Therapeutic Effects of Mirabilis jalapa Linn. Yellow Flower Extract on Iron Homeostasis and Fetal Development in Pregnant Rats with Anemia

Abstract

Iron deficiency anemia during pregnancy is a global health concern with serious consequences for maternal and fetal morbidity and mortality. In Indonesia, its prevalence remains high, while adherence to conventional iron supplementation is often poor due to side effects and discomfort. This study aimed to investigate the effects of M jalapa yellow flower extract on iron regulatory biomarkers (i.e., matriptase-2 (MT-2), serum iron, and serum ferritin) alongside hemoglobin levels, erythrocyte indices, and fetal morphometry in pregnant anemic rat models. A pre- and post-test control group design was employed. Female Sprague-Dawley rats were rendered anemic by a low-iron diet combined with weekly blood withdrawal (1% of body weight), then mated and divided into 5 groups: N (normal), NG (anemic, untreated), PG (anemic + iron), T1 (anemic + M. jalapa yellow flower extract 0.52 g/kg BW/day), and T2 (anemic + M. jalapa yellow flower extract 1.04 g/kg BW/day). Outcomes were assessed throughout gestation. Molecular docking showed astaxanthin (−10.4 kcal/mol), betaxanthin (−5.2 kcal/mol), and miraxanthin-1 (−6.5 kcal/mol) binding to TMPRSS6. At baseline (W0), hematological and biochemical markers reflected the expected group differences. Over the gestation period, group N showed modest declines yet remained within normal limits, whereas NG remained anemic with minimal improvement. Relative to baseline, T1 showed increased Hb (10.53 → 11.60 g/dL), serum iron (+3.41 → 10.30 µg/dL), ferritin (+0.50 ng/mL), and MT-2 (2.39 → 3.38 ng/mL). At W3, these parameters were higher than in NG (e.g., Hb 8.56 g/dL) and generally comparable to PG for Hb and serum iron (p < 0.05). T2 also increased MT-2, serum iron, and ferritin from baseline, but Hb declined (12.20 → 8.93 g/dL), making it inferior to T1 and PG for Hb (p < 0.05). Compared with NG, T1 significantly improved MCV, MCHC, and fetal weight and length, with T1 outperforming T2 for hemoglobin and fetal growth parameters (p < 0.05). In conclusion, M. jalapa yellow flower extract improved iron metabolism and supported fetal growth in anemic pregnancy models, with T1 (0.52 g/kg BW/day) showing the most favorable outcomes. The higher dose (T2) demonstrated selective biomarker benefits but did not improve Hb levels in anemic pregnant rats.

HIGHLIGHTS

• This study is the first to evaluate the effects of jalapa yellow flower extract on iron metabolism and fetal growth in pregnant anemic rat models.
• Administration of the extract significantly increased matriptase-2, serum iron, serum ferritin, hemoglobin (Hb), and erythrocyte indices (MCV, MCH, MCHC) (p < 0.05).
• The extract improved fetal morphometric parameters, including body weight and length, indicating protection against intrauterine growth restriction.
• The effective dose of 0.52 g/kg BW/day in rats (equivalent to ~9.36 g/kg BW/day in humans) provides an initial reference for dosage translation.
• The findings support the potential development of jalapa yellow flower extract as a standardized phytotherapeutic supplement for iron deficiency anemia in pregnancy, particularly in resource-limited settings.

GRAPHICAL ABSTRACT