Cantharidin and Its Analogues:Anticancer and Ser/Thr Protein Phosphatase Inhibitory Activities

This paper mainly describes the anticancer activities and Ser/Thr protein phosphatase inhibitory activities of cantharidin and its analogues.

Evaluation of bioactive flavonoids in Citri Reticulatae Pericarpium from different regions and its association with antioxidant andα-glucosidase inhibitory activities

Background:To explore the differences of 14 batches of Citri Reticulatae Pericarpium from different regions.Methods:The main aim of this study was to develop a high-performance liquid chromatography method-photodiode array detection for determining the contents of five flavonoids and the chromatographic fingerprints of Citri Reticulatae Pericarpium from different regions.Theα-glucosidase inhibitory activities and antioxidant properties of Citri Reticulatae Pericarpium,based on free-radical scavenging assays against 1,1-diphenyl-2-picrylhydrazyl,2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid),and hydroxyl radicals,were estimated and compared.Results:Among the tested compounds,the content of hesperidin(13.386-68.235 mg/g)was the highest and that of hesperitin(0.045-0.277 mg/g)was the lowest.In comparing different sources of Citri Reticulatae Pericarpium,the contents of narirutin in Citri Reticulatae Pericarpium from Guangdong(0.824-0.851 mg/g)and Sichuan(1.069-1.204 mg/g)provinces of China were lower than in other provinces.In contrast,nobiletin(8.429-12.237 mg/g)and tangeretin(3.947-4.613 mg/g)were most abundant in Guangdong sources of Citri Reticulatae Pericarpium,followed by samples from Sichuan Province(nobiletin:6.761-7.658 mg/g;tangeretin:3.422-3.933 mg/g).Correlation analysis showed that nobiletin and tangeretin were the main contributors to the antioxidant capacity,and narirutin was the main active component inhibiting theα-glucosidase activity of Citri Reticulatae Pericarpium.Conclusion:This work revealed that the intrinsic quality of Citri Reticulatae Pericarpium was affected by different growing regions,which provides a scientific basis for controlling the quality of Citri Reticulatae Pericarpium and rationally developing and utilizing Citri Reticulatae Pericarpium.

A Pair of New Spirocyclic Alkaloid Enantiomers with TrxR Inhibitory Activities Were Isolated from Marine-Derived Aspergillus ruber TX-M4-1

One new spirocyclic alkaloid,5-isopentenyl-cryptoechinuline D(1),along with 11 known compounds(2–12),were iso-lated from a marine fungus Aspergillus ruber TX-M4-1.The structures of compounds 1–12 were elucidated by spectroscopic evi-dences.Compound 1 was initially isolated as an enantiomer,and further separation of 1 by chiral HPLC afforded a pair of enantio-mers,including(-)-5-isopentenyl-cryptoechinuline D(1a)and(+)-5-isopentenyl-cryptoechinuline D(1b).Their absolute configura-tions were elucidated by ECD spectroscopic data.Compounds 1a,5 and 10 could inhibit thioredoxin reductase(TrxR)activity with IC50 values of 6.2,36.3 and 18.6μmol L^(-1),respectively.Surface plasmon resonance(SPR)study also demonsrated the interactions between compounds 6,8 and Niemann-Pick C1 Like 1(NPC1L1)respectively,which indicate that compounds 6 and 8 are potential NPC1L1 inhibitors.

Cucurbitane-Type Triterpene Glycosides from Momordica charantia and Their α-Glucosidase Inhibitory Activities

Ten cucurbitane-type triterpene glycosides,including five new compounds named charantosides H(1),J(2),K(3),momor-characoside A(4),goyaglycoside-l(5),and five known compounds(6-10),were isolated from the EtOAc extract of Momor-dica charantia fruits.The chemical structures of these compounds were identified by 1D and 2D NMR and HRESIMS spectroscopic analyses.Configurations of new compounds were determined by ROESY correlations and comparison of their 13C NMR data with literature reported values.All compounds were evaluated for their inhibition againstα-glucosidase,in which compounds 2,5,7,8,9 showed moderate inhibitory activities with IC50 values ranging from 28.40 to 63.26μM comparing with the positive control(acarbose,IC5087.65±6.51μM).

