Phenylpropanoid-Conjugated Triterpenoids from the Leaves of Actinidia arguta and Their Inhibitory Activity on α-Glucosidase.

Actinidia arguta, commonly called hardy kiwifruit or kiwiberry, has cold-resistant properties and can be cultivated in Asia, including Korea. Seven new triterpenoids (2-4 and 8-11) along with eight known triterpenoids were isolated from the leaves of A. arguta through various chromatographic techniques. The new triterpenoids were defined as actiniargupenes A-C (2-4), actinidic acid derivatives with phenylpropanoid constituent units, dehydroisoactinidic acid (8), and actiniargupenes D-F (9-11), asiatic acid derivatives with phenylpropanoid substituents, on the basis of 1D and 2D NMR and MS data. Among the triterpenoids, those with a phenylpropanoid constituent unit showed inhibitory activity on α-glucosidase, which suggested the importance of the phenylpropanoid moiety. Molecular docking analysis demonstrated the interaction between the 4'-OH group of the phenylpropanoid moiety and α-glucosidase.

Xanthones from the stems of Cudrania tricuspidata and their inhibitory effects on pancreatic lipase and fat accumulation.

Nine new xanthones, cudracuspixanthones I - Q (12-14, 25, 32-36), and 30 known xanthones (1-11, 15-24, 26-31, 37-39) were isolated from the stems of Cudrania tricuspidata (Moraceae). The structures of isolated compounds were established by using 1D and 2D NMR in combination with HR-TOF-MS. Xanthones from the stems of C. tricuspidata exerted pancreatic lipase inhibitory activity. In addition, cudracuspixanthone P (35), a new xanthone, reduced the fat accumulation in liver cells stimulated with fatty acids. Therefore, these compounds might be beneficial in the treatment of metabolic diseases.

Characterization of tyrosinase inhibitory constituents from the aerial parts of Humulus japonicus using LC-MS/MS coupled online assay.

In the screening of natural products for the development as cosmetic ingredients, the EtOAc-soluble fraction of Humulus japonicus showed tyrosinase inhibitory activity. HPLC-MS/MS coupled online tyrosinase assay of EtOAc-soluble fraction of H. japonicus characterized the twenty-eight constituents including two unknown ones and their tyrosinase inhibitory activity. Fractionation of H. japonicus using various chromatographic techniques yielded thirty-eight compounds. The chemical structures of isolated compounds were identified by spectroscopic analysis. As characterized by HPLC-MS/MS analysis, we isolated twenty-four predicted compounds and further identified two unknown ones, named humulusides A (1) and B (2). Additional ten compounds were also identified by purification. Tyrosinase inhibitory activity of isolated compounds were evaluated, which was closely correlated with the results from HPLC-MS/MS coupled online tyrosinase assay. Consistent with predicted data, two major compounds, trans-N-coumaroyltyramine (14) and cis-N-coumaroyltyramine (15) showed tyrosinase inhibition with IC50 values of 40.6 and 36.4 µM. Taken together, H. japonicus is suggested as whitening ingredient in cosmetic products. In addition, HPLC-MS/MS coupled tyrosinase assay is powerful tool for predicting active compounds with short time and limited amounts, although identification of new compounds and verification of predicted data are also needs to be demonstrated by further experiment.

Polyamine derivatives from the bee pollen of Quercus mongolica with tyrosinase inhibitory activity.

Eighteen constituents, including nine new compounds, were isolated from the bee pollen of Quercus mongolica. The structures of the new compounds were established on the basis of combined spectroscopic analysis. Structurally, the nine new compounds are polyamine derivatives with phenolic moieties which were assigned as one putrescine derivative, mogolicine A (2), seven spermidine derivatives, mongolidines A-G (3-5, 8, 12, 14, 17) and one spermine derivative, mogoline A (18). Evaluation of the biological activity of isolated compounds revealed that the polyamine derivatives with coumaroyl and caffeoyl moieties showed tyrosinase inhibition with IC50 values of 19.5-85.8 µM; however, the addition of a methoxy group to phenolic derivatives reduced the inhibitory activity.

Variation of loganin content in Cornus officinalis fruits at different extraction conditions and maturation stages.

