Phenolic-rich extract from the Costa Rican guava (Psidium friedrichsthalianum) pulp with antioxidant and anti-inflammatory activity. Potential for COPD therapy

The potential therapeutic effects of Costa Rican guava (Psidium friedrichsthalianum) extracts for chronic obstructive pulmonary disease were examined. The ethyl acetate fraction displayed the highest antioxidant activity, as compared to the hexane, chloroform, and n-butanol fractions, as well as the crude extract. This fraction was evaluated for its anti-inflammatory activity response relationship against interleukin-8 (IL-8) and inhibition of matrix metalloproteinase-1 (MMP-1) expression before and after treatment with cigarette smoke. The ethyl acetate fraction exhibited inhibitory activity against IL-8 production and MMP-1 expression, showing the most potent inhibitory activities in both assays at 100 μg/mL, and nine compounds (1–9) were found. Phenolic compounds 1-O-trans-cinnamoyl-β-d-glucopyranose (2), ellagic acid (3), myricetin (4), quercitrin (7), and quercetin (9) were identified using standard compounds or literature reports from related species. Compounds 1, 5, 6, and 8 were tentatively identified as 1,5-dimethyl citrate (1), sinapic aldehyde 4-O-β-d-glucopyranose (5), 3,3′,4-tri-O-methylellagic acid-4′-O-d-glucopyranoside (6), and 1,3-O-diferuloylglycerol (8), All nine compounds are reported for the first time in Costa Rican guava.     

Norditerpenoids from Agathis macrophylla

Three new norditerpenoids, (4S,5R,9S,10R)-methyl 19-hydroxy-15,16-dinorlabda-8(17),11E-dien-13-oxo-18-oate (1), (4R,5R,9R,10R,13S/R)-13-hydroxypodocarp-8(14)-en-19-oic acid (2/3) were isolated from Agathis macrophylla, together with 11 known diterpenoids. The structures of these compounds, 1-14, were established, mainly by spectroscopic analysis. The inactivation of protein tyrosine phosphatase 1B (PTP1B) by compounds 5-9 and 11-13 was tested and the cytotoxicity of compounds 1-14 against HL60 cell and SMMC-7721 cell were evaluated. Biological screening studies indicated that compounds 5, 7/8 and 9 were mild inactivators of PTP1B, whilst compounds 1, 4, 6, 7/8, and 10-12 exhibited moderate activity against both of the tested cell lines.     

Phenolic constituents from the flower buds of Lonicera japonica and their 5-lipoxygenase inhibitory activities

Thirteen phenolic constituents, luteolin (1), protocatechuic acid (2), caffeic acid (3), flavoyadorinin-B (4), 4,5-dicaffeoylquinic acid (5), luteolin 7-O-β-d-glucopyranoside (7), 3,5-dicaffeoylquinic acid methyl ester (8), methyl chlorogenate (9), quercetin 3-O-β-d-glucopyranoside (10), 3,5-dicaffeoylquinic acid (11), rhoifolin (12), chlorogenic acid (13), and a novel phenolic glucoside benzoate, vanillic acid 4-O-β-d-(6-O-benzoylglucopyranoside) (6), were isolated from the flower buds of Lonicera japonica. Flavoyadorinin-B (4) was isolated for the first time from a Caprifoliaceae plant. The structures of 1–13 were determined on the basis of chemical and spectroscopic evidence. These compounds were screened for their 5-lipoxygenase inhibitory activity. Only luteolin (1) showed significant inhibitory activity against 5-LOX-catalysed leukotriene production.     

