Allicin Protects Against LPS-induced Cardiomyocyte Injury by Activating Nrf2-HO-1 and Inhibiting NLRP3 Pathways

Overview

Journal BMC Cardiovasc Disord

Publisher Biomed Central

Specialty Cardiology & Vascular Diseases

Date 2023 Aug 18

PMID 37596540

Authors

Fangyuan Sun

Kailiang Xu

Jiayi Zhou

Wei Zhang

Guihe Duan

Ming Lei

Affiliations

Soon will be listed here.

Abstract

Background: Allicin is a bioactive compound with potent antioxidative activity and plays a protective effect in myocardial damage and fibrosis. The role and mechanism of Allicin in septic cardiomyopathy are unclear. In this study, we investigated the effects and underlying mechanisms of Allicin on lipopolysaccharide (LPS) induced injury in H9c2 cardiomyocytes.

Methods: H9c2 cardiomyocyte cells were pretreated with Allicin (0, 25, 50, and 100 µM) for 2 h, followed by incubation with LPS (10 µg/mL) for 24 h at 37 °C. Cell viability (cell counting kit-8 [CCK-8]), apoptosis (TUNEL staining), oxidative stress (malondialdehyde [MDA] and superoxide dismutase [SOD]), and cytokines release (Interleukin beta [IL-β], Interleukin 6 [IL-6], and tumor necrosis factor-alpha [TNF-α]) were determined. The mRNA and protein expression of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and NLR family pyrin domain containing 3 (NLRP3) signaling pathway molecules were quantified by real-time quantitative PCR (RT-qPCR) and western blot, respectively.

Results: Allicin had no effect on H9c2 cell viability but attenuated LPS-induced injury, with increased cell viability, reduction in inflammatory cytokines release, apoptosis, reduced MDA, and increased SOD (P < 0.05). Additionally, Allicin increased Nrf2 and cellular HO-1 expressions in LPS-treated H9c2 cells. Moreover, Allicin modulated the NLRP3 inflammasome, increased the cleaved caspase-1 (p10) protein, and attenuated the LPS-induced increase in NLRP3, pro-IL-1β, and IL-1β proteins. Silencing of Nrf2 by siRNA (siNrf2) significantly attenuated Allicin-induced increase in cell viability and HO-1 and decrease in NLRP3 protein in LPS-stimulated H9c2 cells.

Conclusions: Allicin protects cardiomyocytes against LPS‑induced injury through activation of Nrf2/HO-1 and inhibition of NLRP3 signaling pathways.

Citing Articles

Therapeutic potentials of allicin in cardiovascular disease: advances and future directions.

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References

Vincent J . The Clinical Challenge of Sepsis Identification and Monitoring. PLoS Med. 2016; 13(5):e1002022. PMC: 4871479. DOI: 10.1371/journal.pmed.1002022. View

Tsiotou A, Sakorafas G, Anagnostopoulos G, Bramis J . Septic shock; current pathogenetic concepts from a clinical perspective. Med Sci Monit. 2005; 11(3):RA76-85. View

Rudd K, Johnson S, Agesa K, Shackelford K, Tsoi D, Kievlan D . Global, regional, and national sepsis incidence and mortality, 1990-2017: analysis for the Global Burden of Disease Study. Lancet. 2020; 395(10219):200-211. PMC: 6970225. DOI: 10.1016/S0140-6736(19)32989-7. View

Walley K . Sepsis-induced myocardial dysfunction. Curr Opin Crit Care. 2018; 24(4):292-299. DOI: 10.1097/MCC.0000000000000507. View

Kong W, Kang K, Gao Y, Liu H, Meng X, Yang S . Dexmedetomidine alleviates LPS-induced septic cardiomyopathy via the cholinergic anti-inflammatory pathway in mice. Am J Transl Res. 2017; 9(11):5040-5047. PMC: 5714788. View

Xu X, Liu Q, He S, Zhao J, Wang N, Han X . Qiang-Xin 1 Formula Prevents Sepsis-Induced Apoptosis in Murine Cardiomyocytes by Suppressing Endoplasmic Reticulum- and Mitochondria-Associated Pathways. Front Pharmacol. 2018; 9:818. PMC: 6077999. DOI: 10.3389/fphar.2018.00818. View

