The present study used in vitro and in silico techniques, as well as the metabolomics approach to characterise α-glucosidase inhibitors from different fractions of Clinacanthus nutans. C. nutans is a medicinal plant ...The present study used in vitro and in silico techniques, as well as the metabolomics approach to characterise α-glucosidase inhibitors from different fractions of Clinacanthus nutans. C. nutans is a medicinal plant belonging to the Acanthaceae family, and is traditionally used to treat diabetes in Malaysia. nHexane, n-hexane: ethyl acetate(1:1, v/v), ethyl acetate, ethyl acetate: methanol(1:1, v/v), and methanol fractions were obtained via partitioning of the 80% methanolic crude extract. The in vitro α-glucosidase inhibitory activity was analyzed using all the fractions collected, followed by profiling of the metabolites using liquid chromatography combined with mass spectrometry. The partial least square(PLS) statistical model was developed using the SIMCA P^+14.0 software and the following four inhibitors were obtained:(1) 4,6,8-Megastigmatrien-3-one;(2) N-Isobutyl-2-nonen-6,8-diynamide;(3) 1′,2′-bis(acetyloxy)-3′,4′-didehydro-2′-hydro-β, ψ-carotene; and(4) 22-acetate-3-hydroxy-21-(6-methyl-2,4-octadienoate)-olean-12-en-28-oic acid. The in silico study performed via molecular docking with the crystal structure of yeast isomaltase(PDB code: 3 A4 A) involved a hydrogen bond and some hydrophobic interactions between the inhibitors and protein. The residues that interacted include ASN259, HID295, LYS156, ARG335,and GLY209 with a hydrogen bond, while TRP15, TYR158, VAL232, HIE280, ALA292, PRO312, LEU313,VAL313, PHE314, ARG315, TYR316, VAL319, and TRP343 with other forms of bonding.展开更多
Objective: To identify mutually regulated proteins in PC-3 and DU145 androgen-independent prostate cancer cell lines treated with 1,5-bis(2-hydroxyphenyl)-1,4-pentadiene-3-one(MS17), and to study the molecular pathway...Objective: To identify mutually regulated proteins in PC-3 and DU145 androgen-independent prostate cancer cell lines treated with 1,5-bis(2-hydroxyphenyl)-1,4-pentadiene-3-one(MS17), and to study the molecular pathways that contributed to the anticancer activity of MS17.Methods: PC-3 and DU145 cells were treated with 3 × EC_(50)(15 μM) concentration of MS17 for 24 h and were subjected to protein expression profiling using two-dimensional gel electrophoresis and protein identification by mass spectrometry.Selected differentially expressed proteins with significant P-value of P<0.05 and fold change over 1.5-folds were filtered through and ontologically classified.Mutually regulated proteins were ranked by fold change and identified as common protein targets of MS17.Results: Profiling data revealed that, the mutually down-regulated proteins included ACTB and ACTG associated with structural molecule activity, ACTN1 with cell cycle, ACTN4 with cell migration, HNRPK with apoptosis, PLST with morphogenesis and TERA with proteolysis.However, the expressions of CH60 and HS71 A respectively associated with response to unfolded protein demonstrated opposing regulation in PC-3 and DU145 cells.Pathway analysis of the differentially expressed proteins in PC-3 cells demonstrated the modulation of top pathways associated with cell-cell adhesion and cytoskeletal organization while in DU145 cells the pathways were associated with proteosomal degradation, regulation of electrolytes and water, regulation control of germ cells and organization of filament assembly/disassembly.Conclusions: The findings of the present study provide an understanding on the anti-tumorigenic activity of MS17 at the proteome level and warrant further research for its potential application for the management and treatment of androgen-independent prostate cancer.展开更多
Dear Editor,Bacteriophages(otherwise called phages)are a type of virus that infect bacteria.This viral type has found useful applications in the control of bacterial pathogens in foods and food processing environments...Dear Editor,Bacteriophages(otherwise called phages)are a type of virus that infect bacteria.This viral type has found useful applications in the control of bacterial pathogens in foods and food processing environments.In addition,phages may be useful to prevent colonization and shedding of bacteria into the surrounding environment.展开更多
