Development and optimization of green extraction of naringin in Citrus grandis ‘Tomentosa’ using natural deep eutectic solvents (NADES) and investigation of lung cancer therapeutics mechanisms

What if the key to a potent lung cancer therapy was hiding in a citrus peel, and we could extract it using a solvent as green as the fruit itself?

Citrus grandis 'Tomentosa' (CGT), a cornerstone of traditional Chinese medicine, has long been used to soothe coughs and bronchitis. But its most abundant flavonoid, naringin, is now stepping into the spotlight for a far more serious role: fighting lung cancer. The challenge? Extracting it without harming the planet. Conventional methods rely on harsh organic solvents like methanol and ethanol, which are effective but far from green. Enter Natural Deep Eutectic Solvents (NADES)—a new class of eco-friendly solvents that are both sustainable and surprisingly powerful. In this study, researchers optimized an ultrasonic-assisted extraction method using a choline chloride-levulinic acid NADES, achieving a naringin yield of 4.7%—significantly higher than methanol (4.1%) or ethanol (4.0%). The process was gentle: 40% water, a 1:65 solid-to-liquid ratio, 60°C, 40 minutes, and 300W of ultrasound. But the story doesn't end at extraction. The CGT extracts were screened for lung cancer therapeutic activity, revealing a cocktail of bioactive compounds—poncirin, isosinensetin, sinensetin, nobiletin, didymin, neohesperidin, and naringenin—that target key proteins like CYP17A1, CYP19A1, and AR, and modulate pathways such as EGFR tyrosine kinase inhibitor resistance. This isn't just a greener way to extract a molecule; it's a clearer picture of how nature's chemistry can fight a formidable disease.

Key Points

• NADES green extraction yields 4.7% naringin, beating methanol and ethanol.
• Ultrasonic-assisted method uses mild, eco-friendly conditions.
• CGT extracts target lung cancer via multiple pathways and proteins.