•Six neolignan glucosides, named isodonosides I–VI were isolated.•A megastigmane glucoside named isodonmegastigmane VII was isolated.•The absolute configurations of constituents were determined by ECD Cotton effects and modified Mosher's method.•Significant cell protective effects of neolignan glucosides were found on benzo[a]pyrene-induced cytotoxicity.Six neolignan glucosides, named isodonosides I–VI, and a megastigmane glucoside named isodonmegastigmane I, were isolated together with 15 known compounds from the methanolic extract of aerial parts of Isodon japonicus cultivated in Tokushima, Japan. The chemical structures of the compounds were elucidated based on their MS and NMR spectroscopic analysis. The absolute configurations of the neolignan and megastigmane glucosides were determined by derivatizations, by ECD (electronic circular dicroism) Cotton effect approximation, and by the modified Mosher's method. In addition, a significant cell protective effects of neolignan glucosides on benzo[a]pyrene-induced cytotoxicity was found.Six neolignan glucosides, isodonosides I–VI, and a megastigmane glucoside isodonmegastigmane I were isolated from the aerial parts of Isodon japonicus.Download high-res image (136KB)Download full-size image

An alkaloid with a novel skeleton, oxazonigelladine (1), and four new dolabellane-type diterpenes, damasterpenes I (2) – IV (5), were isolated from the seeds of Nigella damascena. Oxazonigelladine has an isoxazolidinone partial structure bearing a direct bond between a nitrogen atom and an oxygen atom. This small and simple structure is quite rare in the nature. Surprisingly, despite the unstable bond between nitrogen and oxygen, oxazonigelladine was isolated with good stability. On the other hand, damasterpenes are dolabellane-type diterpenes with phenylacetyl, benzoyl, acetyl or nicotinoyl moieties. This report deals with the structure determination including the absolute configuration by X-ray crystallographic analysis and CD analysis.Download high-res image (210KB)Download full-size image

•Two new ent-kaurane diterpenes were isolated from the aerial parts of I. japonicus.•Absolute configuration was elucidated by X-ray crystallographic analysis.•Antimutagenic effects of the ent-kaurane diterpenes were evaluated.From the methanolic extract of the aerial parts of Isodon japonicus, two new ent-kaurane diterpenes, isodonterpenes I and II, were isolated together with 10 known diterpenes. Their chemical structures were elucidated on the basis of chemical and physicochemical evidence. The absolute configuration of isodonterpene I was elucidated by Cu-Kα X-ray crystallographic analysis. Antimutagenic activities of the major diterpenes were evaluated by the Ames test. This study represents the first evaluation of the antimutagenic activities of ent-kaurane diterpenes.Download high-res image (162KB)Download full-size image

•A new nitrogen-containing phenolic glycoside, moringaside A, was isolated from the leaves of Moringa oleifera.•A new megastigmane glycoside, moringamegastigmane A, was isolated from the leaves of M. oleifera.•Their chemical structures of new constituents were elucidated.•Among the compounds from M. oleifera, niazirin significantly stimulated acylated ghrelin secretion in vitro.A new nitrogen-containing phenolic glycoside, moringaside A (1), and a new megastigmane glycoside, moringamegastigmane A (2), were isolated from the leaves of Moringa oleifera together with 16 known compounds. The chemical structures of the isolated compounds were elucidated on the basis of chemical and physicochemical evidence. To the best of our knowledge, there are few reports of compounds that effect acylated ghrelin secretion. Among the constituents of M. oleifera, niazirin (5) significantly stimulated the secretion of acylated ghrelin in vitro using rat primary gastric cells. This result suggests that 5 is a promising therapeutic agent for anorexia.Download high-res image (171KB)Download full-size image

We review the biofunctional effects of the flower buds of Camelliasinensis and C. sinensis var. assamica, such as antihyperlipidemic, antihyperglycemic, antiobesity, and gastroprotective effects in vivo, and antiallergic, pancreatic lipase inhibitory, and amyloid β (Aβ) aggregation inhibitory activities in vitro. Although the biofunctional effects of tea leaves have been extensively studied, less attention has been given to those of the flowers and seeds of the tea plant. Our studies focused on the saponin constituents of the extracts of the flower buds of C. sinensis cultivated in Japan and China, and C. sinensis var. assamica cultivated in India, and we review their beneficial biofunctions for health promotion.

Seven oleanane-type triterpene saponin bisdesmosides, perennisaponins N–T (1–7), were newly isolated from a methanol extract of daisy, the flowers of Bellis perennis L. (Asteraceae). The structures were determined based on chemical and physicochemical data and confirmed using previously isolated related compounds as references. The isolates, including 13 previously reported perennisaponins A–M (8–20), exhibited anti-proliferative activities against human digestive tract carcinoma HSC-2, HSC-4, and MKN-45 cells. Among them, perennisaponin O (2, IC50 = 11.2, 14.3, and 6.9 μM, respectively) showed relatively strong activities. The mechanism of action of 2 against HSC-2 was found to involve apoptotic cell death.

