Anti-oxidative and inhibitory activities on nitric oxide (NO) and prostaglandin E<Subscript>2</Subscript> (COX-2) production of flavonoids from seeds of <Emphasis Type="Italic">Prunus tomentosa</Emphasis> Thunberg

Chemical investigation of the 80% Me₂CO extract from the seeds of Prunus tomentosa led to the isolation and identification of six flavonoids: kaempferol (1), kaempferol 3-O-α-L-rhamnopyranoside (2; afzelin), kaempferol 3-O-β-D-(6-acetyl)-glucopyranosyl(1→4)-α-L-rhamnopyranoside (3; multiflorin A), kaempferol 3-O-β-D-glucopyranosyl(1→4)-α-L-rhamnopyranoside (4; multiflorin B), quercetin 3-O-α-L-rhamnopyranoside (5; quercitrin), and quercetin 3-O-β-D-glucopyranosyl (1→4)-α-L-rhamnopyranoside (6; multinoside A). Anti-oxidative and inhibitory activities on nitric oxide (NO) and prostaglandin E₂ production in interferon-γ (INF-γ) and lipopolysaccharide (LPS)-activated RAW 264.7 cells in vitro (COX-2) of the isolated compounds were evaluated. Compounds 1, 5, and 6 exhibited potent anti-oxidative activity in the DPPH radical scavenging assay with IC₅₀ values of 57.2, 59.4, and 54.3 μg/mL respectively. The positive control, ascorbic acid, had an IC₅₀ of 55.5 μg/mL. Compounds 1, 5, and 6 also reduced COX-2 levels in a dose dependent manner with IC₅₀ values of 10.2, 8.7, and 9.6 μg/mL respectively, with the positive control, indomethacin, having an IC₅₀ of 5.1 μg/mL. All six compounds inhibited NO production in a dose dependent manner with IC₅₀ values of 35.1, 42.8, 40.0, 44.8, 43.7, and 43.9 μg/mL respectively, while the positive control, L-NMMA, had an IC₅₀ of 42.1 μg/mL.     

Free radical scavenging and antielastase activities of flavonoids from the fruits of <Emphasis Type="Italic">Thuja orientalis</Emphasis>

Bioassay-guided fractionation of the MeOH extract of Thuja orientalis fruits using a DPPH (2,2-diphenyl-1-picrylhydrazyl) assay led to the isolation of 9 flavonoids: cupressuflavone (1), amentoflavone (2), robustaflavone (3), afzelin (4), (+)-catechin (5), quercitrin (6), hypolaetin 7-O-β-xylopyranoside (7), isoquercitrin (8) and myricitrin (9). Their chemical structures were determined by spectroscopic analyses. The free radical scavenging and human neutrophil elastase (HNE) inhibitory activities were evaluated for the isolated compounds. By DPPH scavenging assay, compounds 5, 6, 7, 8 and 9 showed anti-oxidant activities with IC₅₀ values of 28.66, 31.19, 18.30, 26.63 and 15.10 μM, respectively. By ABTS [2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt] scavenging assay, these compounds also exhibited potent anti-oxidant activities with IC₅₀ values of 6.77, 13.96, 6.97, 22.79 and 9.96 μM, respectively. Of note, compounds 1, 2 and 3 showed significant HNE inhibitory activities with IC₅₀ values of 8.09, 1.27 and 1.33 μM, respectively.     

Chemical and biologically active constituents of <Emphasis Type="Italic">Pteris multifida</Emphasis>

A new compound, 4-caffeoyl quinic acid 5-O-methyl ether (2), together with 12 known compounds—identified as (2R,3R)-pterosin L 3-O-β-d-glucopyrannoside (3), β-sitosterol β-d-glucopyranoside (4), apigenin 7-Ο-β-d-glucopyranoside (5), luteolin 7-Ο-β-d-glucopyranoside (6), sucrose (7), caffeic acid (8), pterosin C 3-Ο-β-d-glucopyranoside (9), pteroside C (10), 4,5-dicaffeoyl quinic acid (11), pteroside A (12), wallichoside (13) and (2S)-5,7,3′,5′-tetrahydroxyflavanone (14)—were isolated from Pteris multifida. The structure of the new compound was determined by means of physical, chemical and spectroscopic evidence. Compounds 5 and 6 were the main constituents of the plant, with yields of 0.19% and 0.16%, respectively. The cytotoxic activities of 2, 3, and 9–13 were evaluated against a human cell line (KB cells). Among the isolated compounds, pterosin C 3-Ο-β-d-glucopyrannoside (9) and 4,5-dicaffeoylquinic acid (11) showed a significant selective cytotoxicity (IC₅₀ 2.35 and 5.38, respectively), while moderate activity was observed for compound 2 (IC₅₀ 12.3). The chemosystematics of Pteris species is also discussed.     

