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Therapeutic effect of pachymic acid on diethylnitrosamine induced hepatoma in rats by regulating Hippo signaling pathway
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DOI   10.11656/j.issn.1672-1519.2024.01.19
Key Words   pachymic acid;Hippo;diethylnitrosamine;liver cancer;therapeutic effects
Author NameAffiliation
SHI Mingliang No. 1 Department of General Surgery, The First Affiliated Hospital of Henan University, Kaifeng 475000 
WANG Xiaolei No. 1 Department of General Surgery, The First Affiliated Hospital of Henan University, Kaifeng 475000 
SHEN Yang No. 1 Department of General Surgery, The First Affiliated Hospital of Henan University, Kaifeng 475000 
ZHU Shuo No. 1 Department of General Surgery, The First Affiliated Hospital of Henan University, Kaifeng 475000 
WANG Hangyu Department of Gastroenterology, The First Affiliated Hospital of Henan University, Kaifeng 475000, China 
Abstract
    [Objective] To investigate the therapeutic effect of pachymic acid on diethylnitrosamine(DEN) induced hepatoma in rats by regulating Hippo signal pathway. [Methods] SD rats were randomly grouped into a control group,a model group,low-dose(3.5 mg/kg) pachymic acid group, middle dose (7 mg/kg) pachymic acid group, high-dose( 14 mg/kg) pachymic acid group, and fluorouracil(50 mg/kg) group,with 10 rats in each group. The liver cancer model was induced by intraperitoneal injection of DEN in the model group and the administration group rats,while the control group rats were intraperitoneally injected with an equal dose of 0.9% sodium chloride solution. After treatment with pachymic acid and fluorouracil,the serum levels of alanine transaminase(ALT) and aspartate transaminase(AST) were detected;the weight changes,liver index,number of liver surface cancer nodules,and maximum cancer nodule volume of rats in each group were measured;hematoxylin-eosin(HE) staining was applied to detect the pathological morphology of liver tissue of rats in each group and compare the number of inflammatory cell infiltration;the serum levels of inflammatory factors such as interleukin(IL)-6,IL-17,tumor necrosis factor-α(TNF-α) and oxidative stress factors such as superoxide dismutase(SOD), catalase(CAT) and malondialdehyde(MDA) were measured with the kits;Western Blot was applied to detect the expression of Hippo signaling pathway related proteins [Yes-related protein(YAP),LATS1] in the liver tissues of rats in each group. [Results] Compared with the control group,the liver tissue of the model group rats showed obvious carcinogenesis,weight after administration,the levels of serum SOD and CAT were obviously reduced (P<0.05), and the levels of serum ALT,AST,IL-6,IL-17,TNF-α and MDA,liver index,number of liver surface cancer nodules,maximum cancer nodule volume,number of inflammatory cell infiltratio,the protein expression of LATS1 in liver tissue,and p-YAP1/YAP1 were obviously increased(P<0.05);compared with the model group,the canceration symptoms of liver tissue of rats in the low,medium and high dose pachymic acid groups and the fluorouracil group were alleviated,weight after administration,and the levels of serum SOD and CAT were increased(P<0.05),and the levels of serum ALT,AST,IL-6,IL-17,TNF-α and MDA,liver index,number of liver surface cancer nodules,maximum cancer nodule volume,number of inflammatory cell infiltratio,the protein expression of LATS1 in liver tissue,and p-YAP1/YAP1 were decreased(P<0.05),pachymic acid groups were dose-dependent(P<0.05);there was no obvious difference in each index between the high dose pachymic acid group and the fluorouracil group(P>0.05). [Conclusion]Pachymic acid can reduce the activity of Hippo signaling pathway,inhibit DEN induced inflammation and oxidative stress,alleviate liver tissue damage and canceration symptoms in rats,and improve liver function in rats.

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