A Study on Anti-oxidative Activity of Soybean Peptideswith Linoleic Acid Peroxidation Systems

Soybean bioactive peptides（SBPs） were prepared from the isolated soybean protein by proteolysis with an alkaline protease, alcalase, at 50℃ and pH = 8.0. The dependence of hydrolysis time on hydrolysis degree and molecular weight distribution were examined. The hydrolysate was fractionated on a Sephadex G-25 column and the anti-oxidative activities of the fractions were detected by the method of pyrogallol auto-oxidation. The average chain length of soybean peptides that have anti-oxidative activity was estimated to be about 7. The anti-oxidative properties of the soy- bean peptide were also studied by using linoleic acid peroxidation systems. The optimal condition of the peroxidation system was set up, Vc/Cu^2 ＋ as the inducer at pH = 7.4 and 25 ℃. In addition, soybean peptides show higher antioxidative activity compared with GSH.

Synthesis and Anti-tumor Activity of Novel Amide Derivatives of Ursolic Acid

Ursolic acid was modified at C3 and C28 position to obtain fourteen derivatives including twelve novel compounds, and their chemical structures were characterized by IR, ^1H NMR and MS. Cell growth inhibitory effects of the derivatives against Hela cell were evaluated by MTT assay. All these derivatives were found to have stronger cell growth inhibitory than their parent compound, ursolic acid. The derivatives with a substituted acetyl group at C3 hydroxyl group show better activities than those with an unsubstituted hydroxyl group.

Antioxidant and Anti-inflammatory Capacity of Ferulic Acid Released from Wheat Bran by Solid-state Fermentation of Aspergillus niger

Objective A strain of Aspergillus niger(A. niger), capable of releasing bound phenolic acids from wheat bran, was isolated. This strain was identified by gene sequence identification. The antioxidant and anti-inflammatory capacity of ferulic acid released from wheat bran by this A. niger strain(FA-WB) were evaluated. Methods Molecular identification techniques based on PCR analysis of specific genomic sequences were conducted; antioxidant ability was examined using oxygen radical absorbance capacity(ORAC), cellular antioxidant activity(CAA) assays, and erythrocyte hemolysis assays. RAW264.7 cells were used as a model to detect anti-inflammatory activity. Results The filamentous fungal isolate was identified to be A. niger. ORAC and CAA assay showed that FA-WB had better antioxidant activity than that of the ferulic acid standard. The erythrocyte hemolysis assay results suggested that FA-WB could attenuate AAPH-induced oxidative stress through inhibition of reactive oxy gen species(ROS) generation. FA-WB could significantly restore the AAPH-induced increase in intracellular antioxidant enzyme activities to normal levels as well as inhibit the intracellular malondialdehyde formation. TNF-?, IL-6, and NO levels indicated that FA-WB can inhibit the inflammation induced by lipopolysaccharide(LPS). Conclusion Ferulic acid released from wheat bran by a new strain of A. niger had good anti-inflammatory activity and better antioxidant ability than standard ferulic acid.

Anti-inflammatory and Immunomodulatory Effects of Marine n-3 Polyunsaturated Fatty Acids on Human Health and Diseases

The pharmaceutical effects of n-3 polyunsaturated fatty acids(n-3 PUFAs) as dietary nutrients on human health and diseases have gained much attention and are investigated for decades. Docosahexaenoic acid(DHA), eicosapentaenoic acid(EPA) and docosapentaenoic acid(DPA) are the three major n-3 PUFAs enriched in marine organisms, such as fish, shrimp, algae, and so on. It has been well known that n-3 PUFAs, especially DHA and EPA, are beneficial in reducing the risk of cardiovascular and cerebrovascular diseases. Accumulating evidence suggests that n-3 PUFAs might cure inflammatory diseases through several mechanisms, such as plasma membrane remodeling of lymphocytes, down-regulating pro-inflammatory cytokines, and alternating adhesion molecule expressions. Several molecular targets of n-3 PUFAs on immune-regulation have also been identified, such as GPR120(FFA4), protein kinase C(PKC), and PPAR-γ. However, it remains inconclusive if dietary n-3 PUFAs function the same both in vitro and in vivo based on cohort studies. This review will focus on the molecular targets and mechanisms of anti-inflammatory and immunomodulatory effects of n-3 PUFAs on human health and diseases, such as obesity, tumor, diabetes, and autoimmune diseases.

