Compatibility with Fructus Ligustri Lucidi Effectively Mitigates Idiosyncratic Liver Injury of Epimedii Folium by Modulating NOD-like Receptor Family Pyrin Domain Containing 3 Inflammasome ActivationOACSTPCD
Compatibility with Fructus Ligustri Lucidi Effectively Mitigates Idiosyncratic Liver Injury of Epimedii Folium by Modulating NOD-like Receptor Family Pyrin Domain Containing 3 Inflammasome Activation
Background:Idiosyncratic drug-induced liver injury(IDILI)is a serious side effect of drugs,Epimedii Folium(EF)is unequivocally implicated in idiosyncratic liver injury onset,potentially due to its ability to perturb the NOD-like receptor family pyrin domain containing 3(NLRP3)inflammasome.Fructus Ligustri Lucidi(FLL),a frequently used medicinal combination with EF,has not yet been investigated for its ability to ameliorate EF-associated hepatotoxicity.Aims and Objectives:Study on the mechanism of compatibility of FLL to alleviate liver injury caused by EF.Materials and Methods:Western blot was used to determine the expression of related proteins,ELISA was used to detect the secretion of related inflammatory factors IL-1β,IL-18,IL-6 and TNF-α,liver injury indexes were detected and liver pathological tissue staining was used to evaluate the liver injury.Results:Our results demonstrated that EF exerted a particular augmenting effect on the stimulation of the NLRP3 inflammasome mediated by nigericin or ATP,whereas FLL suppressed the NLRP3 inflammasome stimulation.Furthermore,an equal EF to FLL ratio significantly reduced the stimulatory effects of EF.Moreover,EF has the potential to induce hepatic injury and augment pro-inflammatory cytokine synthesis in rats subjected to LPS.However,when combined with FLL,the detrimental effects of EF were mitigated.Conclusions:FLL possesses the capacity to attenuate EF-associated hepatotoxicity by suppressing EF-triggered NLRP3 inflammasome activation.Thus,FLL holds promise for improving the clinical safety profile of EF,shedding light on the potential of compatibility and detoxification theories in traditional Chinese medicine.
Xiao-Mei Zhao;Yu-Rong Li;Zhao-Fang Bai;Xiao-He Xiao;Zhi-Xin Wu;Yan Wang;Ying-Jie Xu;Ye Xiu;Xu Dong;Jun-Jie Li;Gui-Ji Lv;Si-Hao Wang
Department of Pharmacy,Chengdu University of Traditional Chinese Medicine,Chengdu,China||Department of Hepatology,The Fifth Medical Center of PLA General Hospital,Beijing,ChinaDepartment of Military Patient Management,The Fifth Medical Center of PLA General Hospital,Beijing,ChinaDepartment of Hepatology,The Fifth Medical Center of PLA General Hospital,Beijing,China||Department of Hepatology,China Military Institute of Chinese Materia,The Fifth Medical Center of PLA General Hospital,Beijing,China||Department of Hepatology,National Key Laboratory of Kidney Diseases,Beijing,ChinaDepartment of Pharmacy,Chengdu University of Traditional Chinese Medicine,Chengdu,China||Department of Hepatology,The Fifth Medical Center of PLA General Hospital,Beijing,China||Department of Hepatology,China Military Institute of Chinese Materia,The Fifth Medical Center of PLA General Hospital,Beijing,China||Department of Hepatology,National Key Laboratory of Kidney Diseases,Beijing,ChinaDepartment of Hepatology,The Fifth Medical Center of PLA General Hospital,Beijing,China
Epimedii FoliumFructus Ligustri Lucidiidiosyncratic drug-induced liver injuryNOD-like receptor family pyrin domain containing 3 inflammasometraditional Chinese medicine
《世界中医药杂志（英文版）》 2024 (002)
159-170 / 12
This work was supported by the State Key Program of National Natural Science of China(81930110),Military Logistics Research Project on Health Special Project(23BJZ33),and the Key Project at Central Government Level:The ability establishment of sustainable use for valuable Chinese medicine resources(2060302).
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