2014 Vol. 12, No. 4

Display Method:
TCM-based new drug discovery and development in China
WU Wan-Ying, HOU Jin-Jun, LONG Hua-Li, YANG Wen-Zhi, LIANG Jian, GUO De-An
2014, 12(4): 241-250.
Over the past 30 years,China has significantly improved the drug development environment by establishing a series of policies for the regulation of new drug approval.The regulatory system for new drug evaluation and registration in China was gradually developed in accordance with international standards.The approval and registration of TCM in China became as strict as those of chemical drugs and biological products.In this review,TCM-based new drug discovery and development are introduced according to the TCM classification of nine categories.
Network pharmacology-based prediction and verification of the molecular targets and pathways for schisandrin against cerebrovascular disease
LV Yan-Ni, LI Shao-Xia, ZHAI Ke-Feng, KOU Jun-Ping, YU Bo-Yang
2014, 12(4): 251-258.
AIM:To illuminate the molecular targets for schisandrin against cerebrovascular disease based on the combined methods of network pharmacology prediction and experimental verification.METHOD:A protein database was established through constructing the drug-protein network from literature mining data.The protein-protein network was built through an in-depth exploration of the relationships between the proteins.The computational platform was implemented to predict and extract the sensitive sub-network with significant P-values from the protein-protein network.Then the key targets and pathways were identified from the sensitive sub-network.The most related targets and pathways were also confirmed in hydrogen peroxide(H2O2)-induced PC12 cells by Western blotting.RESULTS:Twelve differentially expressed proteins(gene names:NFKB1,RELA,TNFSF10,MAPK1,CHUK,CASP8,PIGS2,MAPK14,CREB1,IFNG,APP,and BCL2) were confirmed as the central nodes of the interaction network(45 nodes,93 edges).The NF-B signaling pathway was suggested as the most related pathway of schisandrin for cerebrovascular disease.Furthermore,schisandrin was found to suppress the expression and phosphorylation of IKK,as well as p50 and p65 induced by H2O2 in PC12 cells by Western blotting.CONCLUSION:The computational platform that integrates literature mining data,protein-protein interactions,sensitive sub-network,and pathway results in identification of the NF-B signaling pathway as the key targets and pathways for schisandrin.
Maslinic acid modulates glycogen metabolism by enhancing the insulin signaling pathway and inhibiting glycogen phosphorylase
LIU Jun, WANG Xue, CHEN Yu-Peng, MAO Li-Fei, SHANG Jing, SUN Hong-Bin, ZHANG Lu-Yong
2014, 12(4): 259-265.
AIM:To investigate the molecular signaling mechanism by which the plant-derived,pentacyclic triterpene maslinic acid(MA) exerts anti-diabetic effects.METHOD:HepG2 cells were stimulated with various concentrations of MA.The effects of MA on glycogen phosphorylase a(GPa) activity and the cellular glycogen content were measured.Western blot analyses were performed with anti-insulin receptor (IR),protein kinase B(also known as Akt),and glycogen synthase kinase-3(GSK3) antibodies.Activation status of the insulin pathway was investigated using phospho-IR,as well as phospho-Akt,and phospho-GSK3 antibodies.The specific PI3-kinase inhibitor wortmannin was added to the cells to analyze the Akt expression.Enzyme-linked immunosorbent assay(ELISA) was used to measure the effect of MA on IR auto-phosphorylation.Furthermore,the effect of MA on glycogen metabolism was investigated in C57BL/6J mice fed with a high-fat diet(HFD).RESULTS:The results showed that MA exerts anti-diabetic effects by increasing glycogen content and inhibiting glycogen phosphorylase activity in HepG2 cells.Furthermore,MA was shown to induce the phosphorylation level of IR-subunit,Akt,and GSK3.The MA-induced activation of Akt appeared to be specific,since it could be blocked by wortmannin.Finally,MA treatment of mice fed with a high-fat diet reduced the model-associated adiposity and insulin resistance,and increased the accumulated hepatic glycogen content.CONCLUSION:The results suggested that maslinic acid modulates glycogen metabolism by enhancing the insulin signaling pathway and inhibiting glycogen phosphorylase.
Alkaloids of Nitraria sibirica Pall.decrease hypertension and albuminuria in angiotensin II-salt hypertension
Mahinur Bakri, YI Yang, CHEN Ling-Dan, Haji Akber Aisa, WANG Mong-Heng
2014, 12(4): 266-272.
