Five new alkaloids from Coptidis Rhizoma–Euodiae Fructus couple and their cytotoxic activities against gastrointestinal cancer cells

A new indoloquinazoline alkaloid, 10-methoxywuchuyuamide I (1), three new benzylisoquinoline alkaloids, named as coptichic aldehyde (2), coptichine (3) and 13-carboxaldehyde-8-oxocoptisine (4), and a new isoindoline alkaloid, named as coptichinamide (5), together with two known alkaloids, wuchuyuamide I (6) and 8-oxocoptisine (7) were isolated from the Coptidis Rhizoma–Euodiae Fructus couple. Their chemical structures were determined by extensive spectroscopic analyses, including IR, UV, EI–MS, HRESI–MS, 1D and 2D NMR data (¹H NMR, ¹³C NMR, ¹H–¹H COSY, HSQC and HMBC). Cytotoxicities of the isolated alkaloids against NCI-N87 and Caco-2 cell lines were evaluated. Four benzylisoquinoline alkaloids 2–4 and 7 showed inhibitory activities against NCI-N87 cell with IC₅₀ values range from 8.92 to 35.98 μM. The alkaloid 3 was a new antiproliferation compound against NCI-N87 cells. The results provided valuable information for further investigation of alkaloid 3 as a chemopreventive agent.     

Bioassay-guided isolation of urease and α-chymotrypsin inhibitory constituents from the stems of Lawsonia alba Lam. (Henna)

Seven constituents were isolated from the stems of Lawsonia alba Lam., following an activity-guided isolation, which include two new constituents, namely lawsorosemarinol (1) and lawsofructose (2), one known compound 2-(β-d-glucopyranosyloxy)-1, 4-naphthoquinone (3) and four compounds, 4-hydroxy coumarine (4), 3-(4-hyroxyphenyl)-triacontyl-(Z)-propenoate (5), 3-(4-hydroxy-3-methoxyphenyl)-triacontyl-(Z)-propenoate (6) and 7-hydroxy-4-methyl coumarin (7) first time isolated from Lawsonia alba. Their structure elucidation was based on spectroscopic data analyses. Compounds 3 and 7 showed a moderate inhibition of urease activity, while rest of them showed less than 50% inhibition. These compounds did not show any significant inhibition against α-chymotrypsin.     

New flavonoids from Campylotropis hirtella with immunosuppressive activity

In an effort to identify natural compounds with immunosuppressive activity, nine new flavonoids, including one isoflav-3-ene derivative (1), one coumaronochromone (2), two isoflavanones (3, 4), one isoflavone derivative (6), one isoflavone (7), three flavonols (8, 9, 10), as well as one known compound, hydroisoflavone C (5), were isolated from the roots of Campylotropis hirtella. The structures of these compounds were elucidated by extensive spectroscopic measurements. All of the compounds were assessed for immunosuppressive activity. Among the isolates, compound 2 showed good inhibitory activity against mitogen-induced splenocyte proliferation with an IC₅₀ of 0.28 μM and relatively low cytotoxicity.     

Chemical constituents of Aloe barbadensis Miller and their inhibitory effects on phosphodiesterase-4D

Aloe barbadensis Mill has been used as food and medicine for a long time. In order to investigate the chemical constituents of A. barbadensis and their inhibitory activities towards phosphodiesterase-4D (PDE4D), 70% methanol extract of the dried A. barbadensis powder was employed. Phytochemical investigation has led to the isolation of three new chromones, 5-(hydroxymethyl)-7-methoxy-2-methylchromone (4), 5-((4E)-2′-oxo-pentenyl)-2-hydroxymethylchromone (6), and 7-hydroxy-5-(hydroxymethyl)-2-methylchromone (7), together with eighteen known compounds. Their chemical structures were determined based on spectroscopic methods including UV, IR, 1D and 2D NMR, and HRMS spectrometry. In addition, their inhibition against PDE4D was evaluated using tritium-labeled adenosine 3′,5′-cyclic monophosphate (³H-cAMP) as the substrate. Inhibition was calculated by the variation of radioactivity after the reaction, and compounds 1–4, 10, and 21 exhibited certain inhibitory activities towards PDE4D, which can provide an explanation why A. barbadensis can serve as anti-inflammatory agents.     

