Flavonoid glycosides isolated from Epimedium brevicornum and their estrogen biosynthesis-promoting effects.

Epimedium brevicornum Maxim has a long history of use in the treatment of estrogen deficiency-related diseases. However, the chemical constituents and mechanism of action of this medicinal plant are not fully understood. In the present study, we isolated four new isoprenylated flavonoid glycosides, as well as 16 known flavonoids (13 isoprenylated flavonoids), from this plant. The chemical structures of the new flavonoid glycosides were elucidated by extensive spectroscopic analysis. The new compounds 1-4 were potent promoters of estrogen biosynthesis in human ovarian granulosa-like KGN cells. ZW1, an isoprenylated flavonoid analogue and a specific inhibitor of phosphodiesterase 5 (PDE5), was synthesized and used to explore the mechanism of the isoprenylated analogues on estrogen biosynthesis. ZW1 treatment increased estrogen production by upregulation of aromatase mRNA and protein expression. ZW1 increased the phosphorylation of cAMP response element-binding protein (CREB). Further study showed that the inhibition of PDE5 by ZW1 increased estrogen biosynthesis partly through suppression of phosphodiesterase 3 (PDE3). Our results suggested that the isoprenylated flavonoids from E. brevicornum may produce beneficial health effects through the promotion of estrogen biosynthesis. PDE5 warrants further investigation as a new therapeutic target for estrogen biosynthesis in the prevention and treatment of estrogen-deficiency related diseases.

Diarylheptanoids of Curcuma comosa with inhibitory effects on nitric oxide production in macrophage RAW 264.7 cells.

Eight new diarylheptanoids, a 1.2:1 mixture of (3S)- and (3R)-1-(4-hydroxyphenyl)-7-phenyl-(4E,6E)-4,6-heptadien-3-ol (1a and 1b), a racemic mixture of (3S)- and (3R)-1-(4-hydroxyphenyl)-3-methoxy-7-phenyl-(4E,6E)-4,6-heptadiene (2a and 2b), a ca. 1:1 mixture of (3S)- and (3R)-1-(4-hydroxy-3- methoxyphenyl)-3-methoxy-7-phenyl)-(4E,6E)-4,6-heptadiene (3a and 3b), 3-acetoxy-1-(3,4-dihydroxyphenyl)-7-phenylheptan-5-ol (4), (3R)-1-(4,5- dihydroxyphenyl)-7-phenyl-(6E)-6-hepten-3,2'-epoxide (5), and thirteen known diarylheptanoids, 6-12, a 3:1 mixture of 13a and 13b, and 14-17, were isolated from the rhizomes of Curcuma comosa from Sakon Nakhon, northeastern part of Thailand. The isolated compounds were evaluated for their anti- inflammatory activities on the inhibition of lipopolysaccharide-induced nitric oxide production in macrophage RAW 264.7 cells and the diarylheptanoids 1a and 1b mixture and 14 exhibited potent inhibitory activity.

Diarylheptanoids, new phytoestrogens from the rhizomes of Curcuma comosa: Isolation, chemical modification and estrogenic activity evaluation.

Three new diarylheptanoids, a 1:2 mixture of (3S)- and (3R)-1-(4-methoxyphenyl)-7-phenyl-(6E)-6-hepten-3-ol (13a and 13b) and 1-(4-hydroxyphenyl)-7-phenyl-(6E)-6-hepten-3-one (15), together with two synthetically known diarylheptanoids 1,7-diphenyl-(1E,3E,5E)-1,3,5-triene (9) and 1-(4-hydroxyphenyl)-7-phenyl-(4E,6E)-4,6-heptadien-3-one (16), and nine known diarylheptanoids, 2, 8, 10-12, 14, a 3:1 mixture of 17a and 17b, and 18, were isolated from the rhizomes of Curcuma comosa Roxb. The absolute stereochemistry of the isolated compounds has also been determined using the modified Mosher's method. The isolated compounds and the chemically modified analogues were evaluated for their estrogenic-like transcriptional activity using RT-PCR in HeLa cell line. Some of the isolated diarylheptanoids and their modified analogues exhibited estrogenic activity comparable to or higher than that of the phytoestrogen genistein. Based on the transcriptional activation of both estrogenic targets, Bcl-xL and ERbeta gene expression, the structural features for a diarylheptanoid to exhibit high estrogenic activity are the presence of an olefinic function conjugated with the aromatic ring at the 7-position, a keto group at the 3-position, and a phenolic hydroxyl group at the p-position of the aromatic ring attached to the 1-position of the heptyl chain.

Iridoid glucosides from the flowers of Barleria lupulina.

A new iridoid diglucoside, lupulinoside, and eight known iridoid glucosides, acetylbarlerin, ipolamiidoside ( 3), 6-O-acetylshanzhiside methyl ester, barlerin, shanzhiside methyl ester, mussaenosidic acid, 8-O-acetylshanzhiside, and shanzhiside have been isolated from the flowers of Barleria lupulina. The structure of the new compound was established as 8-O-acetyl-2'- O-(beta-glucopyranosyl)mussaenoside by spectroscopic, especially 2D NMR, techniques. When tested for anti-herpes simplex type 1 activity, only compound 3 exhibited antiviral properties. None of the compounds showed cytotoxic effects to the vero cells and none of them inhibited cyclooxygenase-2 enzyme.