Efficient preparation of loganin from Cornus officinalis fruits was investigated. First, effect of extraction conditions on loganin yield was measured. The loganin content in C. officinalis extract was greatly affected by ethanol concentration and extraction time whereas extraction temperature exerted relatively little effect. Response surface methodology with Box-Behnken design suggested optimized extraction condition for maximum loganin yield as ethanol concentration, 32.0%; temperature 46.2 °C and extraction time, 46.7 min, which yielded 10.4 µg loganin/mg dried fruit. Next, the effect of maturation stage of C. officinalis fruits on loganin content was investigated. The loganin content in the extract of C. officinalis fruits was decreased as the maturation process. The loganin content in the unripe fruits was 18.0 µg/mg extract whereas reduced to 13.3 µg/mg extract for ripe fruits. Taken together, our present study suggested the importance of extraction condition and maturation stages for efficient preparation of loganin from C. officinalis fruits.

Inositol Derivatives and Phenolic Compounds from the Roots of Taraxacum coreanum.

In this study, the characterization of chemical constituents and biological activity of the roots of Taraxacum coreanum (Asteraceae) was attempted. Phytochemical investigation of the roots of T. coreanum led to the isolation of two new inositol derivatives, taraxinositols A (1) and B (2), and a new phenolic compound, taraxinol (16), together with twenty known compounds including four inositol derivatives, neo-inositol-1,4-bis (4-hydroxybenzeneacetate) (3), chiro-inositol-1,5-bis(4- hydroxybenzeneacetate) (4), chiro-inositol-2,3-bis (4-hydroxybenzeneacetate) (5) and chiro-inositol- 1,2,3-tris (4-hydroxybenzeneacetate) (6), nine phenolic compounds: p-hydroxybenzaldehyde (7), vanillin (8), syringaldehyde (9), vanillic acid (10), 4-methoxyphenylacetic acid (11), 4-hydroxy- phenylacetic acid methyl ester (12), optivanin (13), isoferulic acid (14) and dihydroconiferyl alcohol (15), four coumarins: nodakenetin (17), decursinol (18), prangol (19) and isobyakangelicin (20), and three lignans: syringaresinol-4'-O-ß-d-glucoside (21), syringaresinol (22), and pinoresinol (23). The structures of isolated compounds were determined on the basis of spectroscopic analysis. Among the isolated compounds, vanillic acid, isoferulic acid and syringaresinol showed radical scavenging activity with IC50 values ranging from 30.4 to 75.2 µM.

Optimization of Extraction Condition of Bee Pollen Using Response Surface Methodology: Correlation between Anti-Melanogenesis, Antioxidant Activity, and Phenolic Content.

Bee pollen is flower pollen with nectar and salivary substances of bees and rich in essential components. Bee pollen showed antioxidant and tyrosinase inhibitory activity in our assay system. To maximize the antioxidant and tyrosinase inhibitory activity of bee pollen, extraction conditions, such as extraction solvent, extraction time, and extraction temperature, were optimized using response surface methodology. Regression analysis showed a good fit of this model and yielded the second-order polynomial regression for tyrosinase inhibition and antioxidant activity. Among the extraction variables, extraction solvent greatly affected the activity. The optimal condition was determined as EtOAc concentration in MeOH, 69.6%; temperature, 10.0 °C; and extraction time, 24.2 h, and the tyrosinase inhibitory and antioxidant activity under optimal condition were found to be 57.9% and 49.3%, respectively. Further analysis showed the close correlation between activities and phenolic content, which suggested phenolic compounds are active constituents of bee pollen for tyrosinase inhibition and antioxidant activity. Taken together, these results provide useful information about bee pollen as cosmetic therapeutics to reduce oxidative stress and hyperpigmentation.

Chemical constituents from Nelumbo nucifera leaves and their anti-obesity effects.

Nelumbo nucifera Gaertn. (Nymphaeaceae), commonly called lotus, is widely distributed throughout Eastern Asia. It has been used for food and medicine for a long time. A phytochemical investigation of N. nucifera leaves led to the isolation of 13 megastigmanes (1-13), including a new megastigmane, nelumnucifoside A (1), and a new eudesmane sesquiterpene, nelumnucifoside B (14), eight alkaloids (15-22), and 11 flavonoids (23-33). Their chemical structures were determined based on spectroscopic methods including 1D, 2D NMR and MS spectrometry. The relative and absolute stereochemistry of the compounds was determined by NOESY and CD spectrometry, respectively. Compounds 19 and 22 significantly inhibited pancreatic lipase, whereas compounds 15 and 16 showed a strong inhibitory effect on adipocyte differentiation. Therefore, the leaves of N. nucifera have potential as an anti-obesity agent by inhibiting pancreatic lipase and adipocyte differentiation.