Objective: To identify commonly regulated genes in HPV-infected He La and Ca Ski cervical cancer cells treated with curcumin analogue 1,5-bis(2-hydroxyphenyl)-1,4-pentadiene-3-one(MS17) and to explore potential mechan...Objective: To identify commonly regulated genes in HPV-infected He La and Ca Ski cervical cancer cells treated with curcumin analogue 1,5-bis(2-hydroxyphenyl)-1,4-pentadiene-3-one(MS17) and to explore potential mechanisms that underlie its cytotoxic, anti-proliferative and apoptotic activity. Methods: He La and Ca Ski cells were treated with 2×EC50 and 3×EC50 doses of MS17 for 24 h and the RNA extracts were subjected to one-colour microarray-based gene expression profiling. Pair-wise significant genes(false discovery rate-corrected, P<0.05) were analysed for fold change(FC) compared to control samples. Differentially expressed genes with FC≥2.0(up-regulated; FC≥2.0 and down-regulated; FC≤-2.0) compared to the control samples were filtered through and analysed to create a global gene expression profile. Mutually regulated genes were ranked by FC and categorised by gene ontology. Results: Our data indicated dose-dependent regulation by MS17 and identified top 20 mutually upand down-regulated genes each in He La and Ca Ski cells. Amongst these 17 were commonly regulated in both cell lines. These include the up-regulation of CCL26, DEFB103 B, IL1 RL1, LY96, GCNT3, MMP10, MMP3, GADD45 G and HSPA6, and the down-regulation of TENM2, NEBL, KIFC1, CTDSP1, IGFBP5, LTBP1, NREP and MXD3. These genes were associated with key biological functions that were proposed to mediate the anticancer activity of MS17 in cervical cancer cells such as immune response, metabolic processes, proteolysis, programmed cell death, unfolded protein response, cell adhesion, cytoskeletal organisation, phosphatase activity, signal transduction and transcription regulator activity. Conclusions: Identification of seventeen common genes modulated by MS17 could be used as potential therapeutic targets in both cervical cancer cell lines and the findings of this study could be used to present an insight into the potential antitumor activity of MS17 in cervical cancer.展开更多
Significance increase in dengue cases have been recorded worldwide every year and South East Asian countries have been badly affected.Currently,antiviral drug to treat dengue is still not available but papaya leaves e...Significance increase in dengue cases have been recorded worldwide every year and South East Asian countries have been badly affected.Currently,antiviral drug to treat dengue is still not available but papaya leaves extract(PLE)have been successfully used in treating dengue patients.Carpaine in PLE is the major active compounds that contributes to the anti-thrombocytopenic activity(raising platelet count in patient’s blood).The PLE also contains polyphenols that contribute to antioxidant properties.Studies were carried out to extract and quantify carpaine from young leaves,old leaves and stalks of papaya plant.Carpaine crystalline powders were successfully purified and confirmed by ^(1)H and ^(13)C NMR(Nuclear Magnetic Resonance).Young papaya leaves recorded significantly higher amount of carpaine(P<0.05)as compared with old leaves and stalks.Blending treatment showed significant effect(P<0.05)on the amount of carpaine extracted from the young and old leaves and blended young leaves showed significantly much higher amount of carpaine as compared with the unblended samples(P<0.05).In terms of total polyphenols content(TPC),young leaves(both unblended and blended samples)contained significantly higher amount of TPC(P<0.05)followed by the old leaves and stalks.Results also showed relationship between the TPC and the 1,1-diphenyl-2-picrylhydrazyl(DPPH)assay scavenging activities namely IC_(50)(R^(2)=0.9743)and acid equivalent antioxidant capacity(AEAC)(R^(2)=0.9581).Both young and old leaves also showed significantly higher(P<0.05)DPPH scavenging activities as compared with the stalks in both unblended and blended samples.Young papaya leaves were recommended as source of material to extract carpaine for future development of drug in dengue treatment.展开更多
Coconut water(CW)is a popular natural hydration drink in tropical countries.It is rich in essential electrolytes,vitamins,minerals,and bioactive compounds with functional properties.Therefore,this work aimed to evalua...Coconut water(CW)is a popular natural hydration drink in tropical countries.It is rich in essential electrolytes,vitamins,minerals,and bioactive compounds with functional properties.Therefore,this work aimed to evaluate the functional properties(i.e.,antioxidant and anti-aging activities)and to determine selected bioactive compounds in young and mature CW from the four most popular coconut varieties in Malaysia namely,Aromatic Green Dwarf(PDN),Malaysian Yellow Dwarf(MYD),MATAG(MYD×Tagnanan)and