以中链甘油三酯为油相制备乳液,将天然高分子与小分子表面活性剂复配,构建阿拉伯胶(gum arabic,GA)或乳清分离蛋白(whey protein isolate,WPI)与吐温80(T80)的复合乳液界面。采用逐层添加或混合添加的方式,调控界面组分的吸附次序,构建...以中链甘油三酯为油相制备乳液,将天然高分子与小分子表面活性剂复配,构建阿拉伯胶(gum arabic,GA)或乳清分离蛋白(whey protein isolate,WPI)与吐温80(T80)的复合乳液界面。采用逐层添加或混合添加的方式,调控界面组分的吸附次序,构建不同界面结构的乳液体系。采用体外模拟小肠消化模型和界面流变技术等手段剖析乳液界面结构对脂肪消化速率的影响。结果表明:对于GA、WPI和T80形成的单一乳液体系,GA和WPI的界面弹性模量高于T80界面,黏弹性好。三者抗胆盐取代和延缓脂肪消化能力依次为GA<WPI<T80。在大分子GA或WPI与小分子T80形成的复合乳液体系中,由T80吸附占主导的界面,其延缓脂肪消化和界面抗胆盐取代的能力优于GA或WPI与T80共同吸附的界面结构。展开更多
OBJECTIVE Cisplatin is a formidable chemotherapy agent widely applying in antineoplastic treatments,but its side effects often limit the clinical usage.Metabolic disorders are one of the side effects induced by cispla...OBJECTIVE Cisplatin is a formidable chemotherapy agent widely applying in antineoplastic treatments,but its side effects often limit the clinical usage.Metabolic disorders are one of the side effects induced by cisplatin,which closely relate to the onset of chemotherapy-induced anorexia(CIA)in cancer patients but lacks effective controls.Liujunzi decoction(LJZD)is a traditional Chinese formula that has a promising effect in treating CIA.However,whether LJZD ameliorates CIA through adjusting cisplatin-induced metabolic disorders remain unknow.The present study evaluated the mechanism of cisplatin-induced metabolic disorders,and the effect of LJZD in ameliorating these disturbances.METHODS 42 male Sprague-Dawley(SD)rats(180-220 g)were randomly divided into 3 groups:normal control group(distilled water+saline),model group(distilled water+cisplatin),LJZD group(4.8 g·kg^(-1)Liujunzi decoction ingredients+cisplatin).Intragastrical administered each drug twice a day(7∶00-19∶00)since day 0 for 4 d,animals were intraperitoneal injected with cisplatin 6 mg·kg^(-1)1 h after administration while normal control groups were injected with same volume of saline.On day 3,each group was anesthetized with pentobarbital sodium 45 mg·kg^(-1)(ip),and blood samples were collected from aorta abdominalis.Then the samples were analyzed using an LC-ESI-MS/MS system.Significantly regulated metabolites between groups were determined by VIP≥1 and absolute Log2FC(fold change)≥1.Identified metabolites were mapped to Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway database using Metaboanalyst 5.0(https://www.metaboanalyst.ca/).RESULTS A total of 133,77 and 32 differential metabolites were filtrated in control vs model,control vs LJZD and model vs LJZD groups respectively.Comparing to control,the levels of hexadecanoic acid(Log2FC=6.3153),linoleic acid(Log2FC=5.3478),and 8,11-icosadienoic acid(Log2FC=5.2342)significantly increased,and the levels of N-acetyl-L-tyrosine(Log2FC=-2.6283),cinnamic acid(Log2FC=-2.3381),N-acetylphenylalanine(Log2FC=-2.2501)significantly decreased in model group.The KEGG pathway enrichments of these metabolites indicated that,cisplatin-induced metabolic disorders by disturbing metabolism pathways such as linoleic acid metabolism,biosynthesis of unsaturated fatty acids,and phenylalanine metabolism,which suggested that the onset of CIA was partly associated with the metabolic disorders of linoleic acid,unsaturated fatty acids,and phenylalanine.Compared to control,treatment of LJZD significantly increased the levels of 4-hydroxytryptamine(Log2FC=12.0186),hexadecanoic acid(Log2FC=5.7412),linoleic acid(Log2FC=5.1877)and significantly decreased the levels of N-acetylmethionine(Log2FC=-1.7317),2-aminoethanesulfinic acid(Log2FC=-1.6578),N-acetyl-L-tyrosine(Log2FC=-1.5355).And