Hydroxysafflor yellow A protects against thioacetamide-induced liver fibrosis in rats via suppressing proinflammatory/fibrogenic mediators and promoting hepatic stellate cell senescence and apoptosis  

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作  者:Sayed H.Seif el-Din Olfat A.Hammam Shahira M.Ezzat Samira Saleh Marwa M.Safar Walaa H.El-Maadawy Naglaa M.El-Lakkany 

机构地区:[1]Pharmacology Department,Theodor Bilharz Research Institute,Warak El-Hadar,Imbaba P.O.Box 30,Giza 12411,Egypt [2]Pathology Department,Theodor Bilharz Research Institute,Warak El-Hadar,Imbaba P.O.Box 30,Giza 12411,Egypt [3]Pharmacognosy Department,Faculty of Pharmacy,Cairo University,Cairo 11562,Egypt [4]Pharmacognosy Department,Faculty of Pharmacy,October University for Modern Sciences and Arts,Giza,Egypt [5]Pharmacology and Toxicology Department,Faculty of Pharmacy,Cairo University,Cairo 11562,Egypt [6]Pharmacology and Biochemistry Department,Faculty of Pharmacy,The British University in Egypt,Cairo,Egypt

出  处:《Asian Pacific Journal of Tropical Biomedicine》2023年第8期348-358,共11页亚太热带生物医学杂志(英文版)

基  金:funded by Theodore Bilharz Research Institute (grant number:ID-MS-99/A,Principal investigator:Naglaa M.El-Lakkany).

摘  要:Objective:To evaluate the effect of hydroxysafflor yellow A(HSYA)on thioacetamide-induced liver fibrosis.Methods:Thioacetamide was administered to rats intraperitoneally in doses of 200 mg/kg twice a week for 12 weeks.Thioacetamide-intoxicated rats were given silymarin(50 mg/kg)or HSYA(5 mg/kg)orally every day for 8 weeks.Liver enzymes,fibrosis markers,histological changes as well as immunohistochemistry of TNF-α,IL-6,p21,α-SMA,and caspase-3 were examined.The effect of HSYA on HSC-T6 activation/proliferation and apoptosis was also determined in vitro.Results:HSYA decreased liver enzymes,TNF-α,IL-6,and p21 expressions,hepatic PDGF-B,TIMP-1,TGF-β1,and hydroxyproline levels,as well as fibrosis score(S2 vs.S4)compared to the thioacetamide group.HSYA also downregulatedα-SMA while increasing caspase-3 expression.Surprisingly,at 500μg/mL,HSYA had only a slightly suppressive effect on HSC proliferation,with a 9.5%reduction.However,it significantly reduced TGF-β1,inhibitedα-SMA expression,induced caspase-3 expression,and promoted cell senescence.Conclusions:HSYA may be a potential therapeutic agent for delaying and reversing the progression of liver fibrosis.More research on HSYA at higher doses and for a longer period is warranted.

关 键 词:Hydroxysafflor yellow A THIOACETAMIDE Hepatic stellate cells Inflammatory markers Liver fibrosis p21 α-SMA APOPTOSIS 

分 类 号:R285.5[医药卫生—中药学]

 

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