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.     

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).     

Isolation and quantitative analysis of peroxynitrite scavengers from <Emphasis Type="Italic">Artemisia princeps</Emphasis> var. <Emphasis Type="Italic">orientalis</Emphasis>

Young and mature Artemisia princeps var. orientalis (APO, Compositae) are used as a health food and a medicinal plant, respectively, in Korea. Here, we identified the in vitro potent peroxynitrite (ONOO⁻)-scavenging effect (IC₅₀, 0.26 μg/mL) of the components from the EtOAc fraction. Octadecylsilane column chromatography on the EtOAc fraction yielded two caffeoylquinic acid compounds, 3,5-di-O-caffeoyl-muco-quinic acid (1) and methyl 4,5-di-O-caffeoylquinate (2) by NMR spectroscopic data, which have not been reported before from APO. The IC₅₀ values of compounds 1 and 2 were 0.18 ± 0.01 μg/mL and 0.12 ± 0.00 μg/mL, respectively, lower than that of the positive control (L-penicillamine). HPLC data indicated that young APO (1: 30.3 mg/g dried weight, 2: 27.7 mg/g) contained considerably higher quantities of the two caffeoylquinic acids than mature APO (1: 1.77 mg/g dried weight, 2: 4.10 mg/g).     

Cytotoxic lasiodiplodin derivatives from the fungus <Emphasis Type="Italic">Syncephalastrum racemosum</Emphasis>

Chemical investigation of fungal biomass of the fungus Syncephalastrum racemosum led to the isolation of new natural products (3R),(5S)-5-hydroxy-de-O-methyllasiodiplodin (1), 6-oxode-O-methyllasiodiplodin (2), in addition to five known compounds, de-O-methyllasiodiplodin (3), lasiodiplodin (4), (3R),(5R)-5-hydroxy-de-O-methyllasiodiplodin (5), ergosterol (6), and ergosterol peroxide (7). Their structures were elucidated by spectroscopic techniques. The absolute configuration of 1 was determined by a modified Mosher’s method. Compound 1 showed cytotoxicity against cholangiocarcinoma, KKU-M139, KKU-M156, and KKU-M213 cell lines with IC₅₀ values in the range of 14–19 μg/mL, while 3 showed cytotoxicity against KB, BC1, and NCI-H187 cell lines with IC₅₀ values of 12.67, 9.65, and 11.07 μg/mL, respectively.     

An oxepinoflavone from <Emphasis Type="Italic">Artocarpus elasticus</Emphasis> with cytotoxic activity against P-388 cells

A new oxepinoflavone, artoindonesianin E1 (1), was isolated from the wood of Artocarpus elasticus, along with four known prenylated flavones: artocarpin (2), cycloartocarpin (3), cudraflavones A (4) and C (5). The structure of the new compound was identified by spectroscopic methods. Upon cytotoxic evaluation against murine leukemia P-388 cells, the new compound showed IC₅₀ 5.0 μg/mL.     

Melanogenesis inhibitory compounds from Saussureae Radix

Ten compounds were isolated from the EtOAc soluble part of the MeOH extract of Saussureae Radix, with their effects on melanin production also evaluated in B-16 mouse melanoma cell lines stimulated with 3-isobutyl-1-methylxanthine (IBMX), an elevator of cellular cAMP. The compounds were identified as aplotaxene (1), 1β-hydroxy arbusculin A (2), costunolide (3), dehydrocostuslactone (4), 11β,13-dihydrocostunolide (5), reynosin (6), heptadec-(9Z)-enoic acid (7), β-sitosterol (8), linoleic acid methyl ester (9) and betulinic acid methyl ester (10). Compounds 2, 9 and 10 were identified from Saussureae Radix for the first time. Furthermore, compounds 2, 3 and 6 showed potent inhibitory effects on the IBMX-induced melanogenesis, in dose-dependent manners, with IC₅₀ values of 11, 3 and 2.5 μg/mL, respectively. As a positive control, arbutin exhibited an IC₅₀ value of 29 μg/mL.     

<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.     