SESQUITERPENES FROM CURCUMA PHAEOCAULIS AND THEIR INHIBITORY ACTIVITIES ON NITRIC OXIDE PRODUCTION IN RAW 264.7 CELLS

Curcumfa phaeocaulis Valeton is used in traditional Chinese medicines for the treatment of blood-related disorders such as blood stasis and inflammation.Our previous studies have found that sesquiterpenes were mainly isolated from C.wenyujin and C.phaeocaulis,while diarylheptanoids were the major compounds from C.kwangsiensis.And most of the isolated compounds exhibited remarkable

Flavonoids from Litchi(Litchi chinensis Sonn.) Seeds and Their Inhibitory Activities on α-Glucosidase

With the bioactivity-guided method,a new flavanone glycoside,together with nine known flavonoids were isolated from 50% aqueous ethanol of litchi（Litchi chinensis Sonn.） seeds.The chemical structure of the new compound was elucidated via 1D and 2D nuclear magnetic resonance（NMR） techniques and mass spectrometry to be （2S）-pinocembrin-7-O-（6＂-O-α-L-arabinosyl-β-D-glucopyranoside）（1）,and the nine known compounds were determined to be quercetin（2）,phlorhizin（3）,pinocembrin-7-O-glucoside（4）,kaempferol-7-O-β-D-glucopyranoside（5）,onychin（6）,nairutin（7）,narcissin（8）,pinocembrin-7-O-[（6＂-O-β-D-glucopyranoside）-β-D-glucopyranoside]（9） and pinocembrin-7-O-[（2＂,6＂-di-O-α-L-rhamnopyranosyl）-β-D-glucopyranoside]（10）.Some of the isolated flavonoids were tested for their inhibitory effects on α-glucosidase.And compounds 2 and 3 showed stronger inhibitory activity than positive control.

The influence of Lactobacillus plantarum fermentation in selenium-enriched Brassica napus L.:changes in the nutritional constituents,bioactivities and bioaccessibility

Selenium(Se)-enriched Brassica napus L.is a valuable organic Se supplement.In this study,the fermentation broth enriched with organic Se(FFS)was prepared using Lactobacillus plantarum to ferment the substrate of Se-enriched Brassica napus L.Significant increases were observed after fermentation in total sugars,reducing sugars,soluble proteins,total phenolic content(TPC),and total flavonoid content(TFC).The organic Se was retained at a concentration of 54.75 mg/g in the freeze-dried sample.Principal component analysis and cluster analysis showed good separation between the FFS and unfermented(FS)groups.Fragrant 2-ethyloxetane had the highest content among all volatiles,while sinapine had the highest content among all phenolic compounds.The fermentation process showed remarkable improvement in the abundance and concentration of volatile compounds and phenolic contents,making FFS exhibit strong antioxidant activity and inhibitory capacity againstα-glucosidase activity.The bioaccessibility of phenolic compounds was significantly greater in FFS compared to FS.ADMET analysis revealed that the majority of phenolic compounds contained in FFS did not exhibit mutagenicity toxicity,hepatotoxicity,skin sensitization,or blood-brain barrier penetration,indicating a favorable level of biosafety.Overall,our study provides a new insight into the further utilization of Se-enriched Brassica napus L.in foods.

Inhibitory Effects of Sixteen Fungicides on Mycelial Growth and Spore Germination of Monilinia fructicola

[Objective]The paper was to compare the indoor toxicities of sixteen fungicides on mycelial growth and spore germination of Monilinia fructicola,to screen out effective fungicides and to discuss use characteristics of various types of fungicides.[Method]The inhibitory activities of 16 fungicides on mycelial growth and spore germination were determined by mycelial growth rate method and spore germination method.[Result]The EC50 values of 16 fungicides against mycelial growth ranged from 0.0184 to 61.5305 mg/L.Prochloraz,tetramycin,fenbuconazole and fludioxonil had strong inhibitory activities on mycelial growth,and their EC50 values were 0.0184,0.0456,0.0531 and 0.0814 mg/L,respectively,significantly lower than those of other 12 fungicides.The EC50 values of 16 fungicides against spore germination ranged from 0.0084 to 189.3938 mg/L.Tetramycin and chlorothalonil had strong inhibitory activities on mycelial growth,and their EC50 values were 0.0084 and 0.0378 mg/L,respectively,significantly lower than those of other 14 fungicides.[Conclusion]The 16 fungicides had great value in preventing and controlling peach brown rot.Benzimidazoles,diformimides and ergosterol inhibitors had good inhibitory activities on mycelial growth.Strobilurins,succinate dehydrogenase inhibitors and multiple-site protective fungicides had good inhibitory activities on spore germination.The agricultural antibiotics tetramycin,phenazine-1-carboxylic acid and pyrrole fungicide fludioxonil had good inhibitory activities on mycelial growth and spore germination.

