OBJECTIVE:To investigate the effects of Jinlida granules(津力达颗粒,JLD)on body weight,glucose tolerance,intestinal inflammation and barrier function in high-fat diet(HFD)-induced obese rats and explore the regulation...OBJECTIVE:To investigate the effects of Jinlida granules(津力达颗粒,JLD)on body weight,glucose tolerance,intestinal inflammation and barrier function in high-fat diet(HFD)-induced obese rats and explore the regulation of the gut microbiota as a potential treatment mechanism.METHODS:Sprague-Dawley rats were divided into control,HFD,low-dose JLD(L-JLD),high-dose JLD(HJLD),and sitagliptin groups.The rats,with the exception of those in the control group,were fed a HFD to establish an obesity model while simultaneously receiving 0.5%carboxymethyl cellulose,L-JLD,H-JLD or sitagliptin for 25 weeks.We assessed body weight,conducted oral glucose tolerance tests,and analysed faecal samples using metagenomic sequencing.Haematoxylin-eosin(HE),Masson and immunohistochemical(IHC)staining were employed to evaluate histological changes in the colon tissue.Immunofluorescence(IF)staining was used to measure the expression levels of Zonula occludens-1(ZO-1)and Claudin-1 in colon tissue.The colon tissue was also subjected to transcriptomic evaluation.RESULTS:JLD treatment significantly reduced body weight and enhanced glucose tolerance in obese rats.It alleviated colonic tissue damage,decreased collagen deposition,inhibited macrophage infiltration,and increased the expression of the tight junction proteins ZO-1 and Claudin-1.Metagenomic analysis revealed JLDinduced shifts in the gut microbiota composition(increasing the abundance of Turicibacter,Faecalibaculum,Coriobacteriaceae and Lactobacillus reuteri),enriching beneficial bacteria and metabolic pathways(increasing the biosynthesis of various secondary metabolites,ascorbate and aldarate metabolism,oxidative phosphorylation,C5-branched dibasic acid metabolism and beta-alanine metabolism).Transcriptomic analysis revealed downregulation of inflammatory and immune pathways(inhibition of the tumour necrosis factor signalling pathway,advanced glycation end products-receptor for advanced glycation end products signalling pathway,toll-like receptor signalling pathway,and interleukin-17 signalling pathway),suggesting a comprehensive modulatory effect of JLD on intestinal health and metabolic function.CONCLUSIONS:JLD granules effectively improve glucose tolerance and ameliorate obesity-related intestinal dysfunctions in HFD-induced obese rats.These benefits are likely mediated through the modulation of the gut microbiota,the suppression of intestinal inflammation,the enhancement of barrier function,and the attenuation of proinflammatory pathways.Our findings offer novel insights into the therapeutic potential of JLD,emphasizing its role in integrating gut microbiota management into the treatment of metabolic disorders.展开更多
基金Supported by the National Key Research and Development Program'Modernization Research of Traditional Chinese Medicine':Cardiovascular Event Chain(Metabolic Syndrome,Atherosclerosis,Myocardial Infarction,Arrhythmia,Heart Failure)(No.2017YFC700500)the Key R&D Program of Hebei:Traditional Chinese Medicine Innovation Project:Clinical Research on the Treatment of Diabetes Foot with Collateral Drugs and the Mechanism of Its Influence on Collateral Vessel Reconstruction(No.223777155D)+1 种基金the Scientific Research Project of Hebei Provincial Administration of Traditional Chinese Medicine:Clinical Study on Jinlida Granules in Treating Intestinal Dysfunction of diabetes and Its Effect on Short Chain Fatty Acids(No.2023179)the Scientific Research Project of Hebei Provincial Administration of Traditional Chinese Medicine:Clinical Study on Tongluo Therapy for Diabetes Foot and Its Influence on Microcirculation(No.2018200)。
文摘OBJECTIVE:To investigate the effects of Jinlida granules(津力达颗粒,JLD)on body weight,glucose tolerance,intestinal inflammation and barrier function in high-fat diet(HFD)-induced obese rats and explore the regulation of the gut microbiota as a potential treatment mechanism.METHODS:Sprague-Dawley rats were divided into control,HFD,low-dose JLD(L-JLD),high-dose JLD(HJLD),and sitagliptin groups.The rats,with the exception of those in the control group,were fed a HFD to establish an obesity model while simultaneously receiving 0.5%carboxymethyl cellulose,L-JLD,H-JLD or sitagliptin for 25 weeks.We assessed body weight,conducted oral glucose tolerance tests,and analysed faecal samples using metagenomic sequencing.Haematoxylin-eosin(HE),Masson and immunohistochemical(IHC)staining were employed to evaluate histological changes in the colon tissue.Immunofluorescence(IF)staining was used to measure the expression levels of Zonula occludens-1(ZO-1)and Claudin-1 in colon tissue.The colon tissue was also subjected to transcriptomic evaluation.RESULTS:JLD treatment significantly reduced body weight and enhanced glucose tolerance in obese rats.It alleviated colonic tissue damage,decreased collagen deposition,inhibited macrophage infiltration,and increased the expression of the tight junction proteins ZO-1 and Claudin-1.Metagenomic analysis revealed JLDinduced shifts in the gut microbiota composition(increasing the abundance of Turicibacter,Faecalibaculum,Coriobacteriaceae and Lactobacillus reuteri),enriching beneficial bacteria and metabolic pathways(increasing the biosynthesis of various secondary metabolites,ascorbate and aldarate metabolism,oxidative phosphorylation,C5-branched dibasic acid metabolism and beta-alanine metabolism).Transcriptomic analysis revealed downregulation of inflammatory and immune pathways(inhibition of the tumour necrosis factor signalling pathway,advanced glycation end products-receptor for advanced glycation end products signalling pathway,toll-like receptor signalling pathway,and interleukin-17 signalling pathway),suggesting a comprehensive modulatory effect of JLD on intestinal health and metabolic function.CONCLUSIONS:JLD granules effectively improve glucose tolerance and ameliorate obesity-related intestinal dysfunctions in HFD-induced obese rats.These benefits are likely mediated through the modulation of the gut microbiota,the suppression of intestinal inflammation,the enhancement of barrier function,and the attenuation of proinflammatory pathways.Our findings offer novel insights into the therapeutic potential of JLD,emphasizing its role in integrating gut microbiota management into the treatment of metabolic disorders.