Polyacetylenes from the adventitious roots of Centella asiatica with glucose uptake stimulatory activity.

Centella asiatica (L.) Urban is an herbaceous perennial plant of the Apiaceae family that has diverse medicinal uses. Its active components are saponin, phenolics, and polyacetylenes. Plant cell cultures have been exploited for the efficient production of metabolites with pharmacological activity. In this work, we prepared adventitious root cultures of C. asiatica and analyzed their content and biological activity. Adventitious root extracts were found to increase glucose uptake by differentiated L6 skeletal muscle cells and to be more efficient than the extract of whole plants. Chromatographic fractionation of the extracts from adventitious roots of C. asiatica led to the isolation of two known polyacetylenes, araliadiol (1) and 8-acetoxy-1,9-pentadecadiene-4,6-diyn-3-ol (2), in addition to a new polyacetylene, which we have named centellidiol (3). All the three polyacetylenes stimulated glucose uptake in a dose-dependent manner. The methanol extract of adventitious roots contained 0.53% and 0.82% of compounds 1 and 2, respectively, which are values that were 15 and 21 times higher that are found in mother plants. We therefore suggest that the high content of these polyacetylenes contributes to the high efficacy of C. asiatica adventitious root cultures. Overall, adventitious root cultures of C. asiatica can be part of a secure supply of effective ingredients including polyacetylenes.

Learning the dynamics of objects by optimal functional interpolation.

Many areas of science and engineering rely on functional data and their numerical analysis. The need to analyze time-varying functional data raises the general problem of interpolation, that is, how to learn a smooth time evolution from a finite number of observations. Here, we introduce optimal functional interpolation (OFI), a numerical algorithm that interpolates functional data over time. Unlike the usual interpolation or learning algorithms, the OFI algorithm obeys the continuity equation, which describes the transport of some types of conserved quantities, and its implementation shows smooth, continuous flows of quantities. Without the need to take into account equations of motion such as the Navier-Stokes equation or the diffusion equation, OFI is capable of learning the dynamics of objects such as those represented by mass, image intensity, particle concentration, heat, spectral density, and probability density.

A new pancreatic lipase inhibitor from Broussonetia kanzinoki.

A new phenolic compound, broussonone A (1) were isolated from the stem barks of Broussonetia kanzinoki (Moraceae), together with two diphenylpropanes, broussonin A (2), broussonin B (3), two flavans, 7,4'-dihydroxyflavan (4), 3',7-dihydroxy-4'-methoxyflavan (5), and two flavones, 3,7-dihydroxy-4'-methoxyflavone (6), 3,7,3'-trihydroxy-4'-methoxyflavone (7). Compound 1 showed noncompetitive inhibitory activity on pancreatic lipase with an IC(50) of 28.4 µM. In addition, compounds 1-5 significantly inhibited adipocyte differentiation in 3T3-L1 cells as measured fat accumulation using Oil Red O assay.

Anti-adipogenic chromone glycosides from Cnidium monnieri fruits in 3T3-L1 cells.

Seven new chromone glycosides, monnierisides A (3), B (10), C (11), D (12), E (13), F (15) and G (16) were isolated from Cnidium. monnieri, together with ten known chromone derivatives, undulatoside A (1), cnidimol C (2), saikochromoside A (4), cnidimoside A (5), cnidimoside B (6), 2-methyl-5-hydroxy-6-(2-butenyl-3-hydroxymethyl)-7-(ß-d-glucopyranosyloxy)-4H-1-benzopyran-4-one (7), cnidimol D (8), hydroxycnidimoside A (9), umtatin (14) and 6'-hydroxylangelicain (17). The structures of isolated compounds were determined on the basis of spectroscopic analysis including 1D, 2D NMR and HR-MS. Among the compounds isolated, compounds 5, 6, 9 and 10 significantly inhibited adipocyte differentiation as measured by fat accumulation in 3T3-L1 cells using Oil Red O staining.

New phenolic compounds with anti-adipogenic activity from the aerial parts of Pulsatilla koreana.

