Journal of Natural Medicines

, Volume 70, Issue 3, pp 634–644 | Cite as

Amentoflavone enhances osteogenesis of human mesenchymal stem cells through JNK and p38 MAPK pathways

  • Xuan Zha
  • Zhoumei Xu
  • Yuyu Liu
  • Liangliang Xu
  • Hongxin Huang
  • Jingjing Zhang
  • Liao Cui
  • Chenhui Zhou
  • Daohua Xu
Original Paper


Amentoflavone is a bioflavonoid found in a variety of traditional Chinese medicines such as Gingko and Selaginella tamariscina. It has been reported that amentoflavone has anti-inflammatory, antioxidant, antiviral and anticancer effects. However, the effect of amentoflavone on osteogenic differentiation of human mesenchymal stem cells (hMSCs) has not been studied. In this study, we aim to explore the effect of amentoflavone on the proliferation and osteogenic differentiation of hMSCs. The results showed that amentoflavone significantly enhanced the proliferation, alkaline phosphatase (ALP) activity and mineralization in hMSCs. Western blot analysis revealed that the expression of runt-related transcription factor 2 and osterix proteins was upregulated in amentoflavone-treated hMSCs. Furthermore, we investigated the possible signaling pathways responsible for osteogenic differentiation of hMSCs by amentoflavone. We found that amentoflavone significantly increased the levels of phosphorylated JNK and p-p38. The amentoflavone-induced increases of ALP and mineralization were significantly diminished when the JNK and p38 MAPK pathways were blocked by selected inhibitors (SP600125, SB203580) in hMSCs. Furthermore, in vivo evidence indicated that amentoflavone protected against the dexamethasone-induced inhibition of osteoblast differentiation in tg(sp7:egfp) zebrafish larvae. Thus, we showed for the first time that amentoflavone improves the osteogenesis of hMSCs through the JNK and p38 MAPK pathway. Amentoflavone may be beneficial in treating bone-related disorders.


Human mesenchymal stem cells Amentoflavone Osteogenesis JNK and p38 MAPK pathways Osteoporosis 



This project was supported by the National Natural Science Foundation of China (30772768, 81102450), Science and Technology Planning Project of Guangdong Province (2013B031800013), Natural Science Foundation of Guangdong Province (2014A030313534), Administration of Traditional Chinese Medicine of Guangdong Province (20151263), Social Science and Technology Development Project of Dongguan (2014108101052), Science and Technology Planning Project for Medical Treatment and Public Health of Dongguan (2014105101294) and Initiating Fund of Scientific Research for Doctors of Guangdong Medical University (B2013016).

Compliance with ethical standards

Conflict of interest

The authors declare no conflict of interest.


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Copyright information

© The Japanese Society of Pharmacognosy and Springer Japan 2016

Authors and Affiliations

  • Xuan Zha
    • 1
  • Zhoumei Xu
    • 1
  • Yuyu Liu
    • 1
  • Liangliang Xu
    • 2
  • Hongxin Huang
    • 3
  • Jingjing Zhang
    • 3
  • Liao Cui
    • 1
  • Chenhui Zhou
    • 4
  • Daohua Xu
    • 1
    • 5
    • 6
  1. 1.Department of PharmacologyGuangdong Medical UniversityDongguanChina
  2. 2.Department of Orthopaedics and TraumatologyThe Chinese University of Hong Kong, Prince of Wales HospitalHong KongChina
  3. 3.Affiliated Hospital of Guangdong Medical UniversityZhanjiangChina
  4. 4.School of NursingGuangdong Medical UniversityDongguanChina
  5. 5.Institution of Traditional Chinese Medicine and New Pharmacy DevelopmentGuangdong Medical UniversityDongguanChina
  6. 6.Guangdong Key Laboratory for Research and Development of Natural DrugsGuangdong Medical UniversityZhanjiangChina

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