Astragalus polysaccharide upregulates hepcidin and reduces iron overload in mice via activation of p38 mitogen-activated protein kinase

Ren F, Qian XH, Qian XL · Biochemical and Biophysical Research Communications · 2016 March

DOI 10.1016/j.bbrc.2016.02.088

Objective

The study aimed to investigate the effects of astragalus polysaccharide (APS) on hepcidin expression and iron metabolism, specifically exploring its potential therapeutic implications for managing iron overload in thalassemia patients.

Conclusions

Astragalus polysaccharide (APS) significantly increased hepcidin expression in HepG2 and L-02 cell lines and reduced iron concentrations in serum, liver, spleen, and heart in mice. These effects were associated with increased interleukin-6 (IL-6) expression and enhanced p38 MAPK phosphorylation, which are known regulators of hepcidin. The study also demonstrated that inhibition of p38 MAPK signaling with SB203580 antagonized the effects of APS on hepcidin and IL-6 expression, suggesting that APS induces hepcidin via the IL-6/p38 MAPK pathway. These findings propose APS as a potential therapeutic agent for managing iron overload conditions, particularly in thalassemia patients.

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Insights

Astragalus Polysaccharide (APS) can potentially be used as a treatment for iron overload in thalassemia patients by promoting the production of hepcidin.

The researchers discovered that Astragalus Polysaccharide (APS), a kind of plant-extracted compound, could greatly stimulate the production of hepcidin, a key liver-produced hormone maintaining iron homeostasis, in two different types of liver cells (HepG2 and L-02) as well as in mice liver. Evidence of Immunohistochemical staining and Western blot analysis affirmed APS's effect on hepcidin production. The activation of p38 MAPK and release of IL-6 mediated the induction of hepcidin by APS. After the administration of APS, the subsequent decrease in iron concentration in vital organs like the liver, spleen, heart, and serum substantiated APS's role as an iron chelator. Furthermore, it was found that pre-treatment with SB203580, a known inhibitor of p38 MAPK signaling, could inhibit the upregulation effects of APS on hepcidin and IL-6 expressions, confirming that APS's iron chelation effect is correlated with the p38 MAPK signaling pathway activation. In conclusion, APS's ability to stimulate hepcidin production and reduce iron levels suggests its potential utility as a treatment for iron overload, especially in thalassemia patients.