Journal of Natural Medicines

, Volume 71, Issue 1, pp 27–35 | Cite as

Glycyrrhetinic acid protects H9c2 cells from oxygen glucose deprivation-induced injury through the PI3K/AKt signaling pathway

  • Liqin Wang
  • Yuyan Zhang
  • Haitong Wan
  • Weifeng Jin
  • Li Yu
  • Huifen Zhou
  • Jiehong Yang
Original Paper


Glycyrrhetinic acid (GA) is an ingredient of triterpene saponins found in Gancao (Radix Glycyrrhizae). Here, we investigated the protective effects of GA in H9c2 cells, and explored its possible mechanism of action. Different concentrations of GA were used to treat H9c2 cells under oxygen glucose deprivation. We analyzed cell necrosis and apoptosis using optical microscopy, Hoechst 33342 staining, FITC-annexin V/PI double-staining and lactate dehydrogenase (LDH), creatine kinase-MB (CK-MB) and interleukin (IL)-1β assays. Changes in related pro-apoptosis and anti-apoptosis proteins were detected by Western blot. Optical microscopy showed that GA improved cell morphology, including cell shrinkage, cauliflower-like membrane blebbing, and even some cell debris. Meanwhile, GA also ameliorated cell nuclei characteristics such as nucleus size, chromatin condensation and bright staining from Hoechst 33342 staining. GA also lowered the apoptotic rate and the levels of LDH, CK-MB and IL-1β in a dose-dependent manner. Furthermore, GA treatment increased Bcl-2 protein expression and decreased caspase-8 and Bax protein expression, while elevating the Bcl-2/Bax ratio. GA preconditioning increased p-AKt protein expression; however, after adding LY 294002, the p-AKt expression decreased obviously. Our results demonstrated that GA could protect H9c2 cells from apoptosis in a dose-dependent manner, and the potential mechanism might be related to the PI3K/AKt signaling pathway.


Glycyrrhetinic acid H9c2 Apoptosis Mechanism PI3K/AKt signaling pathway 



This study is supported by grants from the National Nature Science Foundation of China (No. 81473412); Zhejiang Provincial Program for the Cultivation of High-level Innovative Health talents; Zhejiang Provincial Chinese Medicine (Combine Traditional Chinese and Western Medicine) Key Subject (No. 2012-XK-A06).

Complicance with ethical standards

Conflict of interest

All the authors have no potential conflicts of interest to declare.


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Copyright information

© The Japanese Society of Pharmacognosy and Springer Japan 2016

Authors and Affiliations

  • Liqin Wang
    • 1
  • Yuyan Zhang
    • 1
  • Haitong Wan
    • 1
  • Weifeng Jin
    • 1
  • Li Yu
    • 1
  • Huifen Zhou
    • 1
  • Jiehong Yang
    • 1
  1. 1.Zhejiang Chinese Medical UniversityHangzhouPeople’s Republic of China

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