In traditional Chinese medicine,Nitraria sibirica Pall.(Nitrariaceae) is used to treat hypertension.This study determined the effects of the total alkaloids of the leaves of Nitraria sibirica(NSTA) on blood pressure and albuminuria in mice treated with angiotensin II and a high-salt diet(ANG/HS).Adult mice were divided into three groups:control;infused with angiotensin II and fed a diet containing 4% NaCl(ANG/HS;and ANG/HS plus injection of NSTA(1 mg穔g-1穌-1,i.p.).After treatment of these regimens,daily water and food intake,kidney weight,blood pressure,urinary albumin excretion,renal concentrations of inflammatory markers,including soluble intercellular adhesion molecule-1(sICAM-1) and monocyte chemoattractant protein-1(MCP-1),and the expression of renal fibrosis markers were determined.Compared to the control group,the ANG/HS group had higher blood pressure and urinary albumin excretion.Treatment with NSTA in ANG/HS mice for three weeks significantly reduced blood pressure and urinary albumin excretion.ANG/HS treatment caused elevated levels of sICAM-1 and MCP-1,as well as increased fibrosis markers.Concurrent treatment with ANG/HS and NSTA attenuated the levels and expression of renal inflammatory and fibrosis markers.Treatment with NSTA effectively reduces hypertension-induced albuminuria through the reduction of renal inflammatory and fibrosis markers.
Hepatoprotective and in vivo antioxidant activities of the hydroethanolic leaf extract of Mucuna pruriens(Fabaceae) in antitubercular drugs and alcohol models
Mercy B. Obogwu, Abidemi J. Akindele, Olufunmilayo O. Adeyemi
2014, 12(4): 273-283.
AIM:Hepatotoxicity is a significantly increasing health problem worldwide,and the extent of the problem has stimulated interest in the search for hepatotherapeutic agents from plants.This study investigated the hepatoprotective and in vivo antioxidant activities of the hydroethanolic extract of Mucuna pruriens leaves in antitubercular and alcohol-induced hepatotoxicity assays in rats.METHOD:In each of the models used,seven groups were allotted.The different groups received normal saline(10 mLkg-1,p.o.);hepatotoxicant(isoniazid-rifampicin,INH-RIF,100 mgkg-1,i.p.or 20% ethanol 5 gkg-1,p.o.) and normal saline(10 mLkg-1,p.o.);hepatotoxicant and extract at doses of 100,200,and 400 mgkg-1 p.o.;hepatotoxicant and silymarin 50 mgkg-1 p.o.;and extract at 400 mgkg-1 p.o..On the 21st day of treatment,blood was collected for assessment of serum biochemical parameters and harvested liver samples were assessed for antioxidants.RESULTS:The hepatotoxicants significantly(P0.05-0.001) increased the levels of alanine transaminase(ALT),aspartate transaminase(AST),alkaline phosphatase(ALP),bilirubin,and malondialdehyde(MDA);and reduced the levels of catalase(CAT),superoxide dismutase(SOD),glutathione peroxidase(GPx),and reduced glutathione GSH compared to control.M.pruriens significantly reversed(P0.05-0.001) the elevation in the level of ALT,AST,ALP,and bilirubin caused by the hepatotoxicants.The extract(200 and 400 mgkg-1) significantly reversed(P0.05) the diminution in the level of in vivo antioxidants and increased the level of MDA produced by INH-RIF.M.pruriens(100-400 mgkg-1) elicited significant reduction(P0.001) in the level of MDA compared to the alcohol group.Silymarin also reversed the deleterious effects of the hepatotoxicants.CONCLUSION:The hydroethanolic extract of Mucuna pruriens leaves possesses hepatoprotective activity with enhancement of in vivo antioxidants as a possible mechanism of action.
F-01A,an antibiotic,inhibits lung cancer cells proliferation
WANG Jing, WU Xiao-Peng, SONG Xin-Ming, HAN Chang-Ri, CHEN Zhong, CHEN Guang-Ying
2014, 12(4): 284-289.
AIM:In an effort to identify novel,small molecules which can affect the proliferation of lung cancer cells,F-01A,a polyether antibiotic isolated from the fermentation broth of Streptomyces was tested.METHOD:F-01A was tested for its antitumor properties on the lung cancer cell line SPC-A-1,at six doses(0.1,0.5,1,2.5,and 5 molL-1),using various cellular assays.Cell viability was measured by the MTT assay,Hochest 33258 was used to study nuclear morphology;DNA ladder and the loss of mitochondrial membrane potential were also evaluated.RESULTS:F-01A induces apoptosis against SPC-A-1 cells in a dose-dependent manner.The IC50 is 0.65 molL-1,and the inhibition at 5 molL-1 is 87.89%.Further,JC-1 staining indicates F-01A could induce the loss of mitochondrial membrane potential,and the DNA fragment is evident.CONCLUSION:Mechanistic analysis showed that F-01A induced apoptosis of cancer cells probably in the mitochondrial pathway.The antitumor actions of F-01A involve activation of the apoptotic pathway against SPC-A-1 cells,and it may be valuable for further drug development.