Targeting amino acid metabolism in cancer growth and anti-tumor immune response

Recent advances in amino acid metabolism have revealed that targeting amino acid metabolic enzymes in cancer therapy is a promising strategy for the development of novel therapeutic agents. There are currently several drugs in clinical trials that specifically target amino acid metabolic pathways in tumor cells. In the context of the tumor microenvironment,however,tumor cells form metabolic relationships with immune cells,and they oftencompete for common nutrients. Many tumors evolved to escape immune surveillance by taking advantage of their metabolic flexibility and redirecting nutrients for their own advantage. This review outlines the most recent advances in targeting amino acid metabolic pathways in cancer therapy while giving consideration to the impact these pathways may have on the anti-tumor immune response.

Antiviral effects of hepatitis B virus S gene-specific anti-gene locked nucleic acid in transgenic mice

AIM To assess the antiviral effects of hepatitis B virus(HBV) S gene-specific anti-gene locked nucleic acid(LNA) in transgenic mice.METHODS Thirty HBV transgenic mice were acclimatized to laboratory conditions and positive for serum HBV surface antigen(HBs Ag) and HBV DNA, were randomly divided into 5 groups(n = 7), including negative control(blank control, unrelated sequence control), positive control(lamivudine, anti-sense-LNA), and anti-gene-LNA experimental group. LNA was injected into transgenic mice by tail vein while lamivudine was administeredby gavage. Serum HBV DNA and HBs Ag levels were determined by fluorescence-based PCR and enzymelinked immune sorbent assay, respectively. HBV S gene expression amounts were assessed by reverse transcription polymerase chain reaction. Positive rates of HBsA g in liver cells were evaluated immunohistochemistry.RESULTS Average rate reductions of HBs Ag after treatment on the 3 rd, 5 th, and 7 th days were 32.34%, 45.96%, and 59.15%, respectively. The inhibitory effect of antigene-LNA on serum HBs Ag peaked on day 7, with statistically significant differences compared with pretreatment(0.96 ± 0.18 vs 2.35 ± 0.33, P < 0.05) and control values(P < 0.05 for all). Average reduction rates of HBV DNA on the 3 rd, 5 th, and 7 th days were 38.55%, 50.95%, and 62.26%, respectively. This inhibitory effect peaked on the 7 th day after treatment with anti-gene-LNA, with statistically significant differences compared with pre-treatment(4.17 ± 1.29 vs 11.05 ± 1.25, P < 0.05) and control values(P < 0.05 for all). The mR NA levels of the HBV S gene(P < 0.05 for all) and rates of HBsA g positive liver cells(P < 0.05 for all) were significantly reduced compared with the control groups. Liver and kidney function, and histology showed no abnormalities. CONCLUSION Anti-gene-LNA targeting the S gene of HBV displays strong inhibitory effects on HBV in transgenic mice, providing theoretical and experimental bases for gene therapy in HBV.

Syntheses, Characterization and Antitumour Activities of Rare Earth Metal Complexes with 2-(((4,6-dimethyl)-2-Pyrimidinyl)thio)-Acetic Acid

Eight rare earth metal （ Ⅲ ） complexes with 2- （ （（4,6-dimethyl）-2-pyrimidinyl） thio）-acetic acid, LnL3· n H2O [HL = 2-（（（4,6-dimethyl）-2-pyrimidinyl）thio）-acetic acid; Ln = La, Ce, Pr, Nd, Sm Eu, Gd, Tb; n = 4 or 5], were prepared and characterized by elemental analysis, complexometric titration, thermal analysis, conductivity, IR and ^1H- NMR. The results reveal that carboxyl group of the hgand coordinates with rare earth ions in bidentate mode after deprotonated. The water molecules exist as crystal water in the complexes. The anti-tumour activities of HL and some complexes were tested by both the MTT and SRB methods. The results show that the suppression ratios of some complexes against the tested tumour cells （HL-60 human leukemia cell lines, BGC-823 human gastric carcinoma cell lines, hela human cervix adenocarcinoma cell lines and Bel-7402 human hepatic carcinoma cell lines） are superior to HL.