MAWA(MYD×West African Tall).Spectrophotometric and liquid chromatography methods were used to quantify the changes in the tested parameters.It is shown that the quantification of selected bioactive compounds and functional activities of CW displayed a mixed pattern at different maturation.Results from antioxidant,anti-aging activities,amino acids profile and bioactive compounds such as gallic acid,catechin,trans-zeatin,and dihydrozeatin were measured to decrease with the coconuts’maturation.Meanwhile,the amount of kinetin,kinetin riboside and trans-zeatin riboside increased with the maturation of the coconuts.Specifically,CW from young MYD showed the highest antioxidant and anti-aging activities and possessed diverse bioactive compounds that could serve as novel sources of natural functional ingredients targeted for skin anti-aging.In addition,the sensory evaluation showed that the taste of young and mature CW is acceptable for consumption with the young PDN,young MYD and mature MYD displaying the highest score.To the best of our knowledge,the present work reported the first attempt to elucidate the inhibitory activities of CW towards elastase and collagenase enzymes.展开更多
Some of the common practices to assess the composition of plant extract,including Carica papaya seed extract(CPSE)are direct injection of the extract,compound separation using polyethylene glycol capillary column(DB-W...Some of the common practices to assess the composition of plant extract,including Carica papaya seed extract(CPSE)are direct injection of the extract,compound separation using polyethylene glycol capillary column(DB-WAX),and non-linear-temperature programming(NLTP)of GC/MS analysis.This study specifically compared the coating of capillary column,sample derivatization,and temperature programming of GC/MS to determine the composition of CPSE.The retention indices(RI)of the detected compounds were determined and compared to the reference RI.In particular,5%phenyl-95%methylpolysiloxane(HP-5MS)-,DB-WAX-,and biscyanopropyl polysiloxane(HP-88)-coated capillary columns were used to identify the composition of CPSE.For this study,HP-5MS column,which separated the highest number of compounds(26 compounds)from CPSE,was deemed as the most suitable column.The GC/MS analysis of derivatized CPSE identified 21 compound groups,where fatty acids and fatty acid methyl esters served as the major compounds(80.23%),followed by these compounds in decreasing order:amides>nitriles>sterols>fatty aldehydes>organic acids.A stronger correlation determination between the carbon number and alkane retention time of linear-temperature programming(LTP)(R^(2)=0.9859)was found,as compared to its correlation determination with NLTP(R^(2)=0.9175),which exhibited an almost equal RI of LTP to the reference RI.Conclusively,GC/MS analysis for the derivatized CPSE using HP-5MS column separation and LTP is highly recommended.展开更多
基金the Ministry of Agriculture of Malaysia for NKEA Research Grant Scheme fund (NRGS SP15-0600182)International Islamic University Malaysia for Publication Research Initiative Grant fund (PRIGS18-027-0027)
文摘The present study used in vitro and in silico techniques, as well as the metabolomics approach to characterise α-glucosidase inhibitors from different fractions of Clinacanthus nutans. C. nutans is a medicinal plant belonging to the Acanthaceae family, and is traditionally used to treat diabetes in Malaysia. nHexane, n-hexane: ethyl acetate(1:1, v/v), ethyl acetate, ethyl acetate: methanol(1:1, v/v), and methanol fractions were obtained via partitioning of the 80% methanolic crude extract. The in vitro α-glucosidase inhibitory activity was analyzed using all the fractions collected, followed by profiling of the metabolites using liquid chromatography combined with mass spectrometry. The partial least square(PLS) statistical model was developed using the SIMCA P^+14.0 software and the following four inhibitors were obtained:(1) 4,6,8-Megastigmatrien-3-one;(2) N-Isobutyl-2-nonen-6,8-diynamide;(3) 1′,2′-bis(acetyloxy)-3′,4′-didehydro-2′-hydro-β, ψ-carotene; and(4) 22-acetate-3-hydroxy-21-(6-methyl-2,4-octadienoate)-olean-12-en-28-oic acid. The in silico study performed via molecular docking with the crystal structure of yeast isomaltase(PDB code: 3 A4 A) involved a hydrogen bond and some hydrophobic interactions between the inhibitors and protein. The residues that interacted include ASN259, HID295, LYS156, ARG335,and GLY209 with a hydrogen bond, while TRP15, TYR158, VAL232, HIE280, ALA292, PRO312, LEU313,VAL313, PHE314, ARG315, TYR316, VAL319, and TRP343 with other forms of bonding.