Scopoletin from the flower buds of <Emphasis Type="Italic">Magnolia fargesii</Emphasis> inhibits protein glycation,aldose reductase,and cataractogenesis <Emphasis Type="Italic">Ex Vivo</Emphasis>

Five compounds previously known structures, scopoletin (1), northalifoline (2), stigmast-4-en-3-one (3), tiliroside (4), and oplopanone (5) were obtained from the flower buds of Magnolia fargesii using chromatographic separation methods. The structures of 1–5 were identified by the interpretation of their spectroscopic data including 1D- and 2D-NMR as well as by comparison with reported values. Three compounds 1–3 were found from M. fargesii for the first time in this study. All the isolates (1–5) were subjected to in vitro bioassays to evaluate the inhibitory activity on advanced glycation end products formation and rat lens aldose reductase (RLAR). Compound 1 showed a remarkable inhibitory activity on advanced glycation end products formation with IC₅₀ value of 2.93 μM (aminoguanidine: 961 μM), and showed a significant RLAR inhibitory activity with IC₅₀ value of 22.5 μM (3.3-tetramethyleneglutaric acid: 28.7 μM). Compound 4 exhibited potent inhibitory activity against RLAR (IC₅₀ = 14.9 μM). In the further experiment ex vivo, cataractogenesis of rat lenses induced with xylose was significantly inhibited by compound 1 treatment.     

Kaempferol glycosides and cardenolide glycosides,cytotoxic constituents from the seeds of <Emphasis Type="Italic">Draba nemorosa</Emphasis> (Brassicaceae)

Bioassay-directed fractionation of a methanolic extract from the seeds of Draba nemorosa (Brassicaceae) led to isolation of a new flavonol glycoside, drabanemoroside (5, kaempferol 3-O-α-L-rhamnopyranosyl-(1→2)-α-L-arabinopyranose) along with four known flavonoid derivatives (1–4), four cardenolide glycosides (6–9). Kaempferol glycosides 2 and 5 showed strong cytotoxicity against human small lung cancer cell line A549 and melanoma SK-Mel-2 with an IC₅₀ of 0.5 μg/mL and 1.9 μg/mL, respectively. Cardenolide glycosides 6–9 showed potent cytotoxicity (A549) in the range of 0.01–0.032 μg/mL. Their structures were characterized based on spectroscopic data (2D NMR, HRTOFMS, IR, and UV) and comparison of literature values. The carbohydrate units were also confirmed by comparing the hydrolysate of 5 with authentic monosaccharides.     

A new acyclic diterpene acid and bioactive compounds from <Emphasis Type="Italic">Knema glauca</Emphasis>

Investigation of the chemical constituents of the fruits of Knema glauca (Myristicaceae) yielded a new acyclic diterpene acid, named glaucaic acid 4, together with four acylphenols, including 1-(2,6-dihydroxyphenyl) tetradecan-1-one 1, malabaricone A 6, dodecanoylphloroglucinol 7 and 1-(2,4,6-trihydroxyphenyl)-9-phenylnonan-1-one 8, two lignans sesamin 2 and asarinin 3, and a flavan, myristinin D 5. In addition, myristinin A 9 and (±)-7,4′-dihydroxy-3′-methoxyflavan 10 were isolated from its leaves and stems, respectively. When tested against small-cell lung cancer (NCI-H187), epidermoid carcinoma (KB) and breast cancer (BC) cell lines, compounds 1, 6–8 and 10 displayed weak to moderate cytotoxicity. The acylphenols 6–8 displayed antituberculosis activity against the microbe Mycobacterium tuberculosis with MIC values of 25, 50 and 100 μg/mL, respectively, and antiviral activity against herpes simplex virus type 1, with 7 as the most active compound (IC₅₀ = 3.05 μg/mL). Malabaricone A 6 was also active against the malarial parasite Plasmodium falciparum with an IC₅₀ value of 2.78 μg/mL.     

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.     

Anthraquinones from the Roots of <Emphasis Type="Italic">Knoxia valerianoides</Emphasis> inhibit the formation of advanced glycation end products and rat lens aldose reductase <Emphasis Type="Italic">in vitro</Emphasis>

Eight known compounds, lucidin (1), lucidin-ω-methyl ether (2), rubiadin (3), damnacanthol (4), 1,3,6-trihydroxy-2-methoxymethylanthraquinone (5), 3,6-dihydroxy-2-hydroxymethyl-9,10-anthraquinone (6), 1,3,6-trihydroxy-2-hydroxymethyl-9,10-anthraquinone 3-O-β-primeveroside (7), and vanillic acid (8), were isolated from EtOAc- and n-BuOH-soluble fractions of the roots of Knoxia valerianoides. The structures of 1–8 were identified by analysis of spectroscopic data as well as by comparison with published values. All the isolates were subjected to in vitro bioassays to evaluate advanced glycation end products (AGEs) formation and rat lens aldose reductase (RLAR) inhibitory activity. Compound 5 showed the most potent inhibitory activity (IC₅₀ = 52.72 μM) against AGEs formation. Compounds 1, 2, and 8 also showed potent inhibitory activity on AGEs formation with IC₅₀ values of 79.28, 62.79, and 93.93 μM, respectively, compared with positive control, aminoguanidine (IC₅₀ = 962 μM). While, compounds 1 and 5–7 showed strong inhibitory activity against RLAR with IC₅₀ values of 3.35, 3.04, 6.39, and 2.05 μM, respectively.     

