Hepcidin and Matriptase-2 as a potential biomarker for responsiveness to oral iron supplementation in adolescents female with iron deficiency anemia

Alkaloid fraction of Mirabilis jalapa Linn. flowers has low cytotoxicity and increases iron absorption through Erythropoietin-Matriptase-2-Hepcidin pathway in iron deficiency Hepatocarcinoma cell model

“…A previous in silico study has identified that Indicaxanthin, Miraxanthin V, and Vulgaxanthin I are able to interact with EPOR with lower binding affinity than EPO–EPOR complexes and having molecular structures similar to the truncated EPO ptoteins ( Suselo et al, 2017a , Suselo et al, 2017b ). From our in vitro results, the EPO levels in cell lysates and supernatants of the iron deficiency HepG2 cell model increased in a dose-dependent manner after administration of the alkaloid fraction of M. jalapa flowers ( Fig.…”

“…Furthermore, interaction with Phe 93 residue plays an important role in nonpolar interactions with EPOR ( Singh et al, 2013 ). The other 10 residues are required for bond stability of phytochemicals to EPOR ( Suselo et al, 2017a , Suselo et al, 2017b ). In previous study, EPO administration in rats increases splenic erythroferrone (ERFE) protein and liver TMPRSS6 protein expression.…”

“…However, the prevalence of iron deficiency anemia (IDA) among pregnant women increased by 11.8 % in 2018, compared to 2013 ( Agency of Health Research and Development, 2019 , Agency of Health Research and Development., 2013 ). Several factors are responsible for the high prevalence of IDA, including non-adherence, negligence, or boredom in taking iron tablets, side effects, and unresponsiveness to iron tablets ( Bregman et al, 2013 , Suselo et al, 2017a , Suselo et al, 2017b , Agency of Health Research and Development, 2019 ). In Indonesia, 61.8 % of adolescent girls in Boyolali regency, Central Java have been reported to be unresponsive to oral iron therapy.…”

“…In Indonesia, 61.8 % of adolescent girls in Boyolali regency, Central Java have been reported to be unresponsive to oral iron therapy. It was shown that this population had higher hepcidin and lower matriptase-2 (MT-2) levels ( Suselo et al, 2017a , Suselo et al, 2017b ), resulting in reductions of iron absorption within the small intestine, iron release from macrophages, and iron storage in the liver, and erythropoiesis ( Fleming, 2008 ).…”

“…According to the results of biocomputational studies, Indicaxanthin is a potential EPO agonist, having dual effects as both an EPO–EPOR complex agonist and a BMPR-1 antagonist. As for other phytochemicals, Miraxanthin V is able to neutralize hepcidin and Boeravinone F is a hepcidin–ferroportin binding inhibitor, which is expected to increase intracellular iron absorption ( Adiparadana et al, 2015 , Suselo et al, 2017a , Suselo et al, 2017b , Yotriana et al, 2018 , Suselo et al, 2020 ). Furthermore, Indicaxanthin, Miraxanthin V, and Boeravinone F are members of the Betaxanthin group (alkaloid compounds) ( Sadowska-Bartosz & Bartosz, 2021 ), which are commonly found in four o'clock flower plants ( Mirabilis jalapa L.).…”