Screening for Anti-tumor Activity of Fractions from Buddleja officinalis Maxim

[Objectives]The anti-tumor activity of fractions from Buddleja officinalis Maxim.by petroleum ether,ethyl acetate,n-butanol and water solvent was studied.[Methods]The ethanol extract from B.officinalis Maxim.was extracted and then concentrated with petroleum ether,ethyl acetate,n-butanol and water,respectively,and the extracts were obtained.The inhibitory effects of the four different fractions on the growth of three tumor cell lines in vitro were detected by CCK-8 method,and the median inhibitory concentration(IC 50 value)was calculated.[Results]The four fractions inhibited the growth of the three tumor cell lines in vitro,among which the n-butanol fraction had the best anti-tumor activity.The IC 50 values of the n-butanol fraction on human gastric cancer(SGC-7901),human breast cancer(MCF-7)and human liver cancer(BEL-7404)cell lines were 0.08,1.58 and 0.12 mg/mL,respectively.[Conclusions]Petroleum ether,ethyl acetate,n-butanol and water fractions from the ethanol extract of B.officinalis Maxim.had certain anti-tumor effects,and the n-butanol fraction had the best anti-tumor activity.

Anti-tumor Activity of Isovanillin and Its Molecular Mechanism

Taking isovanillin and the important products synthesized from raw materials of isovanillin as objects,this paper reviews its pharmacological effects and molecular mechanisms,including inhibiting tumor angiogenesis,blocking cancer cell self-repair,inducing cancer cell DNA fragmentation,cytotoxicity,inhibiting tumor growth,regulating brain nerves,inhibiting renin and other pharmacological effects,etc.,which provide new ideas for the in-depth research and development of isovanillin.

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.

Characterization and Anti-tumor Activity of Glycopeptides from Ganoderma sinensis

The water-soluble part（GS） of Ganoderma sinense Zhao, Xu et Zhang was divided into high molecular（GS-H） and low molecular（GS-L） parts by Cellulose Super Filtration, and GS was also fractionated into four fractions, GS-1, 2, 3, and 4 by ethanol precipitation according to their molecular weights. Chemical analysis shows that GS and GS-1, 2, 3, 4 were complexes of polysaccharide and peptide. The fractions with molecular weights over 4000, GS-1, 2, 3, and GS-H show anti-tumor activities, however, the fractions with molecular weights lower than 4000, GS-4, and GS-L have no anti-tumor activity, indicating that the anti-tumor activity of Ganoderma Sinensis was caused by glucopeptides with molecular weight ranging from 4000 to 20000. Two purified glucopeptides, GS-6b and GS-7b were obtained from GS-H by ion-exchange and gel-permeation chromatography. Their molecular weights, glycosidic linkages, and configurations were detected by means of IR spectrum, sugar composition analysis, and methylation analysis. The polysaccharide parts of GS-6b and GS-7b had glucan backbone consisting of β-1→3 Glc, and side chain containing glucosyl, mannosyl, fucosyl, xylosyl, galactosyl, and glucuronic acid residues attached on 1-2, 1-4, 1-6 positions of the backbone of GS-6b, or 1-6, 1-4 positions of the backbone of GS-7b. The peptide parts in GS-6b and GS-7b were composed of 10 kinds of amino acids, including Asp, Ser, Arg, Gly, Thr, Pro, Ala, Val, Met, and Lys.

Synthesis,Crystal Structure and Anti-tumor Activity of Ethyl 3-(4-methoxyphenyl)-4-oxo-3,3a,4,6-tetrahydro-1H-furo[3,4-c]pyran-3a-carboxylate

The title compound（ethyl 3-（4-methoxyphenyl）-4-oxo-3,3a,4,6-tetrahydro-1H-furo[3,4-c]pyran-3a-carboxylate） has been synthesized,and its crystal structure was characterized by X-ray single-crystal diffraction.The crystal belongs to monoclinic,space group P21/n,with a = 10.124（4）,b = 11.754（4）,c = 13.792（5） ,β = 111.533（3）o,V = 1526.6（10） 3,Z = 4,C17H19O6,Mr = 319.32,Dc = 1.389 g/cm3,F（000） = 676,λ（MoKα） = 0.71073 ,μ = 0.105 mm-1,R = 0.0660 and wR = 0.2027 for 2993 observed reflections（I 2σ（I））.The compound shows potent anti-tumor activity in vitro.

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.