Inhibitory Effects of Six Fungicides against Neocordana musae

[Objective]The paper was to screen effective fungicides to control Cordana leaf spot caused by Neocordana musae.[Method]The toxicities of six fungicides against mycelial growth of N.musae were measured by the method of mycelium growth inhibition.[Result]The average EC50 values of six fungicides against mycelial growth ranged from 0.1029 to 504.065μg/mL.Among them,22.5%picoxystrobin SC and 12.5%epoxiconazole SC showed strong inhibitory activity on mycelial growth,with the average EC50 values of 0.1029 and 0.6851μg/mL,respectively;followed by 50%thiophanate-methyl SC,with an average EC50 value of 1.993.80%Azoxystrobin WG showed a relatively low sensitivity against N.musae,with an average EC50 value of 504.046.[Conclusion]The six fungicides tested have great value in preventing and controlling Cordana leaf spot.22.5%Picoxystrobin SC,12.5%epoxiconazole SC and 50%thiophanate-methyl SC have better inhibitory activities on mycelial growth of N.musae,and can be further used in field trials.

QSAR Studies on the Inhibitory Activityof Levofloxacin-thiadiazole HDACi Conjugates to Histone Deacetylases

A molecular electronegativity distance vector(M)based on 13 atomic types has been used to describe the structures of 19 conjugates(LHCc)of levofloxacin-thiadiazole HDAC inhibitor(HDACi)and related inhibitory activities(pH,i=1,2,6)of LHCc against histone deacetylases(HDACs,such as HDAC1,HDAC2 and HDAC6).The quantitative structure-activity relationships(QSAR)were established by using leaps-and-bounds regression analysis for the inhibitory activities(pH)of 19 above compounds to HDAC1,HDAC2 and HDAC6 along with M.The correlation coefficients(R~2)and the leave-one-out(LOO)cross validation Rfor the pH,pHand pHmodels were 0.976 and 0.949;0.985 and 0.977;0.976 and 0.932,respectively.The QSAR models had favorable correlations,as well as robustness and good prediction capability by R~2,F,R~2,A,Fand Vtests.Validated by using 3876 training sets,the models have good external prediction ability.The results indicate that the molecular structural units:–CH–(g=1,2),–NH,–OH,=O,–O–and–S–are the main factors which can affect the inhibitory activity of pH,pHas well as pHbioactivities of these compounds directly.Accordingly,the main interactions between HDACs inhibitor and HDACs are hydrophobic interaction,hydrogen bond,and coordination with Znto form compounds,which is consistent with the results in reports.

In vitro antioxidant,anti-diabetic,cholinesterase and tyrosinase inhibitory potential of fresh juice from Citrus hystrix and C.maxima fruits

In the present study,antioxidant potential,α-amylase,α-glucosidase,cholinesterase and tyrosinase inhibitory activity of fresh juice from indigenous fruits of Citrus hystrix and C.maxima(Red&White var.)were investigated using an in vitro model.The contents of total phenolics,tannins,and total flavonoids ranged between 836.90 and 909.52 mg gallic acid equivalent(GAE)/L,333.33 and 523.21 mg gallic acid equivalent(GAE)/L and 224.88 and 262.22 mg rutin equivalent/L,respectively.The antioxidant activity of fresh juice was evaluated by employing different in vitro assays such as reducing power assay,DPPH•,ABTS•+and•OH radical scavenging capacities,peroxidation inhibition activity,antihemolytic assay.In addition,75.55%–79.75%ofα-amylase and 70.68%–72.83%ofα-glucosidase enzyme inhibition characteristics were found under in vitro starch digestion bioassay.Also,all the juice samples exhibited excellent tyrosinase(76.95%–80.79%),acetylcholinesterase(75.71%–79.74%)andβ-glucuronidase inhibitory activity(68.13%–69.38%).These results indicated that fresh juice of C.hystrix and C.maxima(Red&White var.)could be used as a source of antioxidant agents,functional food and nutraceuticals.©2014 Beijing Academy of Food Sciences.Production and hosting by Elsevier B.V.All rights reserved.

