Four Flavanocoumarins from the Leaves of Litsea coreana Levl.

Two new flavanocoumarins, 1 and 2 , together with phyllocoumarin ( 3 ) and epiphyllocoumarin ( 4 ), were isolated from the leaves of Litsea coreana Levl. in Anhui Province, China. The structures of 1 – 4 were elucidated by spectroscopic methods. Biological tests revealed that 1 – 4 exhibited moderate anti‐inflammatory activities through inhibition of TNF‐α and IL‐1 production in primary mouse peritoneal macrophages activated with lipopolysaccharides (LPS).     

Synthesis,Characterization, and Anti‐Amoebic Activity of N‐(Pyrimidin‐2‐yl)benzenesulfonamide Derivatives

A new series of N‐(pyrimidin‐2‐yl)benzenesulfonamide derivatives, 3a – 3i and 4a – 4i , was synthesized from pyrimidin‐2‐amines, 2a – 2i , with the aim to explore their effects on in vitro growth of Entamoeba histolytica. The chemical structures of the compounds were elucidated by elemental analysis, FT‐IR, ¹H‐ and ¹³C‐NMR, and ESI mass‐spectral data. In vitro anti‐amoebic activity was evaluated against HM1 : IMSS strain of Entamoeba histolytica. The IC₅₀ values were calculated by using the double dilution method. The results were compared with the IC₅₀ value of the standard drug ‘metronidazole’. The selected compounds were tested for their cytotoxic activities by cell‐viability assay using H9C2 cardiac myoblasts cell line, and the results indicated that all the compounds displayed remarkable >80% viabilities to a concentration of 100 μg/ml.     

Synthesis and Biological Evaluation of New Natural Phenolic (2E,4E,6E)‐Octa‐2,4,6‐trienoic Esters

In the present study the esterification of the OH groups of resveratrol, caffeic acid, ferulic acid, and β‐sitosterol with an antioxidant polyconjugated fatty acid, (2E,4E,6E)‐octa‐2,4,6‐trienoic acid, was achieved. As the selective esterification of OH groups of natural compounds can affect their biological activity, a selective esterification of resveratrol and caffeic acid was performed by an enzymatic approach. The new resulting compounds were characterized spectroscopically (FT‐IR, NMR mono, and bidimensional techniques); when necessary the experimental data were integrated by quantum chemical calculations. The antioxidant, anti‐inflammatory and proliferative activity was evaluated. The good results encourage the use of these molecules as antioxidant and/or anti‐inflammatory agents in dermocosmetic application.     

A New DNA‐Intercalative Cytotoxic Allylic Xanthone from Swertia corymbosa

Phytochemical investigation of the CHCl₃ fraction of Swertia corymbosa resulted in the isolation of a new 3‐allyl‐2,8‐dihydroxy‐1,6‐dimethoxy‐9H‐xanthen‐9‐one ( 1 ), along with four known xanthones, gentiacaulein ( 3 ), norswertianin ( 4 ), 1,3,6,8‐tetrahydroxyxanthone ( 5 ), and 1,3‐dihydroxyxanthone ( 6 ). Structure of compound 1 was elucidated with the aid of IR, UV, NMR, and MS data, and chemical transformation via new allyloxy xanthone derivative ( 2 ). Compounds 1 – 6 exhibited various levels of antioxidant and anti‐α‐glucosidase activities. Absorption and fluorescence spectroscopic studies on 1 – 6 indicated that these compounds could interact with calf thymus DNA (CT‐DNA) through intercalation and with bovine serum albumin (BSA) in a static quenching process. Compound 1 was found to be significantly cytotoxic against human cancer cell lines HeLa, HCT116, and AGS, and weakly active against normal NIH 3T3 cell line.     

Anti-inflammatory and anti-tumor-promoting effects of 5-deprenyllupulonol C and other compounds from Hop (Humulus lupulus L.)