基金financially supported by the Fundamental Research Grant Scheme,(FRGS/1/2016/SKK08/MUSM/02/1)under the Ministry of Higher Education,Malaysia
文摘Objective: To identify mutually regulated proteins in PC-3 and DU145 androgen-independent prostate cancer cell lines treated with 1,5-bis(2-hydroxyphenyl)-1,4-pentadiene-3-one(MS17), and to study the molecular pathways that contributed to the anticancer activity of MS17.Methods: PC-3 and DU145 cells were treated with 3 × EC_(50)(15 μM) concentration of MS17 for 24 h and were subjected to protein expression profiling using two-dimensional gel electrophoresis and protein identification by mass spectrometry.Selected differentially expressed proteins with significant P-value of P<0.05 and fold change over 1.5-folds were filtered through and ontologically classified.Mutually regulated proteins were ranked by fold change and identified as common protein targets of MS17.Results: Profiling data revealed that, the mutually down-regulated proteins included ACTB and ACTG associated with structural molecule activity, ACTN1 with cell cycle, ACTN4 with cell migration, HNRPK with apoptosis, PLST with morphogenesis and TERA with proteolysis.However, the expressions of CH60 and HS71 A respectively associated with response to unfolded protein demonstrated opposing regulation in PC-3 and DU145 cells.Pathway analysis of the differentially expressed proteins in PC-3 cells demonstrated the modulation of top pathways associated with cell-cell adhesion and cytoskeletal organization while in DU145 cells the pathways were associated with proteosomal degradation, regulation of electrolytes and water, regulation control of germ cells and organization of filament assembly/disassembly.Conclusions: The findings of the present study provide an understanding on the anti-tumorigenic activity of MS17 at the proteome level and warrant further research for its potential application for the management and treatment of androgen-independent prostate cancer.
基金Research University Grant Scheme(RUGSgrant number 9329400)University Putra Malaysia,partly funded the research
文摘Dear Editor,Bacteriophages(otherwise called phages)are a type of virus that infect bacteria.This viral type has found useful applications in the control of bacterial pathogens in foods and food processing environments.In addition,phages may be useful to prevent colonization and shedding of bacteria into the surrounding environment.
基金financially supported by the Fundamental Research Grant Scheme(No.FRGS/1/2013/SKK01/MUSM/02/1)under the Ministry of Higher Education,Malaysia
文摘Objective: To identify commonly regulated genes in HPV-infected He La and Ca Ski cervical cancer cells treated with curcumin analogue 1,5-bis(2-hydroxyphenyl)-1,4-pentadiene-3-one(MS17) and to explore potential mechanisms that underlie its cytotoxic, anti-proliferative and apoptotic activity. Methods: He La and Ca Ski cells were treated with 2×EC50 and 3×EC50 doses of MS17 for 24 h and the RNA extracts were subjected to one-colour microarray-based gene expression profiling. Pair-wise significant genes(false discovery rate-corrected, P<0.05) were analysed for fold change(FC) compared to control samples. Differentially expressed genes with FC≥2.0(up-regulated; FC≥2.0 and down-regulated; FC≤-2.0) compared to the control samples were filtered through and analysed to create a global gene expression profile. Mutually regulated genes were ranked by FC and categorised by gene ontology. Results: Our data indicated dose-dependent regulation by MS17 and identified top 20 mutually upand down-regulated genes each in He La and Ca Ski cells. Amongst these 17 were commonly regulated in both cell lines. These include the up-regulation of CCL26, DEFB103 B, IL1 RL1, LY96, GCNT3, MMP10, MMP3, GADD45 G and HSPA6, and the down-regulation of TENM2, NEBL, KIFC1, CTDSP1, IGFBP5, LTBP1, NREP and MXD3. These genes were associated with key biological functions that were proposed to mediate the anticancer activity of MS17 in cervical cancer cells such as immune response, metabolic processes, proteolysis, programmed cell death, unfolded protein response, cell adhesion, cytoskeletal organisation, phosphatase activity, signal transduction and transcription regulator activity. Conclusions: Identification of seventeen common genes modulated by MS17 could be used as potential therapeutic targets in both cervical cancer cell lines and the findings of this study could be used to present an insight into the potential antitumor activity of MS17 in cervical cancer.