comparing to the model group,4-hydroxytryptamine(Log2FC=12.0186),7,12-diketocholic acid(Log2FC=2.0998),N-acetylneuraminic acid(Log2FC=2.0560)markedly increased,and 3-hydroxy-3-methylpentane-1(Log2FC=-1.9202),5-dioic acid(Log2FC=-1.7166),N-isovaleroylglycine,hexanoyl glycine(Log2FC=-1.4958)markedly decreased in LJZD group.It was worth noting that,there were 23 differential metabolites filtrated both in control vs model and model vs LJZD groups,which were the key metabolites of LJZD in treating CIA.Among these 23 common metabolites,there were 16 metabolites excluding the control vs LJZD group,that was,LJZD had no effect in normal rats while being able to ameliorated cisplatin-induced metabolic disorders by regulating these 16 metabolites.Cisplatin-induced downregulation of 11 metabolites such as hydrocinnamic acid,(±)12(13)epoxy-9Z-octadecenoic acid,cinnamic acid were upregulated after LJZD treatment,and cisplatin-induced upregulation of imidazoleacetic acid,2′-deoxycytidine-5′-monophosphate and other 5 metabolites were downregulated by LJZD.The KEGG pathway analysis indicated that the linoleic acid metabolism,histidine metabolism,and pyrimidine metabolism were the most enriched metabolic pathway.Thus,cisplatin-induced metabolic disturbances mainly by disturbing linoleic acid metabolism,histidine metabolism,and pyrimidine metabolism,and LJZD interacted with these metabolic pathways to reduce metabolic disorders and thus ameliorated CIA.CONCLUSION Cisplatin-induced anorexia was closely related to the metabolic disorders of linoleic acid metabolism,biosynthesis of unsaturated fatty acids,and phenylalanine metabolism.The mechanism of LJZD in ameliorating CIA was in concerned with the metabolic adjustments,relating to the regulation of linoleic acid metabolism,histidine metabolism,and pyrimidine metabolism.展开更多
文摘以中链甘油三酯为油相制备乳液,将天然高分子与小分子表面活性剂复配,构建阿拉伯胶(gum arabic,GA)或乳清分离蛋白(whey protein isolate,WPI)与吐温80(T80)的复合乳液界面。采用逐层添加或混合添加的方式,调控界面组分的吸附次序,构建不同界面结构的乳液体系。采用体外模拟小肠消化模型和界面流变技术等手段剖析乳液界面结构对脂肪消化速率的影响。结果表明:对于GA、WPI和T80形成的单一乳液体系,GA和WPI的界面弹性模量高于T80界面,黏弹性好。三者抗胆盐取代和延缓脂肪消化能力依次为GA<WPI<T80。在大分子GA或WPI与小分子T80形成的复合乳液体系中,由T80吸附占主导的界面,其延缓脂肪消化和界面抗胆盐取代的能力优于GA或WPI与T80共同吸附的界面结构。
基金National Natural Science Foundation of China(82174143)and Scientific Research Foundation of Guangdong Pharmaceutical University(51348136)。
文摘OBJECTIVE Cisplatin is a formidable chemotherapy agent widely applying in antineoplastic treatments,but its side effects often limit the clinical usage.Metabolic disorders are one of the side effects induced by cisplatin,which closely relate to the onset of chemotherapy-induced anorexia(CIA)in cancer patients but lacks effective controls.Liujunzi decoction(LJZD)is a traditional Chinese formula that has a promising effect in treating CIA.However,whether LJZD ameliorates CIA through adjusting cisplatin-induced metabolic disorders remain unknow.The present study evaluated the mechanism of cisplatin-induced metabolic disorders,and the effect of LJZD in ameliorating these disturbances.METHODS 42 male Sprague-Dawley(SD)rats(180-220 g)were randomly divided into 3 groups:normal control group(distilled water+saline),model group(distilled water+cisplatin),LJZD group(4.8 g·kg^(-1)Liujunzi decoction ingredients+cisplatin).Intragastrical administered each drug twice a day(7∶00-19∶00)since day 0 for 4 d,animals were intraperitoneal injected with cisplatin 6 mg·kg^(-1)1 h after administration while normal control groups were injected with same