Chemical constituents from Eupatorium chinense roots and their inhibitory activities on α-glucosidase and protein tyrosine phosphatase 1B
This study aims to investigate the chemical constituents of Eupatorium chinense roots and their antidiabetic activi-ties.Normal-phase silica gel column chromatography,thin-layer chromatography,gel column chromatography and semi-prepar-ative high-performance liquid chromatography were used to investigate the chemical constituents of roots of E.chinense.Fifteen compounds were isolated and then identified as 8 S-9-hydroxy thy mol(1),8,10-dehydro-9-hydroxythymol(2),1-[4-hydroxy-3-methoxy-5-(3-methylbut-3-en-1-ynyl)phenyl]ethenone(3),speciosin L(4),(R)-8-hydroxy-9-isobutyryloxy thymol(5),1,4-[13C]-1,2,3,4-tetrahydro-5-naphthyl-amin(6),eupatriol(7),3β,6-hydroxytremetone(8),6-methoxyluteolin(9),(2R,3S)-5-acetyl-6-hydroxyl-2-isopropenyl-3-ethoxy-dihydrofuran(10),(2R,3S)-5-Acetyl-6-hydroxy-2-isopropenyl-3-ethoxy-benzodihydrofuran(11),6-hydroxy-2H-benzofuran-3-one(12),3,5-dimethyl-2,3-dihydrobenzofuran(13),2,4-bis-(5-acetyl-6-hydroxy-benzofuran-2-yl)-4-methyl-pent-1-ene(14),1,1'-[[(2E)-4-methylpent-2-ene-2,4-diyl]bis(6-hydroxy-1-benzofuran-2,5-diyl)]diethanone(15).Among them,compound 3 was isolated for the first time from Eupatorium and compound 14 was isolated for the first time from E.chinense.The inhibitory activities of α-glucosidase and protein tyrosine phosphatase 1B(PTP1B)of the compounds were determined by p-nitrophenyl-β-galactopyranoside method and p-nitrophenyl phosphate method.Compounds 3,4,5 and 12 showed good α-glucosidase inhibitory activity with IC50 values of 3.7,10.1,21.3 and 22.5 μg/mL,respectively,with compound 3 showing better inhibitory activity than the benign drug acarbose(4.6 µg/mL);compounds 1,3,4 and 12 showed good PTP1B inhibitory activity with IC50 values of 15.2,8.6,2.2 and 21.2 μg/mL,respectively,of which the inhibitory activity of compound 3 was superior to that of the benign drug oleanolic acid(12.5 µg/mL),and the inhibitory activity of compound 4 was superior to that of the positive drugs sodium orthovanadate(7.5 μg/mL)and oleanolic acid(12.5 μg/mL).It was shown that both alkyne compounds 3 and 4 have more pronounced α-glucosidase and PTP1B inhibitory activities.Molecular docking technique was used to calculate the interactions of compounds 3 and 4 withα-glucosidase and PTP 1B,respectively,and the calculated results showed that compounds 3 and 4 have strong binding to bothα-glucosidase and PTP1 B.This thesis presents the first dual-targeted study of the antidiabetic activities of the chemical con-stituents of E.chinense roots,and the results suggest that compounds 3 and 4 could be used as antidiabetic lead compounds for subsequent studies.
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