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Journal of Inflammation
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Open Access 01-12-2024 | Septicemia | Research

Carvacrol alleviates LPS-induced myocardial dysfunction by inhibiting the TLR4/MyD88/NF-κB and NLRP3 inflammasome in cardiomyocytes

Authors: Lu Xu, Xu Yang, Xiao-Ting Liu, Xia-Yun Li, Han-Zhao Zhu, Yan-Hua Xie, Si-Wang Wang, Yao Li, Ye Zhao

Published in: Journal of Inflammation | Issue 1/2024

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Abstract

Background

Sepsis-induced myocardial dysfunction (SIMD) may contribute to the poor prognosis of septic patients. Carvacrol (2-methyl-5-isopropyl phenol), a phenolic monoterpene compound extracted from various aromatic plants and fragrance essential oils, has multiple beneficial effects such as antibacterial, anti-inflammatory, and antioxidant properties. These attributes make it potentially useful for treating many diseases. This study aims to investigate the effects of CAR on LPS-induced myocardial dysfunction and explore the underlying mechanism.

Results

H9c2 cells were stimulated with 10 µg/ml LPS for 12 h, and c57BL/6 mice were intraperitoneally injected with 10 mg/kg LPS to establish a septic-myocardial injury model. Our results showed that CAR could improve cardiac function, significantly reduce serum levels of inflammatory cytokines (including TNF-α, IL-1β, and IL-6), decrease oxidative stress, and inhibit cardiomyocyte apoptosis in LPS-injured mice. Additionally, CAR significantly downregulated the expression of TLR4, MyD88, and NF-κB in LPS-injured mice and H9c2 cells. It also inhibited the upregulation of inflammasome components (such as NLRP3, GSDMD, and IL-1β) in H9c2 cells triggered by LPS.