A new phloroglucinol derivative, 5‐deprenyllupulonol C ( 1 ), along with four other phloroglucinol derivatives, 2 – 5 , five chalcones, 6 – 10 , four flavanones, 11 – 14 , two flavonol glycosides, 15 and 16 , and five triterpenoids, 17 – 21 , were isolated from the female inflorescence pellet extracts of hop (Humulus lupulus L.). Upon evaluation of these compounds against the Epstein? Barr virus early antigen (EBV‐EA) activation induced by 12‐O‐tetradecanoylphorbol 13‐acetate (TPA) in Raji cells, twelve compounds, i.e., 1 – 4, 11 – 14, 17 – 19 , and 21 , showed potent inhibitory effects on EBV‐EA induction, with IC₅₀ values in the range of 215–393 mol ratio/32 pmol TPA. In addition, eleven compounds, i.e., 1 – 4, 6, 11, 12, 14, 17, 18 , and 20 , were found to inhibit TPA‐induced inflammation (1 μg/ear) in mice, with ID₅₀ values in the range of 0.13–1.06 μmol per ear. Further, lupulone C ( 2 ) and 6‐prenylnaringenin ( 14 ) exhibited inhibitory effects on skin‐tumor promotion in an in vivo two‐stage mouse‐skin carcinogenesis test based on 7,12‐dimethylbenz[a]anthracene (DMBA) as initiator and with TPA as promoter.     

Antiviral activity of Distictella elongata (Vahl) Urb. (Bignoniaceae), a potentially useful source of anti-dengue drugs from the state of Minas Gerais, Brazil

Aims: To investigate the in vitro antiviral activity of Distictella elongata (Vahl) Urb. ethanol extracts from leaves (LEE), fruits (FEE), stems and their main components. Methods and Results: The antiviral activity was evaluated against human herpesvirus type 1 (HSV‐1), murine encephalomyocarditis virus (EMCV), vaccinia virus Western Reserve (VACV‐WR) and dengue virus 2 (DENV‐2) by the 3‐(4, 5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) colorimetric assay. LEE presented anti‐HSV‐1 [EC₅₀ 142·8 ± 5·3 μg ml^?1; selectivity index (SI) 2·0] and anti‐DENV‐2 activity (EC₅₀ 9·8 ± 1·3 μg ml^?1; SI 1·5). The pectolinarin ( 1 ) isolated from LEE was less active against HSV‐1 and DENV‐2. A mixture of the triterpenoids ursolic, pomolic and oleanolic acids was also obtained. Ursolic and oleanolic acids have shown antiviral activity against HSV‐1. A mixture of pectolinarin ( 1 ) and acacetin‐7‐O‐rutinoside ( 2 ) was isolated from FEE and has presented anti‐DENV‐2 activity (EC₅₀ 11·1 ± 1·6 μg ml^?1; SI > 45). Besides the antiviral activity, D. elongata has disclosed antioxidant effect. Conclusions: These data shows that D. elongata has antiviral activity mainly against HSV‐1 and DENV‐2, besides antioxidant activity. These effects might be principally attributed to flavonoids isolated. Significance and Impact of the Study: Distictella elongata might be considered a promising source of anti‐dengue fever phytochemicals.     

An Eco‐Friendly Enantioselective Access to (R)‐Naringenin as Inhibitor of Proinflammatory Cytokine Release

(RS)‐Naringenin is a flavanone well‐known for its beneficial health‐related properties, such as its anti‐inflammatory activity. The preparative enantioselective chromatographic resolution of commercial (RS)‐naringenin was performed on a Chiralpak AD‐H column (500×50 mm i.d., d_p 20 μm) using MeOH as eluent. The developed method is in accordance with the principles of green chemistry, since the environmental impact was lowered by recycling of the eluent, and allowed the production of gram amounts of each enantiomer with high purity (chemical purity >99%, enantiomeric excess (ee) >94%). Racemic and enantiomeric naringenin were subjected to an exhaustive in vitro investigation of anti‐inflammatory activity, aimed at evaluating the relevance of chirality. The assay with cultured human peripheral blood mononuclear cells (hPBMC) activated by phytohemagglutinin A revealed that (R)‐naringenin was more effective in inhibiting T‐cell proliferation than the (S)‐enantiomer and the racemate. Moreover, (R)‐naringenin significantly reduced proinflammatory cytokine levels such as those of TNF‐α and, with less potency, IL‐6. These results evidenced the anti‐inflammatory potential of naringenin and the higher capacity of (R)‐naringenin to inhibit both in vitro hPBMC proliferation and cytokine secretion at non toxic doses. Thus, (R)‐naringenin is a promising candidate for in vivo investigation.     