Anti-inflammatory Effects and Mechanisms of Usnic Acid

The anti-inflammatory effect and mechanism of Usnic acid （UA） were explored on lipopoly-saccharide （LPS）-stimulated RAW264.7 cell line.The effects of UA on pro-inflammatory cytokines including tumor necrosis factor-alfa （TNF-α）,interleukin-6 （IL-6） and interleukin-1 beta （IL-1β）,pro-inflammatory mediators such as nitric oxide （NO）,inducible nitric oxide synthase （iNOS） and cyclooxygenase-2 （COX-2） were studied by sandwich ELISA,real-time PCR and western blot analyses.Similarly,the effect of UA on anti-inflammatory cytokine interleukin-10 （IL-10） and anti-inflammatory mediator heme oxygenase-1 （HO-1） were also studied following the same methods.Furthermore,nuclear factor-κB （NF-κB） was assayed by immunocytochemistry.The results showed that UA has anti-inflammatory effect by down-regulatinng iNOS,COX-2,IL-1β,IL-6 and TNF-α,COX-2 gene expression through the suppression of NF-κB activation and increasing anti-inflammatory cytokine IL-10 and anti-inflammatory mediator HO-1 production.

Advances in Research on Anti-cancer Mechanism of 18β Glycyrrhetinic Acid

Glycyrrhiza uralensis Fisch has been used to treat the symptoms of organ fever, food poisoning, typhoid fever, sore throat, cough due to lung heat, children's diseases and so on since the ancient times. It is a solid Chinese herbal medicine which is good for the health. In recent years, it has been found that licorice extract also has excellent anti-cancer effect. The 18β glycyrrhetinic acid, obtained by hydrolysis of precursor glycyrrhizic acid, is a relatively efficient anti-cancer ingredient. 18β glycyrrhetinic acid can exert anti-cancer effects by inhibiting cancer cell proliferation, inducing apoptosis of cancer cells, inhibiting invasion and metastasis of cancer cells, preventing oxidation, inhibiting neovascularization, inhibiting lymphangiogenesis, and regulating hormone secretion. This paper reviewed the advances in research of the anticancer mechanism of 18β glycyrrhetinic acid, to provide a theoretical basis for future research.

Preparation of Ternary Lanthanide Complexes with Unsaturated Acid and 1,10-Phenanthroline, and Their Anti-Inflammatory Action

Four ternary lanthanide complexes with unsaturated acid and 1,10-phenanthroline are prepared in methanol and characterized by elemental analysis, molar conductance, UV, IR, (()~1H) NMR and XPS. The results from this paper show that the complexes Ln(phen)(SA)_3·2H_2O or Ln(phen)(CA)_3·H_2O (Ln=Ce(Ⅲ), Sm(Ⅲ) and Eu(Ⅲ), (phen=1,10-)phenanthroline, SA=Sorbate and CA=Cinnamate) has better anti-inflammatory effect than cerium nitrate and their gremores are steadier than cerium nitrate gremor. And there is a kind of medicament which can replace the cerium nitrate gremor completely in treating burn.

Design, synthesis and in vitro evaluation of L-amino acid esters prodrugs of acyclic nucleoside phosphonates as anti-HBV agent

A series of novel L-amino acid esters prodrugs of acyclic nucleoside phosphonates was synthesized and their anti-HBV activity was evaluated in HepG2 2.2.15 cells. Compound 1d exhibited more potent anti-HBV activity and lower cytotoxicity than those of adefovir dipivoxil with EC50 and CC50 values of 0.207 μmol/L and 2530 μmol/L, respectively.

Enantioselective esterification of(R,S)-2-(4-methylphenyl)propionic acid via Novozym 435:Optimization and application

This paper reports on the resolution of(R,S)-2-(4-methylphenyl)propionic acid(MPPA)enantiomers by enzymatic esterification in organic solvent.Novozym 435(CALB)has the best catalytic performance compared with other lipases.Of the alcohols screened,n-hexanol is the best acyl acceptor and gives the highest enzyme activity and enantioselectivity in n-hexane.Response surface methodology(RSM)was used to evaluate the influence of the factors,such as temperature,enzyme amount,substrate concentration and reaction time on the substrate conversion(c)and enantiomeric excess(ee).The correlation coefficient R2 for enantiomeric excess and the conversion are 0.9827 and 0.9910,respectively,indicating that can accurately predict the experimental results.By simulation and optimization,the optimal conditions were obtained,involving 600 mmol·L^-1 MPPA concentration(0.60 mmol),850 mmol·L^-1 hexanol concentration(0.85 mmol),58 mg enzyme amount,75℃temperature and 4.5 h reaction time,respectively.Under the optimized conditions,the experimental values of conversion and enantiomeric excess were 89.34%and 97.84%,respectively,which are in good agreement with the model predictions.

