Cardioprotective Potential of Cymbopogon Citratus Essential Oil Against Isoproterenol-induced Cardiomyocyte Hypertrophy: Possible Involvement of NLRP3 Inflammasome and Oxidative Phosphorylation Complex Subunits

Overview

Journal Curr Med Sci

Specialty General Medicine

Date 2024 Apr 19

PMID 38639827

Authors

Xiao-Yun Ding

Hao Zhang

Yu-Mei Qiu

Meng-Die Xie

Hu Wang

Zheng-Yu Xiong

Ting-Ting Li

Chun-Ni He

Wei Dong

Xi-Lan Tang

Affiliations

Soon will be listed here.

Abstract

Objective: Cymbopogon citratus (DC.) Stapf is a medicinal and edible herb that is widely used for the treatment of gastric, nervous and hypertensive disorders. In this study, we investigated the cardioprotective effects and mechanisms of the essential oil, the main active ingredient of Cymbopogon citratus, on isoproterenol (ISO)-induced cardiomyocyte hypertrophy.

Methods: The compositions of Cymbopogon citratus essential oil (CCEO) were determined by gas chromatography-mass spectrometry. Cardiomyocytes were pretreated with 16.9 µg/L CCEO for 1 h followed by 10 µmol/L ISO for 24 h. Cardiac hypertrophy-related indicators and NLRP3 inflammasome expression were evaluated. Subsequently, transcriptome sequencing (RNA-seq) and target verification were used to further explore the underlying mechanism.

Results: Our results showed that the CCEO mainly included citronellal (45.66%), geraniol (23.32%), and citronellol (10.37%). CCEO inhibited ISO-induced increases in cell surface area and protein content, as well as the upregulation of fetal gene expression. Moreover, CCEO inhibited ISO-induced NLRP3 inflammasome expression, as evidenced by decreased lactate dehydrogenase content and downregulated mRNA levels of NLRP3, ASC, CASP1, GSDMD, and IL-1β, as well as reduced protein levels of NLRP3, ASC, pro-caspase-1, caspase-1 (p20), GSDMD-FL, GSDMD-N, and pro-IL-1β. The RNA-seq results showed that CCEO inhibited the increase in the mRNA levels of 26 oxidative phosphorylation complex subunits in ISO-treated cardiomyocytes. Our further experiments confirmed that CCEO suppressed ISO-induced upregulation of mt-Nd1, Sdhd, mt-Cytb, Uqcrq, and mt-Atp6 but had no obvious effects on mt-Col expression.

Conclusion: CCEO inhibits ISO-induced cardiomyocyte hypertrophy through the suppression of NLRP3 inflammasome expression and the regulation of several oxidative phosphorylation complex subunits.

References

Yang J, Chen Y, Li X, Xu D . New insights into the roles of glucocorticoid signaling dysregulation in pathological cardiac hypertrophy. Heart Fail Rev. 2021; 27(4):1431-1441. DOI: 10.1007/s10741-021-10158-x. View

Chai R, Xue W, Shi S, Zhou Y, Du Y, Li Y . Cardiac Remodeling in Heart Failure: Role of Pyroptosis and Its Therapeutic Implications. Front Cardiovasc Med. 2022; 9:870924. PMC: 9058112. DOI: 10.3389/fcvm.2022.870924. View

Ekpenyong C, Akpan E, Nyoh A . Ethnopharmacology, phytochemistry, and biological activities of Cymbopogon citratus (DC.) Stapf extracts. Chin J Nat Med. 2015; 13(5):321-37. DOI: 10.1016/S1875-5364(15)30023-6. View

Salaria D, Rolta R, Sharma N, Patel C, Ghosh A, Dev K . and antioxidant and anti-inflammatory potential of essential oil of (DC.) Stapf. of North-Western Himalaya. J Biomol Struct Dyn. 2021; 40(24):14131-14145. DOI: 10.1080/07391102.2021.2001371. View

Li C, Luo Y, Zhang W, Cai Q, Wu X, Tan Z . A comparative study on chemical compositions and biological activities of four essential oils: Cymbopogon citratus (DC.) Stapf, Cinnamomum cassia (L.) Presl, Salvia japonica Thunb. and Rosa rugosa Thunb. J Ethnopharmacol. 2021; 280:114472. DOI: 10.1016/j.jep.2021.114472. View

Lu J, Qiu Y, Guo L, Song P, Xu J, Wan G . Potential Therapeutic Effect of Citronellal on Diabetic Cardiomyopathy in Experimental Rats. Evid Based Complement Alternat Med. 2021; 2021:9987531. PMC: 8612793. DOI: 10.1155/2021/9987531. View