Two new dammarane-type triterpene oligoglycosides, bacomosaponins A and B, and three new phenylethanoid glycosides, bacomosides A, B1, and B2, were isolated from the whole plant of Bacopa monniera Wettst. The chemical structures of the new constituents were characterized on the basis of chemical and physicochemical evidence. In the present study, bacomosaponins A and B with acyl groups were obtained from the whole plant of B. monniera. This is the first report of acylated dammarane-type triterpene oligoglycosides isolated from B. monniera. In addition, dammarane-type triterpene saponins significantly inhibited the aggregation of 42-mer amyloid β-protein.

Four new alkaloids, hemerocallisamines IV–VII, were isolated from the methanol extract of flower buds of daylily. The chemical structures of the new compounds were elucidated on the basis of chemical and physicochemical evidence. The absolute stereochemistry of the hemerocallisamines IV–VI was elucidated by the application of the modified Mosher’s method, HPLC analysis, and optical rotation. In the present study, the isolated alkaloids significantly inhibited the aggregation of Aβ42 in vitro. This is the first report about bioactive alkaloids with a γ-lactam ring from daylily. In addition, isolated nucleosides showed accelerative effects on neurite outgrowth under the non-fasting condition.

•A new monoterpene glycoside, floralalbiflorin I, was isolated from the flowers of Paeonia suffruticosa.•A new flavonol glycoside, lactifloraoside I, was isolated from the flowers of Paeonia lactiflora.•Their chemical structures of the new constituents were elucidated.•The major constituents significantly showed the inhibitory effects on Cu2+-induced LDL oxidation.•1,2,3,4,6-Penta-O-galloyl-β-d-glucopyranoside showed the most potent inhibitory effect.A new monoterpene glycoside, floralalbiflorin I (1), and a new flavonol glycoside, lactifloraoside I (2), were isolated from the flowers of Paeonia suffruticosa and Paeonia lactiflora (Paeoniaceae) together with 28 known compounds. The chemical structures of the isolated compounds were elucidated on the basis of chemical and physicochemical evidence. Among the major constituents of P. suffruticosa and P. lactiflora flowers, 1,2,3,4,6-penta-O-galloyl-β-d-glucopyranoside (10) [inhibition: 42.4% at 1 μM] and flavonoids having the catechol moiety showed significant inhibitory effect on Cu2+-induced low-density lipoprotein (LDL) oxidation.

•The MeOH extract from Bellis perennis flowers showed collagen synthesis promoting activity in NHDFs.•Seven oleanane-type triterpene saponins, perennisosides XIII–XIX, were isolated.•Several saponins exhibited collagen synthesis promoting activity.The methanol extract from Bellis perennis (Asteraceae) flowers was found to promote collagen synthesis in normal human dermal fibroblasts (NHDFs). Seven oleanane-type triterpene saponins, perennisosides XIII–XIX, and two known saponins, bellissaponins BS5 and BS9, were isolated from the methanol extract. The structures were determined based on chemical and physicochemical data, and confirmed using previously isolated related compounds as references. Among the isolates, including 19 previously reported saponins, perennisosides XVIII, I, II, VII, IX, and XI, asterbatanoside D, bernardioside B2, and bellissaponins BS5 and BS9 significantly promoted collagen synthesis at 3–30 μM without cytotoxicity.Graphical abstractSeven oleanane-type triterpene saponins, perennisosides XIII–XIX were isolated from Bellis perennis flowers. Among the saponin constituents, perennisosides XVIII, I, II, VII, IX, and XI, asterbatanoside D, bernardioside B2, and bellissaponins BS5 and BS9, significantly promoted collagen synthesis at 3–30 μM without cytotoxicity.

The methanolic extract from the dried rhizomes of Curcuma comosa cultivated in Thailand was found to inhibit the release of β-hexosaminidase as a maker of degranulation from rat basophil leukemia (RBL-2H3) cells. Two new diarylheptanoids, diarylcomosols IV and V, were isolated from the methanolic extract. The chemical structures of the new compounds were elucidated on the basis of chemical and physicochemical evidence. The isolated diarylheptanoids showed inhibitory activity, and the structural requirements of the active constituents for the inhibition were clarified.

A methanol extract of everlasting flowers of Helichrysum arenarium L. Moench (Asteraceae) was found to inhibit the increase in blood glucose elevation in sucrose-loaded mice at 500 mg/kg p.o. The methanol extract also inhibited the enzymatic activity against dipeptidyl peptidase-IV (DPP-IV, IC50 = 41.2 μg/ml), but did not show intestinal α-glucosidase inhibitory activities. From the extract, three new dimeric dihydrochalcone glycosides, arenariumosides V–VII (2–4), were isolated, and the stereostructures were elucidated based on their spectroscopic properties and chemical evidence. Of the constituents, several flavonoid constituents, including 2–4, were isolated, and these isolated constituents were investigated for their DPP-IV inhibitory effects. Among them, chalconaringenin 2′-O-β-D-glucopyranoside (16, IC50 = 23.1 μM) and aureusidin 6-O-β-D-glucopyranoside (35, 24.3 μM) showed relatively strong inhibitory activities.