Three new phenolic compounds, pulsatillosides A (1), B (2), and C (3), were isolated from the aerial parts of Pulsatilla koreana, together with two known flavonoid glycosides, trans-tiliroside (4) and kaempferol-3-O-ß-glycoside (5). The structures of the isolated compounds were determined on the basis of spectroscopic analysis including 1D, 2D NMR and HR-MS. Among the isolated compounds, compounds 1-3 significantly inhibited adipocyte differentiation as measured by fat accumulation in 3 T3-L1 cells using Oil Red O staining.

Luteolin downregulates IL-1ß-induced MMP-9 and -13 expressions in osteoblasts via inhibition of ERK signalling pathway.

The inhibitory effect of four structurally related flavonoids, apigenin, baicalein, luteolin and quercetin on the matrix metalloproteinase (MMP)-9 and -13 expressions in osteoblasts was investigated. Treatment with IL-1ß induced both MMP-9 and -13 mRNA expressions as measured by quantitative real-time PCR. Luteolin and apigenin decreased IL-1ß-induced MMP-9 and -13 mRNA expressions, whereas baicalein and quercetin showed little effects. Related to signalling, treatment with IL-1ß induced ERK phosphorylation as measured by Western blotting. Further studies showed that transfection with a constitutively active form of the Ras protein (Ras(V12)) induced stronger ERK phosphorylation and upregulated MMP-9 and -13 mRNA expressions. However, transfection with a dominant-negative form of the Ras protein (Ras(N17)) inhibited the ERK activation and MMP-9 and -13 mRNA expressions induced by IL-1ß, which supported the involvement of ERK signalling in IL-1ß-induced MMP-9 and -13 expressions. Treatment with luteolin effectively inhibited the IL-1ß-induced ERK activation in dose-dependent manner. Taken together, luteolin might inhibit IL-1ß-induced MMP-9 and -13 expressions, in part, via inhibition of ERK signalling.

Curcubinoyl flavonoids from wild ginseng adventitious root cultures.

Wild ginseng (Panax ginseng) adventitious root cultures were prepared by elicitation using methyl jasmonate and investigated further to find new secondary metabolites. Chromatographic fractionation of wild ginseng adventitious root cultures led to the isolation of eleven compounds. The chemical structures of isolated compounds were identified as four known flavanone derivatives (1-4), one new curcubinoyl derivative, jasmogin A (5) and six new curcubinoyl-flavanone conjugates, jasmoflagins A-F (6-11) by extensive spectroscopic analysis. Newly isolated curcubinoyl derivatives showed inhibitory activity against lipopolysaccharide-stimulated nitric oxide production in RAW 264.7 macrophages. Therefore, our present study suggested that elicitor stimulated plant cell cultures might contribute to the production of new metabolites.

Aromatic Constituents from the Leaves of Actinidia arguta with Antioxidant and α-Glucosidase Inhibitory Activity.

As the leaf of Actinidia arguta has shown antioxidant activity, a study was conducted to identify the active ingredients. Forty-eight compounds were isolated from the leaves of A. arguta through various chromatographic techniques. Further characterization of the structures on the basis of 1D and 2D NMR and MS data identified several aromatic compounds, including phenylpropanoid derivatives, phenolics, coumarins, flavonoids and lignans. Among them, five compounds were newly reported, naturally occurring, and named argutosides A-D (1-4), which consist of phenylpropanoid glycosides that are conjugated with a phenolic moiety, and argutoside E (5), which is a coumarin glycoside that is conjugated with a phenylpropanoid unit. The isolated compounds showed good antioxidant and α-glucosidase inhibitory activity with differences in activity depending on the structures. Molecular docking analysis demonstrated the interaction between the hydroxyl and carbonyl groups of compounds 1 and 5 with α-glucosidase. Taken together, the leaves of A. arguta are rich in aromatic compounds with diverse structures. Therefore, the leaves of A. arguta and their aromatic components might be beneficial for oxidative stress and glucose-related diseases.

Organic acid conjugated phenolic compounds of hardy kiwifruit (Actinidia arguta) and their NF-κB inhibitory activity.

