit 8 (CCK-8) and Cell-Light 5-ethynyl-2-deoxyuridine (EdU) staining, and inflammatory factors tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6), interleukin 1β (IL-1β), oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH) and Fe2+ were calculated by ELISA and kits. Western blotting was used to quantitatively analyze nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), glutathione peroxidase 4 (GPX4) and Acyl-CoA synthetase long-chain family (ACSL4) expression differences. Knocking down Nrf2 to study whether curcumin acts through the Nrf2/HO-1 pathway. The results show that curcumin significantly improved cell viability in lipopolysaccharide (LPS)-induced H9c2 cells (p < 0.01). Curcumin also significantly reduced inflammatory factor levels in LPS-induced cardiomyocytes (p < 0.001). Curcumin down-regulated ROS and MDA levels (p < 0.001), and up-regulated SOD and GSH levels (p < 0.001). A decrease in both Fe2+ content and protein expression of ACSL4 (p < 0.001), and increased protein expression of glutathione peroxidase 4 (GPX4) (p < 0.001) were observed with curcumin. By knocking down Nrf2 curcumin’s therapeutic effect against LPS was eliminated. So curcumin can inhibit LPS-induced oxidative stress, inflammation and ferroptosis in cardiomyocytes by regulating Nrf-2/HO-1 signaling.
Cardiomyocytes; Curcumin; Sepsis; Nrf2/HO-1; Ferroptosis; Oxidative stress; Inflammation
Yao Shi,Xiaobo Yang,Hong Jiang,Shanxia Wu,Yan Hong,Wei Su,Xuan Wang. Curcumin exerts anti-inflammatory, antioxidant and anti-ferroptotic effects through the Nrf2/HO-1 pathway to protect cardiomyocytes against sepsis. Signa Vitae. 2024. 20(5);46-53.
[1] Yang X, Gong J, Cai X, Yuan YJ. Overexpression of HIC1 plays a protective effect on renal cell injury caused by lipopolysaccharide by inhibiting IL-6/STAT3 pathway. Signa Vitae. 2022; 18: 147–153.
[2] Srzić I, Nesek Adam V, Tunjić Pejak D. Sepsis definition: what’s new in the treatment guidelines. Acta Clinica Croatica. 2022; 61: 67–72.
[3] Hochstadt A, Meroz Y, Landesberg G. Myocardial dysfunction in severe sepsis and septic shock: more questions than answers? Journal of Cardiothoracic and Vascular Anesthesia. 2011; 25: 526–535.
[4] Blagov AV, Kozlov S, Blokhina T, Sukhorukov VN, Orekhov AN. Targeting mitochondrial dynamics proteins for the development of therapies for cardiovascular diseases. International Journal of Molecular Sciences. 2022; 23: 14741.
[5] Kazemi J, Shahsavarani H, Pakzad P, Shokrgozar M. WNT-targeted compound and phytoestrogen promoted cardiogenic differentiation of human induced pluripotent stem cells (hiPSCs) in vitro. Journal of Men’s Health. 2021; 18: 34.
[6] Fang X, Ardehali H, Min J, Wang F. The molecular and metabolic landscape of iron and ferroptosis in cardiovascular disease. Nature Reviews Cardiology. 2023; 20: 7–23.
[7] Sadeghi M, Dehnavi S, Asadirad A, Xu S, Majeed M, Jamialahmadi T, et al. Curcumin and chemokines: mechanism of action and therapeutic potential in inflammatory diseases. Inflammopharmacology. 2023; 31: 1069–1093.
[8] Joe B, Vijaykumar M, Lokesh BR. Biological properties of curcumin-cellular and molecular mechanisms of action. Critical Reviews in Food Science and Nutrition. 2004; 44: 97–111.
[9] Pourbagher-Shahri AM, Farkhondeh T, Ashrafizadeh M, Talebi M, Samargahndian S. Curcumin and cardiovascular diseases: focus on cellular targets and cascades. Biomedicine & Pharmacotherapy. 2021; 136: 111214.
