Estrogen receptor α mediates the effects of notoginsenoside R1 on endotoxin-induced inflammatory and apoptotic responses in H9c2 cardiomyocytes

Zhong,Lei; Zhou,Xing‑Lu; Liu,Yan‑Song; Wang,Yi‑Min; Ma,Fei; Guo,Bao‑Liang; Yan,Zhao‑Qi; Zhang,Qing‑Yuan

doi:10.3892/mmr.2015.3394

July-2015 Volume 12 Issue 1

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July-2015 Volume 12 Issue 1

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Article Open Access

Estrogen receptor α mediates the effects of notoginsenoside R1 on endotoxin-induced inflammatory and apoptotic responses in H9c2 cardiomyocytes

Authors:
- Lei Zhong
- Xing‑Lu Zhou
- Yan‑Song Liu
- Yi‑Min Wang
- Fei Ma
- Bao‑Liang Guo
- Zhao‑Qi Yan
- Qing‑Yuan Zhang
View Affiliations / Copyright

Affiliations: Department of General Surgery, Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, P.R. China, Department of Internal Medicine, Cancer Hospital Affiliated to Harbin Medical University, Harbin, Heilongjiang 150040, P.R. China

Copyright: © Zhong et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].
Pages: 119-126
|
Published online on: February 27, 2015

https://doi.org/10.3892/mmr.2015.3394
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Abstract

Estrogen receptors (ERs) are important for preventing endotoxin‑induced myocardial dysfunction. Therefore, plant‑derived phytoestrogens, which target ERs may also affect endotoxin‑induced toxicity in cardiomyocytes. Our previous study revealed that notoginsenoside‑R1 (NG‑R1), a predominant phytoestrogen from Panax notoginseng, protects against cardiac dysfunction. However, the effects of NG‑R1 on cardiomyocytes and the precise cellular/molecular mechanisms underlying its action remain to be elucidated. In the present study, pretreatment with NG‑R1 suppressed the lipopolysaccharide (LPS)‑induced degradation of inhibitor of nuclear factor‑κB (NF‑κB) α, the activation of NF‑κB and caspase‑3, and the subsequent myocardial inflammatory and apoptotic responses in H9c2 cardiomyocytes. An increase in the mRNA and protein expression of ERα was also observed in the NG‑R1‑treated cardiomyocytes. However, the expression pattern of ERβ remained unaltered. Furthermore, the cardioprotective properties of NG‑R1 against LPS‑induced apoptosis and the inflammatory response in cardiomyocytes were attenuated by ICI 182780, a non‑selective ERα antagonist, and methyl‑piperidino‑pyrazole, a selective ERα antagonist. These findings suggested that NG‑R1 reduced endotoxin‑induced cardiomyocyte apoptosis and the inflammatory response via the activation of ERα. Therefore, NG‑R1 exerted direct anti‑inflammatory and anti‑apoptotic effects on the cardiomyocytes, representing a potent agent for the treatment of myocardial inflammation during septic shock.

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