Establishment of Quality Standard for Freeze-dried Tablets of Polygonatum sibiricum and Study on Anti-tumor Activity of Diosgenin

[Objectives]The paper was to establish the quality standard for freeze-dried tablets of Polygonatum sibiricum and to explore the antitumor activity of its extract diosgenin.[Methods]Taking freeze-dried powder samples of P.sibiricum from 4 different producing areas as materials,and referring to the quality standard of P.sibiricum in the Chinese Pharmacopoeia(2020 edition),the contents of total ash,moisture,extract,total sugar and diosgenin were determined by total ash determination method,drying method,hot dipping method,0.2%anthrone-sulfuric acid method and HPLC,respectively.The antitumor activities of diosgenin against A431(human epidermal carcinoma cells),H1975(human lung adenocarcinoma cells)and Ramos(human B lymphoblastoma cells)were investigated by MTT assay.[Results]The moisture content of the samples was 2.8%-4.7%(not more than 18.0%);the total ash content was 1.9%-3.4%(not more than 4.0%);the ethanol-soluble extract content was 72.99%-78.99%(not less than 45.0%);and the total sugar content was 7.95%-9.94%(not less than 7.0%).The lowest content of diosgenin was 0.18%,and diosgenin was significantly resistant to A431.[Conclusions]The content determination method established in the study is simple,accurate and reproducible.

3D-QSAR Studies on the Anti-tumor Activity of N-Aryl-salicylamide Derivatives

In the present work,comparative molecular field analysis(CoMFA)techniques were used to perform three-dimensional quantitative structure-activity relationship(3D-QSAR)studies on the anti-tumor activity(pHi,i=1,2,3,4)of N-aryl-salicylamide derivatives against four cancer cell lines,including A549,MCF-7,SGC-7901,and Bel-7402.12 compounds were randomly selected as the training set to establish the prediction models,which were verified by the test set of 5 compounds containing template molecule.The contributions of steric and electrostatic fields to pH1,pH2,pH3,and pH4 were 23.8% and 76.2%,20.1% and 79.9%,18.7% and 81.3%,and 14.3%and 85.7%,respectively.The cross-validation(Rcv 2)and non-cross-validation coefficients(R2)were 0.826 and 0.963 for pH1,0.867 and 0.974 for pH2,0.941 and 0.989 for pH3,and 0.797 and 0.961 for pH4,respectively.The CoMFA models were then used to predict the activities of the compounds,and it was found that the models had strong stability and good predictability.Based on the CoMFA contour maps,some key structural factors responsible for the anticancer activity of the series of compounds were revealed.The results provide some useful theoretical references for understanding the mechanism of action,designing new N-aryl-salicylamide derivatives with high anti-tumor activity,and predicting their activities.

Extraction, Purification and Anti-tumor Activity of Polysaccharide from Mycelium of Mutant Cordyceps Militaris

A water-soluble polysaccharide（named MCMP） was isolated from the mycelium with high yield mutation Cordyceps militaris by hot-water extraction, deproteinization by sevage, alcohol precipitation, anion-exchange and gel filtration chromatography CL-6B. The polysaccharide contained mannose, rhamnose, galactose and glucose in a molar ratio of 59.36：1：8.31：39.50, of which the average molecular weight is 8100. In our research, Hep-G2 cells, Hela cells and mesangial cells were chosen to determine the anti-tumor activity of the polysaccharide. The results of MTT assay show that polysaccharides of the mutant strain presented inhibitory activity on the cells proliferation after 48 h incubation.

Evaluation of cytotoxic and anti-tumor activity of partially purified serine protease isolate from the Indian earthworm Pheretima posthuma

Objective:To isolate,partially purify and evaluate the cytotoxic and antitumor activity of a serine protease from the chosen Indian earthworm Pheretima posthuma.Methods:Whole animal extract was prepared and purified its protein constituents by size and charge based chromatographic separation techniques using Sephadex G-50 and DEAE-Cellulose resin respectively.Average molecular weight of the protein isolate was determined and analyzed for its cytotoxic property against Vero cells in different dilutions(1:20 and 1:40)and anti-tumor activity by MTT assay(a colorimetric assay)using breast cancer cell line MCF-7,with tamoxifen as standard.Results:One of the protein constituents after purification was characterized as serine protease by Caseinolytic plate diffusion assay.Average molecular weight of this purified isolate was determined,by SDS-PAGE analysis with standard protein ladder,as of 15 kDa.The performed tests suggested that the 15kDa fraction has potent cytotoxic activity and satisfactory antitumor activity as well in vitro.Conclusions:Exact molecular mechanism of the cytotoxic and antitumor activities is yet to be explored and currently we are working on ultra-purification and biophysical characterization of this fraction.Further investigation into the mechanism(s)of cytotoxic and antitumor activities at molecular level would be useful in treatment of various classes of cancer and viral infections in future.

