1.Impact of magnolol on liver injury in rats with severe acute pancreatitis by regulating RIPK1/RIPK3/MLKL signaling pathway
Guanghua CHEN ; Zonglin PANG ; Yunxin YANG ; Hui LI
Chinese Journal of Immunology 2025;41(7):1700-1704,1713
Objective:To investigate the impact of magnolol(MG)on liver injury in rats with severe acute pancreatitis(SAP)through receptor interacting protein kinase(RIPK)1/RIPK3/mixed lineage kinase domain-like protein(MLKL)signaling pathway and its mechanism.Methods:The SAP rat model was induced by sodium taurocholate.The rats were randomly grouped into sham operation group(Sham group),model group(SAP group),MG group,RIPK1 inhibitor Necrostatin-1 group(Nec-1 group),and magnolol+RIPK1 inhibitor Necrostatin-1 group(MG+Nec-1 group).The pathological tissue morphology of pancreas and liver were observed by HE staining;the apoptosis rate of hepatocyte was observed by TUNEL staining;an automated biochemical analyzer was used to deter-mine serum ALT,AST and AMY contents;ELISA kits were used to detect the contents of TNF-α,IL-1β and IL-6;Western blot was used to detect the protein expression levels of p-RIPK1,RIPK1,p-RIPK3,RIPK3,p-MLKL and MLKL.Results:Compared with Sham group,pancreatic and hepatic cells in SAP group had edema and hemorrhage,and inflammatory cells increased,the expression levels of serum ALT,AST,AMY,TNF-α,IL-1β,IL-6,and p-RIPK1/RIPK1,p-RIPK3/RIPK3,p-MLKL/MLKL ratio in liver tissue were obviously increased(P<0.05).Compared with SAP group,pancreatic and liver injury in MG group and Nec-1 group were obviously reduced,the expression levels of serum ALT,AST,AMY,TNF-α,IL-1β,IL-6 and p-RIPK1/RIPK1,p-RIPK3/RIPK3,p-MLKL/MLKL ratio in liver tissue were obviously decreased(P<0.05),the MG and Nec-1 groups showed no significant differences in any measured indices(P>0.05);the effect on SAP in MG+Nec-1 group was better than that in MG group and Nec-1 group.Conclu-sion:MG can alleviate liver injury in SAP rats by inhibiting RIPK1/RIPK3/MLKL signaling pathway.
2.Impact of magnolol on liver injury in rats with severe acute pancreatitis by regulating RIPK1/RIPK3/MLKL signaling pathway
Guanghua CHEN ; Zonglin PANG ; Yunxin YANG ; Hui LI
Chinese Journal of Immunology 2025;41(7):1700-1704,1713
Objective:To investigate the impact of magnolol(MG)on liver injury in rats with severe acute pancreatitis(SAP)through receptor interacting protein kinase(RIPK)1/RIPK3/mixed lineage kinase domain-like protein(MLKL)signaling pathway and its mechanism.Methods:The SAP rat model was induced by sodium taurocholate.The rats were randomly grouped into sham operation group(Sham group),model group(SAP group),MG group,RIPK1 inhibitor Necrostatin-1 group(Nec-1 group),and magnolol+RIPK1 inhibitor Necrostatin-1 group(MG+Nec-1 group).The pathological tissue morphology of pancreas and liver were observed by HE staining;the apoptosis rate of hepatocyte was observed by TUNEL staining;an automated biochemical analyzer was used to deter-mine serum ALT,AST and AMY contents;ELISA kits were used to detect the contents of TNF-α,IL-1β and IL-6;Western blot was used to detect the protein expression levels of p-RIPK1,RIPK1,p-RIPK3,RIPK3,p-MLKL and MLKL.Results:Compared with Sham group,pancreatic and hepatic cells in SAP group had edema and hemorrhage,and inflammatory cells increased,the expression levels of serum ALT,AST,AMY,TNF-α,IL-1β,IL-6,and p-RIPK1/RIPK1,p-RIPK3/RIPK3,p-MLKL/MLKL ratio in liver tissue were obviously increased(P<0.05).Compared with SAP group,pancreatic and liver injury in MG group and Nec-1 group were obviously reduced,the expression levels of serum ALT,AST,AMY,TNF-α,IL-1β,IL-6 and p-RIPK1/RIPK1,p-RIPK3/RIPK3,p-MLKL/MLKL ratio in liver tissue were obviously decreased(P<0.05),the MG and Nec-1 groups showed no significant differences in any measured indices(P>0.05);the effect on SAP in MG+Nec-1 group was better than that in MG group and Nec-1 group.Conclu-sion:MG can alleviate liver injury in SAP rats by inhibiting RIPK1/RIPK3/MLKL signaling pathway.

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