Sesquiterpenoids from Tussilago farfara: Full structure elucidation, anti-diabetic and anti-inflammatory signaling pathways

Four new sesquiterpenoids (1-4), including the first example of a novel 2,3-seco oplopane carbon skeleton (1), along with 19 known analogues, were isolated from the flower buds of Tussilago farfara (coltsfoot). The intractable relative and absolute configurations on the flexible sidechains and substituents of these structures were for the first time determined by using a combination of spectroscopic techniques, chemical methods, chiral gas chromatography, and quantum chemical calculations. All compounds were assessed for their anti-diabetic activity on an insulin-stimulated glucose uptake model in C2C12 myotubes and anti-inflammatory activity on an LPS-induced NO inhibitory model in RAW264.7 macrophages. Six compounds exhibited significant glucose uptake activity and further study on compound 3 revealed that it could activate the IRS-1/Akt/GSK-3β signaling pathway. Twenty-one compounds showed remarkable inhibitory effects against NO production, and among them, compounds 2 and 6 suppressed the expression of iNOS and phosphorylation of NF-κB in a dose-dependent manner.