Synthesis,Crystal Structure,Thermal Stability and Anti-tumor Activity In Vitro of Bis(tricyclohexyltin) Pimelicarboxylate

Bis（tricyclohexyltin） pimelicarboxylate, [（CH2）5（CO2SnCy3）2] （1）, has been synthesized by the reaction of tricyclohexyltin hydroxide with pimelic acid and characterized by means of 1R, 1H and 13C NMR, elemental analysis and X-ray diffraction. Complex 1 crystallizes in triclinic space group Pi with a = 11.569（3）, b = 12.0419（2）, c = 17.3988（4） A, α = 81.4310（10）, β = 79.8270（10）, ）, = 69.7060（10）°, V = 2227.60（9） A3, Z = 2, C43H7604Sn2, Mr = 894.42, Dc = 1.333 g.cm-3, μ = 1.157 mm-1, F（000） = 932, GOOF = 1.339, the final R = 0.0452 and wR = 0.1333 for 6709 observed reflections （1〉 2σ（I）. Complex 1 shows discrete dimeric structures and the tin atoms have a distorted tetrahedral geometry. The 1D chain structure of complex 1 is formed by intermolecular Sn…O interactions. Complex 1 displays good thermal stability under 553 K and has selective antibacterial property. Complex 1 is strong in vitro anti-tumor activity against five human tumor cell lines, Colo205, HepG2, MCF-7, Hela and NCI-H460, and is significantly higher than that in the clinical use of carboplatin.

Study on Anti-tumor Activity and Mechanism of Isoorientin

Isoorientin can play an anti-tumor effect through interfering with tumor cell proliferation, inducing tumor cell apoptosis, regulating reactive oxygen species level, inducing tumor cell autophagy, blocking tumor cell infiltration and metastasis, inhibiting tumor neovascularization and other pathways. This paper reviews the research progress of anti-tumor activity and mechanism of isoorientin in recent years.

Effect of anti-asthma Chinese medicine Chuankezhi on the anti-tumor activity of cytokine-induced killer cells

Chuankezhi(CKZ),a new Chinese medicine,plays an important role in immunoregulation.Cytokineinduced killer(CIK)cells have been commonly used for immunotherapy in recent years.In this study,we aimed to investigate the immunoregulatory effect of CKZ on CIK cells.Peripheral blood monocytes were isolated from healthy donors,and CIK cells were generated by culturing monocytes with interferon-gamma(IFN-γ)and interleukin 2.Different concentrations of CKZ were added on day 2.After incubation for 14days in culture,the antitumor effects of CIK cells were measured by cytotoxicity assay.Flow cytometry was used to explore the effect of CKZ on CIK cell immunophenotype,intracellular cytokine production,and apoptosis.The effect of CKZ on the antitumor activity of CIK cells in nude mice was also investigated.CKZ increased the percentage of CD3+CD56+CIK cells but did not significantly change the percentage of CD4+,CD8+,or CD4+CD25+CIK cells.CKZ-conditioned CIK cells showed a greater ability to kill tumor cells,as well as a higher frequency of IFN-γand TNF-αproduction,compared with the CIK cells in the control group.CKZ also suppressed the apoptosis of CIK cells in vitro.Furthermore,CKZ combined with CIK cells had a stronger suppressive effect on tumor growth in vivo than the CIK,CKZ,or normal saline control groups.Our results indicate that CKZ enhances the antitumor activity of CIK cells and is a potential medicine for tumor immunotherapy.

Preparation and Photodynamic Anti-tumor Activity of Magnetic Polylactic Acid Nanoparticles Loaded with Photosensitizer

A novel magnetic nanocarrier was strategically designed and successfully prepared.Photosensitizer 2,7,12,18-tetramethyl-3,8-di-(1-propoxyethyl)-13,17-bis-(3-hydroxypropyl)porphyrin(PHPP)was encapsulated into polylactic acid(PLA)-coated Fe3O4 nanoparticles.The diameter of nanocarrier is 30-50 nm by transmission electron micrograph(TEM).The encapsulation efficiency of photosensitizer is 27.98% calculated from UV-vis absorption spectra.The nanocarrier shows obvious photocytotoxic activity to Hela299 tumor cells in vitro.