Glycosidase inhibitory phenolic compounds from the seed of Psoralea corylifolia

The seeds of Psoralea corylifolia were extracted into five different polar solvents: chloroform, 50% ethanol in water, ethanol, methanol and water. All extracts were evaluated for glycosidase inhibitory activity. The chloroform extract (CE) showed the lowest IC₅₀ values against α-glucosidase (82.9 μg/ml) and α-mannosidase (132 μg/ml). Chromatography of CE yielded nine phenolic compounds which were identified as isovabachalcone (1), 4′-O-methylbavachalcone (2), isobavachromene (3), corylifolin (4), bavachinin (5), psoralidin (6), neobavaisoflavone (7), corylifol A (8), and bakuchiol (9). All isolated compounds, apart from compound 5, possessed α-glucosidase inhibitory activities. Among them, compounds 6–8 exhibited potent inhibition with IC₅₀s of 13.7, 27.7 and 11.3 μM, respectively. Furthermore, compounds 2 and 6 showed α-mannosidase inhibitory activity. Mechanistic analysis of their inhibition modes against α-glucosidase showed that compounds (6 and 7) were noncompetitive, whereas compound 8 was mixed. Furthermore, the most active glycosidase inhibitors (2, 6–8) were proven to be present in the native seed in high quantities by an HPLC chromatogram.     

New flavonol glycosides from Barbeya oleoides Schweinfurth

Three new flavonol glycosides, 3′,5′ dimethoxymyricetin-4″-O-α-l-rhamnopyranosyl (1–4) β-d-glucopyranoside (1), 3′-methoxyquercetin-4″-O-α-l-rhamnopyranosyl (1–4) β-d-glucopyranoside (2) and 3′-methoxyqurecetin-6″-O-α-l-rhamnopyranosyl (1–6) β-d-glucopyranoside (3), have been isolated from the aerial part of Barbeya oleoides Schweinf., along with twelve known compounds, uvaol (4), ursolic acid (5), corosolic acid (6), arjunolic acid (7), β-sitosterol-3-O-β-d-glucoside (8), (+)–catechin (9), (-)-epicatechin (10), isorhamnetin-4′-O-glucoside (11), arjunglucoside I (12), d-(-)-bornesitol (13), gallocatechin (14) and epigallocatechin (15). Compounds 4–15 were isolated for the first time from Barbeyaceae. Structure elucidation of compounds 1–3 was based on MS and NMR data. The ethyl acetate extract of the stems as well as compounds 5, 6, 14 and 15 showed significant antimicrobial activity, while the ethanol extracts of leaves, stems and compounds 4, 7, 8, 13–15 have dose-dependent spasmolytic action.     

Bioassay-guided screening and isolation of α-glucosidase and tyrosinase inhibitors from leaves of Morus alba

In this study, bioassay-guided fractionation of extracts from the leaves of Morus alba L. led to the isolation of 15 bioactive constituents with α-glucosidase and tyrosinase inhibitory activities, among which prenylated stilbenes were proved to be a new group of α-glucosidase inhibitors apart from iminosugars derived from Morus alba. Their structures were identified on the basis of extensive spectroscopic analysis and chemical evidence, as well as comparing with data from the literature. Among them, compounds (2R)/(2S)-Euchrenone a₇ (6a/6b), Chalcomoracin (7), Moracin C (8), Moracin D (9) and Moracin N (10) exhibited a significant degree of α-glucosidase inhibitory activity with IC₅₀ of 6.28, 2.59, 4.04, 2.54 and 2.76 μM, respectively, while (2R)/(2S)-Euchrenone a₇ (6a/6b), Moracin N (10), Quercetin (13), Norartocarpetin (14), the interconvertible epimeric mixture of (2R)/(2S)-7-methoxyl-8-ethyl-2′,4′-dihydroxylflavane-2″-O-β-d-glucopyranoside (1a/1b) and the interconvertible enantiomers of (2R)/(2S)-7-methoxyl-8-hydroxyethyl-2′,4′-dihydroxylflavane (5a/5b) displayed a potent tyrosinase inhibitory effect with IC₅₀ of 0.260, 0.924, 0.523, 0.0824, 0.616 and 0.528 μM, respectively. Especially, (2R)-7-methoxyl-8-ethyl-2′,4′-dihydroxylflavane-2″-O-β-d-glucopyranoside (1a), (2S)-7-methoxyl-8-ethyl-2′,4′-dihydroxylflavane-2″-O-β-d-glucopyranoside (1b), (2S)-8-hydroxyethyl-7,4′-dimethoxylflavane-2′-O-β-d-glucopyranoside (2), (2R)-7-methoxyl-8-hydroxyethyl-2′,4′-dihydroxylflavane (5a) and (2S)-7-methoxyl-8-hydroxyethyl-2′,4′-dihydroxylflavane (5b) were identified as new compounds.     

