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The inhibition of amyloid β (Aβ) aggregation and degradation of Aβ aggregates are promising approaches for treating and preventing Alzheimer's disease. In our search for Aβ42 aggregation inhibitors, we isolated seven undescribed meroterpenoids, sargasilides A (1)‒G (7), from brown alga (Sargassum siliquastrum) collected at Noto Peninsula in Japan. We structurally elucidated the isolated meroterpenoids using spectroscopic data and evaluated their activities using Thioflavin T assay and transmission electron microscopy. Among the seven compounds isolated, sargasilide B had the strongest inhibitory activity. From the comparison of structure and activity, the geometric isomerism of olefins and length of isoprene side chains are important for the activity of meroterpenoids isolated from brown alga., Competing Interests: Declarations. Conflict of interest: The authors declare that they have no conflict of interest related to this report or the study it describes., (© 2024. The Author(s) under exclusive licence to The Japanese Society of Pharmacognosy.)

We report on the chemical characteristics of the red alga Laurencia japonensis , collected off the coast of Yoshio, Katsuura, Boso Peninsula, Japan. We isolated two new brominated C 15 -acetogenins in this species, which we name katsuurenyne A ( 1 ) and katsuurenyne B ( 2 ), along with two already known halogenated terpenes [2,10-dibromo-3-chloro-α-chamigrene ( 7 ) and aplysiadiol ( 8 )]. We extensively analysed spectral data (from IR, ESI-MS, 1D-NMR and 2D-NMR) to confirm the structure of these compounds.

Schizonepeta tenuifolia Briquet, commonly known as Japanese catnip, is used for the treatment of colds, headaches, fevers, and skin rashes in traditional Asian medicine (China, Japan and Korea). The volatile oil and its constituents have various demonstrated biological activities, but there is currently limited information regarding the site of biosynthesis. Light microscopy and scanning electron microscopy indicated the presence of three distinct glandular trichome types which, based on their morphological features, are referred to as peltate, capitate and digitiform glandular trichomes. Laser scanning microscopy and 3D reconstruction demonstrated that terpenoid-producing peltate glandular trichomes contain a disk of twelve secretory cells. The oil of peltate glandular trichomes, collected by laser microdissection or using custom-made micropipettes, was demonstrated to contain (-)-pulegone, (+)-menthone and (+)-limonene as major constituents. Digitiform and capitate glandular trichomes did not contain appreciable levels of terpenoid volatiles. The yield of distilled oil from spikes was significantly (44%) higher than that from leaves, while the composition of oils was very similar. Oils collected directly from leaf peltate glandular trichomes over the course of a growing season contained primarily (-)-pulegone (>80% at 32 days after germination) in young plants, while (+)-menthone began to accumulate later (>75% at 80 days after germination), at the expense of (-)-pulegone (the levels of (+)-limonene remained fairly stable at 3-5%). The current study establishes the morphological and chemical characteristics of glandular trichome types of S. tenuifolia, and also provides the basis for unraveling the biosynthesis of essential oil in this popular medicinal plant., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

The compositions of terpenoids from the solvent extracts of two silicified wood samples were analyzed using a GC/MS method. Chromatographic analysis showed that several biomolecules were preserved unaltered in the Miocene-aged Japanese wood. These were α-terpineol, α-cedrene, thujopsene, widdrol and ferruginol, among others. In addition to the bioterpenoids, the fossil woods contained a series of geoterpenoids that were generated from their biological precursors before and after burial. These were cadalene, daucalene, pseudowiddrene and cuparene. The chemical composition of both analyzed fossil samples suggest that the silicified woods collected in the Noto Peninsula belong to the Cupressaceae family; this was confirmed by morphological analysis. Both samples were identified as Taxodioxylon cunninghamioides, which is the most common Miocene wood in Japan.

