The Action of JAK/STAT3 and BMP/HJV/SMAD Signaling Pathways on Hepcidin Suppression by Tucum-do-Cerrado in a Normal and Iron-Enriched Diets

• Main Authors: Sandra Fernandes Arruda, Larissa Valadares Ramos, Júlia Lima de Alencar Barbosa, Natália Aboudib Campos Hankins, Pedro Augusto Matos Rodrigues, Marcela de Sá Barreto da Cunha
• Format: Article
• Language: English
• Published: MDPI AG 2020-05-01
• Series: Nutrients
• Subjects: tucum-do-cerrado; hepcidin; pSMAD1/5/8; pSTAT3; iron
• Online Access: https://www.mdpi.com/2072-6643/12/5/1515

The Brazilian savanna fruit, tucum-do-cerrado (<i>Bactris</i><i> </i><i>setosa</i> Mart.) reduces hepatic hepcidin levels. Therefore, we investigated the effect of tucum-do-cerrado on the TfR/HFE and/or BMP/HJV/SMAD and JAK/STAT pathways, in normal and excess iron conditions. Rats were treated with: control diet (CT); control diet +15% tucum-do-cerrado (Tuc); iron-enriched diet (+Fe); or iron-enriched diet +15% tucum-do-cerrado (Tuc+Fe). Tucum-do-cerrado (Tuc) decreased hepatic Hamp and<i> </i><i>Hjv</i> mRNA levels but did not alter <i>Bmp6</i>, <i>Smad7</i>, <i>Tfr1</i>, and <i>Hfe</i> mRNA levels; pSMAD1/5/8 and pSTAT3 protein levels; labile iron pool (LIP); and inflammatory biomarkers, compared to the CT group. The iron-enriched diet increased <i>Hamp</i> mRNA levels, as well as pSMAD1/5/8 and pSTAT3 protein levels, while no difference was observed in <i>Hjv</i>, <i>Bmp6</i>, <i>Smad7</i>, <i>Tfr1</i>, and <i>Hfe</i> mRNA levels and LIP compared to the CT group. The association of tucum-do-cerrado with the iron-enriched diet (Tuc+Fe) decreased <i>Hamp</i>, <i>Hjv</i>, <i>Bmp6</i>, and <i>Hfe</i> mRNA levels and pSTAT3 protein content compared to the +Fe group, while increased <i>Hamp</i> and decreased <i>Hfe</i> mRNA levels compared to the Tuc group. Therefore, the inhibition of hepatic hepcidin by tucum-do-cerrado consumption may involve the downregulation of intestinal <i>Dmt1</i> and hepatic <i>Hjv</i> expression and deacetylation mediated by SIRT1 by a mechanism that is independent of tissue iron content. However, in excess iron conditions, the modulation of hepatic hepcidin expression by tucum-do-cerrado seems to be partially mediated by the inflammatory signaling pathway, as well as involves the chelating activity of tucum-do-cerrado.