[10] Zhuang L, Kong Y, Yang S, Lu F, Gong Z, Zhan S, et al. Dynamic changes of inflammation and apoptosis in cerebral ischemia‑reperfusion injury in mice investigated by ferumoxytol-enhanced magnetic resonance imaging. Molecular Medicine Reports. 2021; 23: 282.
[11] Farkhondeh T, Samarghandian S, Pourbagher‐Shahri AM, Sedaghat M. The impact of curcumin and its modified formulations on Alzheimer’s disease. Journal of Cellular Physiology. 2019; 234: 16953–16965.
[12] Wongcharoen W, Phrommintikul A. The protective role of curcumin in cardiovascular diseases. International Journal of Cardiology. 2009; 133: 145–151.
[13] Tang X, Ding H, Liang M, Chen X, Yan Y, Wan N, et al. Curcumin induces ferroptosis in non-small-cell lung cancer via activating autophagy. Thoracic Cancer. 2021; 12: 1219–1230.
[14] Wei Z, Shaohuan Q, Pinfang K, Chao S. Curcumin attenuates ferroptosis-induced myocardial injury in diabetic cardiomyopathy through the Nrf2 pathway. Cardiovascular Therapeutics. 2022; 2022: 3159717.
[15] Karimi A, Naeini F, Niazkar HR, Tutunchi H, Musazadeh V, Mahmoodpoor A, et al. Nano-curcumin supplementation in critically ill patients with sepsis: a randomized clinical trial investigating the inflammatory biomarkers, oxidative stress indices, endothelial function, clinical outcomes and nutritional status. Food & Function. 2022; 13: 6596–6612.
[16] Zhong W, Qian K, Xiong J, Ma K, Wang A, Zou Y. Curcumin alleviates lipopolysaccharide induced sepsis and liver failure by suppression of oxidative stress-related inflammation via PI3K/AKT and NF-κB related signaling. Biomedicine & Pharmacotherapy. 2016; 83: 302–313.
[17] Cao G, Zeng Y, Zhao Y, Lin L, Luo X, Guo L, et al. H2S regulation of ferroptosis attenuates sepsis-induced cardiomyopathy. Molecular Medicine Reports. 2022; 26: 335.
[18] Merx MW, Weber C. Sepsis and the heart. Circulation. 2007; 116: 793–802.
[19] Lu X, Wang J, Chen X, Jiang Y, Pan ZK. Rolipram protects mice from Gram-negative bacterium Escherichia coli-induced inflammation and septic shock. Scientific Reports. 2020; 10: 175.
[20] Xu J, Lin C, Wang T, Zhang P, Liu Z, Lu C. Ergosterol attenuates LPS-induced myocardial injury by modulating oxidative stress and apoptosis in rats. Cellular Physiology and Biochemistry. 2018; 48: 583–592.
[21] Chen L, Liu P, Feng X, Ma C. Salidroside suppressing LPS-induced myocardial injury by inhibiting ROS‐mediated PI3K/Akt/mTOR pathway in vitro and in vivo. Journal of Cellular and Molecular Medicine. 2017; 21: 3178–3189.
[22] Wang R, Li D, Ouyang J, Tian X, Zhao Y, Peng X, et al. Leonurine alleviates LPS-induced myocarditis through suppressing the NF-кB signaling pathway. Toxicology. 2019; 422: 1–13.
[23] Fujisawa S, Atsumi T, Ishihara M, Kadoma Y. Cytotoxicity, ROS-generation activity and radical-scavenging activity of curcumin and related compounds. Anticancer Research. 2004; 24: 563–569.
[24] Li H, Sureda A, Devkota HP, Pittalà V, Barreca D, Silva AS, et al. Curcumin, the golden spice in treating cardiovascular diseases. Biotechnology Advances. 2020; 38: 107343.
[25] Chousterman BG, Swirski FK, Weber GF. Cytokine storm and sepsis disease pathogenesis. Seminars in Immunopathology. 2017; 39: 517–528.