Ten new austalide meroterpenoids (1-10) were isolated from the alga-derived fungi Penicillium thomii KMM 4645 and Penicillium lividum KMM 4663. Their structures were elucidated by extensive spectroscopic analysis and by comparison with related known compounds. The absolute configurations of some of the metabolites were assigned by the modified Mosher's method and CD data. Compounds 1, 2, 8, and 9 were able to inhibit AP-1-dependent transcriptional activity in JB6 Cl41 cell lines at noncytotoxic concentrations. Austalides 1-5, 8, and 9 exhibited significant inhibitory activity against endo-1,3-β-D-glucanase from a crystalline stalk of the marine mollusk Pseudocardium sachalinensis.

Over the past twenty years, our research group has been studying the chemical constituents of mushrooms. From nineteen species, namely, Amanita virgineoides Bas (Amanitaceae), Daedaleopsis tricolor (Bull.: Fr.) Bond. et Sing. (Polyporaceae), Grifolafrondosa (Fr.) S. F. Gray (Polyporaceae), Hericium erinaceum (Bull.: Fr.) Pers. (Hericiaceae), Hypsizigus marmoreus (Peck) Bigelow (Tricholomataceae), Lactarius piperatus (Scop.: Fr.) S. F. Gray (Russulaceae), Lentinula edodes (Berk.) Sing. (Pleurotaceae), Lyophyllyum connatum (Schum.: Fr.) Sing. (Tricholomataceae), Naematoloma sublateritium (Fr.) Karst. (Strophariaceae), Ompharia lapidescens Schroeter (Polyporaceae), Panellus serotinus (Pers.: Fr.) Kuhn. (Tricholomataceae), Pholiota nameko (T. Ito) S. Ito et Imai in Imai (Strophariaceae), Pleurotus eringii (DC.: Fr.) Quel. (Pleurotaceae), Polyporus umbellatus Fries (Polyporaceae), Russula delica Fr. (Russulaceae), Russula sanguinea (Bull.) Fr. (Russulaceae), Sarcodon aspratus (Berk.) S. Ito (Thelephoraceae), Tricholoma matsutake (S. Ito et Imai) Sing. (Tricholomataceae), and Tricholomaportentosum (Fr.) Quel. (Tricholomataceae), we isolated eight new sesquiterpenoids, six new meroterpenoids, three new triterpenoids, and twenty eight new sterols. In this review, structural features of these new compounds are discussed.

A new dammarane-type triterpenoid saponin, chikusetsusaponin VII (1), and nineteen known triterpenoid saponins, ginsenoside Rb1 (2), ginsenoside Rb3 (3), ginsenoside Rc (4), ginsenoside Rd (5), ginsenoside Re (6), ginsenoside Rg1 (7), ginsenoside Rg2 (8), ginsenoside Rh1 (9), notoginsenoside R1 (10), notoginsenoside R2 (11), notoginsenoside Fe (12), chikusetsusaponin IVa (13), chikusetsusaponin IV (14), chikusetsusaponin V (15), chikusetsusaponin VI (16), chikusetsusaponin FK6 (17), gypenoside XVII (18), 28-desglucosylchikusetsusaponin IV (19), and zingibroside R1 (20), were isolated from rhizomes, taproots, and lateral roots of Panax japonicus C. A. Meyer, so-called "Satsuma-ninjin," grown in southern Miyazaki Prefecture, Japan. The structure of new chikusetsusaponin VII was elucidated on the basis of spectral and physicochemical evidence. Although the chemical composition of the rhizome was found to be similar to that of the "Chikusetsu-ninjin," the saponin composition of lateral root of "Satsuma-ninjin" was found to be close to that of lateral root of P. ginseng. The total yield of oleanolic acid saponins of the taproot was less than that of rhizome, but the total yield of dammarane-type saponins of the taproot was found to be similar to that of rhizome.

