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A cytotoxic principle was newly isolated from Chrysosplenium grayanum Maxim. (Saxifragaceae) and identified as beta-peltoboykinolic acid (1) on the basis of spectral data. Cytotoxicity of compound 1 was tested against various human cancer cell lines in vitro, and antitumor effect of this compound was demonstrated on Meth.A mouse fibrosarcoma. The experiment of combined treatment with compound 1, mitomycin C, and OK-432 resulted in enhancing the antitumor effect against B16-BL6 mouse melanoma in C57BL/6 mice.

The 70% EtOH extract of Scoparia dulcis showed inhibitory activity against beta-glucuronidase from bovine liver. Bioassay-directed fractionation of the active extract led to the isolation of three labdane-type diterpene acids, scoparic acid A [1] [6-benzoyl-12-hydroxy-labda-8(17), 13-dien-18-oic acid], scoparic acid B [2] [6-benzoyl-14,15-dinor-13-oxo-8(17)-labden-18-oic acid], and scoparic acid C [3] [6-benzoyl-15-nor-14-oxo-8(17)-labden-18-oic acid], the structures of which were established by spectral means, including X-ray analysis. Scoparic acid A was found to be a potent beta-glucuronidase inhibitor.

The lipid soluble fraction of Panax ginseng C. A. Meyer has been found to possess a stimulatory effect on a para-neuronal culture cell line, namely PC12 cells. Addition of the diethyl ether extract (0.025-0.1 mg/ml) of Ginseng radix to a culture medium promoted the outgrowth of neurites from cells dose-dependently as well as their ready differentiation to respond to carbachol and high KCl-evoked membrane depolarization to induce free Ca2+ accumulation in the cells within a week of culture. Effective constituents of the extract were confined to four major substances detected in the extremely lipophilic front area on silica gel TLC.

Bioassay-guided fractionation of Gardeniae Fructus extract (GFE), which stimulates the proliferation of cultured endothelial cells, led to the isolation of glycerol and D-mannitol. Both compounds significantly increased the incorporation of [3H]thymidine and [14C]leucine into the acid-insoluble fraction of bovine aortic endothelial cell layers in culture. This clearly indicated that glycerol and D-mannitol are active components of GFE on endothelial cell proliferation. On the other hand, they did not change the number of cultured vascular smooth muscle cells from bovine aorta. Glycerol and D-mannitol may be beneficial drugs for vascular disorders.

For several years we have screened natural products having aldose reductase (AR) inhibitory activity. 3,3',4-Tri-O-methylellagic acid 4'-sulfate potassium salt (2) was isolated from a Mexican herb "Sinfito" (Potentilla candicans) as a potent AR inhibitory active constituent. 2 was more potent (IC50 = 8.0 x 10(-8)M) than ellagic acid, which is one of the natural inhibitors of AR. So we examined the synthesis of ellagic acid derivatives and found that the sulfate group is one of the important function.

The structure of scopadulcic acid B (2, SDB), a major ingredient of the Paraguayan herb "Typychá kuratũ" (Scoparia dulcis L.), was elucidated mainly by comparison of its spectral data with that of scopadulcic acid A (1). SDB inhibited both the K(+)-dependent adenosine triphosphatase (ATPase) activity of a hog gastric proton pump (H+, K(+)-ATPase) with a value of 20-30 microM for IC50 and proton transport into gastric vesicles. Pharmacokinetic studies of SDB in rats indicated that plasma SDB concentrations after i.v. injection of the sodium salt of SDB (SDB-Na) were described reasonably well by a two-compartment open model with Michaelis-Menten elimination kinetics. Plasma concentrations after oral administration of SDB-Na or SDB showed a much slower decline than what was expected following the i. v. study. It was suggested that the sustained plasma level of SDB after oral administration of SDB-Na or SDB was accounted for by relatively slow but efficient gastro-intestinal absorption in rats.

The anti-inflammatory active fraction of the Paraguayan crude drug, "Alhucema," Lavandula latifolia Vill. afforded four compounds: coumarin (1), 7-methoxycoumarin (2), trans-phytol (3) and caryophyllene oxide (4). 1 showed a weakly inhibitory effect on carrageenin-induced paw edema in rats on topical application and 4 showed an inhibitory effect on histamine-induced contraction in guinea pig ileum.

The phloroglucinol derivatives isolated from Mallotus japonicus Muell. Arg. (Euphorbiaceae) and their derivatives were evaluated for their capacity to produce cytotoxicity in HeLa cells and to inhibit the replication of herpes simplex virus type 1 (HSV-1). The characterizations of an isolated new acetophenone, mallophenone (16), and cyclization products of mallotojaponin (1), isomallotochromene (17), mallotochroman (18) and isomallotochroman (19), were also described. All tested derivatives inhibited the replication of HSV-1 with ED50 in the range of 88 ng--48 micrograms/ml. The derivatives 12 and 19 were found in vitro therapeutic index with 10.9 and 9.1, respectively, and they were considered to be active antivirals.