[26] Zhu H, Zhang L, Jia H, Xu L, Cao Y, Zhai M, et al. Tetrahydrocurcumin improves lipopolysaccharide-induced myocardial dysfunction by inhibiting oxidative stress and inflammation via JNK/ERK signaling pathway regulation. Phytomedicine. 2022; 104: 154283.
[27] Yin X, Zhu G, Wang Q, Fu YD, Wang J, Xu B. Ferroptosis, a new insight into acute lung injury. Frontiers in Pharmacology. 2021; 12: 709538.
[28] Xie Y, Hou W, Song X, Yu Y, Huang J, Sun X, et al. Ferroptosis: process and function. Cell Death & Differentiation. 2016; 23: 369–379.
[29] Fang X, Wang H, Han D, Xie E, Yang X, Wei J, et al. Ferroptosis as a target for protection against cardiomyopathy. Proceedings of the National Academy of Sciences. 2019; 116: 2672–2680.
[30] Li N, Wang W, Zhou H, Wu Q, Duan M, Liu C, et al. Ferritinophagy-mediated ferroptosis is involved in sepsis-induced cardiac injury. Free Radical Biology and Medicine. 2020; 160: 303–318.
[31] Dodson M, Castro-Portuguez R, Zhang DD. NRF2 plays a critical role in mitigating lipid peroxidation and ferroptosis. Redox Biology. 2019; 23: 101107.
[32] Andreas M, Oeser C, Kainz F, Shabanian S, Aref T, Bilban M, et al. Intravenous heme arginate induces HO-1 (Heme Oxygenase-1) in the human heart. Arteriosclerosis, Thrombosis, and Vascular Biology. 2018; 38: 2755–2762.
[33] Wu X, Zhou X, Lai S, Liu J, Qi J. Curcumin activates Nrf2/HO‐1 signaling to relieve diabetic cardiomyopathy injury by reducing ROS in vitro and in vivo. The FASEB Journal. 2022; 36: e22505.
Science Citation Index Expanded (SciSearch) Created as SCI in 1964, Science Citation Index Expanded now indexes over 9,200 of the world’s most impactful journals across 178 scientific disciplines. More than 53 million records and 1.18 billion cited references date back from 1900 to present.
Journal Citation Reports/Science Edition Journal Citation Reports/Science Edition aims to evaluate a journal’s value from multiple perspectives including the journal impact factor, descriptive data about a journal’s open access content as well as contributing authors, and provide readers a transparent and publisher-neutral data & statistics information about the journal.
Chemical Abstracts Service Source Index The CAS Source Index (CASSI) Search Tool is an online resource that can quickly identify or confirm journal titles and abbreviations for publications indexed by CAS since 1907, including serial and non-serial scientific and technical publications.
Index Copernicus The Index Copernicus International (ICI) Journals database’s is an international indexation database of scientific journals. It covered international scientific journals which divided into general information, contents of individual issues, detailed bibliography (references) sections for every publication, as well as full texts of publications in the form of attached files (optional). For now, there are more than 58,000 scientific journals registered at ICI.
Geneva Foundation for Medical Education and Research The Geneva Foundation for Medical Education and Research (GFMER) is a non-profit organization established in 2002 and it works in close collaboration with the World Health Organization (WHO). The overall objectives of the Foundation are to promote and develop health education and research programs.
Scopus: CiteScore 1.3 (2023) Scopus is Elsevier's abstract and citation database launched in 2004. Scopus covers nearly 36,377 titles (22,794 active titles and 13,583 Inactive titles) from approximately 11,678 publishers, of which 34,346 are peer-reviewed journals in top-level subject fields: life sciences, social sciences, physical sciences and health sciences.
Embase Embase (often styled EMBASE for Excerpta Medica dataBASE), produced by Elsevier, is a biomedical and pharmacological database of published literature designed to support information managers and pharmacovigilance in complying with the regulatory requirements of a licensed drug.
Top