Dicaffeoylquinic acid derivatives and flavonoid glucosides from glasswort (Salicornia herbacea L.) and their antioxidative activity

Two novel antioxidant compounds, isoquercitrin 6″-O-methyloxalate (6) and methyl 4-caffeoyl-3-dihydrocaffeoyl quinate (salicornate, 7), were isolated from Salicornia herbacea L.. Six known compounds were also identified as 3,5-dicaffeoylquinic acid (1), quercetin 3-O-β-d-glucopyranoside (2), 3-caffeoyl-4-dihydrocaffeoylquinic acid (3), methyl 3,5-dicaffeoyl quinate (4), 3,4-dicaffeoylquinic acid (5), and isorhamnetin 3-O-β-d-glucopyranoside (8). Their chemical structures were determined by spectroscopic data from ESI–MS and NMR. The isolated dicaffeoylquinic acid derivatives (1, 3, 4, 5, and 7) showed similar activities for scavenging 1,1-diphenyl-2-picrylhydrazyl radicals and inhibiting formation of cholesteryl ester hydroperoxide during copper ion-induced rat blood plasma oxidation. The two flavonol glucosides (2 and 6), which have no substitutions in the B ring of their aglycones, also had similar activity. However, compound 8, which has the same structure as 2 except for the presence of a methoxyl group in the C-3′ position of the B ring, showed predominantly lower antioxidant activity than the other isolated compounds.     

Tyrosinase inhibitors from paper mulberry (Broussonetia papyrifera)

Fractionation of a chloroform-soluble extract from twigs of Broussonetia papyrifera, led to the isolation of one new compound, 3,5,7,4′-tetrahydroxy-3′-(2-hydroxy-3-methylbut-3-enyl)flavone (1), and 10 known compounds, uralenol (2), quercetin (3), isolicoflavonol (4), papyriflavonol A (5), broussoflavonol F (6), 5,7,3′,5′-tetrahydroxyflavanone (7), luteolin (8), isoliquiritigenin (9), broussochalcone A (10) and 5,7,3′,4′-tetrahydroxy-3-methoxyflavone (11). Their structures were identified by interpretation of MS, ¹H NMR, ¹³C NMR, HMQC and HMBC data. Their inhibitory activities on mushroom tyrosinase using l-tyrosine as substrate were investigated and the IC₅₀ values of 3,5,7,4′-tetrahydroxy-3′-(2-hydroxy-3-methylbut-3-enyl)flavone, uralenol, quercetin and broussoflavonol F were found to be 96.6, 49.5, 57.8, and 82.3 μM, respectively, better than arbutin, a well-known tyrosinase inhibitor.     

Isolation and structure elucidation of phenolic compounds from Cyclopia subternata Vogel (honeybush) intact plant and in vitro cultures

In the presented work, an insight was made into the polyphenolic composition of intact plant material and in vitro cultures of indigenous South African plant Cyclopia subternata Vogel (honeybush). Ethyl acetate fractions of methanol extracts were separated by means of gravity column chromatography and/or semipreparative HPLC on two serially connected monolithic RP-18 columns. The structures of the isolated compounds were determined by means of 1D and 2D NMR techniques and additionally confirmed by LC-DAD-ESI-MS. Apart from the previously described honeybush components, that is mangiferin (1), scolymoside (2), hesperidin (3) and narirutin (4), three additional compounds: iriflophenone 3-C-β-glucoside (benzophenone) (5), phloretin 3′,5′-di-C-β-glucoside (dihydrochalcone) (6), and isorhoifolin (flavone) (7) were identified for the first time in the herb of C. subternata. Additionally, three isoflavone glucosides, namely calycosin 7-O-β-glucoside (8), rothindin (9) and ononin (10), which had not been previously reported in Cyclopia plants, were identified in the callus of the above species. As far as the authors are concerned, this is the first report on the presence of benzophenone and dihydrochalcone derivatives in Cyclopia genus.     

