Inhibitory Effect on Nitric Oxide Release in LPS-Stimulated Macrophages and Free Radical Scavenging Activity of Croton Linearis Jacq. Leaves

Oxidative stress is an important component of many diseases including cancer, along with inflammatory and neurodegenerative processes. Natural antioxidants have emerged as promising substances to protect the human body against reactive oxygen and nitrogen species. The present study evaluates the inhibition of nitric oxide (NO) production in LPS-stimulated RAW 264.7 murine macrophages and the free radical scavenging activity of Croton linearis Jacq. leaves. UPLC-QTOF-MS analysis identified 18 compounds: nine alkaloids with a morphinane, benzylisoquinoline or aporphine nucleus, and nine O-glycosylated-flavonoids with quercetin, kaempferol and isorhamnetin as the aglycones. The crude extract (IC(50) 21.59 µg/mL) and the n-hexane fraction (IC(50) 4.88 µg/mL) significantly reduced the NO production in LPS-stimulated macrophages but with relatively high cytotoxicity (CC(50) 75.30 and CC(50) 70.12 µg/mL, respectively), while the ethyl acetate fraction also showed good activity (IC(50) 40.03 µg/mL) without affecting the RAW 264.7 cell viability. On the other hand, the crude extract, as well as the dichloromethane and ethyl acetate fractions, showed better DPPH and ABTS free radical scavenging activities. Considering the chemical composition and the activity observed for Croton linearis leaves, they may be considered a good source of antioxidants to combat oxidative damage-related diseases.