We identified the soldier-specific compounds in the Japanese subterranean termite, Reticulitermes speratus, to clarify their ethological roles. Silica gel column chromatography separated one major soldier-specific compound in the hexane fraction accounting for 70-80% of the total amount of the fraction, while cuticular hydrocarbons constituted the rest. We identified the compound as β-selinene by gas chromatography-mass spectrometry (GC-MS) and nuclear magnetic resonance (NMR) spectroscopy. Comparative GC analyses of the major exocrine glands detected the compound in the soldier's frontal gland. Both soldiers and workers made aggregation to the hexane fraction, as well as to the crushed heads and head extract of the soldiers. They did not aggregate to cuticular hydrocarbons, making it likely that β-selinene was the aggregation pheromone in this species. The opportunistic predator of this termite, Lasius japonicus, was also attracted to the compounds. The ant workers, therefore, would use the termite aggregation pheromone as a kairomone for hunting them.

The rapid and highly separative ultra high-performance liquid chromatography (UHPLC)-UV method was adopted and validated to investigate the flavonol glycoside compositions in ginkgo leaf products on the Japanese market. The result indicates that certain products contained amounts of flavonol glycosides approximately equivalent to the medicinal product. Additionally, we examined the correlations between the total amount of flavonol glycosides and of terpene lactones in various ginkgo leaf products.

During the course of our screening program to isolate isoprenoids from marine Actinobacteria, 523 actinobacterial strains were isolated from 18 marine sponges, a tunicate, and two marine sediments. These strains belonged to 21 different genera, but most were members of Streptomyces, Nocardia, Rhodococcus, and Micromonospora. Some Actinobacteria have been reported to use the mevalonate pathway for the production of isoprenoids as secondary metabolites. Therefore, we investigated whether these strains possessed the 3-hydroxyl-3-methylglutaryl coenzyme A reductase (hmgr) gene, which indicates the presence of the mevalonate pathway. As a result, six strains belonging to the genera Streptomyces (SpC080624SC-11, SpA080624GE-02, and Sp080513GE-23), Nocardia (Sp080513SC-18), and Micromonospora (Se080624GE-07 and SpC080624GE-05) were found to possess the hmgr gene, and these genes were highly similar to hmgr genes in isoprenoid biosynthetic gene clusters. Among the six strains, the two strains SpC080624SC-11 and SpA080624GE-02 produced the novel isoprenoids, JBIR-46, -47, and -48, which consisted of phenazine chromophores, and Sp080513GE-23 produced a known isoprenoid, fumaquinone. Furthermore, these compounds showed cytotoxic activity against human acute myelogenous leukemia HL-60 cells.

One of bacteria collected from Lake Sagami, Japan, Brevibacillus sp., was found to have a lytic activity of cyanobacteria, but did not produce active compounds. Instead, the co-culturing of Microcystis with the Brevibacillus sp. enhanced the production of two volatile compounds, beta-cyclocitral and 3-methyl-1-butanol, and the former had a characteristic lytic activity. It was confirmed that these volatile compounds were derived from the cyanobacteria themselves. beta-Ionone, geosmin and 2-methylisoborneol derived from cyanobacteria and similar volatile compounds, terpenoids, produced by plants also had a lytic activity. The minimum inhibitory concentration values of the cyanobacterial metabolites were estimated to be higher than those of compounds from plants except for a few compounds. Among them, beta-cyclocitral only produced a characteristic color change of culture broth from green to blue. This color change is similar to the phenomenon observed when a sudden decline in growth of cyanobacteria begins in a natural environment.

Marine opisthobranchs are mollusks scarcely protected by a shell which can be either reduced or completely absent. It is generally accepted that they possess chemical defenses (allelochemicals) against predators. These protective molecules can derive from dietary habits (algae, sponges, tunicates, soft corals, etc.) and can be used either in their intact form or as derived metabolites. Added to this, other compounds are biogenetically obtained. These defensive compounds are very often concentrated in the external parts of the animal and are also released into the mucous secretion to deter predators. The chemical defenses of sea hares (order Anaspidea) and sea slugs (order Nudibranchia) are well studied. This review highlights the allelochemicals reported from Japanese anaspideans and nudibranchs, with particular attention to the finding of our group.

