Research Projects

Chronic obstructive pulmonary disease (COPD) affects over 65 million people worldwide, making it the third leading cause of death. To treat COPD and related lung disorders, understanding inflammatory responses and drugs targeting progressive apoptosis pathways in lung epithelial cells is crucial. Folates, vitamins B9 involved in one-carbon metabolism, have limited conversion efficiency in humans into biological derivatives. Most folate in organisms exists as 5-methyltetrahydrofolate. A preliminary study on BEAS-2B cells revealed that biological folate derivatives protect cells from oxidative stress, with 5-methyltetrahydrofolate and 10-formyltetrahydrofolate showing higher cytoprotective activity compared to synthetic folic acid. The study also revealed that reactive oxygen species scavenging activity of the folate derivatives was evident. Inflammatory markers such as NF-kB, IL6, TNF-α, and MCP-1 were suppressed after supplementation with biological folate derivatives. FOLR1, an active folate transporter, is involved in the movement of folate across cell membranes. The lung expresses the highest rate of the active folate transporter, FLOR1, among human organs. FOLR1 is highest expressed in alveolar epithelial type 2 cells (AEC2), which are critical for maintaining lung homeostasis and repair and regeneration. Restoration of lung health relies heavily on protecting AEC2 cells and promoting cell division. Analysis of FOLR1 in BEAS-2B cells shows upregulation under smoke-induced stress, suggesting the rapid depletion of intracellular folate due to reactive oxygen species. Intranasal application of folate derivatives can assure the supply of folate to lung epithelial cells, providing better antioxidant and antiinflammatory activity.