Uddin_2022_Fitoterapia__105164

Fourteen flavones (1-14) including twelve polymethoxylated flavones, two A-type proanthocyanidins (oligomeric flavonoids) (15, 16), one benzoyl glucoside (17), one triterpenoid (18), and one phenylpropanoid (19) were isolated from the leaves of the South Asian medicinal plant Ceriscoides campanulata (Roxb.) Tirveng (Rubiaceae). The structures of the compounds were identified based on their spectroscopic and spectrometric data and in comparison with literature data. Isolated compounds were tested in vitro against inflammatory enzymes (COX-2, iNOS), pro-inflammatory cytokines (IL-1beta, IL-6, TNF-alpha), esophageal squamous carcinoma cell line (TE13), and carbohydrate digestion enzymes (alpha-amylase, alpha-glucosidase). Proanthocyanidins 15 and 16 significantly attenuated the LPS-induced inflammatory response of COX-2, iNOS, IL-1beta, IL-6, TNF-alpha in RAW 264.7 cells. Proanthocyanidins also satisfactorily inhibited the regrowth (64%), migration (51%), and formation of tumor-sphere (48%) in ESCC cell line TE13 at 50% toxic concentration. Compounds 15 and 16 showed the most potent effect against mammalian alpha-amylase (IC(50) 8.4 +/- 0.3 microM and 3.5 +/- 0.02 microM, respectively) compared to reference standard acarbose (IC(50) 5.9 +/- 0.1 microM). As yeast alpha-glucosidase inhibitors, compounds 15 and 16 also displayed significant activities (IC(50) 6.2 +/- 0.3 and 4.7 +/- 0.1 microM, respectively), while compounds 1-6 displayed weaker alpha-glucosidase inhibitory activities, ranging from 49 to 142 microM, compared to acarbose (IC(50) 665 +/- 42 microM). In an anticholinesterase assay, compounds 1, 2, 6 (IC(50) 51 +/- 2, 53 +/- 7, 64 +/- 5 microM, respectively), and 4 (IC(50) 44 +/- 1 microM) showed moderate inhibitory activities against acetylcholinesterase and butyrylcholinesterase, respectively. Furthermore, molecular docking and molecular dynamic simulation analyses of compounds 15 and 16 were performed against human pancreatic alpha-amylase and human lysosomal acid alpha-glucosidase to elucidate the interactions of these compounds in the respective enzymes' active sites.