The drugs extending healthspan in clinic have always been searched.Nitazoxanide is an FDA-approved clinical antiprotozoal drug.Nitazoxanide is rapidly metabolized to tizoxanide after absorption in vivo.Our previous st...The drugs extending healthspan in clinic have always been searched.Nitazoxanide is an FDA-approved clinical antiprotozoal drug.Nitazoxanide is rapidly metabolized to tizoxanide after absorption in vivo.Our previous studies find that nitazoxanide and its metabolite tizoxanide induce mild mitochondrial uncoupling and activate cellular AMPK,oral nitazoxanide protects against experimental hyperlipidemia,hepatic steatosis,and atherosclerosis.Here,we demonstrate that both nitazoxanide and tizoxanide extend the lifespan and healthspan of Caenorhabditis elegans through Akt/AMPK/sir 2.1/daf16 pathway.Additionally,both nitazoxanide and tizoxanide improve high glucose-induced shortening of C.elegans lifespan.Nitazoxanide has been a clinical drug with a good safety profile,we suggest that it is a novel anti-aging drug.展开更多
Lipid metabolism disorders contribute to hyperlipidemia and hepatic steatosis.It is ideal to develop drugs simultaneous improving both hyperlipidemia and hepatic steatosis.Nitazoxanide is an FDA-approved oral antiprot...Lipid metabolism disorders contribute to hyperlipidemia and hepatic steatosis.It is ideal to develop drugs simultaneous improving both hyperlipidemia and hepatic steatosis.Nitazoxanide is an FDA-approved oral antiprotozoal drug with excellent pharmacokinetic and safety profile.We found that nitazoxanide and its metabolite tizoxanide induced mild mitochondrial uncoupling and subsequently activated AMPK in Hep G2 cells.Gavage administration of nitazoxanide inhibited high-fat diet(HFD)-induced increases of liver weight,blood and liver lipids,and ameliorated HFD-induced renal lipid accumulation in hamsters.Nitazoxanide significantly improved HFD-induced histopathologic changes of hamster livers.In the hamsters with pre-existing hyperlipidemia and hepatic steatosis,nitazoxanide also showed therapeutic effect.Gavage administration of nitazoxanide improved HFD-induced hepatic steatosis in C57BL/6J mice and western diet(WD)-induced hepatic steatosis in Apoe-/-mice.The present study suggests that repurposing nitazoxanide as a drug for hyperlipidemia and hepatic steatosis treatment is promising.展开更多
基金supported by the National Natural Science Foundation of China(Nos.82373864 and 82170472).
文摘The drugs extending healthspan in clinic have always been searched.Nitazoxanide is an FDA-approved clinical antiprotozoal drug.Nitazoxanide is rapidly metabolized to tizoxanide after absorption in vivo.Our previous studies find that nitazoxanide and its metabolite tizoxanide induce mild mitochondrial uncoupling and activate cellular AMPK,oral nitazoxanide protects against experimental hyperlipidemia,hepatic steatosis,and atherosclerosis.Here,we demonstrate that both nitazoxanide and tizoxanide extend the lifespan and healthspan of Caenorhabditis elegans through Akt/AMPK/sir 2.1/daf16 pathway.Additionally,both nitazoxanide and tizoxanide improve high glucose-induced shortening of C.elegans lifespan.Nitazoxanide has been a clinical drug with a good safety profile,we suggest that it is a novel anti-aging drug.
基金supported by the National Natural Science Foundation of China(Nos.81773725 and 91739102)。
文摘Lipid metabolism disorders contribute to hyperlipidemia and hepatic steatosis.It is ideal to develop drugs simultaneous improving both hyperlipidemia and hepatic steatosis.Nitazoxanide is an FDA-approved oral antiprotozoal drug with excellent pharmacokinetic and safety profile.We found that nitazoxanide and its metabolite tizoxanide induced mild mitochondrial uncoupling and subsequently activated AMPK in Hep G2 cells.Gavage administration of nitazoxanide inhibited high-fat diet(HFD)-induced increases of liver weight,blood and liver lipids,and ameliorated HFD-induced renal lipid accumulation in hamsters.Nitazoxanide significantly improved HFD-induced histopathologic changes of hamster livers.In the hamsters with pre-existing hyperlipidemia and hepatic steatosis,nitazoxanide also showed therapeutic effect.Gavage administration of nitazoxanide improved HFD-induced hepatic steatosis in C57BL/6J mice and western diet(WD)-induced hepatic steatosis in Apoe-/-mice.The present study suggests that repurposing nitazoxanide as a drug for hyperlipidemia and hepatic steatosis treatment is promising.