Synthesis,Crystal Structure and Antitumor Activity of a Novel Zn(Ⅱ)Complex with 2-(Nicotinoyloxy)acetic Acid Ligand

A novel Zn（Ⅱ） complex, [ZnL2（H2O）4]·H2O（1, HL = 2-（nicotinoyloxy）acetic acid）, was synthesized using Zn（OAc）2·2H2O and 2-（nicotinoyloxy）acetic acid as raw materials. Its structure has been elucidated by elemental analysis, IR and single-crystal X-ray diffraction. The structural analysis revealed that complex 1 crystallizes in triclinic, space group P1 and the Zn（Ⅱ） atom is six-coordinated with two N atoms from two different 2-（nicotinoyloxy）acetate anion ligands and four O atoms from coordinated water molecules. Complex 1 forms a 3D network structure by O–H···O hydrogen bonds. The antitumor activities of 2-（nicotinoyloxy）acetic acid ligand and its Zn（Ⅱ） complex were evaluated against human lung adenocarcinoma A549 cells, human hepatoma SMMC-7721 cells and human colon carcinoma Wi Dr cells.

Anti-viral Effects of Urosolic Acid on Guinea Pig Cytomegalovirus In Vitro

This study examined the anti-viral effect of ursolic acid on guinea pig cytomegalovirus (GPCMV) and explored the steps of viral replication targeted by ursolic acid. Cytopathic effect assay and MTT method were employed to determine the 50% cellular cytotoxicity (CC50), 50% effective concentration (EC50) and therapeutic index (TI) with GPCMV. To investigate the specific anti-viral effect of ursolic acid at different temperatures and time points, two other medicines, ganciclovir and Jinyebaidu (JYBD), serving as controls, were studied for comparison. Our results showed that the CC50 of ganciclovir, JYBD and ursolic acid were 333.8, 3015.6, 86.7 μg/mL, respectively; EC50 of ganciclovir, JYBD and ursolic acid was 48.1, 325.5 and 6.8 μg/mL, respectively; TI of ganciclovir, JYBD and ursolic acid was 7, 9, 13, respectively. Similar with ganciclovir, ursolic acid could inhibit the viral synthesis, but did not affect the viral adsorption onto and penetration into cells. We are led to conclude that the anti-cytomegalovirus effect of ursolic acid is significantly stronger than ganciclovir or JYBD, and the cytotoxic effect of ursolic acid lies in its ability to inhibit viral synthesis.

Anti-Endotoxic Effects of Syringic Acid of Radix Isatidis

The anti-endotoxic effect of syringic acid (SA) isolated from Radix Isatidis (Banlangen, BLG) was studied. SA was extracted and isolated from BLG and diluted into 1 % solution. The content of SA-pretreated endotoxin (ET) was quantitatively determined using Limulus test. The ability of fever induction of ET pretreated with SA was measured using endotoxin-induced fever test in rabbits. The LPS-induced death in mice pretreated with and without SA was compared. Results showed that after pretreatment with SA, 83. 16 % of ET was destroyed, the ET-induced fever in rabbits relieved markedly and the LPS-induced death rate in mice dropped from 68 % to 20 %. It was concluded that SA isolated from BLG had anti-endotoxic effects.

Synthesis and Anti-tumor Activity of Novel Glycyrrhetinic Acid Derivatives

Twenty-five derivatives of glycyrrhetinic acid（GA） modified on the A-ring,at C30 and C11 positions were synthesized.Their in vitro cytotoxicity against various cancer cell lines[henrietta lacks strain of cancer cells（HeLa）,human hepatocellular liver carcinoma cells（HepG2） and human gastric carcinoma cells（BGC-823）] was evaluated by standard MTT[3-（4,5-dimethyl-2-thiazol-yl）-2,5-diphenyl-2H-tetrazolium bromide] assay.All the tested derivatives were found to have stronger cell growth inhibitory than their parent compound GA.Among them,compounds 3a,5a,and 8d have similar activity on HeLa cell line,and compound 8a has similar activity on HeLa,HepG2 and BGC-823 cell lines as Gefitinib.

