Cells were seeded into cell culture dishes (10 cm in diameter), at a density of 1 × 106 cells per dish, and cultured for 12 h to allow their adhesion to the dish, and then replaced with fresh medium containing two concentration levels, IC30 and IC50, of Cos, Dehy, CD, or VOSL, respectively, whereas, the same volume of fresh medium without test compounds were added to the cells as a blank control. After incubation for 48 h, cell culture medium was removed and the adherent cells were washed twice with PBS quickly, and then the metabolic activity of adherent cells were quenched with liquid nitrogen, and the intracellular cAMP was extracted and determined as Shao et al.59 with a few modifications. Briefly, 1.0 mL of cold methanol-water (v/v = 4/1) containing 0.1% formic acid was added into the culture dish, and then the adherent cells were scraped, collected and transferred to 2 mL centrifuged tubes, and then ultrasonicated for 3 min (4 s off, 6 s on) in ice bath. After that, the resulting samples were centrifuged at 4 °C for 10 min at 15000 g, and 0.6 mL supernatant was transferred into a 1.5 mL centrifuged tubes, and then dried using nitrogen stream. The residues were resolved with 200 μL acetonitrile-water (v/v = 1/4), and centrifuged at 4 °C for 10 min at 15000 g, 150 μL supernatant was transferred into a glass auto-sampler for LC-MS/MS analysis.