HFE GENE

Iron dysregulation remains a critical global health challenge, affecting billions through conditions ranging from iron deficiency anemia to hereditary hemochromatosis. This study investigated the effects of Piper guineense (Uziza) leaf extract on HFE gene, TFRC gene and survival rate of Drosophila melanogaster. Fresh Uziza leaves were collected, authenticated and extracted using 70% ethanol maceration. Five experimental groups (n=60 flies per replicate, three replicates each) were established: Control, 100 mg/mL, 200 mg/mL, 300 mg/mL, and 400 mg/mL Piper guineense extract treatments. Survival was monitored over 21 days, followed by molecular analysis using conventional PCR, agarose gel electrophoresis, and quantitative realtime PCR with Gpdh as the housekeeping gene. Results revealed a striking hormetic response pattern, with 100 mg/mL treatment significantly enhancing survival (66.67% ± 4.67%) compared to controls (48.33% ± 3.06%), representing 30.3% mortality reduction. Higher concentrations (300-400 mg/mL) demonstrated dose-dependent toxicity. HFE gene expression showed significant dose-dependent upregulation, peaking at 300 mg/mL (2.65-fold increase, p < 0.001), with progressive increases at 100 mg/mL (1.42-fold), 200 mg/mL (2.08-fold), and 400 mg/mL (1.98-fold) compared to controls. Statistical analysis (one-way ANOVA, F(4,10) = 6.82, p < 0.05) confirmed significant inter-group differences. The dissociation between optimal survival (100 mg/mL) and maximal gene expression (300 mg/mL) indicates that moderate transcriptional activation represents beneficial adaptation, while robust upregulation signals cellular distress. These findings demonstrate that Piper guineense bioactive compounds modulate iron metabolism gene expression through mechanisms likely involving iron chelation and oxidative stress signaling. The narrow therapeutic window emphasizes the critical importance of dose optimization for potential therapeutic applications in iron-related disorders.