Based on network pharmacology to explore the mechanism of hepatotoxicity of Fructus Meliae Toosendan

Objective:To explore the potential mechanism of hepatotoxicity induced by Fructus Meliae Toosendan(FMT)through network pharmacology.Methods:The active components and targets of FMT were identified and screened by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform Database,PubChem Database and Swiss Target Prediction database,etc.Genecards,pharmGKB,and OMIM databases were used to collect relevant targets of hepatotoxicity,and intersect them with the targets of active ingredients to obtain the potential targets of hepatotoxicity caused by FMT.A compound-target network was constructed with Cytoscape 3.8.0 software.The String 11.0 database was used to construct the protein-protein interaction(PPI)network of the targets and to screen out the core targets.In addition,Gene Ontology(GO)terms and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses were conducted by R software,and then the pathways directly related to hepatotoxicity were integrated.Results:In this study,9 active ingredients of FMT and 265 targets were obtained.There are 533 hepatotoxicity-related targets,and 76 potential targets for hepatotoxicity caused by FMT,among which quercetin,melianone,and nimbolin A are the key active components for hepatotoxicity caused by FMT,and MYC,STAT3,JUN,and RELA were the core target proteins of FMT’s hepatotoxicity.There were 2353 GO entries(P<0.05),including 2181 Biological Process(BP),41 Cellular Component(CC)and 131 Molecular Function(MF).KEGG enrichment analysis revealed 165 pathways(P<0.05),of which Th17 cell differentiation,HIF-1 signaling pathway,PI3K-Akt signaling pathway were strongly correlated with the hepatotoxicity of FMT.Conclusion:Through network pharmacology,it was found that many potential components in azadirachia chinaberry may be involved in the regulation of apoptosis,excessive inflammatory response and mitochondrial dynamics through multi-target and multi-pathway,resulting in the generation of hepatotoxicity.

超声提取川楝子中阿魏酸的最佳工艺研究

使用超声波法提取川楝(Melia toosendan)子中的阿魏酸,采用HPLC法检测阿魏酸的含量。设计单因素试验,考察了提取溶剂、提取温度、料液比、提取时间、提取次数等试验条件对阿魏酸提取率的影响,以优化提取条件。优化的超声提取条件为,体积比为95∶5的甲醇-甲酸为提取溶剂,料液比1∶30(m∶V,g/mL),提取温度55℃,提取时间30 min,提取次数2次,最高提取率达0.012 6 mg/g。

苦楝树皮提取物和菟丝特混合处理对菟丝子生长及其主要生理指标的影响

研究苦楝树(Melia azedarach)皮乙醇提取物和菟丝特的混合药剂对日本菟丝子(Cuscuta japonica)生长及其主要生理指标的影响。结果表明,低浓度的混合药剂对菟丝子无明显伤害作用,但高浓度的混合药剂处理30 d后菟丝子藤茎大面积萎蔫枯死。高浓度混合药剂处理下日本菟丝子可溶性糖和丙二醛含量升高,可溶性蛋白含量降低。在高浓度(40 g/L)苦楝树皮乙醇提取物处理下,日本菟丝子超氧化物歧化酶(SOD)、过氧化物酶(POD)和过氧化氢酶(CAT)活性随着菟丝特浓度的升高呈现出先升高后降低的趋势。在高浓度(14 mg/L)菟丝特处理下,日本菟丝子POD和CAT活性也随着苦楝树皮乙醇提取物浓度的升高呈现出先升高后降低的趋势。表明高浓度混合药剂通过影响菟丝子体内蛋白质等生物大分子的代谢、破坏菟丝子体内保护酶系统的平衡对菟丝子发挥防治作用。

值得引种开发利用的经济林木——印度楝

印度楝(Azadirachta indica A.Juss.)又名Melia azadirachta、Melia indica(A.Juss) Brand,俗称neem、neem tree、margosa tree,属楝科(Meliaceae)。原产印度-巴基斯坦次大陆及缅甸。印度楝速生常绿,树高10～20米,直径30～80厘米,树皮灰色、厚,呈鳞片状,内皮粉红色。具收敛性无涩味,树皮单宁含量高。核果,长圆形,13～20毫米长,由淡黄色转变为紫色,果肉带苦味;种核大,椭圆形,内含一粒大籽。树龄四、五年生时。

Antibacterial efficacy of the seed extracts of Melia azedarach against some hospital isolated human pathogenic bacterial strains

Objective:To investigate the antibacterial potential of the polar and non-polar extracts of the seeds of Melia azedarach(M.azedarach) L.(Meliaceae) against eighteen hospital isolated human pathogenic bacterial strains.Methods:Petrol,benzene,ethyl acetate,methanol,and aqueous extracts at five different concentrations(1,2,5,10 and 15 mg/mL) were evaluated.Disk diffusion method was followed to evaluate the antibacterial efficacy.Results:All extracts of the seeds demonstrated significant antibacterial activity against tested pathogens.Among all extracts,ethyl acetate extract revealed the highest inhibition comparatively.The present study also favored the traditional uses reported earlier.Conclusions:Results of this study strongly confirm that the seed extracts of M.azedarach could be effective antibiotics,both in controlling gram-positive and gram-negative human pathogenic infections.