基金funded by the Fundamental Research Grant Scheme,Ministry of Higher Education Malaysia(No.FRGS/1/2016/STG01/UNIM/02/2)。
文摘Significance increase in dengue cases have been recorded worldwide every year and South East Asian countries have been badly affected.Currently,antiviral drug to treat dengue is still not available but papaya leaves extract(PLE)have been successfully used in treating dengue patients.Carpaine in PLE is the major active compounds that contributes to the anti-thrombocytopenic activity(raising platelet count in patient’s blood).The PLE also contains polyphenols that contribute to antioxidant properties.Studies were carried out to extract and quantify carpaine from young leaves,old leaves and stalks of papaya plant.Carpaine crystalline powders were successfully purified and confirmed by ^(1)H and ^(13)C NMR(Nuclear Magnetic Resonance).Young papaya leaves recorded significantly higher amount of carpaine(P<0.05)as compared with old leaves and stalks.Blending treatment showed significant effect(P<0.05)on the amount of carpaine extracted from the young and old leaves and blended young leaves showed significantly much higher amount of carpaine as compared with the unblended samples(P<0.05).In terms of total polyphenols content(TPC),young leaves(both unblended and blended samples)contained significantly higher amount of TPC(P<0.05)followed by the old leaves and stalks.Results also showed relationship between the TPC and the 1,1-diphenyl-2-picrylhydrazyl(DPPH)assay scavenging activities namely IC_(50)(R^(2)=0.9743)and acid equivalent antioxidant capacity(AEAC)(R^(2)=0.9581).Both young and old leaves also showed significantly higher(P<0.05)DPPH scavenging activities as compared with the stalks in both unblended and blended samples.Young papaya leaves were recommended as source of material to extract carpaine for future development of drug in dengue treatment.
基金Universiti Putra Malaysia for funding the present work[grant no.:IPM-9595500 and IPS-9688500]financing the first author’s postgraduate studies(Graduate Research Fellowship)MARDI Bagan Datuk Station for supplying the coconuts.
文摘Coconut water(CW)is a popular natural hydration drink in tropical countries.It is rich in essential electrolytes,vitamins,minerals,and bioactive compounds with functional properties.Therefore,this work aimed to evaluate the functional properties(i.e.,antioxidant and anti-aging activities)and to determine selected bioactive compounds in young and mature CW from the four most popular coconut varieties in Malaysia namely,Aromatic Green Dwarf(PDN),Malaysian Yellow Dwarf(MYD),MATAG(MYD×Tagnanan)and MAWA(MYD×West African Tall).Spectrophotometric and liquid chromatography methods were used to quantify the changes in the tested parameters.It is shown that the quantification of selected bioactive compounds and functional activities of CW displayed a mixed pattern at different maturation.Results from antioxidant,anti-aging activities,amino acids profile and bioactive compounds such as gallic acid,catechin,trans-zeatin,and dihydrozeatin were measured to decrease with the coconuts’maturation.Meanwhile,the amount of kinetin,kinetin riboside and trans-zeatin riboside increased with the maturation of the coconuts.Specifically,CW from young MYD showed the highest antioxidant and anti-aging activities and possessed diverse bioactive compounds that could serve as novel sources of natural functional ingredients targeted for skin anti-aging.In addition,the sensory evaluation showed that the taste of young and mature CW is acceptable for consumption with the young PDN,young MYD and mature MYD displaying the highest score.To the best of our knowledge,the present work reported the first attempt to elucidate the inhibitory activities of CW towards elastase and collagenase enzymes.
基金This work was supported by the Malaysia Fundamental Research Grant Scheme(FRGS19-041-0649 or FRGS/1/2018/STG04/UIAM/03/1)of Ministry of Higher Education Malaysiathe Research University Grant(vote number 9328200)of Universiti Putra Malaysia.
文摘Some of the common practices to assess the composition of plant extract,including Carica papaya seed extract(CPSE)are direct injection of the extract,compound separation using polyethylene glycol capillary column(DB-WAX),and non-linear-temperature programming(NLTP)of GC/MS analysis.This study specifically compared the coating of capillary column,sample derivatization,and temperature programming of GC/MS to determine the composition of CPSE.The retention indices(RI)of the detected compounds were determined and compared to the reference RI.In particular,5%phenyl-95%methylpolysiloxane(HP-5MS)-,DB-WAX-,and biscyanopropyl polysiloxane(HP-88)-coated capillary columns were used to identify the composition of CPSE.For this study,HP-5MS column,which separated the highest number of compounds(26 compounds)from CPSE,was deemed as the most suitable column.The GC/MS analysis of derivatized CPSE identified 21 compound groups,where fatty acids and fatty acid methyl esters served as the major compounds(80.23%),followed by these compounds in decreasing order:amides>nitriles>sterols>fatty aldehydes>organic acids.A stronger correlation determination between the carbon number and alkane retention time of linear-temperature programming(LTP)(R^(2)=0.9859)was found,as compared to its correlation determination with NLTP(R^(2)=0.9175),which exhibited an almost equal RI of LTP to the reference RI.Conclusively,GC/MS analysis for the derivatized CPSE using HP-5MS column separation and LTP is highly recommended.