Compound Astragalus and Salvia miltiorrhiza extract exerts anti-tumor activity by intervening the interaction of microRNA-145/microRNA-21 and Smad3C/3L phos-phorylation in hepatocellular carcinoma

OBJECTIVBE To investigate the intervention of compound Astragalus and Salvia miltiorrhiza extract(CASE) consisted of astragalosides,astragalus polysaccharides and salvianolic acids on the interaction of microRNA-145/microRNA-21(miR-145/miR-21) and Smad3 C/3 L phosphorylation(pSmad3 C/pSmad3 L) down-stream of transforming growth factor-β(TGF-β)/mitogen activated protein kinase(MAPK) signaling in hepatocellular carcinoma(HCC) progression by in vitro and in vivo experi.ments.METHODS In HepG2 cells and xenografts of nude mice,antagomir/agomir and plasmids of Smad3 C/3 L phosphorylation site mutation(Smad3 3 S-A/Smad3 EPSM) were used to intervene miR-145/miR-21 and pSmad3 C/pSmad3 L expression respectively,then incorporative CASE treatment.Cell proliferation,migration,apoptosis,tumor growth and histopathologic characteristics of xenografts,relevant proteins of TGF-β/Smad pathway and miR-145/miR-21 were evaluated.RESULTS CASE up-regulated miR-145 while down-regulated miR-21,inhibited cell proliferation,migration and tumor growth,accelerated cell apoptosis in HepG2 cells respectively transfected with Smad3 WT,Smad3 EPSM,Smad3 3 S-A plasmids in cultured dishes and xenografts of nude mice,the above effects were more evident in HepG2 cells with increased pSmad3 C.In TGF-β1-stimulated HepG2 cells and xenografts of nude mice,CASE antagonized the facilitating effects of miR-145 antagomir/miR-21 agomir on cell migration,proliferation,tumor growth and inhibiting effects of miR-145 antagomir/miR-21 agomir on cell apoptosis;CASE increased miR-145 down-regulated by miR-145 antagomir and decreased miR-21 up-regulated by miR-21 agomir,reduced protein level of pSmad3 L and their proteins including TβRⅡ,pERK1/2,pJNK1/2 and pp38 while elevated pSmad3 C expression.CONCLUSION These results suggest that pSmad3 C/pSmad3 L maybe interact with miR-145/miR-21 in HCC progression,which may be one of important molecular mechanisms of CASE's anti-HCC effects.

Immunomodulatory Function of Pien Tze Huang in T Cell-Mediated Anti-tumor Activity against B16-F10,MC38 and Hep1-6 Tumor Models

Objective To investigate the anti-tumor effects of Pien Tze Huang(PZH)in mouse models of B16–F10 melanoma,MC38 colorectal cancer,Hep1-6 hepatocellular carcinoma and chemically induced hepatocellular carcinoma model.Methods Various tumor models,including B16–F10,MC38 and Hep1-6 tumor hypodermic inoculation models,B16–F10 and Hep1-6 pulmonary metastasis models,Hep1-6 orthotopic implantation model,and chemically induced hepatocellular carcinoma model,were utilized to evaluate the anti-tumor function of PZH.Tumor growth was assessed by measuring tumor size and weight of solid tumors isolated from C57BL/6 mice.For cell proliferation and death of tumor cells in vitro,as well as T cell activation markers,cytokine production and immune checkpoints analysis,single-cell suspensions were prepared from mouse spleen,lymph nodes,and tumors after PZH treatment.Results PZH demonstrated significant therapeutic efficacy in inhibiting tumor growth(P<0.01).Treatment with PZH resulted in a reduction in tumor size in subcutaneous MC38 colon adenocarcinoma and B16–F10 melanoma models,and decreased pulmonary metastasis of B16–F10 melanoma and Hep1-6 hepatoma(P<0.01).However,in vitro experiments showed that PZH only had slight impact on the cell proliferation and survival of tumor cells(P>0.05).Nevertheless,PZH exhibited a remarkable ability to enhance T cell activation and the production of interferon gamma,tumor necrosis factor alpha,and interleukin 2 in CD4^(+)T cells in vitro(P<0.01 or P<0.05).Importantly,PZH substantially inhibited T cell exhaustion and boosted cytokine production by tumor-infiltrating CD8^(+)T cells(P<0.01 or P<0.05).Conclusion This study has confirmed a novel immunomodulatory function of PZH in T cell-mediated anti-tumor immunity,indicating that PZH holds promise as a potential therapeutic agent for cancer treatment.