The structure and stereochemistry of scopadulin, a novel aphidicolane-type diterpene isolated from Scoparia dulcis L. have been established from spectral data and single-crystal X-ray analysis of its acetone solvate.

Two new phloroglucinol derivatives, isomallotolerin (1) and isomallotochromanol (2), were isolated from the cytotoxic fraction of the pericarps of Mallotus japonicus. The new derivatives were identified as 3-(3-methyl-2-hydroxybut-3-enyl)-5-(3-acetyl-2,4-dihydroxy-5-methy l-6- methoxybenzyl)-phlorisobutyrophenone (1) and 6-acetyl-5,7-dihydroxy-8-(3-acetyl-2,4-dihydroxy-5-methyl-6-methoxybenzy l)-2,2- dimethyl-3-hydroxychroman (2) from chemical and spectral data. Isomallotolerin and its acetate were found to be cytotoxic to KB cell line.

A cytotoxic alkylresorcinol was isolated from Lysimachia japonica THUNB. (Primulaceae) and identified as grevillol (2). It was tested for cytotoxicity against KB, B-16, PC-13, L-5178Y, P-388, and HEp-2 cells in vitro. Synthetic related compounds were also tested for cytotoxicity against the KB cell line, and the structure-activity relationships are discussed.

Two new cytotoxic chromene derivatives, butyrylmallotochromene [10] and isobutyrylmallotochromene [11], were isolated from the pericarps of Mallotus japonicus. The new derivatives were identified as 5,7-dihydroxy-6-(2',4'-dihydroxy-3'-acetyl-5'-methyl-6'-methoxybenzyl)-8 - butyryl-2,2-dimethylchromene [10] and 5,7-dihydroxy-6-(2',4'-dihydroxy-3'-acetyl-5'-methyl-6'-methoxybenzyl)-8 - isobutyryl-2,2-dimethylchromene [11] by means of spectral data. These compounds and their respective acetylation and methylation products were found to be cytotoxic against KB cell lines.

Three new lanostanoids--ganodermenonol (1), ganodermadiol (2), and ganodermatriol (3) [isolated as its triacetate derivative (3a)]--were isolated from the MeOH extract of Ganoderma lucidum, together with ergosterol and its peroxide. The new compounds were identified as 26-hydroxy-5 alpha-lanosta-7,9(11),24-trien-3-one (1), 5 alpha-lanosta-7,9(11),24-triene-3 beta, 26-diol (2), and 5 alpha-lanosta-7,9(11),24-triene-3 beta, 26,27-triol (3) by their respective spectral data.

Two new phloroglucinol derivatives, mallotolerin (8) and mallotochromanol (9), were isolated from the cytotoxic fraction of the pericarps of Mallotus japonicus. The new derivatives were identified as 3-(3-methyl-2-hydroxybut-3-enyl)-5-(3-acetyl-2,4-dihydroxy-5-me thy l-6- methoxybenxyl)-phlorbutyrophenone (8) and 8-acetyl-5,7-dihydroxy-6-(3-acetyl-2,4-dihydroxy-5-methyl-6- methoxybenxyl)2,2-dimethyl-3-hydroxychroman (9) by their respective chemical and spectral data. These compounds were found to be cytotoxic against KB and L-5178Y cell lines in culture and to be moderately effective in inhibiting the growth of Ehrlich carcinoma in mice. Cytotoxic activities of the isolated phloroglucinol derivatives (1-9) from the pericarps are also discussed.

Two new phloroglucinol derivatives, named mallotophenone and mallotochromene, were isolated from the pericarps of Mallotus japonicus together with two known compounds, 3-(3,3-dimethylallyl)-5-(3-acetyl-2,4-dihydroxy-5-methyl-6- methoxybenzyl)-phloracetophenone and 2,6-dihydroxy-3-methyl-4-methoxyacetophenone. The new derivatives were confirmed to be 5-methylene-bis-2,6-dihydroxy-3-methyl-4-methoxyacetophenone and 8-acetyl-5,7-dihydroxy-6-(3-acetyl-2,4-dihydroxy-5-methyl-6- methoxybenzyl)2,2-dimethylchromene by their respective chemical and spectral data. Several of the phloroglucinol derivatives isolated from this tree were cytotoxic against the KB system and L-5178Y in cell culture.

Aldose reductase (AR) inhibitory activity-directed fractionation of the 70% ethanolic extract of Para-parai mí, Phyllanthus niruri, has led to the isolation of three active components, ellagic acid (1), brevifolin carboxylic acid (4) and ethyl brevifolin carboxylate (5). Among them, 1 showed the highest inhibitory activity, being about 6 times more potent than quercitrin, which is a known natural inhibitor of AR.