Chemical constituents of <Emphasis Type="Italic">Melandrium firmum</Emphasis> Rohrbach and their anti-inflammatory activity

In our ongoing search for anti-inflammatory agents originating from Korean medicinal plants, we found that the hexane and BuOH fractions of the MeOH extract from the whole plants of Melandrium firmum Rohrbach inhibited 5-lipoxygenase (5-LOX) activity. By activity-guided fractionation, eleven compounds, α-spinaterol (1), ursolic acid (2), ergosterol peroxide (3), α-spinaterol glucoside (4), 2-methoxy-9-β-D-ribofuranosyl purine (5), aristeromycin (6), ecdysteron (7), polypodoaurein (8), (-)-bornesitol (9), mannitol (10) and cytisoside (11) were isolated from the hexane and BuOH fractions using column chromatography. Compounds 2, 5, 6, 8, 9, 10 and 11 were isolated for the first time from this plant. Compounds 1, 3, 4 and 7 inhibited 5-LOX activity with IC₅₀ values of 21.04 μM, 42.30 μM, 32.82 μM, and 17.18 μM, respectively. Ming Shan Zheng and Nam Kyung Hwang contributed equally to this work.     

Antitubercular triterpenes and phytosterols from <Emphasis Type="Italic">Pandanus tectorius </Emphasis>Soland. var. <Emphasis Type="Italic">laevis</Emphasis>

Bioassay-guided chromatographic purification of the antitubercular chloroform extract of Pandanus tectorius Soland. var. laevis leaves afforded a new tirucallane-type triterpene, 24,24-dimethyl-5β-tirucall-9(11),25-dien-3-one (1), squalene and a mixture of the phytosterols stigmasterol and β-sitosterol. Microplate Alamar Blue Assay (MABA) showed that 1 inhibited the growth of Mycobacterium tuberculosis H₃₇Rv with a MIC of 64 μg/mL, while squalene and the sterol mixture have MICs of 100 and 128 μg/mL, respectively.     

A new abietane diterpenoid from Isodon inflexus

A new ent-abietane diterpenoid, 3α,6β-dihydroxy-7,17-dioxo-ent-abieta-15(16)-ene (1), and three known ent-kaurane diterpenids, kamebacetal A (2), kamebakaurin (3), and excisanin A (4), and a known triterpenoid, ursolic acid (5), were isolated from the aerial parts of Isodon inflexus. Their chemical structures were determined by extensive analysis of spectroscopic data including 1D-and 2D-NMR experiments. All isolates (1–5) were evaluated for their potential to inhibit LPS-induced nitric oxide production in RAW264.7 cells. Of these, compounds 1–4 inhibited the production of NO with IC₅₀ values ranging from 1.0 to 26.5 μM.     

Cytotoxic 10-(indol-3-yl)-[13]cytochalasans from the fungus <Emphasis Type="Italic">Chaetomium elatum</Emphasis> ChE01

Nine 10-(indol-3-yl)-[13]cytochalasans such as a new chaetoglobosin V (1); two new natural products, prochaetoglobosin III (2) and prochaetoglobosin III_ed (3); six known chaetoglobosins B-D (4–6), F (7), and G (8) and isochaetoglobosin D (9) in addition to two known sterols, 24(R)-5α,8α-epidioxyergosta-6–22-diene-3β-ol (10) and ergosterol (11), were isolated from the fungus Chaetomium elatum ChE01. The structures of these compounds were elucidated by spectroscopic methods. Compounds 1–9 showed cytotoxicity against the human breast cancer (IC₅₀ 2.54–21.29 μM) and cholangiocarcinoma cell lines (IC₅₀ 3.41–86.95 μM).     