Bioactive sesquiterpenoids from the solid culture of the edible mushroom Flammulina velutipes growing on cooked rice

The edible mushroom Flammulina velutipes was cultivated on cooked rice. Six new cuparene sesquiterpenes, enokipodins E-J (1-6), and two new sterpurane sesquiterpenes, sterpurols A (10) and B (11), with four known sesquiterpenes, 2,5-cuparadiene-1,4-dione (7), enokipodins B (8) and D (9), and sterpuric acid (12), were isolated from the solid culture of F. velutipes. The structures of new metabolites were elucidated by NMR experiments. The absolute configurations in new compounds were assigned by X-ray crystallographic analysis, the modified Mosher method, and CD data analysis. Bioactivity screening indicated that compounds 5-9 displayed weak antibacterial activity against Bacillus subtilis; 2, 3, and 5 showed weak antifungal activity against Aspergilus fumigatus; 6-9 showed both moderate cytotoxicity against the human tumor cell lines (HepG2, MCF-7, SGC7901, and A549) and antioxidant activity in DPPH scavenging assay. These results suggest that the solid culture of F. velutipes on cooked rice could be a good functional food.     

Glycolipids from the aerial parts of Orostachys japonicus with fatty acid synthase inhibitory and cytotoxic activities

Inhibition of fatty acid synthase (FAS) has been proposed as a new therapeutic target for the treatment of cancer. In our preliminary study, a MeOH extract of the aerial parts of Orostachys japonicus A. Berger (Crassulaceae) inhibited FAS activity (>95% inhibition at 62.5 μg/mL). Through bioassay-guided fractionation, we isolated three cerebrosides (1-3), including one new compound (1), and seven glyceroglycolipids (4-10) from a FAS inhibitory hexane-soluble fraction of the MeOH extract of O. japonicus. On the basis of physicochemical and spectroscopic analyses including 1D and 2D NMR, HRFABMS, and ESIMS/MS, the structure of the new compound 1 was 1-O-(β-d-glucopyranosyl)-(2S,3S,4R,6Z,10E)-2-[(2′R,6′Z,9′Z)-2-hydroxyeicosa-6′,9′-dienoylamino)]-1,3,4-trihydroxytetracosa-6,10-diene, and it was named orostachyscerebroside A. Compounds 1-10 were tested for their in vitro FAS inhibitory activity, and compounds 1, 4, 5, 6, 7, and 8 inhibited the enzyme with micro-molar IC₅₀ values both in the incorporation of [³H] acetyl CoA (from 52.2 to 108.0 μM) and in the oxidation of NADPH (from 19.5 to 30.3 μM). Interestingly, compounds 1, 4, 5, 6, 7, and 8 with FAS inhibitory activity showed cytotoxic activity against HL-60 (human leukemia) and A549 (human lung adenocarcinoma) cancer cells, while none of them displayed cytotoxicity against MCF-7 (human breast adenocarcinoma) cells. This is the first report on the inhibition of FAS by glycolipids from O. japonicus and their cytotoxic activity and may provide a scientific basis for the folk remedy using the plant to treat cancer.     

Abietane diterpenoids from Isodon lophanthoides var. graciliflorus and their cytotoxicity

Seven new (1–7) and three known (8–10) abietane diterpenoids were isolated from the methanolic extract of the aerial parts of Isodon lophanthoides var. graciliflorus (Lamiaceae), a folk Chinese medicine and an herb for functional beverages. They were identified as 16-acetoxylsugiol (1), graciliflorin E (2), graciliflorin F (3), 15-O-methylgraciliflorin F (4), 15-hydroxy-20-deoxocarnosol (5), 3β-hydroxysempervirol (6), 15-hydroxy-1-oxosalvibretol (7), abieta-8,11,13-triene-14,19-diol (8), 6,12,15-trihydroxy-5,8,11,13-abietatetraen-7-one (9), and 3α-hinokiol (10) based on the spectroscopic data including COSY (correlated spectroscopy), HMBC (heteronuclear multiple bond correlation), and HR-ESI-MS (high-resolution electrospray ionization mass spectrometry). All the compounds except 10 were obtained from I. lophanthoides for the first time. Compounds 1, 2, 5, 6, 8, and 9 exhibited in vitro cytotoxicity against A549 (human lung adenocarcinoma), MCF-7 (human breast adenocarcinoma), and HeLa (human cervical carcinoma) cell lines with the IC₅₀ values of 1.79–52.67 μM.     

