ReferenceID 4909

Trans-cinnamaldehyde suppresses microtubule detyrosination and alleviates cardiac hypertrophy

Eur J Pharmacol

Background: Trans-cinnamaldehyde (TCA) is a main compound of Cinnamomum cassia, used in traditional Chinese medicine to treat many ailments. Increasing evidence has demonstrated the therapeutic effects of TCA in cardiova

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Reference Id
4909
Evidence Id
21499
Core Evidence Id
21499
Source Reference Id
3082
Herb2 Reference Id
HBREF003879
Subject Paper Key
HBIN020653_34883072
Pubmed Id
34883072
Doi
10.1016/j.ejphar.2021.174687
Paper Title
Trans-cinnamaldehyde suppresses microtubule detyrosination and alleviates cardiac hypertrophy
Paper Abstract
Background: Trans-cinnamaldehyde (TCA) is a main compound of Cinnamomum cassia, used in traditional Chinese medicine to treat many ailments. Increasing evidence has demonstrated the therapeutic effects of TCA in cardiovascular diseases. Purpose: The present study aimed to determine whether TCA exerts antihypertrophic effects in vitro and in vivo and to elucidate the underlying mechanisms of these effects. Methods: Neonatal rat cardiac myocytes (NRCMs) and adult mouse cardiac myocytes (AMCMs) were treated with 50 μΜ phenylephrine (PE) for 48 h. Tubulin detyrosination, store-operated Ca 2+ entry (SOCE), stromal interaction molecule-1 (STIM1)/Orai1 translocation, and calcineurin/nuclear factor of activated T-cells (NFAT) signaling pathways were analyzed in NRCMs. Meanwhile, tubulin detyrosination, junctophilin-2, T-tubule distribution pattern, Ca 2+ handling, and sarcomere shortening were observed in AMCMs. Male C57BL/6 mice were stimulated with PE (70 mg/kg per day) with or without TCA treatment for 2 weeks. Cardiac hypertrophy and tubulin detyrosination were also assessed. Results: TCA was confirmed to alleviate cardiac hypertrophy induced by PE stimulation in vitro and in vivo. PE-induced cardiac hypertrophy was associated with excessive tubulin detyrosination and overexpression of vasohibin 1 (VASH1) and small vasohibin binding protein (SVBP), two key proteins responsible for tubulin detyrosination. These effects were largely blocked by TCA administration. PE treatment also enhanced SOCE with massive translocation of STIM1 and Orai1, Ca 2+ mishandling, reduced sarcomere shortening, junctophilin-2, and T-tubule redistribution, all of which were significantly ameliorated by TCA administration. Conclusion: Our study indicated that the therapeutic effects of TCA against cardiac hypertrophy may be associated with its ability to reduce tubulin detyrosination.
Journal
Eur J Pharmacol
Publish Year
2021
Experiment Subject
mouse; rat
Experiment Type
Cell Experiment
Phenotype Related
Nrcms; Cardiovascular Diseases; Cardiac Hypertrophy; Pe-induced Cardiac Hypertrophy
Paper Title Cn
Paper Title En
Trans-cinnamaldehyde suppresses microtubule detyrosination and alleviates cardiac hypertrophy
Bilingual Status
semi_complete