Eight new acylated oleanane-type triterpene oligoglycosides, floraassamsaponins I, II, III, IV, V, VI, VII, and VIII, were isolated from the flower buds of Camellia sinensis var. assamica. The chemical structures of new constituents were characterized on the basis of chemical and physicochemical evidence. In the present study, floraassamsaponins I and II with sugar moiety at 28-position were obtained from the flower buds of C. sinensis var. assamica. In the past, acylated triterpene oligoglycosides with sugar moiety at 28-position have not been isolated from the flower buds of Camellia sinensis var. sinensis. This finding is interesting from the perspective of chemotaxonomy of Camellia plants. In addition, acylated oleanane-type triterpene saponins significantly inhibited the aggregation of Aβ42.

Five new diterpene glycosides, auricuosides I (1), II (2), III (3), IV (4), and V (5), a new flavonol glycoside, auricuoflavonoside I (6), and a new megastigmane glycoside, auricuomegastigmane I (7), were isolated from the seeds of Cassia auriculata, together with 11 known constituents. The chemical structures of seven new constituents were characterized on the basis of chemical and physicochemical evidence. In the present study, auricuosides I (1)–V (5) were obtained from the seeds of C. auriculata. To the best of our knowledge, there is no report about the isolation of kaurenolides with hydroxy group at 14-position from plants. This finding is interesting from the perspective of chemotaxonomy and biosynthesis of kaurenolide.

Three new megastigmane glycosides named floraosmanosides I–III and a new γ-decalactone named floraosmanolactone I together with 16 known constituents were isolated from the flowers of Osmanthus fragrans var. aurantiacus cultivated in Guangxi Zhuang Autonomous Region, China. The chemical structures of the new compounds were elucidated on the basis of chemical and physicochemical evidence. Among them, ligustroside and (+)-pinoresinol significantly inhibited nitric oxide production in lipopolysaccharide-activated RAW264.7 macrophages.

A rare glutamine derivative, hemerocallisamine I (1), was isolated from the methanolic extract of the flower buds of daylily, together with a new pyrrole alkaloid hemerocallisamine II (2) and a new γ-lactam derivative, hemerocallisamine III (3). The chemical structures of the new compounds were elucidated on the basis of chemical and physicochemical evidence. For hemerocallisamine I (1), the absolute configuration was determined by Mo–Kα X-ray crystallographic analysis. This is the first report of a glutamine derivative with a pyrrole ring from natural plants.

The methanolic extract from the flower buds of Cananga odorata showed an inhibitory effect on melanogenesis in theophylline-stimulated murine B16 melanoma 4A5 cells. From the methanolic extract, two new lignan dicarboxylates, canangalignans I and II, three new terpenoids, canangaterpenes I, II, and III, and eight known compounds were isolated. The structures of these compounds were elucidated on the basis of chemical/physicochemical evidence. Several mono- and sesquiterpene analogues significantly inhibited melanogenesis. In particular, canangaterpene I and (3R,3aR,8aS)-3-isopropyl-8a-methyl-8-oxo-1,2,3,3a,6,7,8,8a-octahydroazulene-5-carbaldehyde exhibited a potent inhibitory effect on melanogenesis [inhibition (%): 34.7 ± 4.2 (p < 0.01), 45.5 ± 5.7 (p < 0.01) at 1 μM, respectively] without inducing cytotoxicity. Moreover, the biological effect of these compounds was much stronger than that of the reference compound, arbutin. Thus, these isolated terpenoid derivatives may be promising therapeutic agents for the treatment of several skin disorders.

Three new terpenoid derivatives, canangaterpenes IV–VI, were isolated from the flower buds of Cananga odorata, cultivated in Thailand, together with eight known flavonoids. The chemical structures of the new compounds were elucidated on the basis of chemical and physicochemical evidence. The inhibitory effects of the isolated compounds on aldose reductase were also investigated. Several terpenoid derivatives and flavonoids were shown to inhibit aldose reductase.

Seven new acylated sucroses, mumeoses P–V, were isolated from the flower buds of Prunus mume, cultivated in Zhejiang province, China. Their chemical structures were elucidated on the basis of chemical and physicochemical evidence. Moreover, mumeoses C, D, and R, were shown to substantially inhibit aldose reductase.

In a previous study, retrofractamide A from the fruit of Piper chaba was shown to promote adipogenesis in 3T3-L1 cells. In the present study, retrofractamide A and its derivatives were synthesized, and their adipogenetic effects in 3T3-L1 cells were examined. Among the tested compounds, an amide composed of 9-(3′,4′-methylenedioxyphenyl)-nona-2E,4E,8E-trienoic acid and an n-butyl or n-pentyl amine showed strongest activity. Moreover, the amide with the n-pentyl amine moiety significantly increased the uptake of 2-deoxyglucose into the cells, and also increased the mRNA levels of adiponectin, peroxisome proliferator-activated receptor γ2 (PPARγ2), glucose transporter 4 (GLUT4), fatty acid-binding protein (aP2), and CCAAT/enhancer-binding protein (C/EBP) α and β in a similar manner as the PPARγ agonist troglitazone, although it had less agonistic activity against PPARγ.