<Emphasis Type="Italic">In vitro</Emphasis> Na<Superscript>+</Superscript>/K<Superscript>+</Superscript>-ATPase inhibitory activity and antimicrobial activity of sesquiterpenes isolated from <Emphasis Type="Italic">Thujopsis dolabrata</Emphasis>

A series of sesquiterpenes and hinokitiol-related compounds (1–15) was isolated from the essential oil of Thujopsis dolabrata Sieb. et Zucc. var. hondai Makino, and their structures were determined by combined spectroscopic analyses. The inhibitory effects of these compounds on microbial cell growth and Na⁺/K⁺-ATPase were evaluated in vitro. It was found that (−)-elema-1,3,11(13)-trien-12-ol (5), α,β,γ-costol (8), and chamigrenol (11) inhibit the activities of Na⁺/K⁺-ATPase, with IC₅₀ values of 11.2 ± 0.11, 12.2 ± 0.09, and 15.9 ± 0.54 μg/mL, respectively. Thujopsene (1), cedrol (9), γ-cuparenol (10), and chamigrenol (11) showed potent antibacterial activity, with MIC values in the range of 25–50 μg/mL, and β-thujaplicin (12) exhibited a broad spectrum of antibacterial and antifungal activity. These results indicate that these isolated compounds are promising candidates for the development of potent Na⁺/K⁺ ATPase inhibitors and antimicrobial agents.     

A new triterpenoid from <Emphasis Type="Italic">Panax ginseng</Emphasis> exhibits cytotoxicity through p53 and the caspase signaling pathway in the HepG2 cell line

A new triterpenoid, 20(R),22(ξ),24(S)-dammar-25(26)-ene-3β,6α,12β,20,22,24-hexanol (1), and three known triterpenoids, β-D-glucopyranoside,(3β,12β)-12,20-dihydroxydammar-24-en-3-yl,6-acetate (2), 20(R)-ginsenoside Rg₃ (3), and 20(R)-ginsenoside Rh₂ (4), were isolated from the leaves of Panax ginseng. Their structures were determined by chemical analysis and spectral methods (IR, 1D and 2D NMR, HR-ESI-MS). Compounds 1–4 were exhibited various degrees of cytotoxicity in the human hepatoma cell line, HepG2. Compound 1 had the highest cytotoxic potency, with an IC₅₀ value of 20.1 μM, by stimulating p53-mediated cell cycle arrest at the G1 to S phase transition, leading to apoptosis via activation of the caspase signaling pathway.     

Constituents with α-glucosidase and advanced glycation end-product formation inhibitory activities from <Emphasis Type="Italic">Salvia miltiorrhiza</Emphasis> Bge.

The 75% ethanol extract from roots of Salvia miltiorrhiza Bge. (Dan shen) afforded two new compounds, 3-hydroxy-2-(2′-formyloxy-1′-methylethyl)-8-methyl-1,4-phenanthrenedione (1), (8′R)-isosalvianolic acid C methyl ester (2), and 14 known compounds. Their structures were established on the basis of spectral analysis. The ability of the compounds to inhibit α-glucosidase activity and formation of advanced glycation end-products (AGEs) was evaluated. All compounds displayed various degrees of inhibitory effects against α-glucosidase; moreover, compounds 2, 6, 11, 14, and 16 exhibited much more potent inhibition against AGEs than the positive control (aminoguanidine, AG, IC₅₀ 0.11 μM). This is the first time that compounds from this plant have been reported to have inhibitory activity against α-glucosidase.     

Topoisomerase I and II inhibitory constituents from the bark of Tilia amurensis

Two coumarins (1 and 6), one flavan-3-ol (2), one fatty acid (3), and two lignan glycosides (4 and 5) were isolated from the EtOAc and CH₂Cl₂ extract of the bark of Tilia amurensis. Their chemical structures were identified by comparing their physicochemical and spectral data with those of published in literatures. Compounds 4, 5, and 6 were isolated from Tilia genus for the first time. Compounds 2 and 3 showed potent inhibitory activity against both DNA topoisomerase I (IC₅₀ values; 49 μM and 4 μM, respectively, with 18 μM of positive control compound, comptothecin) and DNA topoisomerase II (IC₅₀ values; 13 μM and 3 μM, respectively, with 50 μM of positive control compound, etoposide). However, all compounds did not showed cytotoxicity against the human colon adenocarcinoma cell line (HT-29), the human breast adenocarcinoma cell line (MCF-7), and human liver hepatoblastoma cell line (HepG-2).     