Seven new nitrogenous terpenoids, (1R,6R,7S,10S)-10-isothiocyanatocadin-4-ene (1), (1S,2S,5S,6S,7R,8S)-13-isothiocyanatocubebane (2), (1R,3S,4R,7S,8S,12S,13S)-7-isocyanoamphilecta-10,14-diene (3), (1S,3S,4R,7S,8S,12S,13S)-8-isocyanoamphilecta-11(20),14-diene (4), (3S,4R,7S,8S,11S,13S)-8-isocyanoamphilecta-1(12),14-diene (5), 8-isocyanatocycloamphilect-10-ene (6), and 8-isothiocyanatocycloamphilect-10-ene (7), were isolated from the Okinawan sponge Stylissasp., along with 12 known related compounds. Structural determinations of these compounds were made by spectroscopic analysis, and assessment was made of their cytotoxicity toward HeLa cells.

Three new sesterterpenes (1-3) were isolated from a marine sponge of the genus Spongia, and their structures were determined on the basis of spectroscopic analysis. The compounds 1-3 exhibited cytotoxicity against HeLa cells with IC(50) values of 19.5, 15.0, and 5.3 microg/mL, respectively.

Five new sesterterpenes have been isolated from a lipophilic extract of a sponge, Ircinia sp., and their structures elucidated by spectroscopic and chemical methods. The absolute configurations of two metabolites (1, 3) were established by chemical degradation. These compounds showed moderate cytotoxicity against KB cells.

Lipid compositions of mangrove trees were studied in relation to the salt-tolerance mechanism. Leaves and roots were obtained from seven mature mangrove trees on Iriomote Island, Okinawa: Bruguiera gymnorrhiza, Rhizophora stylosa, Kandelia candel, Lumnitzera racemosa, Avicennia marina, Pemphis acidula and Sonneratia alba. Lipids of mangrove leaves mainly consisted of 11 lipid classes: polar lipids, unknown (UK) 1-6, sterols, triacyl glycerols, wax ester and sterol ester (UK 3 and 4 were found to be tri-terpenoid alcohol in this study). Of these lipid classes, sterol ester was the main lipid in all species comprising 17.6-33.7% of total lipids. Analysis of the chemical structure found that the sterol esters mainly consisted of fatty acid esters of tri-terpenoid alcohols. One major tri-terpenoid alcohol was identified to be lupeol by interpretation of infrared resonance, nuclear magnetic resonance and mass spectrometry. Because of the unique anatomy of the mangrove root, lipid analyses were made separately for epidermis, cortex and innermost stele, respectively. The concentration of free tri-terpenoid alcohols showed a higher tendency in the outside part than in the inside portion of the roots, suggesting their protective roles. Relevance of lipid composition to salt tolerance was studied with propagules of K. candel and B. gymnorrhiza planted with varied salt concentrations. The proportions of free tri-terpenoids increased with salinity in both leaves and roots of K. candel, and only in roots of B. gymnorrhiza. No salt-dependent changes were noted in the phospholipid and fatty acid compositions in both species. These findings suggested that salt stress specifically modulated the terpenoid concentrations in mangroves.

Four monoterpene hydroperoxides were isolated from aerial parts of Chenopodium ambrosioides along with ascaridole (1), the anthelmintic principle of this plant, as anti-trypanosomal compounds. The structures of these monoterpenes were determined to be (-)-(2S,4S)- and (-)-(2R,4S)-p-mentha-1(7),8-dien-2-hydroperoxide (2a and 3a) and (-)-(1R,4S)- and (-)-(1S,4S)-p-mentha-2,8-dien-1-hydroperoxide (4a and 5a) on the basis of spectroscopic methods and chemical correlations. In vitro trypanocidal activities of ascaridole (1) and these hydroperoxides (2a-5a) against epimastigotes of Trypanosoma cruzi were 23, 1.2, 1.6, 3.1, and 0.8 microM, respectively. Fresh leaves of C. ambrosioides also contained isomeric hydroperoxides 6a and 7a, and the content ratio of 2a-7a suggested that these hydroperoxides were formed through the singlet-oxygen oxidation of limonene.

