Four Isosteroidal Alkaloids from Fritillaria Alleviate Lipopolysaccharide-Induced Inflammation in vitro and in vivo through MyD88-and TRIF-Dependent Signaling PathwaysOA
Objective:To investigate the anti-inflammatory effects and mechanisms of action of4 steroidal alkaloids(ebeiedinone,imperialine,chuanbeinone,and peimisine)in Fritillaria.Methods:This study established a lipopolysaccharide(LPS)-induced inflammatory model using mouse leukemia cells of monocyte macrophage(RAW 264.7)cells.The cell toxicity,nitric oxide(NO)release,expression levels of inflammatory factors,and expression levels of anti-inflammatory mechanism proteins and mRNA of ebeiedinone,imperialine,chuanbeinone,and peimisine on RAW 264.7 cells were detected by cell counting kit-8(CCK8)assay,Griess assay,enzyme-linked immunosorbent assay,Western blot,and real-time quantitative PCR,respectively.An acute lung injury(ALI)rat model was established.Hematoxylin and eosin staining was used to observe the morphological and pathological characteristics of lung tissue in each group of rats.The expression levels of inflammatory factors and anti-inflammatory mechanism proteins and mRNA in the ALI rat model induced by the 2 alkaloids(ebeiedinone,peimisine)were detected.Results:The 4 alkaloids reduced the release of NO,downregulated the expression of pro-inflammatory factors,regulated the expressions of the TIR domaincontaining adapter protein inducing interferon-beta(TRIF),myeloid differentiation factor 88(MyD88),nuclear factor kappa-B(NF-κB),and mitogen-activated protein kinases(MAPKs)signaling pathways in LPS-induced RAW 264.7 cells,exerting an anti-inflammatory effect(P<0.05 or P<0.01).Ebeiedinone and peomisine improved pulmonary edema and inflammation levels,regulated the expressions of MyD88,NF-κB,and MAPKs signaling pathways in the ALI rat model,exerting anti-inflammatory effects(P<0.05 or P<0.01).Conclusion:The 4 alkaloids of Fritillaria exert anti-inflammatory effects in vivo and in vitro through MyD88-and TRIF-dependent signaling pathways,thereby protecting rats from ALI.
AGA Er-bu;PAI Ming-xin;ZHANG Meng-rui;TSE Wai Ming;TSE Kathy Wai Gaun;LUO You-fu;YE Ben-gui
State Key Laboratory of Biotherapy and Cancer Center,West China Hospital,West China Medical School,Sichuan University,Chengdu,610041,China Medical College of Xizang University,Lhasa,850002,ChinaKey Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry,Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology,West China School of Pharmacy,Sichuan University,Chengdu,610041,ChinaKey Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry,Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology,West China School of Pharmacy,Sichuan University,Chengdu,610041,ChinaNin Jiom Medicine Manufactory(H.K.)Limited,Hong Kong SAR,999077,ChinaNin Jiom Medicine Manufactory(H.K.)Limited,Hong Kong SAR,999077,ChinaState Key Laboratory of Biotherapy and Cancer Center,West China Hospital,West China Medical School,Sichuan University,Chengdu,610041,ChinaMedical College of Xizang University,Lhasa,850002,China Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry,Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology,West China School of Pharmacy,Sichuan University,Chengdu,610041,China
医药卫生
Fritillariaisosteroidal alkaloidsmouse leukemia cells of monocyte macrophageinflammationlipopolysaccharide
《Chinese Journal of Integrative Medicine》 2026 (1)
P.54-63,10
Supported by the Major Science and Technology Research Project in the Science and Technology Projects of Xizang Axtonomoxs Region,China(Nos.XZ202301ZY0009G,XZ202201ZD0001G01/06)。
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