Efficacy of boswellic acid on lysosomal acid hydrolases,lipid peroxidation and anti-oxidant status in gouty arthritic mice

Objective:To evaluate the efficacy of boswellic acid against monosodium urate crystal-induced inflammation in mice.Methods:The mice were divided into four experimental groups.GroupⅠserved as control;mice in groupⅡwere injected with monosodium urate crystal;groupⅢconsisted of monosodium urate crystal-induced mice who were treated with boswellic acid(30mg/kg/b.w.);groupⅣcomprised monosodium urate crystal-induced mice who were treated with indomethacin(3mg/kg/b.w.).Paw volume and levels/activities of lysosomal enzymes,lipid peroxidation,anti-oxidant status and inflammatory mediator TNF-αwere determined in control and monosodium urate crystal-induced mice.In addition,the levels ofβ-glucuronidase and lactate dehydrogenase were also measured in monosodium urate crystal-incubated polymorphonuclear leucocytes(PMNL)in vitro.Results:The activities of lysosomal enzymes,lipid peroxidation,and tumour necrosis factor-αlevels and paw volume were increased significantly in monosodium urate crystal-induced mice,whereas the activities of antioxidant status were in turn decreased.However,these changes were modulated to near normal levels upon boswellic acid administration.In vitro,boswellic acid reduced the level ofβ-glucuronidase and lactate dehydrogenase in monosodium urate crystal-incubated PMNL in concentration dependent manner when compared with control cells.Conclusions:The results obtained in this study further strengthen the anti-inflammatory/antiarthritic effect of boswellic acid,which was already well established by several investigators.

Evaluation of the Anti-Inflammatory Activities of 5,8,11-<i>cis</i>-Eicosatrienoic Acid

The main eicosanoids inflammatory mediators, prostaglandins and leukotrienes, are both generated from arachidonic acid (AA;20:4 n-6). AA is a member of polyunsaturated fatty acids (PUFAs). Numerous studies have demonstrated that various contents of PUFAs can modulate the inflammatory responses. However, fewer studies have examined n-9PUFAs and their effects on the inflammatory responses. In the present study, the role of 5,8,11-cis-eicosatrienoic acid (ETrA;20:3 n-9, also called Mead acid) in the inflammatory responses has been investigated. The anti-inflammatory activities of ETrA were examined using an in vitro macrophage system and the inhibitory effect was confirmed by western blot analysis for iNOS and COX-2 expressions. The interactions between ETrA and COX-2 protein were simulated to produce a computer modeling protein-ligand complexes and the results suggest a possible mechanism for the effects of ETrA. In this study, we described a significant inhibition of the inflammatory activities initiated by ETrA. Since ETrA is a substance presented in the tissues of young animals, we therefore anticipate that ETrA can be utilized as a natural therapeutic supplement to inhibit inflammatory activities.

Synthesis and Antibacterial Activity of Urea and hiourea Derivatives at C-8 Alkyl Chain of Anacardic Acid Mixture Isolated from a Natural Product Cashew Nut Shell Liquid (CNSL)

Synthesis and antibacterial activity of some novel urea and thiourea derivatives (7a-7k, 8a-8f) of anacardic acid prepared from commercially available anacardic acid which is obtained from natural product Cashew Nut Shell Liquid (CNSL). Compounds (7a-7k, 8a-8f) were tested for Gram positive and Gram negative bac- terial cultures. Most of the compounds were showed active compared with standard drug ampicilline.

A Placebo-Controlled Study Demonstrates the Long-Lasting Anti-Aging Benefits of a Cream Containing Retinol, DihydroxyMethylChromone (DMC) and Hyaluronic Acid

Retinol is an ingredient used in cosmetic products for reducing the appearance of the signs of aging and photo-damage. Currently, most of these products contain 0.1% of retinol. However, at this concentration, some irritation can occur. We have evaluated in vitro and in a clinical study the potential efficacy of a combination of actives to improve the facial skin aging signs while using low concentration of retinol. We demonstrated, in vitro, that a chromone derivative, 5,7-di-hydroxy-2-methyl chromone (DMC), is able to enhance the collagen synthesis in culture of normal human dermal fibroblasts. The enhancement of retinol anti-wrinkle efficacy by DMC was confirmed in a small scale clinical trial. Specifically, a product associating low concentration of retinol (0.04%) and DMC (0.1%) in combination with low molecular weight hyaluronic acid fragments (50,000 Dalton of average molecular weight) has been applied topically for 8 weeks. Clinical results show significant improvement of various signs of facial skin aging such as wrinkles, pigmentary spots, tone unevenness, dullness and the overall photo-damage score. Improvements were still visible 4 weeks after the cessation of the test product application. This study demonstrates that significant lasting improvement of facial skin aging can be obtained with well tolerated low concentration of retinol when adequately formulated with other anti-aging ingredients.