Two new limonoids from Melia toosendan

Two new limonoid-type triterpenoids, named 12-o-ethyl-l-deacetylnimbolinin B and 1-o-tigloyl-1-o-debenzoylohchinal, have been isolated from the fruit of Melia toosendan Sieb. et Zucc. Their structures were elucidated by spectral methods, including 2D-NMR spectra.

A novel green inhibitor for C-steel corrosion in 2.0 mol·L^-1 hydrochloric acid solution

The corrosion inhibition characteristics of aqueous extract of seeds of Melia azedarach L.(MA) have been studied as eco-friendly green inhibitor for corrosion control of C-steel in 2 mol·L^(-1) HCl solution by gravimetric and electrochemical methods. The results depict that, the extract inhibits efficiently the corrosion of carbon steel in hydrochloric acid. The efficiency of extract is increased with increasing the extract concentration but independent on the studied temperature. The adsorption of the extract components onto the steel surface was found to be spontaneous, and follows Langmuir adsorption isotherm. The surface morphology of C-steel, in the absence and presence of MA extract in 2.0 mol·L^(-1) hydrochloric acid solution, was studied using scanning electron microscopy(SEM).

Vacuum press drying studies on two fast-growing Indian wood species

Two fast-growing Indian species, Melia composita Benth. and Eucalyptus tereticornis Sm., which have different sets of physical properties, were dried together in a vacuum press dryer(VPD) under two drying conditions,i.e., above boiling point(ABP) and below boiling point(BBP). The ABP and BBP conditions were maintained by keeping the temperature constant at 75 ℃ and maintaining two pressure levels: 300 mm of Hg(ABP) and 450 mm of Hg(BBP). In order to understand pressure conditions at the core during vacuum drying, a cylindrical brass pipe was inserted in both wood cores and attached with pressure gauges placed outside of the VPD. The results indicate that the Melia wood core attained equilibrium pressure immediately with the pressure of VPD, while Eucalyptus attained it very slowly, reaching equilibrium at later stages of drying when cracks and checks advanced to the core.The drying rate was higher for Melia than Eucalyptus under both drying conditions. The drying rate of Melia(ABP) was higher than Melia(BBP), however, the drying rate for Eucalyptus(ABP) was not significantly different from the BBP drying rate.

The anti-tubercular activity of Melia azedarach L. and Lobelia chinensis Lour. and their potential as effective anti-Mycobacterium tuberculosis candidate agents

Objective: To evaluate the anti-mycobacterial activity of Melia azedarach L.(M. azedarach) and Lobelia chinensis Lour.(L. chinensis) extracts against the growth of Mycobacterium tuberculosis(M. tuberculosis).Methods: The anti-M. tuberculosis activity of M. azedarach and L. chinensis extracts were evaluated using different indicator methods such as resazurin microtiter assay(REMA) and mycobacteria growth indicator tube(MGIT) 960 system assay. The M. tuberculosis was incubated with various concentrations(50–800 mg/m L) of the extracts for 5 days in the REMA, and for 4 weeks in MGIT 960 system assay.Results: M. azedarach and L. chinensis extracts showed their anti-M. tuberculosis activity by strongly inhibiting the growth of M. tuberculosis in a concentration-dependent manner in the REMA and the MGIT 960 system assay. Particularly, the methanol extract of M. azedarach and n-hexane extract of L. chinensis consistently exhibited their effects by effectively inhibiting the growth of M. tuberculosis in MGIT 960 system for 4 weeks with a single-treatment, indicating higher anti-M. tuberculosis activity than other extracts,and their minimum inhibitory concentrations were measured as 400 mg/m L and 800 mg/m L, respectively.Conclusions: These results demonstrate that M. azedarach and L. chinensis extracts not only have unique anti-M. tuberculosis activity, but also induce the selective antiM. tuberculosis effects by consistently inhibiting or blocking the growth of M. tuberculosis through a new pharmacological action. Therefore, this study suggests the potential of them as effective candidate agents of next-generation for developing a new anti-tuberculosis drug, as well as the advantage for utilizing traditional medicinal plants as one of effective strategies against tuberculosis.

