Mechanisms Of Shibawei Hezi Liniao Pulvis Improve Cognitive Impairment Induced By Glycolipid Metabolism Disorders

Glycolipid metabolism disorder is a nutritional and metabolic disease of livestock and poultry which is linked to the factors of environment,genetics,and diet.The mechanisms mainly exerting an effect on it could involve to biological processes,such as neuroendocrine disorders,inflammatory response,and oxidative stress.At the same time,central nervous system is damaged,which in turn induces brain cognitive impairment.Glycolipid metabolism disorders encephalopathy(GMDE)took place on livestock and poultry can affect behavior,inhibit the growth and development,deteriorate resistance,and increase risk of death.Which seriously undermines the production performance of livestock and poultry.Therefore,it is of great significance to explore new control and treatment solutions for GMDE for livestock and poultry farming.Shibawei hezi liniao pulvis(SHLP)is a classic Chinese herbal compound that is primarily cure kidney-related diseases,and also has effects such as alleviating disorders of glycolipid metabolism,antibacterial,and detoxification.Preliminary research from this study confirmed that SHLP can improve glucose and lipid levels of blood in rodents with GMDE,and oxidative stress-induced hippocampal neuronal damage has also been treated to some extent,but the specific regulatory effects and mechanism are elusive on GMDE.In this study,SD rats and porcine primary hippocampal neuronal cells were studied as research objects.Network pharmacology,molecular biology,and transcriptomics/proteomics were used to understand the regulatory effects and mechanisms of SHLP on cognitive impairment in animals with GMDE.It is expected to contribute new ideas to the prevention and control of GMDE,improving the production performance rate of livestock and poultry.It provides an experimental basis for the promotion and application of SHLP-relative ingredients in livestock and poultry farming.1.Based on Network Pharmacology,SHLP’s cognitive impairment targets in animals induced by glycolipid metabolism disorders were screened.SHLP contains more than 10 important herbs,including saffron,myrobalan,tribulus terrestris,cardamom,turmeric,etc.There are 31 active chemical components and 107 targets for the treatment of GMDE.Five core effective targets such as PTGS2,MMP9,MAPK14,MAPK3 and TLR4 were selected,which were mainly enriched in HIF signaling,Toll-like receptor signaling,TNF signaling and other pathways.SD rats and porcine primary hippocampal neuronal cells were used to verify key gene expression.The results showed that SHLP alleviated neuronal cell damage and activated inflammation response in the hippocampus of GMDE rats.Gene expression of PTGS2 in the brains of GMDE rats was also reduced(P<0.05).In addition,the activity of primary hippocampal neuronal cells induced by high glucose treatment was increased and the gene expression of PTGS2 and TLR4 were decreased after SHLP intervention(P<0.05).These results are consistent with network pharmacological predictions.2.To explore the improvement of SHLP on cognitive impairment in animals induced by glycolipid metabolism disorders.SHLP could effectively enhance the spatial localization learning and cognitive function in GMDE rats.Morphological observations showed that it reduced apoptosis and autophagy in neuronal cells.The results showed that SHLP could reduce neuronal cell damage in the hippocampal region of GMDE rats.At the same time,the expression of cognitive function-related proteins such as GFAP,PSD95,and Syn-1 in the hippocampus was up-regulated by SHLP(P<0.05).SHLP can also down-regulate the protein expression of Aβ1-42 and neuroimmune inflammation-related proteins such as IL-6,IL-1β,TNF-α,IL-1α and i NOS(P<0.05)in the hippocampus of rats.After SHLP was treated with porcine primary hippocampal neurons induced by high glucose condition,the expression of neuroimmune inflammation-related proteins such as IL-6,TNF-α,IL-1β,IL-1α and i NOS in neuronal cells were decreased significantly(P<0.05),which was consistent with in vivo experiments.3.Combined transcriptomics/proteomics analysis of SHLP improvement mechanisms on cognitive impairment in animals induced by glycolipid metabolism disorders.SHLP limited the increase in blood glucose,fructosamine,and serum triglycerides in rats with glycolipid metabolism disorders(P<0.05).The medicine not only alleviated fatty liver formation but also improved learning and memory skills in GMDE rats.Transcriptomics/proteomics sequencing results found that SHLP could downregulate gene transcription levels of Cbln3,Fat2,Gabra6,Lcn2,Cnpy1,Lrg1,Crtam and Ahsg in rat hippocampal tissues with GMDE(P<0.05).The expression of proteins such as C3,Hpx,Itih3,Hba-a1,Hba-a2 were downregulated(P<0.05).The results of KEGG pathway analysis show that it can participate in the regulation of immune inflammation,neurodevelopment and glycolipid metabolism processes through multiple pathways such as RAGE signaling and PPAR signaling.Lrg1 was screened as a key molecular target for drug intervention,and was obtained based on the expression of the target protein and the PPI network of the RAGE signaling pathway.The cell results explained that synaptic function-related proteins in porcine primary hippocampal neuronal cells stimulated by high glucose,PSD95 expression was elevated by SHLP(P<0.01),and protein levels associated with LRG1 and RAGE signaling pathways were depressed by SHLP(P<0.01).In addition,silencing Lrg1 gene expression could also significantly increase PSD95 levels in cells(P<0.05),reduce RAGE protein expression(P<0.01),and inhibit p65 phosphorylation(P<0.01).Animal and cell experiments were consistent.The above results revealed that SHLP could alleviate cognitive impairment by targeting Lrg1 and then inhibiting the activation of the RAGE/NF-κB pathway.Conclusion SHLP can alleviate glycolipid metabolism disorders in GMDE rats,inhibit the inflammatory response in hippocampal neuronal cells,and improve the development process of GMDE in animals.This investigation provides a scientific theoretical basis for the development of effective chemical components of SHLP,and provides an experimental basis for livestock and poultry to prevent glycolipid metabolic diseases and improve production performance.