Conclusion

Taken together, CAR exhibited potential cardioprotective effects against sepsis, which may be mainly attributed to the TLR4/MyD88/NF-κB pathway and the NLRP3 inflammasome.
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Literature
1.
Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, Bellomo R, Bernard GR, Chiche JD, Coopersmith CM, Hotchkiss RS, Levy MM, Marshall JC, Martin GS, Opal SM, Rubenfeld GD, van der Poll T. JL Vincent, DC Angus. The Third International Consensus definitions for Sepsis and septic shock (Sepsis-3). JAMA. 2016;315:801–10.PubMedPubMedCentralCrossRef
2.
3.
4.
Hollenberg SM, Singer M. Pathophysiology of sepsis-induced cardiomyopathy. Nat Rev Cardiol. 2021;18:424–34.PubMedCrossRef
5.
Lin Y, Xu Y, Zhang Z. Sepsis-Induced Myocardial Dysfunction (SIMD): the pathophysiological mechanisms and therapeutic strategies targeting Mitochondria. Inflammation. 2020;43:1184–200.PubMedCrossRef
6.
Khosrojerdi A, Soudi S, Hosseini AZ, Khaligh SG, Hashemi SM. The combination of mesenchymal stem cell- and hepatocyte-derived exosomes, along with imipenem, ameliorates inflammatory responses and liver damage in a sepsis mouse model. Life Sci. 2023;326:121813.PubMedCrossRef
7.
Avlas O, Fallach R, Shainberg A, Porat E, Hochhauser E. Toll-like receptor 4 stimulation initiates an inflammatory response that decreases cardiomyocyte contractility. Antioxid Redox Signal. 2011;15:1895–909.PubMedCrossRef
8.
Li N, Zhou H, Wu H, Wu Q, Duan M, Deng W, Tang Q. STING-IRF3 contributes to lipopolysaccharide-induced cardiac dysfunction, inflammation, apoptosis and pyroptosis by activating NLRP3. Redox Biol. 2019;24:101215.PubMedPubMedCentralCrossRef
9.
Maldonado RF, Sá-Correia I, Valvano MA. Lipopolysaccharide modification in Gram-negative bacteria during chronic infection. FEMS Microbiol Rev. 2016;40:480–93.PubMedPubMedCentralCrossRef
10.
Kuzmich NN, Sivak KV, Chubarev VN, Porozov YB, Savateeva-Lyubimova TN, Peri F. TLR4 signaling pathway modulators as potential therapeutics in inflammation and Sepsis. Vaccines (Basel). 2017;5.
11.
Faria SS, Costantini S, de Lima VCC, de Andrade VP, Rialland M, Cedric R, Budillon A, Magalhães KG. NLRP3 inflammasome-mediated cytokine production and pyroptosis cell death in breast cancer. J Biomed Sci. 2021;28:26.
12.
An N, Gao Y, Si Z, Zhang H, Wang L, Tian C, Yuan M, Yang X, Li X, Shang H, Xiong X, Xing Y. Regulatory mechanisms of the NLRP3 Inflammasome, a Novel Immune-inflammatory marker in Cardiovascular diseases. Front Immunol. 2019;10:1592.PubMedPubMedCentralCrossRef
13.
Dai S, Ye B, Chen L, Hong G, Zhao G, Lu Z. Emodin alleviates LPS-induced myocardial injury through inhibition of NLRP3 inflammasome activation. Phytother Res. 2021;35:5203–13.PubMedCrossRef
14.
Sharifi-Rad M, Varoni EM, Iriti M, Martorell M, Setzer WN, Del Mar M, Contreras B, Salehi A, Soltani-Nejad S, Rajabi M, Tajbakhsh J. Sharifi-Rad. Carvacrol and human health: a comprehensive review. Phytother Res. 2018;32:1675–87.PubMedCrossRef
15.
16.
Suntres ZE, Coccimiglio J, Alipour M. The bioactivity and toxicological actions of carvacrol. Crit Rev Food Sci Nutr. 2015;55:304–18.PubMedCrossRef
17.
Khan F, Khan I, Farooqui A, Ansari IA. Carvacrol Induces Reactive Oxygen Species (ROS)-mediated apoptosis along with cell cycle arrest at G(0)/G(1) in human prostate Cancer cells. Nutr Cancer. 2017;69:1075–87.PubMedCrossRef
18.
Khan F, Singh VK, Saeed M, Kausar MA, Ansari IA. Carvacrol Induced Program Cell death and cell cycle arrest in androgen-independent human prostate Cancer cells via inhibition of Notch Signaling. Anticancer Agents Med Chem. 2019;19:1588–608.PubMedCrossRef
19.