Six new lignans from the leaves and stems of Schisandra sphenanthera

Six new lignans, schisphenlignans F–K (1–6), together with ten known ones, were isolated from the leaves and stems of Schisandra sphenanthera. Their structures were elucidated on the basis of spectroscopic methods, including extensive NMR, MS and CD spectra. In addition, some compounds were tested for their acute activity on insulin sensitivity in 3T3-L1 differentiated adipocytes and anti-HIV-1 activity.     

Two new diterpene derivatives from Euphorbia lunulata Bge and their anti-proliferative activities

A new ent-abietane-type diterpene lactone (1) and a new jatrophane-type diterpenoid (2), together with twelve known compounds including three diterpenes (3–5), five triterpenes (6–10) and four sterides (11–14) were isolated from the ethanol extract of the whole plant of Euphorbia lunulata Bge. The structure of compounds 1 and 2 was elucidated on the basis of 1D and 2D NMR spectra and the HR-ESI-MS data. The structure of compound 2 was further analyzed by an X-ray crystallographic study. The in vitro anti-proliferative activities against MCF-7 and NCI-H460 cell lines for compounds 1–5 (diterpene) were evaluated. The results showed marked activity for compound 1 against the two cell lines with the IC₅₀ values 19.5 (NCI-H460) and 18.6 (MCF-7) μM, while for cis-platinum (a positive cytotoxic control agent) 29.7 (NCI-H460) and 27.7 (MCF-7) μM. Compounds 2–5 exhibited moderate cytotoxic activities for the two cell lines with the IC₅₀ values ranging from 32.1 to 58.2 μM.     

Cytotoxicity and structure activity relationships of phytosterol from Phyllanthus emblica

Fourteen sterols (1–14), including two new sterols, trihydroxysitosterol (2) and 5α,6β,7α-7α-acetoxysitosterol (3), were isolated from the branches and leaves of Phyllanthus emblica L. The isolated compounds and a structurally related sterol 15 from Aphanamixis grandifolia were screened for cytotoxicity in two tumor cell lines (HL-60 and SMMC-7721) and a non-tumor cell line (HL-7702) using RSB assay. Within the series of phytosterol derivatives tested, compound 15 was the most active, displaying potent cytotoxicity against HL-60 with IC₅₀ of 5.10 μmol/L, and most of the active compounds showed selective cytotoxicity against tumor and non-tumor cell lines, especially compound 10 with a safety index of 4.42.     

Hormone-sensitive lipase is involved in the action of hydroxysafflor yellow A (HYSA) inhibiting adipogenesis of 3T3-L1cells

BackgroundSafflor yellow A (SY) has been demonstrated to be beneficial to cardiovascular system. Our previous study showed that hydroxysafflor yellow A (HSYA), a main component of SY, could increase peroxisome proliferator-activated receptor γ mRNA expression. In this study, we investigate the effect of HSYA on the proliferation and adipogenesis of mouse 3T3-L1 preadipocytes.MethodsThe proliferation and adipogenesis of 3T3-L1 cells treated with HSYA was studied by 3-(4,5-dimethylthiazol-2-yl) 2,5-diphenyl tetrazolium bromide (MTT) spectrophotometry, Oil Red O staining and intracellular triglyceride assay methods. HSL mRNA expression and promoter activity were studied by real-time quantitative RT-PCR, transient transfection and dual luciferase reporter gene methods.ResultsHSYA (0.1 mg/L) significantly inhibited the proliferation of 3T3-L1 cells when compared with control cells in 8 h. This effect was further enhanced with the extension time (24 to 96 h) and an increase of concentration of HSYA (1–10 mg/L). The maximal inhibitory action was observed at 0.1 mg/L HSYA in 72 h (86 ± 11.8% vs. 100 ± 4.1%, p < 0.01). HSYA notably reduced the amount of intracellular lipid and triglyceride content in adipocytes to 85% (1 mg/L) and 75% (100 mg/L) on Day 4 following the differentiation, respectively, while increased HSL mRNA expression and promoter activities to 2.7 fold and 1.55 fold, respectively (p < 0.01), in differentiated 3T3-L1 adipocytes.ConclusionsHSYA inhibits the proliferation and adipogenesis of 3T3-L1 preadipocytes. The inhibitory action of HYSA on adipogenesis may be due to the promotion of lipolytic-specific enzyme HSL expression by increasing HSL promoter activity.     

