Chemical Constituents of the Bulbs of Scilla peruviana and Their Pancreatic Lipase Inhibitory Activity.

Scilla species are used as medicinal plants and contain lanosterol-type triterpene glycosides. The phytochemical investigation of the bulbs of Scilla peruviana led to the isolation of 17 compounds, including three new rearranged pentacyclic-lanosterol glycosides (1-3) and two new homoisoflavanone glycosides (12 and 13). The structures of the undescribed compounds were determined by extensive spectroscopic analyses, including two-dimensional (2D) NMR. Among the triterpene glycosides, 2, 3, and 6 showed significant pancreatic lipase inhibitory activity in a concentration-dependent manner in vitro. The oral administration of scillascilloside D-2 (6) reduced serum triglyceride levels in a dose-dependent manner in soybean oil-loaded mice.

Biochemical and biophysical properties of a novel homoisoflavonoid extracted from Scilla persica HAUSSKN.

In this study isolation and structural elucidation of a homoisoflavonoid, 3-(3',4'-dihydroxybenzyl)-8-hydroxy-5,7-dimethoxychroman-4-one (Scillapersicone 1), is reported from Scilla persica HAUSSKN. The structure was solved by a single crystal X-ray analysis. The unit cell parameters are a=11.7676 (2)Å, b=20.1174 (4)Å, c=7.8645 (9)Å, ß=93.544 (2)°, V=1858.23 (7)Å(3), monoclinic space group P21/c and four symmetry equivalent molecules in an unit cell. The structure was consistent with the UV, IR, 1D and 2D NMR, HRFAB-MS data. The optimized molecular geometry agrees closely that obtained from the single crystal X-ray crystallography. Furthermore, cytotoxicity of this compound was evaluated by MTT assay on AGS and WEHI-164 cancerous cell lines.

[Advances on chemical constituents and pharmacological activity of genus Scilla].

The genus Scilla consists of 90 species widely distributed in Europe, Asia and Africa, one and its variant of which can be found in China Some species of the genus have been used in traditional medicine to treat various diseases related to inflammation and pain. Phytochemical studies have demonstrated the presence of triterpene and tritepenoid saponins derived from eucosterol, bufadienolides, alkaloids, stilbenoids and lignan in the plants of this genus. Various bioactivities such as antimicrobial, anti-inflammatory, antioxidant, anti-tumor and glycosidase inhibitory activities, have been reported. In this review, the advance of chemical constituents and pharmacological activities of the Scilla species are summarized for further development and utilization of the resource.

[Homoisoflavanones and stilbenes from fresh bulb of Scilla scilloides].

Mian-Zao-Er was collected from the bulbs of Scilla scilloides (Lindl. ) Druce, belonging to the Hyacinthaceae family. 17 compounds were obtained using various column chromatographies on macroporus resin (HPD100), silica gel, Sephadex LH-20 and ODS, as well as semi-preparative HPLC. Their structures were elucidated on the basis of physicochemical properties and spectral data as 2-hydroxy-7-methoxyscillascillin (1), scillascillin (2), 5,7-dihydroxy-3',4'-dimethoxyspiro 2H-1-benzopyran-7'-bicyclo[4.2.0 ] octa [1,3,5 ] -trien } -4-one (3), socialinone (4), 4-methylresveratrol (5), (E)-resveratrol (6), scillavoneA (7), 3,9-di- hydroeucomnalin (8), 3-(3-hydroxy-4-methoxybenzyl) -5,7-dihydroxychroman-4-one (9), (3R)-5,7,3'-trihydroxy-4'-methoxyspiro (2H-1-benzopyran-7'-bicyclo[4, 2, 0] octa [1, 3, 5]-trien} -4-one (10), scillabene A (11), 2-hydroxyscillascillin (12), 3-(4-hydroxybenzyl) -5,7-dihydroxychroman-4-one (13), 3-( 4-hydroxybenzylidene) -5, 7-dihydroxychroman-4-one (14), 3-( 4-hydroxybenzyl) -5-hydroxy-7,8-dimethoxychroman-4-one (15), 3-(4-hydroxybenzyl) -5-hydroxy-6, 7-dimethoxychroman-4-one (16), and 3-(4-hydroxybenzyl)-5,8-hydroxy-7-methoxychroman-4-one (17). Among them, compounds 3, 4, 6, 9, 13 and 15-17 were isolated from this plant for the first time.

Homoisoflavones as the antioxidants responsible from bulbs of Scilla scilloides.