volume of saline.On day 3,each group was anesthetized with pentobarbital sodium 45 mg·kg^(-1)(ip),and blood samples were collected from aorta abdominalis.Then the samples were analyzed using an LC-ESI-MS/MS system.Significantly regulated metabolites between groups were determined by VIP≥1 and absolute Log2FC(fold change)≥1.Identified metabolites were mapped to Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway database using Metaboanalyst 5.0(https://www.metaboanalyst.ca/).RESULTS A total of 133,77 and 32 differential metabolites were filtrated in control vs model,control vs LJZD and model vs LJZD groups respectively.Comparing to control,the levels of hexadecanoic acid(Log2FC=6.3153),linoleic acid(Log2FC=5.3478),and 8,11-icosadienoic acid(Log2FC=5.2342)significantly increased,and the levels of N-acetyl-L-tyrosine(Log2FC=-2.6283),cinnamic acid(Log2FC=-2.3381),N-acetylphenylalanine(Log2FC=-2.2501)significantly decreased in model group.The KEGG pathway enrichments of these metabolites indicated that,cisplatin-induced metabolic disorders by disturbing metabolism pathways such as linoleic acid metabolism,biosynthesis of unsaturated fatty acids,and phenylalanine metabolism,which suggested that the onset of CIA was partly associated with the metabolic disorders of linoleic acid,unsaturated fatty acids,and phenylalanine.Compared to control,treatment of LJZD significantly increased the levels of 4-hydroxytryptamine(Log2FC=12.0186),hexadecanoic acid(Log2FC=5.7412),linoleic acid(Log2FC=5.1877)and significantly decreased the levels of N-acetylmethionine(Log2FC=-1.7317),2-aminoethanesulfinic acid(Log2FC=-1.6578),N-acetyl-L-tyrosine(Log2FC=-1.5355).And comparing to the model group,4-hydroxytryptamine(Log2FC=12.0186),7,12-diketocholic acid(Log2FC=2.0998),N-acetylneuraminic acid(Log2FC=2.0560)markedly increased,and 3-hydroxy-3-methylpentane-1(Log2FC=-1.9202),5-dioic acid(Log2FC=-1.7166),N-isovaleroylglycine,hexanoyl glycine(Log2FC=-1.4958)markedly decreased in LJZD group.It was worth noting that,there were 23 differential metabolites filtrated both in control vs model and model vs LJZD groups,which were the key metabolites of LJZD in treating CIA.Among these 23 common metabolites,there were 16 metabolites excluding the control vs LJZD group,that was,LJZD had no effect in normal rats while being able to ameliorated cisplatin-induced metabolic disorders by regulating these 16 metabolites.Cisplatin-induced downregulation of 11 metabolites such as hydrocinnamic acid,(±)12(13)epoxy-9Z-octadecenoic acid,cinnamic acid were upregulated after LJZD treatment,and cisplatin-induced upregulation of imidazoleacetic acid,2′-deoxycytidine-5′-monophosphate and other 5 metabolites were downregulated by LJZD.The KEGG pathway analysis indicated that the linoleic acid metabolism,histidine metabolism,and pyrimidine metabolism were the most enriched metabolic pathway.Thus,cisplatin-induced metabolic disturbances mainly by disturbing linoleic acid metabolism,histidine metabolism,and pyrimidine metabolism,and LJZD interacted with these metabolic pathways to reduce metabolic disorders and thus ameliorated CIA.CONCLUSION Cisplatin-induced anorexia was closely related to the metabolic disorders of linoleic acid metabolism,biosynthesis of unsaturated fatty acids,and phenylalanine metabolism.The mechanism of LJZD in ameliorating CIA was in concerned with the metabolic adjustments,relating to the regulation of linoleic acid metabolism,histidine metabolism,and pyrimidine metabolism.
