Sappanin-type homoisoflavonoids from Scilla nervosa inhibits acetylcholinesterase enzyme: a combined in silico and in vitro approach.

Alzheimer's disease is among the major health challenges that currently attract the attention of health care givers and drug discovery and development experts worldwide. This study investigated the acetylcholinesterase inhibitory activity of sappanin-type homisoflavonoids isolated from the inter-bulb surface of Scilla nervosa. Molecular docking, molecular dynamics simulation, ADMET and in vitro studies were performed to identify the hit molecules, understand their binding mode and interaction, druggability and establish their inhibitory potentials against acetylcholinesterase enzyme. The hit compounds 5, 2, 1 and 4 were identified as the hit molecules through the molecular docking. The molecular dynamics simulation and MM-PBSA analysis showed the hit homoisoflavonoids established stability and good binding affinity against the acetylcholinesterase enzyme. Also, 5 elicited the best inhibitory activity followed by 2, 1 and 4 in the in vitro experiment. Furthermore, the selected homoisoflavonoids exhibit interesting drug likeness and pharmacokinetic properties as drug candidate. The results suggest further investigations towards the development of the phytochemicals as possible acetylcholinesterase inhibitors.Communicated by Ramaswamy H. Sarma.

The anatomical, morphological features, and biological activity of Scilla siberica subsp. armena (Grossh.) Mordak (Asparagaceae).

Scilla siberica subsp. armena is known as Siberian Squill which is naturally distributed in Lebanon-Syria, Transcaucasus, and Turkey. It is a perennial bulbous plant with a short vegetation period from March to May. In this study, the antimicrobial, antioxidant, α-amylase, and α-glucosidase inhibitory activities of corm, leaf, and flower methanolic extracts were examined. The anatomy and morphology of the plant organs were investigated by light and electron microscopes. The anatomy of S. siberica subsp. armena was investigated for the first time by electron microscopy in this study. The corm, leaf, and flower methanolic extracts were assessed against E. coli ATCC 8739, S. aureus ATCC 6538, B. subtilis ATCC 19,659, C. albicans ATCC 10,231, C. krusei ATCC 14,243, and C. tropicalis ATCC 750. Among the extracts, that obtained from the blue pollen showed the best antimicrobial activity against C. tropicalis ATCC 750 strain with a MIC value of 312.5 µg/mL. The highest phenolic content was determined in leaf extract with 53.59211 µg GAE/mg extract value. The extract showed the best anti-lipid peroxidation activity with 376.69 µg/mL value. Using DPPH· and ABTS·+ tests, it was determined that the flower and leaf extracts have the best activity (IC50 = 756.13 µg/mL and IC50 = 94.07 µg/mL, respectively). The flower extract exhibited α-glucosidase inhibitory activity with the IC50 value of 5239 µg/mL. Based on the presented results of the in vitro antimicrobial, antioxidant, and antidiabetic activities of the S. siberica subsp. armena, we suggest that natural compounds from S. siberica subsp. armena are of potential use for the improvement of an antidiabetic, antioxidant, and antimicrobial agent.

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.

Scilla bifolia Wax as a Source of Diverse Long-Chain Resorcinols and Alkane-1,3-diols.

GC, GC/MS and NMR analyses of Scilla bifolia washings allowed for the identification of thirty-six long-chain compounds belonging to six homologous series (five of which are from the class of resorcinols, a group of biologically important phenols): 1-alkyl-3,5-dimethoxybenzenes, 5-alkyl-3-methoxy-2-methylphenols, 3-alkyl-5-methoxyphenols, 5-alkyl-2-methylresorcinols (five compounds from each of the series); 5-alkylresorcinols (six compounds) and 1,3-alkanediols (ten compounds). Many of these compounds rarely occur in Nature. Retention indices of these compounds, as well as indices of the corresponding trimethylsilyl derivatives, were reported, some of them for the first time. The exact regiochemistry was unambiguously determined by two-dimensional NMR experiments; in some cases, the complete NMR assignment was augmented by computer spin-simulation of 1 H-NMR spectra.

Sulfadiazine Masquerading as a Natural Product from Scilla madeirensis (Scilloideae).

The structure of 2,4-(4'-aminobenzenamine)pyrimidine (1), a pyrimidine alkaloid previously isolated from the bulbs of Scilla madeirensis (Asparagaceae, synonym Autonoë madeirensis), has been revised. These conclusions were met via comparison of reported NMR and EIMS data with those obtained from synthetic standards. The corrected structure is the antibiotic sulfadiazine (2), which has likely been isolated as a contaminant from the site of collection. The reported bioactivity of 1 as an α1-adrenoceptor antagonist should instead be ascribed to sulfadiazine. Our findings appear to show another example of an anthropogenic contaminant being identified as a natural product and emphasize the importance of considering the biosynthetic origins of isolated compounds within a phylogenetic context.