New limonoids from the fruits of Melia toosendan

Two new limonoids,1α-tigloyloxy-3α-acetoxyl-7α-hydroxyl-12α-ethoxyl nimbolinin（1） and lα-benzoyloxy-3α-acetoxyl-7α- hydroxyl-12α-ethoxyl nimbolinin（2）,were isolated from the fruits of Melia toosendan.Their structures were established on the basis of various NMR spectroscopic analyses,including 2D-NMR techniques（HSQC,HMBC,NOESY） and HR-ESI-MS.

Standardization of DNA Extraction Method from Mature Dried Leaves and ISSR-PCR Conditions for Melia dubia Cav. —A Fast Growing Multipurpose Tree Species

Melia dubia Cav. of family Meliaceae is a fast growing, high value tree species native to India. Isolating DNA from matured dried leaves of M. dubia was difficult due to accumulation of secondary metabolites, majorly polyphenolics, which resulted in dark brown to black colour of the pellet. In this study, a modified STE-(Sucrose, Tris-HCl and Ethylene Diamine Tetra Acetic Acid) CTAB (hexadecyltrimethylammonium bromide) method was standardized for removal of polyphenolics. The protocol developed yielded 200 - 1000 ng/μl of quality DNA without any impurities as evident by A260/280 ratio ranging from 1.75 - 2.0. It was also suitable for extracting quality DNA from other members of Meliaceae like Azadirachta indica and Melia azedarach. In downstream applications, the extracted DNA was used for PCR amplification by using ISSR and SSR markers. ISSR PCR conditions were optimized in a reaction volume of 25 μl, consisting of 30 ng of template DNA, 1.5 mM MgCl2, 200 μM of each of dNTPs and 2 U of Taq polymerase. The best amplification was observed and the same was applicable for SSR markers.

Evaluation of Antifertility Effect and Recovery of the Seed Oil Constituents of Iranian Species of Melia Azadrach L. in Male Rats

Objective To evaluate the fertility effects of seed extract of Melia azadarach L. treatment effects on fertility indices in male Wistar rats. Methods The seed oil extract had been prepared according to conventional methods. The rats were randomly divided into three study groups. Groups A and B received graded doses of 50 mg/kg and 100 mg/kg body weight of the extract oil, respectively on daily basis for 60 d. Animals in control group received I ml of maize oil. At the end of 60 d and 3 months treatment period, 6 animals per group were randomly selected and fertility was evaluated with mating test. GSI （gonadosomatic index） sperm motility, sperm viability, ESR （epididymal sperm reserves）, DSP（daily sperm production） and testosterone concentration were also assessed.Results In the first stage, a significant reduction infertility indices especially in higher dose was observed compared with the control. During the next stage, the significant increase in fertility indices are the indication of reasonable recovery and reversibility of extract activity. Conclusion The seed oil of Melia azadarach L. has antifertility activity, but its effects is reversible.

Extracts of Melia azedarach Increases Mulberry Whitefly Mortality without Affecting Silkworm Survivorship

Melia azedarach L. extracts were studied in comparison with selected synthetic in-secticides against the mulberry whiteflies Pealiusma chili and P. mori under labora-tory conditions. Morus alba (cv. “Early Spring”) leaves infested by mulberry white-flies were exposed to Melia extracts of green fruits, l-cyhalothrin (10% a.i.) and con-trol. Also, white mulberry leaves after treatment with the same insecticides were provided to silkworms for consumption. Results have shown that there were signif-icant differences in the nymphal mortality of the whiteflies among treatments. Melia extracts and l-cyhalothrin were effective in increasing whitefly mortality 24 h after application. Furthermore, Melia extracts didn’t affect silkworm survivorship, which was severely affected by l-cyhalothrin treatment, since all the silkworms fed on treated leaves were found dead. Thus, these extracts might be considered a potential alternative in management of the mulberry whiteflies.

《中国药典》中有毒中药的用法及其注意事项

由于毒剧中药管理使用不善,几年来国内因误服有毒中药,造成严重中毒和死亡事故不断发生。为了加强对有毒中药,特别是毒剧中药的管理和使用,减少因误服毒剧中药而死亡事故的发生,笔者将《中国药典》

Provenance variations in proximate principles,mineral matter,total phenols and phytochemicals of Melia dubia drupes:an unexplored alternate livestock feed stock