Scilla scilloides Druce has been used as a folk medicine to treat dermal inflammation; however, the medicinal property of this plant remains to be entirely clarified. The ethyl acetate extract prepared from bulbs of S. scilloides exhibited antioxidative activities on 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical, hydrogen peroxide (H2O2) and nitric oxide (NO) scavenging assays. Nine homoisoflavones (1-9) yielded from this extract were further examined for their antioxidative activities. Among these chemicals tested, five homoisoflavones (1-3, 5 and 7), six homoisoflavones (1-3 and 5-7) and two homoisoflavones (4 and 5) resulted in showing higher activities than the others in DPPH radical, H2O2 and NO scavenging assays, respectively. Calculated EC50 values indicate 3 as the strongest in the DPPH radical scavenging analysis. These results may indicate a potential role of S. scilloides for its medicinal use and homoisoflavones as the antioxidants responsible.

The cytotoxic effects of Scilla nervosa (Burch.) Jessop (Hyacinthaceae) aqueous extract on cultured HepG2 cells.

ETHNOPHARMACOLOGICAL RELEVANCE: Bulbs of Scilla nervosa, a medicinal plant indigenous to Southern Africa, are traditionally used in aqueous decoctions to treat a diverse range of illnesses. The bulbs contain homoisoflavanones and stilbenoids. Little information is known about the plant's toxicity on the liver, a major detoxifying organ. This study investigated the effects of an aqueous extract of the bulbs in cultured HepG2 liver cells, a model system for investigating the toxicity of xenobiotics. MATERIALS AND METHODS: The concentration that reduced cell viability to 50% (IC(50)) after 24h treatment was derived. Potential mechanisms of toxicity using the IC(50) were investigated as changes in metabolic activity, apoptosis, oxidative damage and DNA fragmentation. In addition, cytochrome P450 3A4 (CYP3A4) activity, which is implicated in drug metabolism and interactions, was also assayed. RESULTS: Cell viability decreased in a concentration-dependent manner and the IC(50) was determined as 0.03 mg/mL. Treating the cells at the IC(50) for 24h resulted in increased intracellular ATP levels, no significant change in phosphatidylserine externalisation, increased caspase-8 activity, decreased caspase-9 activity, no significant change in mitochondrial membrane potential, increased lipid peroxidation, evidence for genotoxicity as demonstrated by DNA fragmentation, and slightly induced CYP3A4 activity. CONCLUSION: Results suggest that liver cells are sensitive to an aqueous extract of the bulbs and there is an increased potential to induce apoptosis, oxidative stress and genotoxicity in vitro.

HPLC analysis and NMR identification of homoisoflavonoids and stilbenoids from the inter-bulb surfaces of Scilla nervosa.

The yellow inter-bulb deposits from Scilla nervosa were analyzed by HPLC and found to contain 19 major components. Twelve of the 19 were identified by comparison of R(t) values with those of authentic homoisoflavonoids and stilbenoids, co-elution and by preparative isolation followed by NMR and MS analyses. Of these, two homoisoflavonoids, 3-(4-hydroxyoxybenzyl)-5,7-dimethoxy-6-hydroxychroman-4-one and 3-(4-methoxybenzyl)-6,7-dimethoxy-5-hydroxychroman-4-one are new.

Isolation of glycosidase-inhibiting hyacinthacines and related alkaloids from Scilla socialis.

An examination of the bulbs of Scilla socialis has resulted in the isolation of 11 hyacinthacines, two pyrrolidines, and three piperidines. The structures of the new alkaloids were elucidated by spectroscopic methods as beta-1-C-ethyldeoxymannojirimycin (5), hyacinthacines B7 (10), C2 (11), C3 (12), C4 (13), and C5 (14), and alpha-5-C-(3-hydroxybutyl)hyacinthacine A2 (15). Although, beta-l-homofuconojirimycin (3) and alpha-7-deoxyhomonojirimycin (alpha-7-deoxy-HNJ, 4) are previously known alkaloids, this is the first report of their occurrence in the plant family Hyacinthaceae. Alkaloid 11 was found to be a good inhibitor of bacterial beta-glucosidase and human placenta alpha-l-fucosidase, with IC50 values of 13 and 17 microM, respectively, while alkaloid 12 showed no inhibitory activity toward alpha-l-fucosidase but was a more potent inhibitor of bovine liver beta-galactosidase (IC50 = 52 microM) than 11. Alkaloids 13 and 14 were shown to be inhibitory toward mammalian alpha-glucosidase (IC50 = 45 and 77 microM, respectively), and alkaloid 14 was demonstrated as a moderate inhibitor of bacterial beta-glucosidase (IC50 = 48 microM).