Zhou N, Zeng M, Li K, Yang Y, Bai Z, Zheng X . An integrated metabolomic strategy for the characterization of the effects of Chinese yam and its three active components on septic cardiomyopathy. Food Funct. 2018; 9(9):4989-4997. DOI: 10.1039/c8fo00688a. View

Tsolaki V, Makris D, Mantzarlis K, Zakynthinos E . Sepsis-Induced Cardiomyopathy: Oxidative Implications in the Initiation and Resolution of the Damage. Oxid Med Cell Longev. 2017; 2017:7393525. PMC: 5625757. DOI: 10.1155/2017/7393525. View

Chen D, Jin Z, Zhang J, Jiang L, Chen K, He X . HO-1 Protects against Hypoxia/Reoxygenation-Induced Mitochondrial Dysfunction in H9c2 Cardiomyocytes. PLoS One. 2016; 11(5):e0153587. PMC: 4854406. DOI: 10.1371/journal.pone.0153587. View

10.

Jiang C, Zhuang C, Zhu K, Zhang J, Muehlmann L, Figueiro Longo J . Identification of a novel small-molecule Keap1-Nrf2 PPI inhibitor with cytoprotective effects on LPS-induced cardiomyopathy. J Enzyme Inhib Med Chem. 2018; 33(1):833-841. PMC: 6009974. DOI: 10.1080/14756366.2018.1461856. View

11.

Zhou R, Yazdi A, Menu P, Tschopp J . A role for mitochondria in NLRP3 inflammasome activation. Nature. 2010; 469(7329):221-5. DOI: 10.1038/nature09663. View

12.

Kalbitz M, Fattahi F, Grailer J, Jajou L, Malan E, Zetoune F . Complement-induced activation of the cardiac NLRP3 inflammasome in sepsis. FASEB J. 2016; 30(12):3997-4006. PMC: 5102118. DOI: 10.1096/fj.201600728R. View

13.

Zhang W, Tao A, Lan T, Cepinskas G, Kao R, Martin C . Carbon monoxide releasing molecule-3 improves myocardial function in mice with sepsis by inhibiting NLRP3 inflammasome activation in cardiac fibroblasts. Basic Res Cardiol. 2017; 112(2):16. DOI: 10.1007/s00395-017-0603-8. View

14.

Yang L, Zhang H, Chen P . Sulfur dioxide attenuates sepsis-induced cardiac dysfunction via inhibition of NLRP3 inflammasome activation in rats. Nitric Oxide. 2018; 81:11-20. DOI: 10.1016/j.niox.2018.09.005. View

15.

Hayat S, Cheng Z, Ahmad H, Ali M, Chen X, Wang M . Garlic, from Remedy to Stimulant: Evaluation of Antifungal Potential Reveals Diversity in Phytoalexin Allicin Content among Garlic Cultivars; Allicin Containing Aqueous Garlic Extracts Trigger Antioxidants in Cucumber. Front Plant Sci. 2016; 7:1235. PMC: 4996993. DOI: 10.3389/fpls.2016.01235. View

16.

Ma L, Li L, Li S, Hao X, Zhang J, He P . Allicin improves cardiac function by protecting against apoptosis in rat model of myocardial infarction. Chin J Integr Med. 2016; 23(8):589-597. DOI: 10.1007/s11655-016-2523-0. View

17.

Liu Y, Qi H, Wang Y, Wu M, Cao Y, Huang W . Allicin protects against myocardial apoptosis and fibrosis in streptozotocin-induced diabetic rats. Phytomedicine. 2012; 19(8-9):693-8. DOI: 10.1016/j.phymed.2012.04.007. View

18.

Ba L, Gao J, Chen Y, Qi H, Dong C, Pan H . Allicin attenuates pathological cardiac hypertrophy by inhibiting autophagy via activation of PI3K/Akt/mTOR and MAPK/ERK/mTOR signaling pathways. Phytomedicine. 2019; 58:152765. DOI: 10.1016/j.phymed.2018.11.025. View

19.

Livak K, Schmittgen T . Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 2002; 25(4):402-8. DOI: 10.1006/meth.2001.1262. View

20.

Zhang B, Li F, Zhao W, Li J, Li Q, Wang W . Protective effects of allicin against ischemic stroke in a rat model of middle cerebral artery occlusion. Mol Med Rep. 2015; 12(3):3734-3738. DOI: 10.3892/mmr.2015.3883. View