Toshihiro Murata

Antiplasmodial Triterpenoids from Ekebergia Capensis.

From the stem bark of Ekebergia capensis, 10 new triterpenoid compounds, ekeberins A (1), B (2), C1 (3), C2 (4), C3 (5), D1 (6), D2 (7), D3 (8), D4 (9), and D5 (10), were isolated together with 17 known compounds. The structures of these new compounds were elucidated on the basis of the results of spectroscopic analysis, and the absolute configuration of compounds 6-10 were determined by partial synthesis from known compounds and using the Mosher ester method. Several of these compounds were screened in vitro against both chloroquine (CQ)-sensitive and -resistant Plasmodium falciparum isolates and were found to exhibit moderate antiplasmodial activity, with compounds 20 (7-deacetoxy-7-oxogedunin) and 27 (2-hydroxymethyl-2,3,22,23-tetrahydroxy-2,6,10,15,19,23-hexamethyl-6,10,14,18-tetracosatetraene) showing IC50 values of 6 and 7 microM, respectively. Compound 27 at a dose of 500 mg/kg showed moderate parasitemia suppression of 52.9% against P. berghei NK 65 in a mouse model.

Matrix Metalloproteinase-2 Inhibitors from Clinopodium chinense var. parviflorum

From the aerial parts of Clinopodium chinense var. parviflorum, nine new phenylpropanoids, clinopodic acids A-I (2-10), were isolated together with a known phenylpropanoid, rosmarinic acid (1). The structures of these new compounds were elucidated on the basis of spectroscopic analysis. Clinopodic acid C (4) showed MMP-2 inhibitory activity (IC(50) 3.26 microM).

A lipase inhibitor monoterpene and monoterpene glycosides from Monarda punctata

An 80% acetone extract of Monarda punctata showed an inhibitory effect on lipase activity in isolated mouse plasma in vitro and carvacrol was obtained as the active constituent. It had an IC₅₀ value of 4.07 mM invitro and suppressed elevations in blood triacylglycerol levels in olive oil-loaded mice. Furthermore, from the whole plant, 22 compounds were isolated. Six monoterpene glycosides, a flavone glucuronide, and other known compounds were identified based on the results of spectroscopic analyses.

Iridoid glycoside constituents of Stachys lanata.

From the aerial parts and roots of Stachys lanata, four new iridoid glucosides, stachysosides E-H (1-4), were isolated together with 30 known compounds. The structures and the stereo configurations of these new compounds were elucidated on the basis of the results of spectroscopic analysis. Compounds 1-4 are esters of monomelittoside.

Lipase inhibitory and LDL anti-oxidative triterpenes from Abies sibirica

A methanol extract of Abies sibirica Ladeb, a Mongolian medicinal plant, had an inhibitory effect on both lipase activity in mouse plasma and LDL anti-oxidative activity, which are preventative factors for arteriosclerosis. The extract was fractionated by silica gel column chromatography and its active constituents were sought. From lipid soluble fractions, 20 terpenoids including seven hitherto unknown triterpenes were isolated. The latter triterpenes had either a γ-lactone ring with a lactol or a derivative thereof. Their chemical structures were determined by spectroscopic methods. The lipase inhibitory activity and LDL anti-oxidative activity of these compounds were evaluated. Some constituents (either lipase inhibitory or LDL anti-oxidative activities) had moderate inhibitory activities.

Constituents of Rhodiola rosea showing inhibitory effect on lipase activity in mouse plasma and alimentary canal.

As a methanol extract of the rhizome of Rhodiola rosea inhibits the activity of lipase in isolated mouse plasma in vitro and in the mouse gastrointestinal tube in vivo, the active components in this plant were investigated. After fractionation and separation processes, rhodionin and rhodiosin were isolated as active ingredients. Their IC50 values were 0.093 mM and 0.133 mM in vitro, respectively. Both compounds significantly suppressed the elevation of the postprandial blood triglyceride level, e.g., by 45.6 % (150 mg/kg, 60 min after oral administration) and 57.6 % (200 mg/kg, 180 min after oral administration), respectively. Consequently, we anticipate the application of this plant and its constituents to the treatment of lifestyle-related diseases such as hyperlipidemia and exogeneous obesity and to health foods.

New phenolic compounds from Meehania urticifolia

A new phenylethanoid glycoside, rashomoside A (1), a new phenolic glucoside, rashomoside B (2), and a new shikimic acid derivative (3) were isolated from Meehania urticifolia together with 12 known flavones (4–15), three known phenylethanoid glycosides (16–18), and 13 other compounds (19–31). The structure of each of these compounds was elucidated based on the results of spectroscopic analysis.

Diastereomers of lithospermic acid and lithospermic acid B from Monarda fistulosa and Lithospermum erythrorhizon.

Monardic acids A (1) and B (2), which are (7R,8R) diastereomers of lithospermic acid (LA) and lithospermic acid B, respectively, were isolated from Monarda fistulosa. A (7S,8R) isomer (3) of LA was also isolated from this plant, and a (7R,8S) isomer (7) of LA was obtained from Lithospermum erythrorhizon. The absolute configuration of 1 was confirmed by analysis of its hydrolysates, 7-epiblechnic acid and 2R-3-(3,4-dihydroxyphenyl)-2-hydroxypropanoic acid. The configuration in the dihydrobenzofuran moieties of 2, 3, and 7 was extrapolated by using the phenylglycine methyl ester method and a Cotton effect at approximately 250-260 nm in their electronic circular dichroism spectra. Diastereomers (1-3 and 7) displayed moderate hyaluronidase inhibitory and histamine release inhibitory activities.

Cholinesterase-inhibitory diterpenoids and chemical constituents from aerial parts of Caryopteris mongolica

A diterpenoid diglucoside (12,19-di-O-β-d-glucopyranosyl-11-hydroxyabieta-8,11,13-triene-19-one), isoscutellarein 7-O-[β-d-xylopyranosyl-(1→2)]-β-d-glucopyranoside, isoscutellarein 7-O-[α-l-rhamnopyranosyl-(1→2)]-β-d-glucopyranoside, hypolaetin 7-O-[6″-O-(p-E-coumaroyl)]-β-d-glucopyranoside, hypolaetin 7-O-[6″-O-(E-caffeoyl)]-β-d-glucopyranoside, and 15 known compounds were isolated from aerial parts of the Mongolian medicinal plant Caryopteris mongolica. The cholinesterase-inhibitory activities of the constituents were estimated. The abietane diterpenoids (12-O-demethylcryptojaponol and 6α-hydroxydemethylcryptojaponol) showed potent inhibitory activity against acetylcholinesterase from human erythrocytes and electric eel, and against butyrylcholinesterase from horse serum.

Monoterpene glycosides, phenylpropanoids, and acacetin glycosides from Dracocephalum foetidum

Chemical investigation of the acetone extract from the aerial parts of the Mongolian medicinal plant Dracocephalum foetidum resulted in the isolation of three limonene glycosides, a caffeic acid trimer, four rosmarinic acid glucosides, and five acacetin acyl glycosides, together with 13 known natural products. The chemical structures of all of the compounds were determined by spectroscopic analyses. Among these compounds three showed hyaluronidase inhibitory activity. In addition, one other compound showed stronger 1,1-diphenyl-2-picrylhydrazyl radical scavenging activity than the positive control Trolox, whereas three other compounds demonstrated a similar activity to that of Trolox.