Triterpenoic acids of Prunella vulgaris var. lilacina and their cytotoxic activities In Vitro

The column chromatographic separation of the MeOH extract from the aerial parts of Prunella vulgaris var. lilacina Nakai led to the isolation of fifteen triterpenoic acids (2–6, 9–13, 16–20), four flavonoids (14, 21–23), four phenolics (7, 8, 15, 24), and a diterpene (1). Their structures were determined by spectroscopic methods to be trans-phytol (1), oleanic acid (2) ursolic acid (3), 2α,3α,19α-trihydroxyurs-12en-28oic acid (4), 2α,3α-dihydroxyurs-12en-28oic acid (5), maslinic acid (6), caffeic acid (7), phydroxy cinnamic acid (8), 2α,3α,19α,23-tetrahydroxyurs-12en-28oic acid (9), 2α,3α,23-trihydroxyurs-12en-28oic acid (10), 2α,3β-dihydroxyurs-12en-28oic acid (11), 2α,3β,24-trihydroxyolea-12en-28oic acid (12), (12R, 13S)-2α,3α,24,trihydroxy-12,13-cyclo-taraxer-14-en-28oic acid (13), quercertin 3-O-β-D-glucopyranoside (14), rosmarinic acid (15), 2α,3α,24-trihydroxyurs-12,20(30)-dien-28oic acid (16), 2α,3α,24-trihydroxyolea-12en-28oic acid (17), 2α,3β,19α,24-tetrahydroxyurs-12en-28oic acid 28-O-Dglucopyranoside (18), 2α,3α,19α,24-tetrahydroxyurs-12en-28oic acid 28-O-D-glucopyranoside (19), prunvuloside A (20), kaempferol 3-O-α-L-rhamnopyranosyl(1→6)-β-D-glucopranoside (21), kaempferol 3-O-β-D-glucopyranoside (22), quercertin 3-O-α-L-rhamnopyranosyl(1→6)-β-D-glucopyranoside (23), and 2-hydroxy-3-(3’,4’-dihydroxyphenly)propanoic acid (24). Compounds 1, 8–12, 17, 21, 23, and 24 were isolated from this plant source for the first time. The isolated compounds were evaluated for their cytotoxicity against A549, SK-OV-3, SK-MEL-2, and HCT15 cells in vitro using the sulforhodamin B bioassay (SRB) method. Compound 3 exhibited moderate cytotoxic activity against A549, SK-OV-3, SK-MEL-2, and HCT15 cells, with ED₅₀ values of 3.71, 3.65, 13.62, and 5.44 μM, respectively.     

Potential anthelmintics: polyphenols from the tea plant <Emphasis Type="Italic">Camellia sinensis</Emphasis> L. are lethally toxic to <Emphasis Type="Italic">Caenorhabditis elegans</Emphasis>

A novel gallate of tannin, (−)-epigallocatechin-(2β→O→7′,4β→8′)-epicatechin-3′-O-gallate (8), together with (−)-epicatechin-3-O-gallate (4), (−)-epigallocatechin (5), (−)-epigallocatechin-3-O-gallate (6), and (+)-gallocatechin-(4α→8′)-epigallocatechin (7), were isolated from the tea plant Camellia sinensis (L.) O. Kuntze var. sinensis (cv., Yabukita). The structure of 8, including stereochemistry, was elucidated by spectroscopic methods and hydrolysis. The compounds, along with commercially available pyrogallol (1), (+)-catechin (2), and (−)-epicatechin (3), were examined for toxicity towards egg-bearing adults of Caenorhabditis elegans. The anthelmintic mebendazole (9) was used as a positive control. Neither 2 nor 3 were toxic but the other compounds were toxic in the descending order 8, 7 ≈ 6, 9, 4, 5, 1. The LC₅₀ (96 h) values of 8 and 9 were evaluated as 49 and 334 μmol L⁻¹, respectively. These data show that many green tea polyphenols may be potential anthelmintics.     

