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

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Abstract

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.

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Acknowledgments

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).

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    Authors and Affiliations

    1. Department of Pharmacology, Guangdong Medical University, 523808, Dongguan, China

      Xuan Zha, Zhoumei Xu, Yuyu Liu, Liao Cui & Daohua Xu

    2. Department of Orthopaedics and Traumatology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, China

      Liangliang Xu

    3. Affiliated Hospital of Guangdong Medical University, 524023, Zhanjiang, China

      Hongxin Huang & Jingjing Zhang

    4. School of Nursing, Guangdong Medical University, 523808, Dongguan, China

      Chenhui Zhou

    5. Institution of Traditional Chinese Medicine and New Pharmacy Development, Guangdong Medical University, 523808, Dongguan, China

      Daohua Xu

    6. Guangdong Key Laboratory for Research and Development of Natural Drugs, Guangdong Medical University, 524023, Zhanjiang, China

      Daohua Xu

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    1. Xuan Zha
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    X. Zha and Z. Xu contributed equally.

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    Zha, X., Xu, Z., Liu, Y. et al. Amentoflavone enhances osteogenesis of human mesenchymal stem cells through JNK and p38 MAPK pathways. J Nat Med 70, 634–644 (2016). https://doi.org/10.1007/s11418-016-0993-1

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