Chemical constituents with antioxidant activities from litchi (Litchi chinensis Sonn.) seeds

Litchi (Litchi chinensis Sonn.) is widely accepted as a delicious fruit in China and its seeds have been commonly used in traditional Chinese medicine to relieve neuralgic pain. In the present study, chemical investigation of the 95% ethanol extract of Litchi chinensis seeds led to the isolation of four new compounds, 2α,3α-epoxy-5,7,3′,4′-tetrahydroxyflavan-(4β-8-catechin) (5), 2β,3β-epoxy-5,7,3′,4′-tetrahydroxyflavan-(4α-8-epicatechin) (7), litchiol A (9) and litchiol B (12), together with 11 known ones, 2,5-dihydroxy-hexanoic acid (1), soscopoletin (2), coumaric acid (3), protocatechuic acid (4), 2α,3α-epoxy-5,7,3′,4′-tetrahydroxyflavan-(4β−8)-epicatechin (6), pterodontriol d-6-O-β-d-glucopyranoside (8), Narirutin (10), naringin (11), dihydrocharcone-4′-O-β-d-glucopyranoside (13), pinocembrin-7-rutinoside (14), pinocembrin-7-neohesperidoside (15). Their structures were mainly elucidated on the basis of NMR, MS, IR, CD and UV spectral evidences. Antioxidant activities of 14 compounds were determined by DPPH radical-scavenging assay and Trolox equivalent antioxidant capacity assay, and the results showed that four compounds, protocatechuic acid (4), 2α,3α-epoxy-5,7,3′,4′-tetrahydroxyflavan-(4β-8-catechin (5), 2α,3α-epoxy-5,7,3′,4′-tetrahydroxyflavan-(4β−8)-epicatechin (6), 2β,3β-epoxy-5,7,3′,4′-tetrahydroxyflavan-(4α-8)-epicatechin (7), exhibited moderate antioxidant activities.     

C-dideoxyhexosyl flavones from the stems and leaves of Passiflora edulis Sims

The stems and leaves of Passiflora edulis Sims, are used as a folk medicine for treating both anxiety and nervousness in American countries. Phytochemical investigation of the n-butanol (n-BuOH) fraction of this plant led to the isolation of four new 2,6-dideoxyhexose-C-glycosyl flavones, including luteolin-8-C-β-digitoxopyranosyl-4′-O-β-d-glucopyranoside (1), apigenin-8-C-β-digitoxopyranoside (2), apigenin-8-C-β-boivinopyranoside (3) and luteolin-8-C-β-boivinopyranoside (4), together with five known compounds (5–9). The structures of these compounds were elucidated by extensive spectroscopic methods. All compounds were evaluated for their neurite outgrowth enhancing activities and the results indicated that luteolin (7) enhanced NGF-induced neurite outgrowth in PC12 cells at 50.0 μM.     

Ursolic acid analogues: non-phenolic functional food components in Jamaican raspberry fruits

