AUTHOR=Gao Yuan , Shi Wei , Tu Can , Li Peng , Zhao Guanyu , Xiao Xiaohe , Wang Jiabo , Bai Zhaofang 

TITLE=Immunostimulatory activity and structure-activity relationship of epimedin B from Epimedium brevicornu Maxim.

JOURNAL=Frontiers in Pharmacology

VOLUME=Volume 13 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2022.1015846

DOI=10.3389/fphar.2022.1015846

ISSN=1663-9812

ABSTRACT=Epimedii Folium (EF), a herbal and dietary supplement, is famous for treating bone fractures, joint diseases, and several chronic illnesses. However, some studies indicated that EF could induce idiosyncratic drug-induced liver injury (IDILI) in the clinic. The NLRP3 inflammasome plays a crucial role in the pathogenesis of various human diseases, including IDILI. In the present study, we showed that epimedin B, a major unhydrolyzed flavonoid glycoside of EF, could specifically facilitate nigericin- or ATP-induced NLRP3 inflammasome activation under synergistic induction of mitochondrial reactive oxygen species. Moreover, epimedin B resulted in activation of Caspase-1 and IL-1β secretion in a lipopolysaccharide (LPS)-mediated susceptibility mouse model. MCC950 pretreatment completely abrogated activation of the NLRP3 inflammasome and prevented liver injury. Importantly, several studies have confirmed that a hydrolyzed flavonoid of EF could enhance activation of the NLRP3 inflammasome and may be involved in the pathogenesis of EF-IDILI. No reports are available on whether the structure-activity relationship associated with the immunostimulatory activity in EF contributes to the pathogenesis of EF-IDILI. These findings have changed our conventional understanding about the more glycogen, the more immunostimulatory activity.