The liver is an important metabolic organ and controls lipid, glucose and energy metabolism. Dysruption of hepatic lipid metabolism is often associated with fatty liver diseases, including nonalcoholic fatty liver dis...The liver is an important metabolic organ and controls lipid, glucose and energy metabolism. Dysruption of hepatic lipid metabolism is often associated with fatty liver diseases, including nonalcoholic fatty liver disease(NAFLD), alcoholic fatty liver diseases(AFLD) and hyperlipidemia. Recent studies have uncovered the contribution of hormones, transcription factors, and inflammatory cytokines to the pathogenesis of dyslipidemia and fatty liver diseases. Moreover, a significant amount of effort has been put to examine the mechanisms underlying the potential therapeutic effects of many natural plant products on fatty liver diseases and metabolic diseases. We review the current understanding of insulin, thyroid hormone and inflammatory cytokines in regulating hepatic lipid metabolism, focusing on several essential transcription regulators, such as Sirtuins(SIRTs), Forkhead box O(FoxO), Sterol-regulatory element-binding proteins(SREBPs). We also discuss a few representative natural products with promising thereapeutic effects on fatty liver disease and dyslipidemia.展开更多
Flavonoids have been reported to exert protective effect against many inflammatory diseases, while the underlying cellular mechanisms are still not completely known. In the present study, we explored the anti-inflamma...Flavonoids have been reported to exert protective effect against many inflammatory diseases, while the underlying cellular mechanisms are still not completely known. In the present study, we explored the anti-inflammation activity of 5, 7, 2', 4', 5'-pentamethoxyflavanone(abbreviated as Pen.), a kind of polymethoxylated flavonoid, both in vitro and in vivo experiments. Pen. was showed no obvious toxicity in macrophages even at high dosage treatment. Our results indicated that Pen. significantly inhibited both mR NA and protein level of proinflammatory cytokines, IL-1β, IL-6, TNF-α and iN OS, which was characteristic expressed on M1 polarized macrophages. These effects of Pen. were further confirmed by diminished expression of CD11c, the M1 macrophage surface marker. Further researches showed that the mechanism was due to that Pen. downregulated the activity of p65, key transcription factor for M1 polarization. On the other hand, Pen. also enhanced M2 polarization with upregulation of anti-inflammatory factors and increase of M2 macrophage surface markers, which lead to the balance of M1 and M2 macrophages. Moreover, in vivo research verified that Pen. treatment alleviated LPS-induced sepsis in mice by increasing survival rate, decreasing inflammatory cytokines and improving lung tissue damage. In summary, our results suggested that Pen. modulated macrophage phenotype via suppressing p65 signal pathway to exert the anti-inflammation activity.展开更多
基金National Natural Science Foundation of China(Nos.81673487,81872917)National Key R&D Program of China(No.2017YFA0506000)+3 种基金National Science&Technology Major Project“Key New Drug Creation and Manufacturing Program”(No.2018ZX09201002)“The Drug Innovation Major Project”of National Science&Technology Ministry(No.2018ZX09711001-003-007)The Open Project of State Key Laboratory of Natural Medicines(No.SKLNMKF202003)partially supported by VA Merit Award I01BX004-033 and Research Career Scientist Award(No.IK6BX004477)。
文摘The liver is an important metabolic organ and controls lipid, glucose and energy metabolism. Dysruption of hepatic lipid metabolism is often associated with fatty liver diseases, including nonalcoholic fatty liver disease(NAFLD), alcoholic fatty liver diseases(AFLD) and hyperlipidemia. Recent studies have uncovered the contribution of hormones, transcription factors, and inflammatory cytokines to the pathogenesis of dyslipidemia and fatty liver diseases. Moreover, a significant amount of effort has been put to examine the mechanisms underlying the potential therapeutic effects of many natural plant products on fatty liver diseases and metabolic diseases. We review the current understanding of insulin, thyroid hormone and inflammatory cytokines in regulating hepatic lipid metabolism, focusing on several essential transcription regulators, such as Sirtuins(SIRTs), Forkhead box O(FoxO), Sterol-regulatory element-binding proteins(SREBPs). We also discuss a few representative natural products with promising thereapeutic effects on fatty liver disease and dyslipidemia.
基金supported by the National Natural Science Foundation of China(Nos.81872916,81673487,and 81473221)"The Drug Innovation Major Project" of National Science & Technology Ministry(No.2018ZX09711001-003-007)+1 种基金the Natural Science Foundation of Jiangsu Province(No.BK20161399)the Fundamental Research Funds for the Central Universities(No.020814380118)
文摘Flavonoids have been reported to exert protective effect against many inflammatory diseases, while the underlying cellular mechanisms are still not completely known. In the present study, we explored the anti-inflammation activity of 5, 7, 2', 4', 5'-pentamethoxyflavanone(abbreviated as Pen.), a kind of polymethoxylated flavonoid, both in vitro and in vivo experiments. Pen. was showed no obvious toxicity in macrophages even at high dosage treatment. Our results indicated that Pen. significantly inhibited both mR NA and protein level of proinflammatory cytokines, IL-1β, IL-6, TNF-α and iN OS, which was characteristic expressed on M1 polarized macrophages. These effects of Pen. were further confirmed by diminished expression of CD11c, the M1 macrophage surface marker. Further researches showed that the mechanism was due to that Pen. downregulated the activity of p65, key transcription factor for M1 polarization. On the other hand, Pen. also enhanced M2 polarization with upregulation of anti-inflammatory factors and increase of M2 macrophage surface markers, which lead to the balance of M1 and M2 macrophages. Moreover, in vivo research verified that Pen. treatment alleviated LPS-induced sepsis in mice by increasing survival rate, decreasing inflammatory cytokines and improving lung tissue damage. In summary, our results suggested that Pen. modulated macrophage phenotype via suppressing p65 signal pathway to exert the anti-inflammation activity.