Liu X, Qiu Y, Huang N, Liu Y, Wang H, Yu Y . Citronellal alleviates doxorubicin-induced cardiotoxicity by suppressing oxidative stress and apoptosis via Na /H exchanger-1 inhibition. J Biochem Mol Toxicol. 2021; 36(3):e22971. DOI: 10.1002/jbt.22971. View

Rhana P, Barros G, Santos V, Costa A, Dos Santos D, Fernandes-Braga W . S-limonene protects the heart in an experimental model of myocardial infarction induced by isoproterenol: Possible involvement of mitochondrial reactive oxygen species. Eur J Pharmacol. 2022; 930:175134. DOI: 10.1016/j.ejphar.2022.175134. View

Li H, Qiu Y, Xie M, Ouyang C, Ding X, Zhang H . Momordicine I alleviates isoproterenol-induced cardiomyocyte hypertrophy through suppression of PLA2G6 and DGK-ζ. Korean J Physiol Pharmacol. 2022; 27(1):75-84. PMC: 9806645. DOI: 10.4196/kjpp.2023.27.1.75. View

10.

Bastos J, Moreira I, Ribeiro T, Medeiros I, Antoniolli A, de Sousa D . Hypotensive and vasorelaxant effects of citronellol, a monoterpene alcohol, in rats. Basic Clin Pharmacol Toxicol. 2009; 106(4):331-7. DOI: 10.1111/j.1742-7843.2009.00492.x. View

11.

Zou G, Wan J, Balupillai A, David E, Ranganathan B, Saravanan K . Geraniol enhances peroxiredoxin-1, and prevents isoproterenol-induced oxidative stress and inflammation associated with myocardial infarction in experimental animal models. J Biochem Mol Toxicol. 2022; 36(8):e23098. DOI: 10.1002/jbt.23098. View

12.

Bai C, Ma Q, Li Q, Yu L, Zhen D, Liu M . Combination of 1,8-cineole and beta-caryophyllene synergistically reverses cardiac hypertrophy in isoprenaline-induced mice and H9c2 cells. Bioorg Chem. 2022; 124:105823. DOI: 10.1016/j.bioorg.2022.105823. View

13.

Althurwi H, Abdel-Kader M, Alharthy K, Salkini M, Albaqami F . Cymbopogon Proximus Essential Oil Protects Rats against Isoproterenol-Induced Cardiac Hypertrophy and Fibrosis. Molecules. 2020; 25(8). PMC: 7221672. DOI: 10.3390/molecules25081786. View

14.

Liao Y, Liu K, Zhu L . Emerging Roles of Inflammasomes in Cardiovascular Diseases. Front Immunol. 2022; 13:834289. PMC: 9021369. DOI: 10.3389/fimmu.2022.834289. View

15.

Zhao M, Zhang J, Xu Y, Liu J, Ye J, Wang Z . Selective Inhibition of NLRP3 Inflammasome Reverses Pressure Overload-Induced Pathological Cardiac Remodeling by Attenuating Hypertrophy, Fibrosis, and Inflammation. Int Immunopharmacol. 2021; 99:108046. DOI: 10.1016/j.intimp.2021.108046. View

16.

Shi Y, Zhao L, Wang J, Liu S, Zhang Y, Qin Q . The selective NLRP3 inflammasome inhibitor MCC950 improves isoproterenol-induced cardiac dysfunction by inhibiting cardiomyocyte senescence. Eur J Pharmacol. 2022; 937:175364. DOI: 10.1016/j.ejphar.2022.175364. View

17.

Xin J, Wu J, Hu G, Gu H, Feng Y, Wang S . α-AR overactivation induces cardiac inflammation through NLRP3 inflammasome activation. Acta Pharmacol Sin. 2019; 41(3):311-318. PMC: 7468364. DOI: 10.1038/s41401-019-0305-x. View

18.

Yue R, Zheng Z, Luo Y, Wang X, Lv M, Qin D . NLRP3-mediated pyroptosis aggravates pressure overload-induced cardiac hypertrophy, fibrosis, and dysfunction in mice: cardioprotective role of irisin. Cell Death Discov. 2021; 7(1):50. PMC: 7961005. DOI: 10.1038/s41420-021-00434-y. View

19.

Xu Z, Zhou X, Hong X, Wang S, Wei J, Huang J . Essential oil of Acorus tatarinowii Schott inhibits neuroinflammation by suppressing NLRP3 inflammasome activation in 3 × Tg-AD transgenic mice. Phytomedicine. 2023; 112:154695. DOI: 10.1016/j.phymed.2023.154695. View

20.

Chen P, Bai Q, Wu Y, Zeng Q, Song X, Guo Y . The Essential Oil of H.Lév. and Vaniot Attenuates NLRP3 Inflammasome Activation in THP-1 Cells. Front Pharmacol. 2021; 12:712907. PMC: 8481632. DOI: 10.3389/fphar.2021.712907. View