Tetramethylpyrazine inhibits angiotensin II-induced cardiomyocyte hypertrophy and tumor necrosis factor-α secretion through an NF-κB-dependent mechanism

Abstract

Tetramethylpyrazine (TMP), a bioactive compound isolated from the Chinese herb, Ligusticum wallichii Franchat, has been reported to play a protective role in cardiac diseases. However, the cellular and molecular mechanisms behind the protective effects of TMP on the heart remain to be elucidated. In this study, we aimed to determine the effects of TMP on angiotensin II (Ang II)-induced hypertrophy in neonatal rat cardiomyocytes and its possible mechanisms of action. In addition, we investigated whether TMP regulates tumor necrosis factor-α (TNF-α) secretion and expression. We found that TMP significantly inhibited the Ang II-induced hypertrophic growth of neonatal cardiomyocytes, as evidenced by the decrease in [3H]leucine incorporation and β-myosin heavy chain (β-MHC) mRNA expression. TMP inhibited Ang II-stimulated TNF-α protein secretion and mRNA expression in the cardiomyocytes. Further experiments revealed that Ang II increased the level of the phosphorylated form of the transcription factor, nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB), as well as NF-κB-DNA binding activity in the cardiomyocytes; treatment with TMP significantly inhibited the Ang II-induced activation of NF-κB. Furthermore, the inhibition of NF-κB by the specific inhibitor, pyrrolidine dithiocarbamate (PDTC), markedly attenuated the Ang II-induced increase in [3H]leucine incorporation, β-MHC mRNA expression and TNF-α protein secretion. Our findings suggest that TMP inhibits Ang II-induced cardiomyocyte hypertrophy and TNF-α production through the suppression of the NF-κB pathway, which may provide new insight into the mechanisms underlying the protective effects of TMP in heart diseases.

Effect of ligustilide on Ang II-induced hypertrophy in cardiomyocytes and the potential mechanisms

“…These treatments have been shown to block the L-type calcium current in the ventricular myocytes and antagonize Ca 2+ influx in myocardial cells (23). Previous studies have also demonstrated that Danshen and Chuanxiong have an inhibitory effect on cardiac hypertrophy, as they have been shown to inhibit the formation of left ventricular hypertrophy in spontaneously hypertensive rats (19–22). LIG is one of the active ingredients in Danshen and Chuanxiong.…”

“…These treatments significantly improve the patient’s clinical symptoms, signs and electrocardiograms. It has been reported that Danshen (19,20) and Chuanxiong (Szechwan Lovage Rhizome) (21,22) exhibit the characteristics of anti-ischemia, anti-hypoxia and calcium channel blockers. These treatments have been shown to block the L-type calcium current in the ventricular myocytes and antagonize Ca 2+ influx in myocardial cells (23).…”

Pioglitazone Induces Cardiomyocyte Apoptosis and Inhibits Cardiomyocyte Hypertrophy Via VEGFR-2 Signaling Pathway

“…18 Briefly, 2 h after treatment with pioglitazone (0-20 µ mol/l) and apatinib (2 µ M), 0.1 µ M Ang II was used to stimulate cardiomyocyte hypertrophy and 1 µ Ci [ 3 H]-leucine was simultaneously added to each well. After stimulation with Ang II for 60 h, cells were harvested by precipitation with 10% trichloroacetic acid on ice for 30 min before being solubilized with 1 mol/l NaOH overnight at 4ºC.…”

Cardiovascular Actions and Therapeutic Potential of Tetramethylpyrazine (Active Component Isolated fromRhizoma Chuanxiong): Roles and Mechanisms

“…Another study showed that TMP inhibits AngII-induced cardiomyocyte hypertrophy and TNF- α production via suppression of the NF- κ B pathway. This could provide new insight into the mechanisms underlying the protective effects of TMP in heart diseases [ 83 ].…”