Comparative evaluation of polysaccharides isolated from Astragalus,oyster mushroom,and yacon as inhibitors of α-glucosidase
ZHU Zhen-Yuan, ZHANG Jing-Yi, CHEN Li-Jing, LIU Xiao-Cui, LIU Yang, WANG Wan-Xiao, ZHANG Yong-Min
2014, 12(4): 290-293.
The incidence of diabetes has increased considerably,and become the third serious chronic disease following cancer and cardiovascular diseases.Though acarbose,metformin,and 1-deoxynojirimycin have good efficacy for clinical application as hypoglycemic drugs,their expensive costs and some degree of side effects have limited their clinical application.Recently,increasing attention has concentrated on the polysaccharides from natural plant and animal sources for diabetes.In order to illustrate the pharmaceutical activity of polysaccharides as natural hypoglycemic agents,polysaccharides isolated from Astragalus,oyster mushroom,and Yacon were evaluated for their inhibitory effects on -glucosidase.Polysaccharides were extracted and purified from Astragalus,Oyster mushroom,and Yacon with hot water at 90℃ for 3 h,respectively.The total sugar content of the polysaccharide was determined by the phenol-sulfuric acid method.The -glucosidase inhibitory activity was measured by the glucose oxidase method.The results exhibited that the inhibitory effects on -glucosidase were in decreasing order,Astragalus oyster mushroom Yacon.The -glucosidase inhibition percentage of Astragalus polysaccharide and oyster mushroom polysaccharide were over 40% at the polysaccharide concentration of 0.4 mgmL-1.The IC50 of Astragalus polysaccharide and oyster mushroom polysaccharide were 0.28 and 0.424 mgmL-1,respectively.The information obtained from this work is beneficial for the use polysaccharides as a dietary supplement for health foods and therapeutics for diabetes.
New 9,19-cycloartane triterpenoid from the root of Cimicifuga foetida
ZHU Di-Fan, NIAN Yin, WANG Hai-Yan, ZHANG Zhi-Run, SONG Yan-Bo, LI Rong-Tao, QIU Ming-Hua
2014, 12(4): 294-296.
AIM:To study the 9,19-cycloartane triterpenes from the roots of Cimicifuga foetida.METHOD:Chromatographic separations by silica gel,C18 reversed phase silica gel,and high-performance liquid chromatography(HPLC) were used.All of the structures were elucidated on the basis of spectroscopic analysis and chemical methods.RESULTS:Five 9,19-cycloartane triterpenes,(3,12,15,24R)-12,2'-diacetoxy-24,25-epoxy-15-hydroxy-16,23-dione-3-O--L-arabinopyranoside(1),actein(2),23-epi-26-deoxyactein(3),asiaticoside B(4),and 12-hydroxycimigenol(5) were isolated from the roots of Cimicifuga foetida.CONCLUSION:Compound 1 is a new triterpene with two acetoxy groups at C-2'and C-12.
A new diterpene from the stems of Trigonostemon heterophyllus
LI Yi-Xing, ZUO Wen-Jian, MEI Wen-Li, CHEN Hui-Qin, DAI Hao-Fu
2014, 12(4): 297-299.
AIM:To investigate the chemical constituents in the stems of Trigonostemon heterophyllus.METHOD:The chemical constituents were isolated by column chromatography on silica gel,Rp-18,and Sephadex LH-20,and their structures were elucidated on the basis of spectroscopic analysis.RESULTS:Three compounds were isolated and identified as a new diterpene,trigonoheterene B(1),together with two known compounds,trigonostemone(2) and trigonochinene B(3).CONCLUSION:Compound 1 is new.Compounds 2 and 3 showed antibacterial activities.
Chemical constituents from the stems of Gymnema sylvestre
LIU Yue, XU Tun-Hai, ZHANG Man-Qi, LI Xue, XU Ya-Juan, JIANG Hong-Yu, LIU Tong-Hua, XU Dong-Ming
2014, 12(4): 300-304.