Lipase inhibitory activity of Lagenaria siceraria fruit as a strategy to treat obesity

Objective:To explore pancreatic lipase inhibitory activity under different extraction conditions in order to track the most potent extract.Methods:The methanolic extract and its fractions in solvents of increasing polarity,ether,chloroform,ethyl acetate,n-butanol and water,were made through cold maceration.Extracts in ethanol,ethyl acetate,acetone and chloroform were similarly prepared.Aqueous extract was prepared through hot decoction method.A reported method was used to determine lipase inhibitory activity of extracts and fractions over wide ranges of concentrations.Results:The extracts and fractions exhibited concentration dependent activity.The IC50(μg/mL)values of methanolic,ethanolic,chloroform,ethyl acetate,acetone,ethyl acetate(after washing with water)and aqueous decoction were 293.40,266.47,157.59,182.12,352.34,257.00,and 190.00,respectively.The activity of chloroform,ethyl acetate and aqueous extracts were close to that of the drug orlistat(IC50 146μg/mL).Out of the fractions of the methanolic extract,the chloroform fraction was most active(IC50 189.6μg/mL).The order of inhibitory activity of the fractions was as follows:chloroform>ether>n-butanolic>aqueous>ethyl acetate.The GC/MS analysis of the most active chloroform faction showed the presence of hexadecanoic acid,methyl hexadecanoate,isopropyl palmitate,methyl 9,12-octadecadienate,and methyl 9,12,15-octadecatrienoate.Conclusions:The study suggests that Lagenaria siceraria has potential to inhibit pancreatic lipase activity,suppressing lipid digestion and thereby diminishing entry of lipids into the body.Regular intake of aqueous decoction of the fruit may therefore be recommended for control of obesity.Fatty acids and their esters may play role as inhibitors of lipase.

In vitro Inhibitory Activity of Shisandra chinensis and Polygonatum sibiricum against Vibrio harveyi and Its Biofilms

[Objective] This study aimed to analyze the in vitro inhibitory activity of Shisandra chinensis and Polygonatum sibiricum against Vibrio harveyi and its biofilms. [Result] By agar diffusion test, in vitro inhibitory activity of 5. chinensis and P. sibiricum against V. harveyi was investigated. The minimal inhibitory concentration （ MIC） and minimal bactericidal concentration （MBC） of 5. chinensis and P. sibiricum against V. harveyi were determined by doubling dilution meth-od. The inhibitory activity of 5. chinensis and P. sibiricum on the formation of V. harveyi biofilms was evaluated by modified MTT assay. [ Result ] Both 5. chinen-sis and P. sibiricum had inhibitory activity against V. harveyi. The inhibition zone diameter of 5. chinensis against V. harveyi was 17. 95 mm; MIC and MBC of 5. chinensis were both 3.125 mg/ml. The inhibition zone diameter of P. sibiricum against V. harveyi was 12. 22 mm; MIC and MBC of P. sibiricum were 3.125 and 6.250 mg/ml, respectively. When the concentration was higher than 6. 25 mg/ml, 5. chinensis decoction had extremely significant inhibitory activity against V. harveyi （P 〈 0. 01） ; when the concentration was higher than 3. 125 mg/ml, P. sibiricum had extremely significant inhibitory activity against V. harveyi （P 〈0. 01）. [ Conclusion] 5. chinensis and P. sibiricum could significantly inhibit V. harveyi and its biofilms.

