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Allicin Ameliorates Cardiac Hypertrophy and Fibrosis through Enhancing of Nrf2 Antioxidant Signaling Pathways

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Abstract

Aim

To evaluate the protective effects of allicin on Ang II-induced cardiac hypertrophy.

Methods

Sprague–Dawley male rats were randomized into 3 groups:1)sham group (saline)(n = 12), 2) Ang II group(n = 9), 3) allicin group (Ang II + allicin)(n = 9). They received infusions of either saline or Ang II (250 ng/kg body weight per min) through mini-osmotic pumps implanted subcutaneously for 2 weeks and given a diet containing 180 mg/kg/day of allicin for 8 consecutive weeks. Hemodynamic, morphological, histological, and biochemical changes were evaluated at corresponding time points.

Results

Ang II infusion increased blood pressure, heart rate and heart weight to body weight ratio, and resulted in anatomical and functional changes, such as increased LV mass, posterior wall thickness and LV end-diastolic diameter, and decreased fractional shortening and EF compared with sham rats. Nrf2 and HO-1 in the hearts of rats in the Ang II group were moderately elevated at both mRNA and protein levels compared to sham group mice, but NQO1 andγ-GCS were significantly lower. GPx activities, levels of GSH and T-AOC in the hearts of the rats in the Ang II group were also significantly lower, and the levels of TBARS, reactive oxygen species and protein carbonyl were significant increased. Allicin attenuated LV mass, posterior wall thickness and LV end-diastolic diameter (1.10 ± 0.04 vs. 1.37 ± 0.05, 2.26 ± 0.08 vs. 2.96 ± 0.12, 7.27 ± 0.36 vs. 8.56 ± 0.41, respectively; all P < 0.05), and increased fractional shortening and EF (28.30 ± 3.21 vs. 25.40 ± 2.57, 60.27 ± 5.63 vs. 51.30 ± 4.78, respectively; both P < 0.05) in the Ang II-induced hypertrophic rats compared to the untreated Ang II rats. Furthermore, allicin treatment attenuated the accumulation of interstitial collagen and collagen I/III (P < 0.01 vs. the untreated Ang II group), decreased the levels of reactive oxygen species, protein carbonyl and TBARS and increased GPx activities. Moreover, allicin significantly increased mRNA expression and protein levels of Nrf2, NQO1, and γ-GCS ( P < 0.01, P < 0.05 vs. the untreated Ang II group).

Conclusion

Allicin could prevent the development of cardiac remodeling and the progression of cardiac hypertrophy to cardiac dysfunction caused by enhancing the Nrf2 antioxidant signaling pathways.

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Abbreviations

ROS:

Reactive oxygen species

Nrf2:

Transcription factor nuclear factor (erythroid-derived 2)-like2

HO-1:

Heme Oxygenase 1

SOD:

Superoxide dismutase

NQO1:

NAD(P)H:- quinine oxidoreductase

GPx:

Glutathione peroxidase

γ-GCS:

γ-glutamylcysteine synthetase

GSH:

Glutathione

T-AOC:

Total antioxidant capability

TBARS:

Thiobarbituric acid reactive substances

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Authors and Affiliations

  1. Institute of Medicine,College of Medicine, Jishou University, Jishou, China

    Xian-Hui Li, Chun-Yan Li, Zhi-Gang Xiang, Jian-Jun Hu, Jiang-Ming Lu, Rong-Bo Tian & Wei Jia

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  1. Xian-Hui Li
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  2. Chun-Yan Li
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  3. Zhi-Gang Xiang
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  4. Jian-Jun Hu
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  5. Jiang-Ming Lu
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  6. Rong-Bo Tian
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  7. Wei Jia
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Corresponding authors

Correspondence to Xian-Hui Li or Jiang-Ming Lu.

Additional information

This work was supported by the grants (no. JSU-CX-2010-38) from the college students’ research learning and innovative experiment plan project of JiShou University and Office of Science and Technology of Xiangxi autonomous region.

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Li, XH., Li, CY., Xiang, ZG. et al. Allicin Ameliorates Cardiac Hypertrophy and Fibrosis through Enhancing of Nrf2 Antioxidant Signaling Pathways. Cardiovasc Drugs Ther 26, 457–465 (2012). https://doi.org/10.1007/s10557-012-6415-z

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  • DOI: https://doi.org/10.1007/s10557-012-6415-z

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