Scillapersicene: a new homoisoflavonoid with cytotoxic activity from the bulbs of Scilla persica HAUSSKN.

The phytochemical investigation of Scilla persica HAUSSKN bulbs led to the isolation of a novel homoisoflavonoid that named Scillapersicene (1) and identified as 3-(3',4'-dihydroxybenzylidene)-8-hydroxy-5,7-dimethoxychroman-4-one along with five known homoisoflavonoids 2-6, whose structures were elucidated using HRFAB-MS, 1D and 2D NMR spectroscopic data. The known compounds were identified as 3-(3',4'-dihydroxybenzyl)-5,8-dihydroxy-7-methoxychroman-4-one (2), 3,9-dihydro-autumnalin (3), autumnalin (4), 3-(3',4'-dihydroxybenzylidene)-5,8-dihydroxy-7-methoxychroman-4-one (5) and scillapersicone (6). All compounds obtained, expect 2 and 4, showed strong cytotoxic activity against AGS cell line. The toxicity on AGS cell line was measured by 1, 3, 5 and 6 with IC50 values of 8.4, 30.5, 10.7 and 24.2 µM, respectively. In addition, the physico-chemical properties of these natural compounds were optimised using density functional method (B3LYP) with standard 6-311+G* basis set. These natural products have low-energy gaps between the first ionisation potentials and highest occupied molecular orbital. In conclusion, the low-energy gap could cause reason for cytotoxic activity of homoisoflavonoids.

Isolation and characterization of homoisoflavonoids from Scilla persica HAUSSKN

abstract Medicinal plants have many traditional claims including the treatment of ailments of infectious origin. In the evaluation of traditional claims, scientific research is extremely important. In this study, five homoisoflavonoids named 3-(4'-hydroxybenzylidene)-5,7-dihydroxy-6-methoxychroman-4-one(Autumnalin),3-(4'-hydroxybenzyl)-5,7-dihydroxy-6-methoxychroman-4-one (3,9-dihydro-autumnalin), 3-(3',4'-dihydroxybenzyl)-5,8-dihydroxy-7-methoxychroman-4-one,3-(3',4'-dihydroxybenzylidene)-5,8-dihydroxy-7-methoxychroman-4-one and 3-(3',4'-dihydroxybenzylidene)-5,7-dihydroxy-6-methoxychroman-4-one, were isolated from the bulbs of the plant Scilla persica HAUSSKN. Their structures were established on the basis of extensive spectroscopic analyses such as NMR, MS, IR and UV.

resumo Plantas medicinais apresentam muitas atribuições tradicionais, incluindo o tratamento de doenças de origem infecciosa. A pesquisa científica é extremamente importante na avaliação dos usos tradicionais. Neste estudo, cinco homoisoflavonóides: 3-(4'-hidroxibenzilideno)-5,7-diidroxi-6-metoxicroman-4-ona(autumnalina), 3-(4'-hidroxibenzil)-5,7-diidroxi-6- metoxicroman-4-ona (3,9-diidro-autumnalina), 3-(3',4'-diidroxibenzil)-5,8-diidroxi-7- metoxicroman-4-ona, 3-(3',4'-diidroxibenzilideno)-5,8-diidroxi-7- metoxicroman-4-ona e 3-(3',4'-diidroxibenzilideno)-5,7-diidroxi-6- metoxicroman-4-ona foram isolados dos bulbos da planta Scilla persica HAUSSKN. Suas estruturas foram estabelecidas com base na extensa análise espectroscópica, como RMN, EM, IV e UV.

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.

Inhibitory effects of the ethyl acetate extract from bulbs of Scilla scilloides on lipoxygenase and hyaluronidase activities.