Polyphenolic compounds isolated from the leaves of Myrtus communis

Four hydrolyzable tannins [oenothein B (1), eugeniflorin D₂ (2), and tellimagrandins I (3) and II (4)], two related polyphenolic compounds [gallic acid (5) and quinic acid 3,5-di-O-gallate (6)], and four myricetin glycosides [myricetins 3-O-β-d-xyloside (7), 3-O-β-d-galactoside (8), 3-O-β-d-galactoside 6″-O-gallate (9), and 3-O-α-l-rhamnoside (10)] were isolated from the leaves of Myrtus communis. Antioxidant activities of the isolated compounds were evaluated by 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging assay.     

A new pyrrole alkaloid isolated from<Emphasis Type="Italic">Arum palaestinum</Emphasis> Boiss. and its biological activities

The phytochemical analysis of the ethyl acetate fraction ofArum palaestinum Boiss. (Araceae) led to the isolation and identification of a new polyhydroxy alkaloid compound; (S)-3,4,5-trihydroxy-1H-pyrrol-2(5H)-one (1), and other five known compounds; caffeic acid (2), isoorientin (3), luteolin (4) and vicenin II (5), as well as the rare compound 3,6,8-trimethoxy, 5,7,3′,4′-tetrahydroxy flavone (6). The structural elucidations of all the compounds were based on spectroscopic data (¹H- and¹³C-NMR, DEPT, HSQC, HMBC and NOE difference techniques) and comparison with literature data. Investigation of the antioxidant activity of the ethyl acetate fraction indicated its strong scavenging capacity for 1, 1-diphenyl-2-picrylhydrazyl (DPPH) radicals (SC₅₀ 3.1 ±0.82 μg/mL). Moreover, the treatment of different human cancer cell lines with the ethyl acetate fraction led to dose-dependant suppression in the proliferation of both breast carcinoma cells (MCF-7; IC₅₀ 59.09±4.1 μg/mL) and lymphoblastic leukemia cells (1301; IC₅₀ 53.1±2.9 μg/mL); however, it was found to have no effect on the growth of hepatocellular carcinoma cells (Hep G2).     

Phytochemical investigation of Tiarella polyphylla

Seven flavonoids (1–7), two triterpenoids (8 and 9) and four steroids (10, 11, 12 and 13) were isolated from the whole plant of Tiarella polyphylla. Based on the physicochemical and spectroscopic analyses, their structures were identified as myricetin (1), astragalin (2), afzelin (3), quercitrin (4), myricitin (5), nicotiflorin (6), isoquercitrin (7), tiarellic acid (8), 3β-hydroxy-20(29)lupen-27-oic acid (9), β-sitosterol-3-O-β-D-glucoside (10), stigmasterol-3-O-β-D-glucoside (11), β-sitosterol (12) and ergosterol endoperoxide (13). All 13 compounds, with the exception of tiarellic acid were isolated for the first time from T. polyphylla. In the anti-complementary assay, the steroids (12 and 13) exhibited potent activities; whereas, the flavonoids (1 to 7) showed weak or no activities, but even the triterpenoids (8 and 9) and steroidal saponins (10 and 11) evoked hemolysis.     

Stilbenes and oligostilbenes from leaf and stem of <Emphasis Type="Italic">Vitis amurensis</Emphasis> and their cytotoxic activity

Chromatographic separation of the EtOAc fraction from the leaf and stem of Vitis amurensis led to the isolation of six oligostilbenoids (i.e., r-2-viniferin (1), trans-amurensin B (2), trans-ɛ-viniferin (3), gnetin H (4), amurensin G (5), (+)-ampelopsin A (8)) and four stilbenoids (i.e., trans-resveratrol (6), (+)-ampelopsin F (7), piceatannol (9), and trans-piceid (10)). The structures have been identified on the basis of spectroscopic evidence and physicochemical properties. The isolates were investigated for cytotoxic activity against three cancer cell lines in vitro using the MTT assay method. Amurensin G (5) and trans-resveratrol (6) showed significant cytotoxic activity against L1210, K562 and HTC116 cancer cell lines with IC₅₀ values ranging from 15.7 ± 2.1 to 30.9 ± 1.8 μM. (+)-Ampelopsin A (8) and trans-piceid (10) exhibited considerable cytotoxic activity against L1210 (IC₅₀ values of 30.6 ± 4.1 and 28.7 ± 2.81 μM, respectively) and K562 (IC₅₀ values of 38.6 ± 0.82 and 24.6 ± 0.76 μM, respectively). Gnetin H (4) showed only weak cytotoxic activity against L1210 with an IC₅₀ value of 40.1 ± 4.23 μM. On the other hand, r-2-viniverin (1), trans-amurensin B (2), trans-ɛ-viniferin (3), (+)-ampelopsin F (7), and piceatannol (9) exhibited no activity on three cancer cell lines.     

