Berberine Effects On Thermoregulation Of Hypothermia And Regulation Of UCP1 Gene Expression

Berberine(BBR)is a kind of isoquinoline alkaloids that used widely in clinical practice as effective antidiarrheal and antimicrobial drugs.In recent years,studies have shown that BBR can play a therapeutic role in cancer,inflammation,diabetes mellitus,dyslipidemias,cardiovascular disease,gastro-intestinal diseases and so on.Moreover,BBR also has the function of thermoregulation,and can inhibit the decrease of mouse body temperature in low temperature condition.This article discussed the BBR mechanism of inhibiting the mice body temperature decrease under cold stress and analyzed the changes of thermogenesis-related gene caused by BBR’s thermoregulation.And it also further analyzed the changes of uncoupling protein 1(UCP1),and intends to use the Ucp1 knockout mice to study the role of UCP1 changes to BBR’s thermoregulation and their causal relationship.In addition,this article further studied the mechanism of UCP1 changes caused by BBR.By adopting the primary cells of brown adipose tissue and HIB-1B cell lines,we analyzed the BBR effect on Ucp1 at the cellular level.In-depth study of BBR’s transcriptional regulation to UCP1,we build the green fluorescent protein recombinant plasmid containing mouse UCP1 gene promoter,and mutated its transcriptional regulatory elements(NFE2 and TATA box)to study the role of these elements.To study BBR effect on Ucp1 mRNA stability,we construct a reporter plasmid containing mouse Ucp1 cDNA,and by knockout its protection element poly A tail to study the berberine mechanism on Ucp1 mRNA stability.The results showed that,under cold stress,BBR could inhibit mice temperature decreasing and significantly increased Ucp1 mRNA and protein expression in brown adipose tissue.By combining to NFE2 enhancer in Ucp1 promoter,berberine could enhance the binding between NFE2 element and its binding protein NFE2L2,thereby directly promote UCP1 gene transcription starting.And berberine could also stabilize Ucp1 mRNA structure by poly A element.The results indicate that BBR could effect on UCP1 gene through nervous system.In conclusion,berberine could increase Ucp1 gene expression,elevate heat production,and eventually suppresse mice body temperature decreasing under cold stress.This paper provides a theoretical basis for studying BBR thermoregulation mechanism and the BBR complexity of gene expression regulation(especially Ucp1 expression).This possesses a certain theoretical and practical significance of body temperature adjusting and body potential protection under cold stress.