Nine new compounds, argutinosides A-I (1-9) together with 20 known compounds (10-29), were isolated from the fruits of Actinidia arguta. Using spectral analysis, the structures of the isolated compounds were identified as 10 succinic acid derivatives, 11 quinic acid derivatives, two shikimic acid derivatives and six citric acid derivatives. The NF-κB transcriptional inhibitory activity of the compounds was evaluated using RAW 264.7 macrophages cells induced by lipopolysaccharide. Among four groups of different organic acid derivatives, the quinic acid derivatives inhibited NF-κB transcriptional activity with an IC50 value of 4.0 µM. Fruit is rich in organic acid and secondary metabolites, which differ depending on the type of fruit. Our present study showed the presence of various organic acids conjugates including nine new 2-methylsuccinic acid phenolic conjugates in kiwiberry and compared their biological activities. This will contribute to application of kiwiberry and also the diversity of different fruits.

Comparison of antibacterial activity and phenolic constituents of bark, lignum, leaves and fruit of Rhus verniciflua.

Rhus verniciflua is commonly known as a lacquer tree in Korea. The bark of R. verniciflua has been used as an immunostimulator in traditional medicine, but also causes allergic dermatitis due to urushiol derivatives. For the development of active natural resources with less toxicity, the antibacterial activity of various parts of R. verniciflua such as bark, lignum, leaves and fruit, together with chemical composition, were investigated. Among the various parts of R. verniciflua, lignum showed the most potent antibacterial activity against fish pathogenic bacteria such as Edwardsiella tarda, Vibrio anguillarum and Streptococcus iniae. Measurement of total phenolic content and flavonoid content clearly showed a high content of phenolic and flavonoids in lignum among the various parts of R. verniciflua. Further analysis showed a close correlation between antibacterial activity and phenolic content. In addition, methyl gallate and fustin, the major constituents of bark and lignum, showed antibacterial activity, which suggested phenolic constituents as active constituents. The content of urushiols, however, was highest in bark, but there was a trace amount in lignum. LC-MS-MS and PCA analysis showed good discrimination with the difference of phenolic composition in various parts of R. verniciflua. Taken together, phenolic compounds are responsible for the antibacterial activity of R. verniciflua. The lignum of R. verniciflua contains high content of phenolic compounds with less urushiols, which suggests efficient antibacterial activity with less toxicity. Therefore, the lignum of R. verniciflua is suggested as a good source for antibacterial material to use against fish bacterial diseases.

Sesquiterpenes from fruits of Torilis japonica with inhibitory activity on melanin synthesis in B16 cells.

Melanin, a dark macromolecular pigment, protects skin from harmful damage. However, abnormal accumulation is responsible for hyperpigmentation disorders. Melanogenesis inhibitors have therefore become important constituents in cosmetic products for depigmentation. Torilis japonica Decandolle (Umbelliferae) is a biennial plant which is distributed in East Asia. Fruits of this plant have been used for the treatment of skin disease and inflammation. In our previous study, torilin, a major sesquiterpene of T. japonica, showed an inhibitory effect on melanin production in α-melanocyte stimulating hormone (α-MSH)-activated B16 melanoma cells. Further extensive chromatographic separation resulted in thirteen compounds. On the basis of spectroscopic analysis, the structures of the compounds isolated were determined to be three new sesquiterpenes, viz. a guaiane-type, epoxytorilinol (1), a eudesmane-type, elematorilone (2) and a cadinane-type, cardinatoriloside (3), together with ten known sesquiterpenes (4-13). Of the compounds isolated, compounds 4-6 and 11-13 inhibited α-MSH-activated melanin production in B16 melanoma cells with IC50 values from 72.9 to 191.0 µM.

Secoiridoids from the stem barks of Fraxinus rhynchophylla with pancreatic lipase inhibitory activity.

Pancreatic lipase digests dietary fats by hydrolysis, which is a key enzyme for lipid absorption. Therefore, reduction of fat absorption by the inhibition of pancreatic lipase is suggested to be a therapeutic strategy for obesity. From the EtOAc-soluble fraction of the stem barks of Fraxinus rhynchophylla (Oleaceae), four secoiridoids such as ligstroside (1), oleuropein (2), 2"-hydroxyoleuropein (3) and hydroxyframoside B (4) were isolated. The inhibitory activity of these compounds on pancreatic lipase was assessed using porcine pancreatic lipase as an in vitro assay system. Compound 4 showed the strongest inhibition on pancreatic lipase, which followed by compounds 1-3. In addition, compound 4 exerted inhibitory effect on pancreatic lipase in a mixed mechanism of competitive and noncompetitive manner. Taken together, F. rhynchophylla and its constituents might be beneficial to obesity.