The Rubus genus produces numerous species that are known for their medicinal properties. Rubus rosifolius, called the red raspberry, grows wild in elevated regions in Jamaica. Phytochemical examination of the ethyl acetate extract of the fruit yielded eight compounds of the 19-α-hydroxyursane type: euscaphic acid (1), 1-β-hydroxyeuscaphic acid (2), hyptatic acid B (3), 19α-hydroxyasiatic acid (4), trachelosperogenin (5), 4-epi-nigaichigoside F1 (6), nigaichigoside F1 (7), and trachelosperoside B-1 (8), as confirmed by NMR spectroscopy. Inhibition of cell proliferation by these compounds were determined by using MCF-7 (breast), SF-268 (CNS), NCI H460 (lung), HCT-116 (colon) and AGS (gastric) human tumour cells. Among the human tumour cell lines assayed, only compounds 3 and 6 displayed significant growth inhibition and was specific to colon tumour cells by 56% and 40%, respectively. These ursolic acid analogues were also tested for anti-inflammatory activity using in vitro cycloxegenase-1 (COX-1) and cycloxegenase-2 (COX-2) enzyme inhibitory assays. Compounds 1, 2 and 3 showed selective COX-1 enzyme inhibitory activity (13%, 25% and 35%) at 25 μg/ml. In the lipid peroxidation (LPO) inhibitory assays, compounds 2, 4, 7 and 6 inhibited LPO by 62%, 60%, 53% and 68%, respectively, at 25 μg/ml.     

Identification of phenolic antioxidants from Sword Brake fern (Pteris ensiformis Burm.)

Sword Brake fern (Pteris ensiformis Burm.) is one of the most common ingredients of traditional herbal drinks in Taiwan. In an effort to identify antioxidants from the aqueous extract of Sword Brake fern (SBF), the 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity-guided isolation was employed. Three new compounds, kaempferol 3-O-α-l-rhamnopyranoside-7-O-[α-d-apiofuranosyl-(1-2)-β-d-glucopyranoside] (1), 7-O-caffeoylhydroxymaltol 3-O-β-d-glucopyranoside (3) and hispidin 4-O-β-d-glucopyranoside (4), together with five known compounds, kaempferol 3-O-α-l-rhamnopyranosid-7-O-β-d-glucopyranoside (2), caffeic acid (5), 5-O-caffeoylquinic acid (6), 3,5-di-O-caffeoylquinic acid (7) and 4,5-di-O-caffeoylquinic acid (8) were isolated and determined on the basis of spectroscopic analyses. HPLC with UV detector was further employed to analyze the content of each compound in SBF based on the retention time by comparison with isolated pure compounds. It was found that the most abundant phenolic compound was compound 3, followed by compounds 7 and 4. The di-O-caffeoylquinic acids (7 and 8) have the strongest DPPH scavenging potential with IC₅₀ around 10 μM and the highest Trolox equivalent antioxidant capacity (TEAC) about 2 mM. This data indicates that SBF is rich in phenolic antioxidants.     

Pentadecyl ferulate,a potent antioxidant and antiproliferative agent from the halophyte Salicornia herbacea

An investigation of the chemical constituents of Salicornia herbacea has led to the isolation of one new natural product, pentadecyl ferulate (6), together with 11 known compounds, including phytol (1), stearolic acid (2), γ-linolenic acid (3), (3Z,6Z,9Z)-tricosa-3,6,9-triene (4), linoleic acid (5), stigmasterol (7), ergosterol (8), dioctyl phthalate (9), dibutyl phthalate (10), vanillic aldehyde (11), and scopoletin (12). The chemical structures of these materials were elucidated mainly by spectroscopic analysis. This work represents the first recorded example of the isolation of compounds 1, 2, 3, 4, 9, 10, and 11 from S. herbacea. The antioxidant experiments revealed that compound 6 possessed strong hydroxy radical and superoxide anion scavenging activities and was the principle antioxidant ingredient in the ethyl acetate extract. The antiproliferative results exhibited that compound 1 selectively inhibited HepG2 cells, whereas compounds 3 and 6 showed potent antiproliferative activities against HepG2 and A549 cells.     