Association of daily sitting time and leisure-time physical activity with body fat among U.S.adults

Background:Prolonged sitting and reduced physical activity lead to low energy expenditures.However,little is known about the joint impact of daily sitting time and physical activity on body fat distribution.We investigated the independent and joint associations of daily sitting time and physical activity with body fat among adults.Methods:This was a cross-sectional analysis of U.S.nationally representative data from the National Health and Nutrition Examination Survey2011-2018 among adults aged 20 years or older.Daily sitting time and leisure-time physical activity(LTPA)were self-reported using the Global Physical Activity Questionnaire.Body fat(total and trunk fat percentage)was determined via dual X-ray absorptiometry.Results:Among 10,808 adults,about 54.6%spent 6 h/day or more sitting;more than one-half reported no LTPA(inactive)or less than 150 min/week LTPA(insufficiently active)with only 43.3%reported 150 min/week or more LTPA(active)in the past week.After fully adjusting for sociodemographic data,lifestyle behaviors,and chronic conditions,prolonged sitting time and low levels of LTPA were associated with higher total and trunk fat percentages in both sexes.When stratifying by LTPA,the association between daily sitting time and body fat appeared to be stronger in those who were inactive/insuufficiently active.In the joint analyses,inactive/insuufficiently active adults who reported sitting more than 8 h/day had the highest total(female:3.99%(95%confidence interval(95%CI):3.09%-4.88%);male:3.79%(95%CI:2.75%-4.82%))and trunk body fat percentages(female:4.21%(95%CI:3.09%-5.32%);male:4.07%(95%CI:2.95%-5.19%))when compared with those who were active and sitting less than 4 h/day.Conclusion:Prolonged daily sitting time was associated with increased body fat among U.S.adults.The higher body fat associated with 6 h/day sitting may not be offset by achieving recommended levels of physical activity.

Structure and immunomodulatory activity of Lentinus edodes polysaccharides modified by probiotic fermentation

Plant-based fermentations provide an untapped source for novel biotechnological applications.In this study,a probiotic named Lactobacillus fermentum 21828 was introduced to ferment Lentinus edodes.Polysaccharides were extracted from fermented and non-fermented L.edodes and purified via DEAE-52 and Sephadex G-100.The components designated F-LEP-2a and NF-LEP-2a were analyzed by FT-IR,HPGPC,HPAEC,SEM,GC-MS and NMR.The results revealed that probiotic fermentation increased the molecular weight from 1.16×10^(4) Da to 1.87×10^(4) Da and altered the proportions of glucose,galactose and mannose,in which glucose increased from 45.94%to 48.16%.Methylation analysis and NMR spectra indicated that F-LEP-2a and NF-LEP-2a had similar linkage patterns.Furthermore,their immunomodulatory activities were evaluated with immunosuppressive mice.NF-LEP and F-LEP improved immune organ indices,immunoglobulin(Ig G and Ig M)and cytokines concentrations;restored the antioxidation capacity of liver;and maintained the balance of gut microbiota.F-LEP displayed better moderating effects on the spleen index,immunoglobulin,cytokines and the diversity of gut microbiota than NF-LEP(200,400 mg/kg).Our study provides an efficient and environment-friendly way for the structural modification of polysaccharides,which helps to enhance their biological activity and promote their wide application in food,medicine and other fields.

Evaluation of Four Anthropogenic Activity Impacts on Heavy Metal Quality of the Kumba River in the South West Region of Cameroon

Anthropogenic activities have contributed to pollution of water bodies through deposition of diverse pollutants amongst which are heavy metals. These pollutants, which at times are above the maximum concentration levels recommended, are detrimental to the quality of the water, soil and crops (plant) with subsequent human health risks. The objective of the work was to evaluate the impacts of human-based activities on the heavy metal properties of surface water with focus on the Kumba River basin. Field observations, interviews, field measurements and laboratory analyses of different water samples enabled us to collect the different data. The results show four main human-based activities within the river basin (agriculture, livestock production, domestic waste disposal and carwash activities) that pollute surface water. Approximately 20.61 tons of nitrogen and phosphorus from agricultural activities, 156.48 tons of animal wastes, 2517.5 tons of domestic wastes and 1.52 tons of detergent from carwash activities were deposited into the river each year. A highly significant difference at 1% was observed between the upstream and downstream heavy metal loads in four of the five heavy metals tested except for copper that was not significant. Lead concentrations were highest in all the activities with an average of 2.4 mg∙L−1 representing 57.81%, followed by zinc with 1.596 mg∙L−1 (38.45%) and manganese with 0.155 mg∙L−1 (3.74%) for the different anthropogenic activities thus indicating that these activities highly lead to pollution of the Kumba River water. The level of zinc and manganese was significantly influenced at ρ 005 by anthropogenic activities though generally the variations were in the order: carwash (3.196 mg∙L−1) < domestic waste disposal (3.347 mg∙L−1) < agriculture (4.172 mg∙L−1) < livestock (4.886 mg∙L−1) respectively and leading to a total of 14.04 tons of heavy metal pollutants deposited each day.