Liu SD, Song MH, Yun W, Lee JH, Kim HB, Cho JH. Effect of carvacrol essential oils on immune response and inflammation-related genes expression in broilers challenged by lipopolysaccharide. Poult Sci. 2019;98:2026–33.PubMedCrossRef
20.
Guan X, Li X, Yang X, Yan J, Shi P, Ba L, Cao Y, Wang P. The neuroprotective effects of carvacrol on ischemia/reperfusion-induced hippocampal neuronal impairment by ferroptosis mitigation. Life Sci. 2019;235:116795.PubMedCrossRef
21.
De Vincenzi M, Stammati A, De Vincenzi A, Silano M. Constituents of aromatic plants: carvacrol. Fitoterapia. 2004;75:801–4.PubMedCrossRef
22.
23.
Chen Y, Ba L, Huang W, Liu Y, Pan H, Mingyao E, Shi P, Wang Y, Li S, Qi H, Sun H, Cao Y. Role of carvacrol in cardioprotection against myocardial ischemia/reperfusion injury in rats through activation of MAPK/ERK and Akt/eNOS signaling pathways. Eur J Pharmacol. 2017;796:90–100.PubMedCrossRef
24.
Yu W, Liu Q, Zhu S. Carvacrol protects against acute myocardial infarction of rats via anti-oxidative and anti-apoptotic pathways. Biol Pharm Bull. 2013;36:579–84.PubMedCrossRef
25.
Jafarinezhad Z, Rafati A, Ketabchi F, Noorafshan A, Karbalay-Doust S. Cardioprotective effects of curcumin and carvacrol in doxorubicin-treated rats: stereological study. Food Sci Nutr. 2019;7:3581–8.PubMedPubMedCentralCrossRef
26.
El-Sayed SM el, Mansour AM, Abdul-Hameed MS. Thymol and Carvacrol Prevent Doxorubicin-Induced cardiotoxicity by abrogation of oxidative stress, inflammation, and apoptosis in rats. J Biochem Mol Toxicol. 2016;30:37–44.
27.
Marconi GD, Della Rocca Y, Fonticoli L, Guarnieri S, Carradori S, Rajan TS, Pizzicannella J, Diomede F. The Beneficial Effect of Carvacrol in HL-1 cardiomyocytes treated with LPS-G: anti-inflammatory pathway investigations. Antioxid (Basel). 2022;11.
28.
Ning L, Rong J, Zhang Z, Xu Y. Therapeutic approaches targeting renin-angiotensin system in sepsis and its complications. Pharmacol Res. 2021;167:105409.PubMedCrossRef
29.
Zhang Y, Liang X, Bao X, Xiao W, Chen G. Toll-like receptor 4 (TLR4) inhibitors: current research and prospective. Eur J Med Chem. 2022;235:114291.PubMedCrossRef
30.
Saljoughian S, Roohinejad S, Bekhit AEA, Greiner R, Omidizadeh A, Nikmaram N, Khaneghah AM. The effects of food essential oils on cardiovascular diseases: a review. Crit Rev Food Sci Nutr. 2018;58:1688–705.PubMedCrossRef
31.
Riaz M, Al Kury LT, Atzaz N, Alattar A, Alshaman R, Shah FA, Li S. Carvacrol alleviates Hyperuricemia-Induced oxidative stress and inflammation by modulating the NLRP3/NF-κB Pathwayt. Drug Des Devel Ther. 2022;16:1159–70.PubMedPubMedCentralCrossRef
32.
Wijesundara NM, Lee SF, Cheng Z, Davidson R, Rupasinghe HPV. Carvacrol exhibits rapid bactericidal activity against Streptococcus pyogenes through cell membrane damage. Sci Rep. 2021;11:1487.PubMedPubMedCentralCrossRef
33.
Wijesundara NM, Lee SF, Davidson R, Cheng Z, Rupasinghe HPV. Carvacrol suppresses inflammatory biomarkers production by Lipoteichoic Acid- and peptidoglycan-stimulated human tonsil epithelial cells. Nutrients. 2022;14.
34.
Yan C, Kuang W, Jin L, Wang R, Niu L, Xie C, Ding J, Liao Y, Wang L, Wan H, Ma G. Carvacrol protects mice against LPS-induced sepsis and attenuates inflammatory response in macrophages by modulating the ERK1/2 pathway. Sci Rep. 2023;13:12809.PubMedPubMedCentralCrossRef
35.
Joshi S, Kundu S, Priya VV, Kulhari U, Mugale MN, Sahu BD. Anti-inflammatory activity of carvacrol protects the heart from lipopolysaccharide-induced cardiac dysfunction by inhibiting pyroptosis via NLRP3/Caspase1/Gasdermin D signaling axis. Life Sci. 2023;324:121743.PubMedCrossRef
36.
