Augmented Anti-leukemic Efficacy of Selenium-Fermented Ferulic Acid Derived from Macrotyloma uniflorum: Insights into in vitro and in vivo Models

INTRODUCTION: Conventional leukemia therapies often damage healthy cells, creating significant public health challenges. Ferulic acid, extracted from Macrotyloma uniflorum (horse gram), has demonstrated antileukemic properties. Fermentation is known to enhance the bioavailability of active compounds, and selenium offers additional health benefits. This study investigated whether selenium supplementation during fermentation improves the yield and antileukemic potency of ferulic acid compared with non-fermented and selenium-free conditions. MATERIALS AND METHODS: Ferulic acid was extracted under three conditions: non-fermented, fermented, and selenium-supplemented fermentation. Yield quantification was performed for each extract. Antileukemic efficacy was evaluated in HL-60 human leukemia cells. in vivo effects were assessed in female Balb/c mice, including blood cell counts and histopathological changes in the liver, spleen, and bone marrow. RESULTS: Fermentation increased ferulic acid yield by more than 50%, and selenium supplementation further enhanced it by more than 70%. All extracts exhibited antileukemic activity, with the selenium-enriched fermented extract showing the highest efficacy. It induced apoptosis more effectively than vinblastine and significantly reduced HL-60 cell viability. in vivo, the extract selectively decreased leukemic blast cells, red and white blood cells, lymphocytes, neutrophils, and monocytes, while sparing basophils and eosinophils. Histopathological analysis revealed protection of the liver, spleen, and bone marrow from ENU-induced damage. DISCUSSION: Selenium-supplemented fermentation significantly enhanced both the yield and antileukemic activity of ferulic acid. The enriched extract demonstrated selective induction of apoptosis in leukemia cells and protective effects on normal tissues, underscoring its biological relevance and therapeutic potential. CONCLUSION: Ferulic acid derived from selenium-supplemented fermented Macrotyloma uniflorum exhibited significantly greater antileukemic potency and therapeutic efficacy than ferulic acid from fermented or non-fermented conditions, highlighting its promise as a natural, effective antileukemic agent.