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Bajitianwan formula extract ameliorates bone loss induced by iron overload via activating RAGE/PI3K/AKT pathway based on network pharmacology and transcriptomic analysis

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Abstract

Osteoporosis (OP) is closely related to iron overload. Bajitianwan (BJTW) is a traditional Chinese medicine formulation used for treating senile diseases such as dementia and osteoporosis. Modern pharmacological researches have found that BJTW has beneficial effect on bone loss and memory impairment in aging rats. This paper aimed to explore the role and mechanism of BJTW in ameliorating iron overload-induced bone loss. Furthermore, BJTW effectively improved the bone micro-structure of the femur in mice, and altered bone metabolism biomarkers alkaline phosphatase (ALP) and osteocalcin (OCN) in serum, as well as oxidative indexes superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR) glutathione (GSH) and malondialdehyde (MDA) in liver. As for network pharmacology, 73 components collected from BJTW regulated 99 common targets merged in the BJTW and OP. The results of RNA-seq indicated that there were 418 potential targets in BJTW low dose group (BJTW-L) and 347 potential targets in BJTW high dose group (BJTW-H). Intriguingly, both PI3K-AKT signaling pathway and the AGEs-RAGE signaling pathway were contained in the KEGG pathways enrichment results of network pharmacology and transcriptomics, which were considered as the potential mechanism. Additionally, we verified that BJTW regulated the expression of related proteins in RAGE/PI3K-AKT pathways in MC3T3-E1 cells. In summary, BJTW has potent effect on protecting against iron overload-induced OP, and its mechanism may be related to the activation of the RAGE/PI3K-AKT signaling pathways.

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Acknowledgements

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Funding

This work was supported by the National Natural Science Foundation of China (82004015, 82174079), the Project of Science and Technology Commission of Shanghai Municipality (21S21902600) and the Health Commission of Shanghai Municipality (ZY (2021–2023)-0203–04).

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  1. Weifan Xu and Tao Jiang contributed equally to this work.

Authors and Affiliations

  1. Department of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou, 350122, Fujian, China

    Weifan Xu, Tao Jiang & Hailiang Xin

  2. Department of Pharmacognosy, School of Pharmacy, Naval Medical University, Shanghai, 200433, China

    Weifan Xu, Tao Jiang, Yiping Jiang, Tianshuang Xia & Hailiang Xin

  3. Department of Pharmacy, Changhai Hospital, Naval Medical University, Shanghai, 200433, China

    Luying Ding

  4. Department of Pharmacy, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200071, China

    Lichao Zhang

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  1. Weifan Xu
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Contributions

WX: Performed experiments, analysis data and wrote the manuscript. TJ: Performed experiments, image editing and optimization. LD: Formulation analysis. YJ and LZ: Review and editing. TX and HX: Designed the research and revised the manuscript. LZ, TX and HX: funding acquisition.

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Correspondence to Tianshuang Xia or Hailiang Xin.

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Xu, W., Jiang, T., Ding, L. et al. Bajitianwan formula extract ameliorates bone loss induced by iron overload via activating RAGE/PI3K/AKT pathway based on network pharmacology and transcriptomic analysis. J Nat Med (2024). https://doi.org/10.1007/s11418-024-01779-1

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