Enhancement of the anti‐inflammatory activity of temporin‐1Tl‐derived antimicrobial peptides by tryptophan,arginine and lysine substitutions

Temporin‐1Tl (TL) is a 13‐residue frog antimicrobial peptide (AMP) exhibiting potent antimicrobial and anti‐inflammatory activity. To develop novel AMP with improved anti‐inflammatory activity and antimicrobial selectivity, we designed and synthesized a series of TL analogs by substituting Trp, Arg and Lys at selected positions. Except for Escherichia coli and Staphylococcus epidermidis, all TL analogs exhibited retained or increased antimicrobial activity against seven bacterial strains including three methicillin‐resistant Staphylococcus aureus strains compared with TL. TL‐1 and TL‐4 showed a little increase in antimicrobial selectivity, while TL‐2 and TL‐3 displayed slightly decreased antimicrobial selectivity because of their about twofold increased hemolytic activity. All TL analogs demonstrated greatly increased anti‐inflammatory activity, evident by their higher inhibition of the production tumor necrosis factor‐α (TNF‐α) and nitric oxide and the mRNA expression of inducible nitric oxide synthase and TNF‐α in lipopolysaccharide (LPS)‐stimulated RAW264.7 macrophage cells, compared with TL. Taken together, the peptide anti‐inflammatory activity is as follows: TL‐2 ≈ TL‐3 ≈ TL‐4 > TL‐1 > TL. In addition, LPS binding ability of the peptides corresponded with their anti‐inflammatory activity. These results apparently suggest that the anti‐inflammatory activity of TL analogs is associated with the direct binding ability between these peptides and LPS. Collectively, our designed TL analogs possess improved anti‐inflammatory activity and retain antimicrobial activity without a significant increase in hemolysis. Therefore, it is evident that our TL analogs constitute promising candidates for the development of peptide therapeutics for gram‐negative bacterial infection. Copyright © 2015 European Peptide Society and John Wiley & Sons, Ltd.     

Sesquiterpenoids from Chloranthus henryi and Their Anti‐neuroinflammatory Activities

Five new and seven known mono‐sesquiterpenoids ( 1 – 5 and 6 – 12 , resp.) together with five known lindenane‐type disesquiterpenoids, 13 – 17 , were isolated from the whole plant of Chloranthus henryi. Based on spectroscopic methods, the new structures were established to be (5S,6R,8S,10R)‐6‐hydroxyeudesma‐4(15),7(11)‐diene‐12,8‐olide ( 1 ), 6α‐hydroxyeudesma‐4(15),7(11),8(9)‐triene‐12,8‐olide ( 2 ), 8,12‐epoxy‐1β‐hydroxyeudesma‐4(15),7,11‐trien‐6‐one ( 3 ), 12‐oxochloraniolide A ( 4 ), and (4α)‐8‐hydroxy‐12‐norcardina‐6,8,10‐trien‐11‐one ( 5 ), respectively. Among the isolates, compound 2 , zederone epoxide ( 8 ), spicachlorantin G ( 13 ), chloramultilide A ( 14 ), shizukaol B ( 15 ), and spicachlorantin B ( 17 ) showed significant anti‐neuroinflammatory effects by inhibiting nitric‐oxide (NO) production in lipopolysaccharide (LPS)‐stimulated murine BV‐2 microglial cells with relatively low cytotoxicity.     

Phenolic Composition,Anti‐Inflammatory,Antioxidant, and Antimicrobial Activities of Alchemilla mollis (Buser) Rothm.

