Studies On The Chemical Constituents Of Eclipta Prostrata (L.) And Their Antihyperglycemic Activity

Eclipta prostrate (L.), family Asteraceae, is growing widely in tropical andsubtropical regions. Genus Ecliptae has four species all over the world, but only Ecliptaprostrate (L.), known as “Mohanlian”, is distributed throughout China. The latestpharmacological research revealed that E. prostrate has wide range of biological activities,such as hemostasis, hepatoprotective, immunomodulatory, antiinflammatory, antitumor,antioxidant, antisenility and antianoxia properties. In drug screening, we found the EtOHextract of E. prostrate has new antihyperglycemic activity. To explore the material basis ofE. prostrate antihyperglycemic activity, we have conducted a phytochemical investigationon the EtOH extract of the aerial parts of E. prostrate.Modern separation technology, such as silica gel, ODS, Sephadex LH-20and MCIcolumn chromatography, were applied to the isolation and purification of petroleum ether,EtOAc and n-BuOH soluble parts of E. prostrate. Spectral analysis technology, includingNMR and MS, were employed in elucidating structure of compounds. At present, we haveisolated eighty four compounds from E. prostrata (L.), mainly including thiopenes,polyacetylenes, coumarins, flavonoids, lignans, triterpenes, phenolic acids and ceramides,successively named,2-(penta-1,3-diynyl)-5-(3,4-dihydroxy-but-1-ynyl)-thiophene (1),5-(3-butene-1-ynyl)-5’-ethoxymethyl-2,2’-bithiophene (2),5-(but-3-yne-1,2-diol)-5′-hydroxymethyl-2,2’-bithiophene (3),5’-isovaleryloxymethyl-5-(4-isovaleryloxy-but-1-ynyl)-2,2’-bithiophene (4),5-methanol-5’-(3-butene-1-ynyl)-2,2’-bithiophene (5),α-terthienyl methanol (6),5-methoxymethyl-2,2’:5’,2’’-terthiophene (7),5-ethoxymethyl-2,2’:5’,2’’-terthiophene (8), α-formylterthienyl (9),(4E,6E)-tetradeca-4,6-dien-8,10,12-triyne-1,3-diol-3-O-β-D-glucopyranoside (10), E-trideca-1,5-dien-7,9,11-triyne-3,4-diol-4-O-β-D-glucopyranoside (11), apigenin (12), luteolin (13), quercetin (14), eriodictyol(15), orobol (16), pratensein (17), wedelolactone (18), isodemethyl wedelolactone (19),pyracanthoside (20), oroboside (21), orobol-5-O-β-D-glccopyranoside (22),3’-O-methylorobol-7-O-β-D-glucoside (23), pratensein-7-O-β-D-glccopyranoside (24), pinoresinol-4-O-β-D-glccopyranoside (25),4,4’-dimethoxy-3’-hydroxy-7,9’:7’,9-diepoxylignan-3-O-β-D-glucopyranoside (26), syringaresinol-4-O-β-D-glccopyroside (27), lanicepside A (28),longifloroside (29), bidensmenthoside A (30), bidensmenthoside B (31), rel-(1S,2S,3S,4R,6R)-1,6-epoxy-menthane-2,3-diol-3-O-β-D-glucopyranoside (32), rel-(1S,2S,3S,4R,6R) -6′-O-caffeoyl-1,6-epoxy-menthane-2,3-diol-3-O-β-D-glucopyranoside (33),(2E,6E)-2,6,10-trimethyl dodeca-2,6,11-triene-1,10-diol-1-O-β-D-glucopyranoside (34),echinocystic acid (35),3β,16β,29-trihydroxy oleanane-12-ene-3-O-β-D-glucopyranoside(36), eclalbasaponin A (37),3-O-(6-O-acetyl-β-D-glucopyranosyl) oleanolic acid (38),eclalbasaponinVIII (39), eclalbasaponinVII (40), lucynoside H (41), eclalbasaponin I (42),eclalbasaponin VI (43),3,28-di-O-β-D-glucopyranosyl-3β,16β-dihydroxy-12-ene-28-oleanlic acid (44),3-O-(2-O-acetyl-β-D-glucopyranosyl) oleanolic acid-28-O-(β-D-glucopyranosyl) ester (45),3-O-(6-O-acetyl-β-D-glucopyranosyl) oleanolic acid-28-O-(β-D-glucopyranosyl) ester (46),3-O-(β-D-glucopyranosyl) oleanolic acid-28-O-(6-O-acetyl-β-D-glucopyranosyl) ester (47),3-O-(β-D-glucopyranosyl)-20-en lupoic acid-28-O-(β-D-glucopyranosyl) ester (48),3-O-[β-D-glucopyranosyl-(1→2)-β-D-glucopyranosyl]-18-ene oleanlic acid-28-O-β-D-glucopyranoside (49),3-O-[β-D-glucopyranosyl-(1→2)-β-D-glucopyranosyl] oleanolic acid-28-O-β-D-glucopyranoside (50), eclalbasaponin III(51), silphioside C (52), β-sitosterolum (53), stigmasterol (54), sitgmasterol-3-O-β-D-glccopyranoside (55),3-O-(6-O-palmitoyl-β-D-glucopyranosyl) stigmasterol (56),tachinoside (57), leonuriside A (58), protocatechuic aldehyde (59), protocatechuic acid (60),ethyl protocatechuate (61),2,6-dihydroxy-4-methoxybenzoate (62), ferulaldehyde (63),caffeic acid (64), caffeic acid ethyl ester (65), ferulic acid ethyl ester (66),(9Z,12Z)-methyloctadeca-9,12-dienoate (67),(9Z,12Z,15Z)-octadeca-9,12,15-trienoate (68), berulide (69),1-O-octadecanoyl-2-O-(9Z,12Z-octadecadienoyl)-3-O-[α-D-galactopyranosyl-(1→6)-O-β-D-galactopyranosyl] glycerol (70), diacylglycolipid (71),1,2-O-(bis-9,12,15-octadecatrienoyl)-3-O-[α-D-galacto-pyranosyl-(1→6)-O-β-D-galactopyranosyl] glycerol(72),(R)-2-hydroxy-N-[(2S,3S,4R, E)-1-O-β-D-glucopyranosyl-1,3,4-trihydroxy heptadec-9-en-2-yl] nonadecanamide (73),(R)-2-hydroxy-N-[(2S,3S,4R,E)-1,3,4-trihydroxyoctadec-10-en-2-yl] tetracosanamide (74), aralia cerebroside (75), methyl-α-D-fructofuranoside(76), ethyl-α-D-fructofuranoside (77), methyl-β-D-glucopyranoside (78), β-adenosine (79),(3S,5R,6S,7E,9R)-3-hydroxy-5,6-epoxy-β-ionyl-3-O-β-D-glccopyranoside (80),calaliukiuenoside (81), junipeionoloside (82), euodionoside A (83), α-tocopherol (84).Compounds2,3,10,11,32–35,44–47and49were identfied to be new compounds.Forty-one compounds,1,5,7,15–17,20,21,23–31,38,41,48,50,52,56–59,61,63–66,70–75and80–83, were isolated from E. prostrata (L.) for the first time.α-amylase and dipeptidyl peptidase IV (DPP-IV) in vitro were tested forantihyperglycemic activities. The experimental results suggested that all the tested samples showed little inhibitory activities in α-amylase test, and the inhibitory rates of α-amylasewere less than45.25%. However, in DPP-IV test, petroleum ether, EtOAc and n-BuOHsoluble part showed inhibitory rates of91.78%,74.56%,42.55%, respectively. Compounds1–9,15–17and65showed significant inhibitory effects, and the inhibitory rates rangedfrom88.33%to100.93%. What’s more, compounds1–9potently inhibited DPP-IV activityin human plasma, with IC50values of0.51~4.42μM. Therefore, it was deduced that DPPIV inhibitor might be low polarity, small molecular weight compounds with aromatic rings.In summary, the petroleum ether soluble part of E. prostrate, along with thiophenederivatives showed antihyperglycemic activity and could be promising candidate agents forthe treatment of patients with type-II diabetes.