A scalable process for extraction and macroporous resin enrichment of podophyllotoxin from eastern red cedar (Juniperus virginiana L.)

Podophyllotoxin (ptox) is a plant-derived pharmaceutical used for medicinal treatments from inflammatory diseases to cancer. Originally sourced from the rhizomes of the Indian mayapple ( Podophyllum emodi Wall.) and leaves of the American mayapple ( Podophyllum peltatum L.), ptox is also found in eastern red cedar (ERC; Juniperus virginiana L.) foliage. This work demonstrated a scalable process to extract ptox from ERC field-dried foliage that was rehydrated and flaked. Optimum extraction conditions were 20 % ethanol, 60° C, 20:1 solvent: feedstock ratio for 1 h, followed by filtration to yield 5.27 mg ptox/g dry foliage. Extract ptox was enriched using three hydrophobic macroporous resins varying in particle size. The small particle size resin (PCG900M; 50–100 µm) exhibited the highest ptox binding capacity (57 mg ptox/g resin) and solvent reduction (11–12 fold), followed by the mid-sized resin (PCG900C; 100–200 µm, 35 mg ptox/g resin, 8 fold solvent reduction), and was lowest for the large particle size resin (PAD900; 300–1200 µm, 29 mg ptox/g resin, 6–7 fold solvent reduction). Conversely, desorbed ptox purity was greatest for PAD900 (19.7 %), intermediate for PCG900C (14.8 %), and lowest for PCG900M (13.1 %). Ptox recovery from ERC extracts was lower for PAD900 (60.0 %) than for both PCG900C (87.3 %) and PCG900M (86.9 %). This optimized process for extraction and enrichment of ptox from ERC foliage offers an incentive for removing ERC trees invading land in rural and increasingly populated areas of the United States. • Extraction and macroporous resin enrichment of podophyllotoxin was achieved • Dried foliage hydration prior to flaking allowed efficient filtration • Particle size of macroporous resins played a role in podophyllotoxin purification • Scalable podophyllotoxin procedures were developed for eastern red cedar foliage