AIM:To study the chemical constituents of stems of Gymnema sylvestre(Retz.) Schult.METHODS:Chromatographic techniques using silica gel,C18 reversed phase silica gel,and prep-HPLC were used.The structures were elucidated on the basis of MS and spectroscopic analysis(1D and 2D NMR),as well as chemical methods.RESULTS:Seven compounds were isolated and their structures were elucidated as conduritol A(1),stigmasterol(2),lupeol(3),stigmasterol-3-O--D-glucoside(4),the sodium salt of 22-hydroxy-longispinogenin-3-O--D-glucopyranosyl-(13)--D-glucurono-pyranosyl-28-O--L-rhamnopyranoside(5),oleanolic acid-3-O--D-glucopyranosyl-(16)--D-glucopyranoside(6),and the sodium salt of 22-hydroxy-longispinogenin 3-O--D-glucuronopyranosyl-28-O--L-rhamnopyranoside(7).The inhibition activities of compounds 1,5-7 on non-enzymatic glycation of protein in vitro were evaluated.CONCLUSION:Compound 7 is a new triterpenoid saponin.It was shown that compounds 1,5-7 have weak inhibition activities for non-enzymatic glycation of protein in vitro.
A new saikogenin from the roots of Bupleurum bicaule
XU Nan, SHI Ya-Nan, ZHONG Xu, CAO Yue, WANG Li, JIA Tian-Zhu
2014, 12(4): 305-308.
AIM:To study the chemical constituents from the roots of Bupleurum bicaule Helm(Apiaceae).METHOD:Silica gel,Sephadex LH-20,MPLC Rp-C18 column chromatography,and HPLC were used for isolation of compounds.The structures were elucidated on the basis of 1D-and 2D-NMR technology and HRESI-MS.Compounds were evaluated in vitro for their inhibitory ability against the proliferation of rat mesangial cells by the MTT method.RESULTS:Twelve compounds were isolated,and their structures were identified on the basis of their spectroscopic and ico-chemical properties as 13,28-epoxy-olean-11-en-3-one(1),saikogenin E(2),saikogenin G(3),11-methoxy-3,16,23,28-tetrahydroxyolean-12-ene(4),saikogenin D(5),prosaikogenin F(6),prosaikogenin A(7),prosaikogenin G(8),prosaikogenin D(9),laccaic acid(10),methyl gallate(11),and ethyl gallate(12).Compounds 1,2,7,8,and 10 were observed to have inhibitory activity against mesangial cell proliferationin to different degrees.CONCLUSION:Compound 1,8,and 10 exhibit significant inhibitory effects on rat mesangial cell proliferation induced by Ang II.
Anti-methicillin-resistant Staphylococcus aureus assay of azalomycin F5a and its derivatives
YUAN Gan-Jun, LI Pei-Bo, YANG Jun, PANG Hui-Zhong, PEI Ying
2014, 12(4): 309-313.
AIM:To discover anti-methicillin-resistant Staphylococcus aureus(anti-MRSA) microbial natural products or their derivatives.METHOD:Azalomycin F5a(1) was prepared through fermentation of Streptomyces hygroscopicus var.azalomyceticus,and its derivatives were synthesized through hydrocarbylation in hydrocarbyl alcoholic-AcOH(4:1) and subsequent demalonylation with 2 molL-1 KOH in MeOH-H2O(7:3).Their activities against MRSA ATCC 33592 and three clinical MRSA isolates were evaluated by the agar diffusion and broth microdilution methods.RESULTS:Four demalonylazalomycin F5a derivatives 2 to 5 were synthesized.The anti-MRSA activity assay indicated that compounds 1 to 5 showed remarkable activity against MRSA,and their minimum inhibitory concentrations(MICs) were respectively 3.0-4.0,0.5-1.0,0.67-1.0,0.67-0.83,and 0.5-0.83 gmL-1.CONCLUSION:Azalomycin F5a and the demalonylazalomycin F5a derivatives 2-5 showed remarkable anti-MRSA activity,and the anti-MRSA activities of 2 to 5 were higher than that of 1,while the anti-MRSA activities of 2 to 5 showed no obvious differences.It was also shown that the malonyl monoester group of azalomycin F5a was less important for its anti-MRSA activity.
Transformation of astragalosides from Radix Astragali under acidic,neutral,and alkaline extraction conditions monitored by LC-ESI-TOF/MS
CHU Chu, LIU E-Hu, QI Lian-Wen, LI Ping
2014, 12(4): 314-320.
AIM:To reveal the profile of astragalosides for better quality evaluation of Radix Astragali,this study was aimed to investigate the transformation of astragalosides under different conditions.METHOD:Seven major astragalosides were selected for evaluation under acidic,neutral and alkaline conditions.The transformation in real plant samples was also examined and the products were characterized by LC-ESI-TOF/MS.RESULTS:In weak acidic solution,all of the astragalosides are stable.In addition,the transformation ratios of the astragalosides under neutral and alkaline conditions were also obtained.CONCLUSION:In neutral solution,malonylastragaloside I was transformed to astragaloside I;and in alkaline solution,substituent group(s) in the xylose moiety of all the astragalosides were eliminated.Since astragalosdie IV is the basic skeleton structure of the astrgalosides,it is a common transformation product of other astragalosides.