Identification and dipeptidyl peptidase Ⅳ(DPP-Ⅳ) inhibitory activity verification of peptides from mouse lymphocytes

The objective of this study was to isolate and identify the intracellular bioactive peptides from mouse lymphocytes before and after lipopolysaccharide(LPS)stimulation,to explore novel peptides and to research the bioactive function.Mouse spleen lymphocytes were isolated and cultured with LPS stimulation(experimental group)or not(control group)to collect intracellular peptides.Totally 385 peptides were analyzed by nanoliter liquid phase-Q Exactive quadrupole ultra-high resolution orbitrap mass spectrometer(Nano LC-Q Exactive Plus)and identifi ed by PEAKS X software.After compared with peptides reported,131 novel peptides were discovered,which then were predicted bioactivity by Peptide Ranker and 6 peptides with high bioactivity were predicted function by BIOPEP-UMW database.Prediction data showed that they may have dipeptidyl peptidase IV(DPP-IV)inhibitory activity.Finally,two peptides showed better potent inhibition were verifi ed with competitive and noncompetitive modes.

Inhibitory Effect of Live-Attenuated Listeria Monocytogenes-based Vaccines Expressing MIA Gene on Malignant Melanoma

Listeria monocytogenes(LM),a Gram-positive facultative intracellular bacterium,can be used as an effective exogenous antigen expression vector in tumor-target therapy.But for successful clinical application,it is necessary to construct attenuated LM stain that is safe yet retains the potency of LM based on the full virulent pathogen.In this study,attenuated LM and recombinants of LM expressing melanoma inhibitory activity(MIA) were constructed successfully.The median lethal dose(LD 50) and invasion efficiency of attenuated LM strains were detected.The recombinants were utilized for immunotherapy of animal model of B16F10 melanoma.The level of MIA mRNA expression in tumor tissue was detected by using real-time polymerase chain reaction(PCR) with specific sequence,meanwhile the anti-tumor immune response was assayed by flow cytometric analysis and enzyme-linked immunosorbent spot(ELISPOT) assay.The results showed the toxicity and invasiveness of attenuated LM were decreased as compared with LM,and attenuated LM expressing MIA,especially the double-genes attenuated LM recombinant,could significantly induce anti-tumor immune response and inhibit tumor growth.This study implicates attenuated LM may be a safer and more effective vector for immunotherapy of melanoma.

Anti-microbial Activities of Protic Ionic Liquids Studied with Microcalorimetry Method

The anti-microbial activities of seven protic ionic liquids（ILs） against Escherichia coli and Staphylococcus aureus were studied by a micro-calorimetric method at 310 K.The bacterial growth rate constants were determined based on the bacterial growth power-time curves,andminimum biocidal concentrations were estimated.The results indicate that the protic ILs studied show inhibitory activities on the bacteria,implying a potential eco-toxicity to the microorganisms in the water system.Moreover,the inhibition effect of ionic liquids is related to the structure of the cation and anion of protic ILs.This type of proactive approach could aid in the assessment of the greenness of ILs to be used in the future.

Development and assessment of tyrosinase inhibitory activity of liposomes of Asparagus racemosus extracts

The purpose of this study was to develop liposomal formulations of Asparagus racemosus root extract(AR1-6)as well as evaluate the physicochemical properties and in vitro tyrosinase inhibitory activity.Liposomes composed of AR1-6 to lipid weight ratio of 1:10 and lecithin(LEC)or Phospholipon
90G(PC90G)as structural phospholipid at 7:3 molar ratio to CHOL were prepared by various methods,i.e.chloroform-film(CF),reverse-phase evaporation(REV),polyol dilution(PD),and freeze-drying of monophase solution(MFD)methods.The results revealed that vesicles prepared by CF and MFD were multilamellar whereas those prepared by REV and PD were oligolamellar in nature with particle sizes ranging from 0.26 to 13.83 mm.The zeta potentials were in the range of
1.5 to
39.3 mV.AR1-6 liposomes with LEC possessed significantly higher entrapment than those with PC90G.The highest entrapment efficiency and in vitro tyrosinase inhibitory activity of 69.08%and 25%,respectively,were obtained from liposomes having LEC and prepared by PD method.The tyrosinase inhibitory activity were in the rank order of LEC>PC90G,and PD>CF>REV>MFD.It could be concluded that the mechanism of vesicle forming in each method of preparation was the key factor influencing physicochemical properties,particularly vesicle type,size,surface charge,and entrapment,which were well correlated with the biological activity.