Phenolic compounds isolated from Zingiber officinale roots inhibit cell adhesion

Inhibitors of cell adhesion molecule-mediated cell adhesion might be novel therapeutic agents for the treatment of various inflammatory diseases. In this study, nine phenolic compounds were isolated from the methanol extracts of Zingiber officinale roots by bioactivity-guided fractionation. The structures of the compounds were determined by spectroscopic analysis (¹H, ¹³C NMR and MS), to be 6-gingerol (1), 8-gingerol (2), 10-gingerol (3), 6-shogaol (4), 8-shogaol (5), 10-shogaol (6), dehydro-6-gingerdione (7), dehydro-10-gingerdione (8) and 6-paradol (9). Compounds 3, 4, 5 and 7 inhibited direct binding between sICAM-1 and LFA-1 of the THP-1 cells in a dose-dependent manner with IC₅₀ values of 57.6, 27.1, 65.4 and 62.0 μM, respectively. Compounds 4 and 7 had an inhibitory effect on direct binding between sVCAM-1 and VLA-4 of THP-1 cells. These results suggest that the phenolic compounds from Z. officinale roots are good candidates for therapeutic strategies aimed at inflammation.     

Three new flavanonol glycosides from leaves of Engelhardtia roxburghiana, and their anti-inflammation, antiproliferative and antioxidant properties

The ethyl acetate fraction of the leaves of Engelhardia roxburghiana Wall exhibited strong anti-inflammatory, anti-proliferative, and antioxidant activities. From this fraction, three new flavanonol glycosides: (2R, 3R)-3,5,7,4′-tetrahydroxyflavanonol-3-O-(3″-O-galloyl)-α-l-rhamnopyranoside (1), (2R, 3R)-3,5,7,3′,4′-pentahydroxyflavanonol-3-O-(3″-O-galloyl)-α-l-rhamnopyranoside (2), (2R, 3R)-3,5,7,3′,4′-pentahydroxyflavanonol-3-O-(3″-O- p-(E)-coumaroyl)-α-l-rhamnopyranoside (3), were isolated. The structures of these compounds were elucidated based on spectroscopic, and chemical analyses. The anti-inflammatory activities of 1-3 were examined as their inhibitory abilities on the expression of IL-1β, TNF-α, MCP-1, and COX-2 mRNA, in lipopolysaccharide-stimulated mouse J774A.1 macrophage cells. At the concentration of 50 μM, 2 and 3 significantly reduced the IL-1β expression, while 1 induced its expression contrarily. Meanwhile, 1 and 3 exhibited significant inhibition of TNF-α expression at the concentration of 10 μM, while 2 could achieve weak but significant inhibition at 50 μM. Furthermore, 1-3 did not suppress the mRNA expression of MCP-1 and COX-2. Compounds 1-3 showed significant anti-proliferative effect in Hep G2 cells. 3 showed the most potent anti-proliferative effect in HT-29 human colon cancer cells, while 1 and 2 had no inhibition. In addition, 1 and 2 exhibited antioxidant activities. The ORAC values of 1 and 2 were 12.8 and 17.0 mmol TE/g and the HOSC values of 1 and 2 were 14.4 and 16.0 mmol TE/g, respectively.     

Antimicrobial activities of some thymol derivatives from the roots of Inula hupehensis

In a search for some naturally occurring antimicrobial compounds found in medicinal plants, herbs and spice extracts, four thymol derivatives were isolated from the roots of Inula hupehensis (a medicinal plant) and identified as the new compound 9-O-β-d-glucopyranosyl-9-hydroxythymol (1), together with 8,9-epoxy-10-isobutyryloxythymyl isobutyrate (2), 8-hydroxy-9, 10-diisobutyloxythymol (3) and 8,9,10-trihydroxythymol (4). These thymol derivatives, with a semi-synthetic compound 9,10-dihydroxy-8-methoxythymol (5), were tested for their antimicrobial activities against three bacteria and six plant pathogenic fungi. Within the series of thymol derivatives tested, compound 3 was the most active, particularly displaying moderate antibacterial activities against Staphylococcusaureus, Methicillin-resistant S. aureus and Escherichia coli with MICs of 62.3, 62.8, and 250 μg/ml. Moreover, this compound exhibited inhibitory activities against three plant pathogenic fungi: Rhizoctonia solani, Phytophthora melonis and Peronophythora litchi, with EC₅₀ values of 157, 180 and 141 μg/ml. To our knowledge, this is the first report that these five thymol derivatives show inhibitory activity against plant pathogenic fungi.