This research was carried out on nine provenances from the north Western Ghats to quantify proximate principles,mineral matter,total phenols and other phytochemicals in Melia dubia drupe pulp.Drupe biometric,biomass attributes,proximate principles,mineral matter and total phenols diff ered signifi cantly among the provenances.The average drupe length and width was 26.5 and 22.3 mm,respectively.Average drupe and pulp fresh weight,pulp dry weight and stone weight were 783.1,552.1,165.1,and 179.8 g/100 drupes,respectively.Pulp,dry matter and moisture per cent were 70.5%,29.9%and 70.0%,respectively.Average crude fi bre,protein,ether extract,total ash and nitrogen-free extract were 8.3%,7.6%,5.1%,6.3%,and 72.6%,respectively.Average Ca,Mg,P and K levels were 0.5%,0.2%,0.2%,and 2.0%,respectively.Total phenols were 0.4%.Cluster analysis showed that the study area may be divided into three distinct provenances,each having diff erent drupe traits and proximate composition,including mineral components.Gas-chromatography mass-spectrometry analysis revealed 27 phytochemicals,many of which possess benefi cial biological attributes.The implications of this provenance variation study should be useful for future improvement in terms of better drupe pulp nutrition for livestock feed.Further study suggests that M.dubia pulp could be categorized as a good feed source with low fi bre,energy,fat and mineral levels.All proximate parameters,mineral matter content and total phenols are within prescribed limits.

Variability in physical properties of plantation-grown progenies of Melia composita and determination of a kiln-drying schedule

Plantation-grown progenies of Melia composita Willd.were studied for variability in several physical properties： density,radial and tangential shrinkage,longitudinal permeability of heartwood and sapwood.Furthermore,flat-sawn planks from each of the progeny were subjected to a quick-drying test for determination of kilndrying schedule.The mean density of the species was 0.39 g cm^（-3） and the wood may be categorized as light wood.Mean radial shrinkage（%） for the species was 2.8% with progeny-wise variation in radial shrinkage from 1.56 to 4.11%.Mean tangential shrinkage（%） for the species was 5.54% with progeny-wise variation in tangential shrinkage from 3.69 to 7.71%.The resultant tangentialradial shrinkage ratio was 1.98（less than two）,which suggests that the wood is relatively stable with respect to drying behavior.Mean sapwood and heartwood longitudinal permeability of the species were 3.38 and 2.02 Darcy,respectively.Higher longitudinal permeability of sapwood and heartwood indicate better drying and preservative properties of the species.Terazawa quick-drying test method suggests that the species is less susceptible to drying defects.During the test,only moderate checks and cracks were observed.A tentative kiln-drying schedule was recommended based on these results.

Triterpenoids and Sterols from the Leaves and Twigs of Melia azedarach

Two new triterpenoids(1 and 2)and a new sterol(3),together with six known constituents(4–9),were isolated from the leaves and twigs of Melia azedarach.Their chemical structures were elucidated on the basis of spectroscopic analysis.

Bioactivity of Indigenous Melia azedarach Extracts against the Tomato Leafminer,Tuta absoluta

Fruit extracts of indigenous Melia azedarach were tested for their insecticidal bioactivity against the tomato leafminer(Tuta absoluta)under laboratory conditions.Tomato plants were exposed to moths,after/before application of treatments.Treatments included:crushed fruit extracts of water(500,000 ppm and 200,000 ppm),methanol and ethyl acetate(200,000 ppm)with and without mineral oil(2%);M.azedarach powder extracts(2,000 ppm)in different solvents:water,methanol,ethanol,ethyl acetate,hexane and chloroform;biorational products:neem oil,mineral oil,micronized sulfur and thyme oil.The released moths were removed from treated/untreated plants at 72 h and effect of treatments on adults,eggs,larvae and pupae were recorded.Results indicated that sulfur caused the lowest number of live moths to be present on treated plants and was not significantly different in its effect from that of M.azedarach extracts and neem oil.Aqueous extracts without and with oil caused the highest%of dry eggs and were comparable to neem oil.Extracts in the two formulations(crushed fruits and/or powder)caused significant direct effects on immature instars:eggs,early larval instars and pupae.M.azedarach extracts and the tested products also caused indirect effect in form of significant decrease in number of developing the 3rd larval instars and new emerging moths compared to the control.Consecutive sprays of these extracts against eggs,larvae and pupae on same treated plants lead to very low number of moths for a second generation of the pest which contributes to low buildup of pest population in a tomato crop.

Melia’s R_h= ct Model Is by No Means Flat

With the support of numerous arguments, it has been shown that Melia’s claim that his cosmological Rh = ct model is flat and infinite is erroneous. In contrast, the model is positively curved, closed and, therefore, finite. With respect to results of Melia’s model, it is identical to our Subluminal Model.

权健 巴厘岛辉煌之旅

2017年5月7日,带着梦想前行的权健人,满怀着家人与伙伴共享荣耀的喜悦,从香港出发,开启了“2017中国权健走向世界辉煌之旅”畅游巴厘岛的华丽旅程。从踏上巴厘岛的第一分钟开始,权健人就受到了巴厘姑娘的鲜花迎接,贵宾的奢华礼遇,彰显着权健人梦想的尊荣,更凝聚着权健人美好的憧憬。