Guo S, Guo L, Fang Q, Yu M, Zhang L, You C, Wang X, Liu Y, Han C. Astaxanthin protects against early acute kidney injury in severely burned rats by inactivating the TLR4/MyD88/NF-κB axis and upregulating heme oxygenase-1. Sci Rep. 2021;11:6679.PubMedPubMedCentralCrossRef
37.
Li Y, Wang N, Ma Z, Wang Y, Yuan Y, Zhong Z, Hong Y, Zhao M. Lipoxin A4 protects against paraquat–induced acute lung injury by inhibiting the TLR4/MyD88–mediated activation of the NF–κB and PI3K/AKT pathways. Int J Mol Med. 2021;47.
38.
39.
40.
Shyni GL, Renjitha J, Raghu BSSKG. Zerumin A attenuates the inflammatory responses in LPS-stimulated H9c2 cardiomyoblasts. J Biochem Mol Toxicol. 2021;35:1–11.PubMedCrossRef
41.
Zhang J, Wang M, Ye J, Liu J, Xu Y, Wang Z, Ye D, Zhao M, Wan J. The anti-inflammatory mediator resolvin E1 protects mice against Lipopolysaccharide-Induced Heart Injury. Front Pharmacol. 2020;11:203.PubMedPubMedCentralCrossRef
42.
Kumar V. Toll-like receptors in sepsis-associated cytokine storm and their endogenous negative regulators as future immunomodulatory targets. Int Immunopharmacol. 2020;89:107087.PubMedPubMedCentralCrossRef
43.
Li Y, Liu X. The inhibitory role of Chinese materia medica in cardiomyocyte apoptosis and underlying molecular mechanism. Biomed Pharmacother. 2019;118:109372.PubMedCrossRef
44.
Li P, Dong X-R, Zhang B, Zhang X-T, Liu J-Z, Ma D-S, Ma L. Molecular mechanism and therapeutic targeting of necrosis, apoptosis, pyroptosis, and autophagy in cardiovascular disease. Chin Med J. 2021;134.
45.
Li P, Dong XR, Zhang B, Zhang XT, Liu JZ, Ma DS, Ma L. Molecular mechanism and therapeutic targeting of necrosis, apoptosis, pyroptosis, and autophagy in cardiovascular disease. Chin Med J (Engl). 2021;134:2647–55.PubMedCrossRef
46.
Peña-Blanco A, García-Sáez AJ. Bax, Bak and beyond - mitochondrial performance in apoptosis. FEBS J. 2018;285:416–31.PubMedCrossRef
47.
Song W, Wei L, Du Y, Wang Y, Jiang S. Protective effect of ginsenoside metabolite compound K against diabetic nephropathy by inhibiting NLRP3 inflammasome activation and NF-κB/p38 signaling pathway in high-fat diet/streptozotocin-induced diabetic mice. Int Immunopharmacol. 2018;63:227–38.PubMedCrossRef
48.
Liu Q, Zhang D, Hu D, Zhou X, Zhou Y. The role of mitochondria in NLRP3 inflammasome activation. Mol Immunol. 2018;103:115–24.PubMedCrossRef
49.
Yu X, Lan P, Hou X, Han Q, Lu N, Li T, Jiao C, Zhang J, Zhang C, Tian Z. HBV inhibits LPS-induced NLRP3 inflammasome activation and IL-1β production via suppressing the NF-κB pathway and ROS production. J Hepatol. 2017;66:693–702.PubMedCrossRef
50.
Garnacho-Montero J, Palacios-García I, Díaz-Martín A, Gutiérrez-Pizarraya A, López-Sánchez JM. EA Gómez, MD Cordero. Sequential changes of NLRP3 inflammasome activation in Sepsis and its relationship with death. Shock. 2020;54:294–300.PubMedCrossRef
51.
52.
Burzynski LC, Clarke MCH. Death is coming and the clot thickens, as pyroptosis feeds the fire. Immunity. 2019;50:1339–41.PubMedCrossRef
53.
McKenzie BA, Mamik MK, Saito LB, Boghozian R, Monaco MC, Major EO, Lu JQ, Branton WG, Power C. Caspase-1 inhibition prevents glial inflammasome activation and pyroptosis in models of multiple sclerosis. Proc Natl Acad Sci U S A. 2018;115:E6065–74.PubMedPubMedCentralCrossRef
Metadata
Title
Carvacrol alleviates LPS-induced myocardial dysfunction by inhibiting the TLR4/MyD88/NF-κB and NLRP3 inflammasome in cardiomyocytes
Authors
Lu Xu
Xu Yang
Xiao-Ting Liu
Xia-Yun Li
Han-Zhao Zhu
Yan-Hua Xie
Si-Wang Wang
Yao Li
Ye Zhao
Publication date
01-12-2024
Publisher
BioMed Central
Published in
Journal of Inflammation / Issue 1/2024
Electronic ISSN: 1476-9255
DOI
https://doi.org/10.1186/s12950-024-00411-z

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