Seven carotenoid metabolites including five loliolide derivatives have been isolated from the brown alga Undaria pinnatifida, including three new compounds. Structures of these compounds were confirmed by spectroscopic analyses and literature data.

Hymenosides G--J were newly isolated from the Japanese fern Hymenophyllum barbatum, in addition to hymenosides A--F. The structures of hymenosides were elucidated by extensive two-dimensional nuclear magnetic resonance and/or chemical evidence. The structures of those aglycones were divided into three types, 1,4-dihydroxy-2-hydroxymethyl-but-2-ene, 1,4-dihydroxy-2-methyl-but-2-ene, and 3-hydroxy-5-hexanolide. The sugar moieties were also established by chemical and spectroscopic methods, which were acylated by phenylacetic acid derivatives. These glycosides had a bitter or weakly pungent taste.

Solvent-extractable organic compounds in the rain and snow collected at local cities in the mountainous region in central Japan, were analyzed by GC/MS and GC. Pinonaldehyde (2,2-dimethyl-3-acetyl-cyclobutyl-ethanal), an atmospheric reaction product of alpha-pinene, was detected in the rain and snow for the first time, and n-alkanes (C17-C33), fatty acids (C8-C23), and benzoic acid were also detected as major organic components. Concentrations of pinonaldehyde, C17-C33 n-alkanes, C8-C11 fatty acids, C12-C23 fatty acids and benzoic acid ranged between <0.02-13, 0.10-35, 0.55-5.7, 4.2-19 and <0.02-6.0 microg/l, respectively. Their composition showed some difference in summer and winter. In summer, fatty acids and benzoic acid were more abundant, while pinonaldehyde and n-alkanes were much less. Higher photochemical reactivity and higher bioactivity in summer could explain these seasonal changes except for pinonaldehyde, which would suffer from further oxidation in the atmosphere after its photochemical production from alpha-pinene. Predominance of pinonaldehyde and C12-C23 fatty acids in the rain and snow showed a remarkable contrast to n-alkanes in aerosol phase, which were the most abundant components. It indicated that oxygenated products from biogenic compounds might be important as cloud condensation nuclei in forest areas.

From the water-soluble portion of the methanol extract of the fruit of Glehnia littoralis Fr. SCHMIDT ex MIQ. (Umbelliferae; "hamabofu" in Japanese), thirty compounds, including three new monoterpenoids and a new monoterpenoid glucoside, a new benzofuran glucoside, a new alkyl glucoside, and a new glucide, were obtained. Their structures were clarified by spectral investigation.

Three geraniol glycosides were isolated from immature fresh ginger rhizomes (Zingiber officinale Roscoe). Their structures were identified as geranyl 6-O-alpha-L-arabinopyranosyl-beta-D-glucopyranoside (1) geranyl 6-O-beta-D-apiofuranosyl-beta-D-glucopyranoside (2) and geranyl 6-O-beta-D-xylopyranosyl-beta-D-glucopyranoside (3) by spectrometric analyses. After incubating each glycoside with a crude enzyme solution prepared from ginger, geraniol was liberated in all of those fractions. This result indicates that the glycosides are related to the formation of geraniol-related compounds in ginger aroma.

Bioassay-guided separation of MeOH extract of Japanese Paeoniae Radix inhibiting contractile responses of guinea pig ileum stimulated with electric field disclosed a new monoterpene glycoside, 6-O-beta-D-glucopyranosyl-lactinolide (1), as an active constituent together with two new monoterpene glycosides (3 and 4) and two new monoterpenes (2 and 5). Furthermore, 1-O-beta-D-glucopyranosyl-paeonisuffrone (2) was found to inhibit histamine release from rat peritoneal exudate cells induced by antigen-antibody reaction.