The current study was designed to evaluate the antioxidant, anti‐inflammatory and antimicrobial activities of Alchemilla mollis (Buser ) Rothm . (Rosaceae) aerial parts extracts. Chemical composition was analyzed by spectrophotometric and chromatographic (HPLC) techniques. The antioxidant properties assessed included DPPH^· and ABTS^·+ radical scavenging, β‐carotene‐linoleic acid co‐oxidation assay. Antimicrobial activity was evaluated with disc diffusion and micro dilution method. In order to evaluate toxicity of the extracts, with the sulforhodamine B colorimetric assay L929 cell line (mouse fibroblast) was used. The anti‐inflammatory activities of the potent antioxidant extracts (methanol, 70% methanol, and water extracts) were determined by measuring the inhibitory effects on NO production and pro‐inflammatory cytokine TNF‐α levels in lipopolysaccharide stimulated RAW 264.7 cells. 70% methanol and water extracts which were found to be rich in phenolic compounds (184.79 and 172.60 mg GAE/g extract) showed higher antioxidant activity. Luteolin‐7‐O‐glucoside was the main compound in the extracts. Ethyl acetate and 70% methanol extracts showed higher antibacterial activity against Staphylococcus aureus and Salmonella enteritidis with MIC value of 125 μg/ml. 70% methanol extract potentially inhibited the NO and TNF‐α production (18.43 μm and 1556.22 pg/ml, respectively, 6 h).     

Protective effect of brown Brazilian propolis against acute vaginal lesions caused by herpes simplex virus type 2 in mice: involvement of antioxidant and anti‐inflammatory mechanisms

Propolis has been highlighted for its antioxidant, anti‐inflammatory and antiviral properties. The purpose of this study was to investigate if brown Brazilian hydroalcoholic propolis extract (HPE) protects against vaginal lesions caused by herpes simplex virus type 2 (HSV‐2) in female BALB/c mice. The treatment was divided in 5 days of pre‐treatment with HPE [50 mg·kg^–1, once a day, intragastric (i.g.)], HSV‐2 infection [10 µl of a solution 1 × 10² plaque‐forming unit (PFU·ml^–1 HSV‐2), intravaginal inoculation at day 6] and post‐treatment with HPE (50 mg·kg^–1) for 5 days more. At day 11, the animals were killed, and the in vivo analysis (score of lesions) and ex vivo analysis [haematological and histological evaluation; superoxide dismutase (SOD), catalase (CAT) and myeloperoxidase (MPO) activities; reactive species (RS), tyrosine nitration levels, non‐protein thiols (NPSH) and ascorbic acid (AA) levels] were carried out. HPE treatment reduced extravaginal lesions and the histological damage caused by HSV‐2 infection in vaginal tissues of animals. HPE was able to decrease RS, tyrosine nitration, AA levels and MPO activity. Also, it protected against the inhibition of CAT activity in vaginal tissues of mice. HPE promoted protective effect on HSV‐2 infected animals by acting on inflammatory and oxidative processes, and this effect probably is caused by its antioxidant and anti‐inflammatory properties. Copyright © 2011 John Wiley & Sons, Ltd.     

Iridoids from Pedicularis verticillata and Their Anti‐Complementary Activity

Three new iridoids named as pediverticilatasin A – C ( 1 – 3 , resp.), together with five known iridoids ( 4 – 8 , resp.) were isolated from the whole plants of Pedicularis verticillata. The structures of three new compounds were identified as (1S,7R)‐1‐ethoxy‐1,5,6,7‐tetrahydro‐7‐hydroxy‐7‐methylcyclopenta[c]pyran‐4(3H)‐one ( 1 ), (1S,4aS,7R,7aS)‐1‐ethoxy‐1,4a,5,6,7,7a‐hexahydro‐7‐hydroxy‐7‐methylcyclopenta[c]pyran‐4‐carboxylic acid ( 2 ), (1S,4aS,7R,7aS)‐1‐ethoxy‐1,4a,5,6,7,7a‐hexahydro‐7‐hydroxy‐7‐methylcyclopenta[c]pyran‐4‐carbaldehyde ( 3 ). Their structures were elucidated on the basis of spectroscopic methods and compared with the NMR spectra data in the literature. All compounds were evaluated for their anti‐complementary activity on the classical pathway of the complement system in vitro. Among which, compounds 1 , 3 , and 6 exhibited anti‐complementary effects with CH₅₀ values ranging from 0.43 to 1.72 mm , which are plausible candidates for developing potent anti‐complementary agents.     