Crystal Structure and Inhibitory Activity against Xanthine Oxidase of Bis(μ_2-chloro)-chloro-(μ-N,N'-(2-pyridylmethylene) Furanmethanoamine Copper(II) Complex

A chloro-bridged dinuclear copper（H） complex with ligand 2-pyridylme-thylene- furfurylamine has been synthesized and characterized by single-crystal X-ray diffraction, and its inhibitory activity on xanthine oxidase （XO） was also evaluated. It crystallizes in the triclinic system, space group P 1 with a = 8.0441（16）, b = 8.5663（17）, c = 10.060（2）A, α = 77.52（3）, β = 72.04（3）, γ = 70.12（3）°, V = 615.3（2）A^3, Z = 1, Dc = 1.731 g/cm^3, F（000） = 322, the final R = 0.0401 and wR = 0.0934 for 1971 observed reflections with I 〉 2σ（I）. X-ray analysis reveals that the Cu（II） cation is five-coordinated by two N atoms of Schiff base and three Cl anions. The C-H…Cl intermolecular and intramolecular hydrogen bonds connect the molecules to form a three-dimensional network. This copper（II） complex shows more potent inhibitory activity against XO with IC50 = 3.48μM than the standard inhibitor allopurinol.

Free Radical Scavenging, Enzyme Inhibitory and Anti-<i>Staphylococcus aureus</i>Properties of the Fruiting Bodies of <i>Ganoderma lucidum</i>, Lingzhi Mushroom

The current study evaluated the antioxidant, α-amylase inhibitory and anti-Staphylococcus aureus activities of the fruiting bodies of Ganoderma lucidum. Methanolic extract of G. lucidum (MEGL) was investigated for its in vitro antioxidant activity using 1,1-diphenyl 2-picrylhydrazyl (DPPH) assay and EC50 value was determined. α-Amylase inhibitory and anti-S. aureus activities were carried out by conventional methods. The mushroom extract showed maximum free radical scavenging activity at a dose of 500 μg/mL with EC50 value of 22.1399 μg/mL. EC50 value for the inhibition of α-amylase activity was found 22.6011 μg/mL. G. lucidum extracts exhibited a concentration-dependent Anti-S. aureus activity. The vast differences of this inhibition between lower and higher doses were assessed significantly (p < 0.05). This study shows that the fruiting body of G. lucidum has moderate antioxidant, α-amylase inhibitory, and anti-S. aureus activities. Thus this mushroom may be the alternative plant source for the antioxidant, anti-diabetic and antibacterial agents and further in vivo studies and isolation of bioactive compounds are required.

Highly Aromatic Norditerpenoid Heterodimers and Monomers from Trigonostemon fragilis

Four new norditerpenoid heterodimers with different dimerization patterns-namely,trigofragiloids A-C(denoted as compounds 1-3)and(+)-and(-)-trigofragiloid D(compound 4)-and three new phenanthrenone norditerpenoids-namely,trigofragiloids E-G(compounds 5-7)-were isolated from Trigonostemon fragilis.Compounds 1 and 2 feature a novel heterodimeric carbon skeleton formed by the conjugation of a tetra-norditerpenoid and an ennea-norditerpenoid;they have been identified as class 2 atropisomers by means of quantum chemical calculations.Compound 3 is an unprecedented phenylpropanoid-norditerpenoid adduct with a new dimerization pattern.Compounds(+)-and(-)-4 are the first example of S-shaped 1,4-dioxane-fused norditerpenoid dimers.Inspired by the structure elucidation of compound 4,two co-occurring analogues,actephilol A and epiactephilol A,were structurally revised as a pair of geometrical isomers and were identified as two pairs of enantiomers,(+)-and(-)-8 and(+)-and(-)-9,respectively.Their structures were characterized using a combined method.Notably,compound 7 exhibits remarkable adenosine triphosphate-citrate lyase(ACLY)inhibition with a halfmaximal inhibition concentration(IC50)value of(0.46±0.11)lmol·L^(-1),as active as the positive control BMS-303141,and a molecular docking study offers deep insight into the interaction between compound 7 and ACLY.