Inhibition of DNA topoisomerases I and II and cytotoxicity of compounds from <Emphasis Type="Italic">Ulmus davidiana</Emphasis> var. <Emphasis Type="Italic">japonica</Emphasis>

Twenty five compounds including ten triterpenes (1–3, 5–11), six flavonoids (12–15, 24, 25), five lignans (17, 18, 21–23), two butenyl clohexnone glycosides (19–20), one fructofuranoside (16) and one fatty acid (4) were isolated from the roots of Ulmus davidiana var. japonica. The structures of those compounds were identified by comparing their physicochemical and spectral data with those of published in literatures. All the compounds were evaluated for DNA topoisomerase inhibitory activities and cytotoxicities. Among the purified compounds, 4 and 19 showed more potent inhibitory acitivities (IC₅₀: 39 and 19 μM, respectively) than camptothecin, as the positive control (IC₅₀: 46 μM) against topoisomerase I. Compounds, 4, 10, 12, 19, 24 and 25 showed strong inhibitory activities toward DNA topoisomerase II (IC₅₀: 0.1, 0.52, 0.47, 0.42, 0.17 μM and 17 nM, respectively), which were more potent than that of etoposide as positive control (IC₅₀: 20 μM). In A549 cell line, 5 and 6 showed cytotoxicities (IC₅₀: 4 μM and 3 μM, respectively, with IC₅₀ of camptothecin as positive control: 10.3 μM). In the HepG2 cell line, 3, 5 and 7 showed cytotoxicity (IC₅₀: 4, 3 and 4 μM, respectively, with IC₅₀ of camptothecin: 0.3 μM). Compounds 6, 12 and 23 showed cytotoxicities in the HT-29 cell line (IC₅₀: 19, 19 and 15 μM, respectively, with IC₅₀ of camptothecin: 2 μM).     

Cholinesterase inhibitors from <Emphasis Type="Italic">Cleistocalyx operculatus</Emphasis> buds

Five flavonoids, myricetin-3′-methylether 3-O-β-d-galactopyranoside (1), myricetin-3′,5′-dimethylether 3-O-β-d-galactopyranoside (2), quercetin (3), kaempferol (4), and tamarixetin (5) were isolated from the buds of Cleistocalyx operculatus (Myrtaceae). The chemical structures of these compounds were determined on the basis of spectroscopic analyses, including 2D NMR. Their anti-Alzheimer effects were evaluated via acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activity assays. All five compounds 1–5 showed potential inhibitory activities against AChE with IC₅₀ values of 19.9, 37.8, 25.9, 30.4 and 22.3 μM, respectively, while compounds 1, 3, 4 and 5 also possessed BChE inhibitory activity with IC₅₀ values of 152.5, 177.8, 62.5, and 160.6 μM, respectively.     

Two new acorane sesquiterpenes from <Emphasis Type="Italic">Illicium henryi</Emphasis>

Two new acorane sesquiterpenes, 10-hydroxyacoronene (1) and 1β-isopropyl-4β-methyl-9β-hydroxy spiro[4.5]dec-6-en-8-one (2), one new natural product, 4-hydroxy-4, 6-dimethyl-1-tetralone (3), and one known acorane sesquiterpene, acoradiepoxide (4) were isolated from the twigs and leaves of Illicium henryi. The structures of the new compounds were elucidated primarily on the basis of analysis of spectroscopic data. In addition, the inhibitory effect on NO production of these compounds were tested. Compounds 1 and 4 exhibited slight inhibitory effects on NO production with IC₅₀ values of 82.4 μg/mL and 76.5 μg/mL, respectively.