New Constituents from the Low Polar Fraction of the Fruits of Crataegus dahurica and Their Anti‐Inflammatory Activity in RAW264.7 Cells

The fruit of Crataegus dahurica Koehne was used to treat the disease of infantile indigestion and dyspepsia as an ethnic medicine and food. As a continuous work on finding the active constituents from the edible herbs, four new biphenyl derivatives ( 1 – 4 ), together with two known compounds ( 5 and 6 ), were obtained from the petroleum ether fraction of the fruits of C. dahurica. Their structures were determined by the extensive 1D and 2D NMR spectra and HR‐MS spectrometry. Furthermore, the anti‐inflammatory activities of all the isolated compounds were investigated, in which compound 4 showed moderately inhibitory effects on NO production in RAW264.7 cells without inducing cytotoxicity.     

Microbial Reactions on 7α‐Hydroxyfrullanolide and Evaluation of Biotransformed Products for Antibacterial Activity

7α‐Hydroxyfrullanolide ( 1 ), a known sesquiterpenoid, was isolated from Sphaeranthus indicus using an antibacterial‐activity‐directed fractionation method. This compound had exhibited a significant antibacterial activity against Gram‐positive bacteria. Chemical and microbial reactions were performed to prepare eight different analogues of compound 1 in order to evaluate these newly synthesized compounds for antibacterial activity. These compounds were 1β,7α‐dihydroxyfrullanolide ( 2 ), 7α‐hydroxy‐1‐oxofrullanolide ( 3 ), 4,5‐dihydro‐7α‐hydroxyfrullanolide ( 4 ), 11,13‐dihydro‐7α‐hydroxyfrullanolide ( 5 ), 13‐acetyl‐7α‐hydroxyfrullanolide ( 6 ), 2α,7α‐dihydroxysphaerantholide ( 7 ), 4α,5α‐epoxy‐7α‐hydroxyfrullanolide ( 8 ), and 4β,5β‐epoxy‐7α‐hydroxyfrullanolide ( 9 ). Microbial reactions on 1 using whole‐cell cultures of Cunninghamella echinulata and Curvularia lunata yielded compounds 2 – 4 . Incubation of compound 1 with the liquid cultures of Apsergillus niger and Rhizopus circinans yielded metabolites 5 – 7 , while 8 and 9 were prepared by carrying out an epoxidation reaction on 1 using meta‐chloroperbenzoic acid (mCPBA). Structures of compounds 2 – 9 were elucidated with the aid of extensive NMR spectral studies. Compounds 2 – 4 were found to be new metabolites. Compounds 1 – 9 were evaluated for antibacterial activity and found to exhibit a wide range of bioactivities. Antibacterial‐activity data of 1 – 9 suggested that the bioactivity of 1 is largely due to the presence of C(4)?C(5), C(11)?C(13), and a γ‐lactone moiety.     

7,8-secolignans from Schisandra wilsoniana and their anti-HIV-1 activities

Two new 7,8‐secolignans, marphenols A and B ( 1 and 2 , resp.), together with a known related derivative, 7,8‐secoholostylone B ( 3 ), were isolated from the stems of Schisandra wilsoniana. The structures of 1 and 2 were elucidated by spectroscopic methods, including extensive 1D‐ and 2D‐NMR techniques. The anti‐HIV‐1 activities of 1 – 3 were evaluated. Compound 1 inhibited HIV‐1_IIIB‐induced syncytia formation with an EC₅₀ value of 0.55 μg ml^?1. It reduced p24 antigen expression in acutely HIV‐1_IIIB‐infected C8166 cells and primary isolate HIV‐1_TC‐2‐infected peripheral blood mononuclear cells (PBMCs), with EC₅₀ values of 3.34 and 0.52 μg ml^?1, respectively. It showed no effects on the HIV‐1_IIIB replication in chronically infected H9 cells as well as fusion inhibition.     