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).     

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.     

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.     

A new cytotoxic coumarin, 7-[(<Emphasis Type="Italic">E</Emphasis>)-3′,7′-dimethyl-6′-oxo-2′,7′-octadienyl] oxy Coumarin,from the leaves of <Emphasis Type="Italic">Zanthoxylum schinifolium</Emphasis>

A new coumarin, 7-[(E)-3′,7′-Dimethyl-6′-oxo-2′,7′-octadienyl]oxy coumarin (1), together with three known compounds, schinilenol (2), schinindiol (3) and 7-[(E)-7′-hydroxy-3′,7′-dimethylocta-2′,5′-dienyloxy]-coumarin (4) were isolated from the methylene chloride fraction of Z. schinifolium by normal and reverse phase column chromatographies. Their structures were determined on the basis of physical and spectroscopic evidences. Compound 1 (IC₅₀ 8.10 μM) showed potent cytotoxicity compared to auraptene (IC₅₀ 55.36 μM) against Jurkat T cells. The other isolated compounds 2 and 4 exhibited weak cytotoxicities.     

Solalyratins A and B,new anti-inflammatory metabolites from <Emphasis Type="Italic">Solanum lyratum</Emphasis>

A new coumestan (solalyratin A, 1) and a novel cyclic eight-membered α,β-unsaturated ketone (solalyratin B, 3), together with three known compounds, puerariafuran (2), coumestrol (4) and 9-hydroxy-2′,2′-dimethylpyrano[5′,6′:2,3]-coumestan (5), were isolated from the whole plant of Solanum lyratum. Their structures were elucidated on the basis of spectroscopic analyses. In vitro, compounds 1–5 showed anti-inflammatory activities, with IC₅₀ values in the range 6.3–9.1 μM.     

Patchouli alcohol: in vitro direct anti-influenza virus sesquiterpene in <Emphasis Type="Italic">Pogostemon cablin</Emphasis> Benth.

During the screening of anti-influenza virus substances from traditional herbal medicines, the methanol extract from the leaves of Pogostemon cablin Benth. showed potent in vitro antiviral activity (99.8% inhibition at a concentration of 10 μg/mL) against influenza virus A/PR/8/34 (H1N1). The anti-influenza virus principle was isolated from the hexane-soluble fraction, through solvent fractionation, repeated silica gel column chromatography, and reversed-phase HPLC. The major active principle was a volatile substance that was identified as a sesquiterpene, patchouli alcohol (1), on the basis of its spectral analyses. When anti-influenza virus activity against A/PR/8/34 was evaluated by the plaque forming assay, patchouli alcohol reduced the number of plaques by 75% at 2 μg/mL and 89% at 10 μg/mL. Patchouli alcohol showed dose-dependent anti-influenza virus activity, and its IC₅₀ value was estimated to be 2.635 μM. Although 11 different sesquiterpenes were tested for antiviral activity against influenza virus A/PR/8/34, no or negligible activity was observed except for patchouli alcohol. Patchouli alcohol did not show anti-influenza virus activity against A/Guizhou/54/89 (H3N2), but showed weak activity against B/Ibaraki/2/85 (IC₅₀ = 40.82 μM). Patchouli alcohol did not show inhibitory activity against influenza virus neuraminidase.     

Diacylglycerol acyltransferase-inhibitory compounds from <Emphasis Type="Italic">Erythrina senegalensis</Emphasis>

Inhibition of acyl CoA:diacylglycerol acyltransferase (DGAT) is proposed to be a drug target for the treatment of obesity and type 2 diabetes. Bioassay-guided fractionation of the CH₂Cl₂-soluble extract of the stem bark of Erythrina senegalensis, using an in vitro DGAT enzyme assay, resulted in the isolation of eight known prenylflavonoids, 8-prenylleutone (1), auriculatin (2), erysenegalensein O (3), erysenegalensein D (4), erysenegalensein N (5), derrone (6), alpinumisoflavone (7), and 6,8-diprenylgenistein (8). Compounds 1, 2–4, 6, and 8 inhibited DGAT activity, with IC₅₀ values ranging from 1.1 ± 0.3 to 15.1 ± 1.1 μg/mL. On the basis of the data obtained, we propose isoflavonoids with isoprenyl groups as a novel class of DGAT inhibitors.