CONTEXT: Scilla scilloides Druce (Liliaceae) is a folk medicine to treat dermal inflammation; however, the medicinal properties of this plant have not been completely established. OBJECTIVE: The current study investigates the potent anti-inflammatory effects of S. scilloides bulbs for its traditional usage using lipoxygenase and hyaluronidase as the inflammation model. To gain insight into the active constituents, nine homoisoflavones (1-9) were subsequently tested. MATERIALS AND METHODS: Lipoxygenase and hyaluronidase inhibition of ethyl acetate extract from the bulbs of this plant within 2000 µg/mL or homoisoflavones within 1000 µM were determined by colorimetric methods. RAW264.7 cells were incubated with 10 or 50 µM homoisoflavones plus lipopolysaccharide (LPS) for 24 h. The culture media were collected and analyzed for determination of the nitric oxide (NO) level by the colorimetric Griess method to measure the extent of inflammation. RESULTS: The extract exhibited inhibitory effects on lipoxygenase and hyaluronidase activities with IC50 values 31.5 and 169 µg/mL, respectively. Among the nine homoisoflavones tested, four (1 and 3-5) resulted in 79.3-97.9% higher lipoxygenase inhibition than 6.7-32.7% of the others at 500 µM. Calculated IC50 values indicated 5 as the compound responsible for strong lipoxygenase inhibition with 15.8 µM as the IC50 value. In the hyaluronidase assay, all homoisoflavones tested at 1000 µM demonstrated 16.2-58.0% inhibition. Incubating the cells in the presence of all nine homoisoflavones tested at 50 µM significantly suppressed the NO production, downward to 1.5-66.0%, in the LPS-activated macrophage cells as a model. DISCUSSION AND CONCLUSION: These results may indicate a potential role of S. scilloides for anti-inflammatory purposes.

[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.

Advances on chemical constituents and pharmacological activity of genus Scilla / 中国中药杂志

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 / 中国中药杂志

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.

Anti-inflammatory and antioxidative effects of a methanol extract from bulbs of Scilla scilloides.

The extract from bulbs of Scilla scilloides exhibited inhibitory effects in lipoxygenase and hyaluronidase assays and various oxidation models in vitro. Incubating the cells in the presence of this extract ameliorated t-butyl hydroperoxide-induced cytotoxicity from 27% to 57% in a macrophage model. The results may indicate the potential role of S. scilloides for its anti-inflammatory and antioxidative effects.

Five new nortriterpenoid glycosides from the bulbs of Scilla scilloides.

Five new norlanostane-type triterpenoid glycosides were isolated from the bulbs of Scilla scilloides DRUCE (Liliaceae). Their chemical structures were determined on the basis of spectroscopic data as well as chemical evidence.

Intradermal therapy (mesotherapy) with lymdiaral in chronic venous insufficiency and associated fibrosclerotic edema damage: a pilot study.

OBJECTIVES: Chronic venous insufficiency (CVI) induces alterations that cause fibrosclerotic edema of the subcutaneous tissue. This study examined the effects of a complex naturopathic compound with vasoactive and antiedema activities (Lymdiaral®) administered intradermally. PATIENTS: 40 patients with signs and symptoms of CVI and associated fibrosclerotic edema of the subcutaneous tissue. OUTCOME MEASURES: Efficacy was assessed by using clinical investigation, subjective and objective measures, and ultrasonography performed at baseline and after treatment. RESULTS: Thirty-four patients completed the study; 6 of the original 40 (15%) had stopped for reasons unrelated to study treatment. The treatment was well tolerated. Fifteen adverse reactions were reported among a total of 378 doses administered (3.97%). None of these reactions were severe or required discontinuation of treatment. Subjective symptoms and objective measures improved, and ultrasonography showed statistically significant changes in hypodermal thickness of the medial aspect of the knees. CONCLUSIONS: Its open-label design and small sample size notwithstanding, this study indicates that intradermal therapy, according to the recommendation of the Italian Society of Mesotherapy, may provide a valuable contribution to the treatment of CVI and related fibrosclerotic edema of the subcutaneous tissue by prolonging the local effect of the pharmacologically active compounds. Comparative studies are needed to identify the broader clinical and economic benefits of local therapy compared with other systemic therapies.

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.

Two new nortriterpenoid glycosides and a new phenylpropanoid glycoside from the bulbs of Scilla scilloides.

Two new norlanostane-type triterpenoid glycosides and a new phenylpropanoid glycoside were isolated from the bulbs of Scilla scilloides DRUCE (Liliaceae), along with two known alkaloids. Their chemical structures were determined on the basis of spectroscopic data as well as chemical evidence.

Three new nortriterpene glycosides and two new triterpene glycosides from the bulbs of Scilla scilloides.

Three new norlanostane-type triterpene glycosides, scillanostasides A, B, and C, and two new lanostane-type triterpene glycosides, scillanostasides D and E, were isolated from the bulbs of Scilla scilloides Druce (Liliaceae) along with one known norlanostane-type triterpene heptaglycoside, scillascilloside G-1. Their chemical structures were determined on the basis of spectroscopic data as well as chemical evidence.