Three lignans and one coumarinolignoid with quinone reductase activity from Eurycorymbus cavaleriei

Four compounds, including one new lignan cavaol H (1), one new coumarinolignoid 5′-hydroxycleomiscosin B (4) and two known lignans (2–3) were isolated from the 95% ethanol extract of the twigs of Eurycorymbus cavaleriei. Their structures were established on the basis of various spectroscopic analyses including 1D-(¹H, ¹³C, and DEPT) and 2D-NMR (COSY, HMQC, and HMBC). The absolute stereochemistry of the two known lignans was firstly reported in this article by ¹H NMR studies on Mosher's ester derivatives. In the present study, quinone reductase induction activities of compounds 1–4 were assayed, compound 4 showed moderate quinone reductase induction with concentration to double the enzyme activity (CD) of 10.5 ± 0.8 μg/mL. Then we established LC-MS-MS analysis of glutathione (GSH) incubation with compound 4 to explain whether compound 4 induced quinone reductase through alkylating of the sulfhydryl groups of Keap1. Reconstructed selected ion chromatogram (SIC) of m/z 706 after compound 4 incubation with GSH was different from that with Tris–HCl buffer solution, which meant the quinone reductase induction activity of compound 4 attributed to alkylating the sulfhydryl groups of Keap1.     

A new acetophenone derivative from flowers of Helichrysum italicum (Roth) Don ssp. italicum

A new acetophenone derivative named gnaphaliol 9-O-propanoate (1) was isolated from the chloroform fraction of EtOH extract of Helichrysum italicum ssp. italicum flowers along with the five known acetophenones 12-acetoxytremetone (2), 13-(2-methylpropanoyloxy)toxol (3), [2,3-dihydro-2-[1-(hydroxymethyl)ethenyl]-5-benzofuranyl]-ethanone (4), 1-[2-[1-[(acetyloxy)methyl]ethenyl]-2,3-dihydro-3-hydroxy-5-benzofuranyl]-ethanone (5) and gnaphaliol (6). The structures of compounds 1–6 were elucidated by extensive spectroscopic methods including 1D- (¹H and ¹³C) and 2D-NMR (DQF-COSY, HSQC, HMBC, TOCSY and ROESY) experiments as well as ESIMS analysis. The isolated compounds were investigated for their cytotoxicity, anti-inflammatory and antioxidant properties. Biological assays on human colonic epithelial cells showed that compound 2 possessed antioxidant effects reducing reactive oxygen species (ROS) production.     

Triterpenoids and α-glucosidase inhibitory constituents from Salacia hainanensis

Thirteen triterpenoids (1–13), including two new lupane triterpenoids, salacinins A and B (1 and 2), as well as one new friedelane triterpenoid, salacinin C (3), were isolated from the roots and stems of Salacia hainanensis. The structures of new compounds were elucidated by extensive spectroscopic analysis including 1D and 2D NMR, and MS experiments. Compound 1 possesses rare 2,3-seco-lupane skeleton. Compounds 4, 6 and 7 showed inhibitory effects on α-glucosidase in vitro.     