Glycosidase-inhibiting pyrrolidines and pyrrolizidines with a long side chain in Scilla peruviana.

2,5-Dideoxy-2,5-imino-d-glycero-d-manno-heptitol (homoDMDP) is widely distributed in Hyacinthaceae plants and can also be regarded as the alpha-1-C-(1,2-dihydroxyethyl) derivative of 1,4-dideoxy-1,4-imino-d-arabinitol (d-AB1). In a search for glycosidase inhibitors in this family of plants, we isolated three new d-AB1 derivatives bearing the 2-hydroxypropyl (1), 1,2-dihydroxypropyl (2), and 1,5,7,12,13-pentahydroxytridecyl (3) side chains at the C-1alpha position, respectively, from the bulbs of Scilla peruviana. Alkaloid 3 was a powerful inhibitor of bacterial beta-glucosidase (IC(50) = 80 nM) and bovine liver beta-galactosidase (IC(50) = 90 nM). This plant coproduced four new pyrrolizidine alkaloids, alpha-5-C-(3-hydroxybutyl)-7-epi-australine (4), alpha-5-C-(3-hydroxybutyl)hyacinthacine A(1) (5), alpha-5-C-(1,3-dihydroxybutyl)hyacinthacine A(1) (6), and alpha-5-C-(1,3,4-trihydroxybutyl)hyacinthacine A(1) (7). Alkaloids 4 and 6 were potent inhibitors of yeast alpha-glucosidase, with IC(50) values of 6.6 and 6.3 microM, respectively, and alkaloid 6 was also a potent inhibitor of bacterial beta-glucosidase with an IC(50) value of 5.1 microM.

Structural elucidation of natural 2-hydroxy di- and tricarboxylic acids and esters, phenylpropanoid esters and a flavonoid from Autonoë madeirensis using gas chromatographic/electron ionization, electrospray ionization and tandem mass spectrometric techniques.

The chemical composition of Autonoë madeirensis bulbs was characterized as part of a systematic phytochemical study of this species. The compounds reported were mainly identified on the basis of gas chromatography/electron ionization, electrospray ionization and tandem mass spectrometry. The structures of the pure compounds were also characterized by means of other physical and spectroscopic data (m.p., IR, UV, NMR). The compounds identified were 2-hydroxy di- and tricarboxylic acids and esters (malic acid, citric acid and their methyl and ethyl esters), cis- and trans-hydroxycinnamic esters (methyl and ethyl p-coumarate and methyl ferulate) and a new flavone diglucoside, 7-O-[beta-glucosyl-(1-->2)-O-beta-glucosyl]apigenin, the interglucosidic linkage (1-->2) of which is, to the best of our knowledge, reported for the first time in a diglucoside of apigenin. The results may contribute to the chemotaxonomy of the Autonoë genus and lead to a rapid tool for the systematic characterization of these compounds in plant extracts.

New polyhydroxylated pyrrolidine, piperidine, and pyrrolizidine alkaloids from Scilla sibirica.

Chromatographic separation of an extract of the bulbs of Scilla sibirica resulted in the isolation of five pyrrolidines, two pyrrolidine glycosides, six piperidines, one piperidine glycoside, and eight pyrrolizidines. 2,5-Dideoxy-2,5-imino-glycero-d-manno-heptitol (homoDMDP, 1) is a common alkaloid in all plants of the Hyacinthaceae examined to date and was also found in S. sibirica. The structures of the new alkaloids were elucidated by spectroscopic methods as 7-deoxy-homoDMDP (4), 2,5-dideoxy-2,5-imino-glycero-d-galacto-heptitol (5), the 4-O-beta-d-mannoside (6) and the 4-O-beta-d-mannobioside (7) of 6-deoxy-homoDMDP (2), 7-deoxyhomonojirimycin (12), 7-deoxyhomomannojirimycin (13), and polyhydroxypyrrolizidines, hyacinthacines A(4) (15), A(5) (16), A(6) (17), A(7) (18), B(4) (20), B(5) (21), and B(6) (22). HomoDMDP (1) is a potent inhibitor of beta-glucosidase and beta-galactosidase, while 6-deoxy-homoDMDP (2) showed significantly less inhibition. However, 7-deoxygenation of 1, leading to 4, showed no effect on the inhibitory activity toward both enzymes. Although 2 is not an inhibitor of alpha-l-fucosidase, the monomannoside of 2 shows inhibitory activity toward alpha-l-fucosidase. Elongation of the beta-mannopyranosyl chain of 6 to give 7 enhanced the inhibitory activity.