An Unusual Tetrahydrofuran Lignan from the Roots of Zanthoxylum planispinum and the Potential Anti‐inflammatory Effects

An unusual tetrahydrofuran lignin, zanthplanispine ( 1 ), together with 14 known lignans ( 2 – 15 ) were isolated from the AcOEt‐soluble fraction from the MeOH extract of Z. planispinum roots. The structures of 1 was elucidated on the basis of 1D‐ and 2D‐NMR experiments as well as HR‐ESI‐MS analysis. The known compounds were identified by the comparison of their NMR data with previously reported in the literatures. Bioassay showed that compounds 1 – 4 could inhibit nitric oxide (NO) production in lipopolysaccharide (LPS) stimulated RAW 264.7 cells. In particular, compound 1 showed significant inhibitory activity with an IC₅₀ value of 36.8 μm .     

A New Anti‐Inflammatory Alkaloid from Roots of Heracleum dissectum

Using various chromatographic methods, a new piperidinone alkaloid, (3S)‐3‐{4‐[(1E)‐3‐hydroxyprop‐1‐en‐1‐yl]‐2‐methoxyphenoxy}piperidin‐2‐one ( 1 ), together with 10 known compounds, bergapten ( 2 ), xanthotoxol ( 3 ), isopimpinellin ( 4 ), isobergapten ( 5 ), heratomol‐6‐O‐β‐d ‐glucopyranoside ( 6 ), scopoletin ( 7 ), apterin ( 8 ), 3‐methoxy‐4‐β‐d ‐glucopyranosyloxypropiophenone, (praeroside; 9 ), tachioside ( 10 ) and coniferin ( 11 ), were isolated from roots of Heracleum dissectum Ledeb . Their structures were elucidated on the basis of physicochemical properties and the detailed interpretation of various spectroscopic data. All the isolated compounds were screened for anti‐inflammatory activity in vitro. As the results, compound 1 and 8 showed significantly inhibitory activity on nitric oxide production in RAW264.7 cells.     

Effects of arginine and leucine substitutions on anti‐endotoxic activities and mechanisms of action of cationic and amphipathic antimicrobial octadecapeptide from rice α‐amylase

Previously, we showed that the antimicrobial cationic and amphipathic octadecapeptide AmyI‐1‐18 from rice α‐amylase (AmyI‐1) inhibited the endotoxic activity of lipopolysaccharide (LPS) from Escherichia coli. In addition, we demonstrated that several AmyI‐1‐18 analogs containing arginine or leucine substitutions, which were designed on the basis of the helical wheel projection of AmyI‐1‐18, exhibited higher antimicrobial activity against human pathogenic microorganisms than AmyI‐1‐18. In the present study, anti‐inflammatory (anti‐endotoxic) activities of five AmyI‐1‐18 analogs containing arginine or leucine substitutions were investigated. Two single arginine‐substituted and two single leucine‐substituted AmyI‐1‐18 analogs inhibited the production of LPS‐induced nitric oxide in mouse macrophages (RAW264) more effectively than AmyI‐1‐18. These data indicate that enhanced cationic and hydrophobic properties of AmyI‐1‐18 are associated with improved anti‐endotoxic activity. In subsequent chromogenic Limulus amebocyte lysate assays, 50% inhibitory concentrations (IC₅₀) of the three AmyI‐1‐18 analogs (G12R, D15R, and E9L) were 0.11–0.13 μm , indicating higher anti‐endotoxic activity than that of AmyI‐1‐18 (IC_50, 0.22 μm ), and specific LPS binding activity. In agreement, surface plasmon resonance analyses confirmed direct LPS binding of three AmyI‐1‐18 analogs. In addition, AmyI‐1‐18 analogs exhibited little or no cytotoxic activity against RAW264 cells, indicating that enhancements of anti‐inflammatory and LPS‐neutralizing activities following replacement of arginine or leucine did not result in significant increases in cytotoxicity. This study shows that the arginine‐substituted and leucine‐substituted AmyI‐1‐18 analogs with improved anti‐endotoxic and antimicrobial activities have clinical potential as dual‐function host defense agents. Copyright © 2017 European Peptide Society and John Wiley & Sons, Ltd.