Two new sesquiterpenes from Artemisia sieversiana

Two new sesquiterpenes, together with 32 known compounds(3–34), were isolated from Artemisia sieversiana Ehrhart ex willd. and the compounds 3–21 were isolated from this plant for the first time. The new compounds were elucidated as 2α,9α-dihydroxymuurol-3(4)-en-12-oic acid (1) and 13α-methyl-(5αH,6αH,7αH,8αH)-austricin 8-O-β-D-glucopyranoside (2), respectively. The structural identification of these compounds was mainly achieved by spectroscopic methods including 1D and 2D NMR techniques, and the structure of compound 1 was confirmed by a single crystal X-ray diffraction experiment. Compounds 1–2 were evaluated for cytotoxic activity in vitro against MCF-7, NCI-H460 and Hep-G2 cell lines, respectively.     

Phenolic glycosides from Curculigo orchioides Gaertn.

Five new chlorophenolic glucosides, curculigine E (1), curculigine F (2), curculigine G (3), curculigine H (5), curculigine I (6) and one new phenolic glycoside, orcinoside H (4), together with eight known phenolic glycosides (7–14) were isolated from the Curculigo orchioides Gaertn. Their structures were established by spectroscopic techniques (IR, UV, MS, 1D and 2D NMR). The isolated phenolic glycosides were evaluated for antiosteoporotic activity against MC3T3-E1 cell line using MTT assays. Compounds 1, 2, 3, and 5 showed moderate antiosteoporotic activity with the proliferation rate of 10.1–14.1%.     

Antifungal compounds from turmeric and nutmeg with activity against plant pathogens

The antifungal activity of twenty-two common spices was evaluated against plant pathogens using direct-bioautography coupled Colletotrichum bioassays. Turmeric, nutmeg, ginger, clove, oregano, cinnamon, anise, fennel, basil, black cumin, and black pepper showed antifungal activity against the plant pathogens Colletotrichum acutatum, Colletotrichum fragariae, and Colletotrichum gloeosporioides. Among the active extracts, turmeric and nutmeg were the most active and were chosen for further investigation. The bioassay-guided fractionation led to the isolation of three compounds from turmeric (1–3) and three compounds from nutmeg (4–6). Their chemical structures were elucidated by spectroscopic analysis including HR-MS, 1D, and 2D NMR as curcumin (1), demethoxycurcumin (2) and bisdemethoxy-curcumin (3), erythro-(7R,8R)-Δ^8′-4,7-dihydroxy-3,3′,5′-trimethoxy-8-O-4′-neolignan (4), erythro-(7R,8R)-Δ8′-7-acetoxy-3,4,3′,5′-tetra-methoxy-8-O-4′-neolignan (5), and 5-hydroxy-eugenol (6). The isolated compounds were subsequently evaluated using a 96-well microbioassay against plant pathogens. At 30 μM, compounds 2 and 3 possessed the most antifungal activity against Phomopsis obscurans and Phomopsis viticola, respectively.     

Chemical constituents from the fibrous root of Ophiopogon japonicus,and their effect on tube formation in human myocardial microvascular endothelial cells

In an effort to identify novel active constituents on the cardiovascular system, a systematic study on macroporous resin adsorption of extracts from the fibrous root of Ophiopogon japonicus was performed in a human myocardial microvascular endothelial cell line (HMMEC) based assay. One novel spirostan, named ophiogenin (1), together with six known spirostans (4–8, 10), and one new sesquiterpene glycoside, named ophioside A (2), together with one known monoterpene glycoside (9) were isolated from the active fractions, and the aglycone of compound 2 that was a new natural compound was obtained from the acid hydrolysis of 2, named ophiopogonol (3). Their structures were determined by spectral and chemical analyses. Furthermore, their effect on HMMEC tube formation was also determined. Our results indicated that compounds 4 and 8 could significantly improve the tube formation and 2 showed moderate increasing effect, while compound 5 exhibited potent inhibitory effect.     

Bioactive phenolics and terpenoids from Manglietia insignis

Four new compounds, maninsigins A–D (1–4), including two new neolignans (1–2) and two new sesquiterpenes (3–4), as well as ten known compounds (5–14), were isolated from the leaves and stems of Manglietia insignis. Their structures were established on the basis of extensive spectroscopic analyses. In addition, some compounds were tested for their cytotoxic and neurite outgrowth-promoting activities, as well as their antagonistic activity toward FXR ligand.     

New steroids and sesquiterpene from Turraea pubescens

Four new compounds, including three new steroids (1–3) and one new sesquiterpene (6), and two new natural products (4–5), as well as three known steroids (7–9) were isolated from the twigs of Turraea pubescens. Compounds 3–5 are C₂₂ steroids isolated from the Meliaceae family for the first time. Their structures were elucidated by extensive NMR and MS analyses. Compound 1 exhibited inhibitory activity against lipopolysaccharide (LPS) induced nitric oxide (NO) production in RAW264.7 cells with an IC₅₀ value of 11.5 μM.     

New norlignan derivatives from Curculigo capitulata

Two new norlignan derivatives, crassifoside I (1) and sinensigenin C (2), were isolated from the rhizomes of Curculigo capitulate, along with six known norlignan derivatives, 1,1-bis(3,4-dihydroxyphenyl)-1-(2-furan)-methane (3), crassifogenin B (4), crassifoside A (5), breviscaside A (6), crassifoside D (7), and curcapital (8). Their structures were elucidated on the basis of spectral evidence and comparisons with literature data. The ¹H and ¹³C NMR data of compound 3 was first assigned. Compounds 3–7 were isolated from this plant for the first time.     

Antibacterial anthranilic acid derivatives from Geijera parviflora

Five anthranilic acid derivatives, a mixture I of three new compounds 11′-hexadecenoylanthranilic acid (1), 9′-hexadecenoylanthranilic acid (2), and 7′-hexadecenoylanthranilic acid (3), as well as a new compound 9,12,15-octadecatrienoylanthranilic acid (4) together with a new natural product, hexadecanoylanthranilic acid (5), were isolated from Geijera parviflora Lindl. (Rutaceae). Their structures were elucidated by extensive spectroscopic measurements, and the positions of the double bonds in compounds 1–3 of the mixture I were determined by tandem mass spectrometry employing ozone-induced dissociation. The mixture I and compound 5 showed good antibacterial activity against several Gram-positive strains.     

Alkyl and phenolic glycosides from Saussurea stella

One alkyl glycoside, saussurostelloside A (1), two phenolic glycosides, saussurostellosides B1 (2) and B2 (3), and 27 known compounds, including eleven flavonoids, seven phenolics, six lignans, one neolignan, one phenethyl glucoside and one fatty acid, were isolated from an ethanol extract of Saussurea stella (Asteraceae). Their structures were elucidated by NMR, MS, UV, and IR spectroscopic analysis. Of the known compounds, (+)-medioresinol-di-O-β-d-glucoside (7), picraquassioside C (10), and diosmetin-3′-O-β-d-glucoside (27) were isolated from the Asteraceae family for the first time, while (+)-pinoresinol-di-O-β-d-glucoside (6), di-O-methylcrenatin (11), protocatechuic acid (14), 1,5-di-O-caffeoylquinic acid (17), formononetin (28), and phenethyl glucoside (29) were isolated from the Saussurea genus for the first time. The anti-inflammatory activities of three new compounds (1–3), five lignans ((−)-arctiin (4), (+)-pinoresinol-4-O-β-d-glucoside (5), (+)-pinoresinol-di-O-β-d-glucoside (6), (+)-medioresinol-di-O-β-d-glucoside (7) and (+)-syringaresinol-4-O-β-d-glucoside (8)), one neolignan (picraquassioside C (10)), and one phenolic glycoside (di-O-methylcrenatin (11)) were evaluated by testing their inhibition of the release of β-glucuronidase from PAF-stimulated neutrophils. Only compound 5 showed moderate inhibition of the release of β-glucuronidase, with an inhibition ratio of 39.1%.