Sipeimine

Sipeimine (Imperialine) is an inhibitor targeting the PI3K/AKT/NF-κB pathway and NLRP3 inflammasome, which can competitively bind to PI3K and p65. Sipeimine inhibits PI3K/AKT phosphorylation, blocks NF-κB nuclear translocation and NLRP3 inflammasome activation. Sipeimine exerts anti-inflammatory activities, inhibits pyroptosis and ferroptosis, and protects the extracellular matrix. Sipeimine can reduce cartilage degradation and synovial inflammation in osteoarthritis and improve PM2.5-induced lung injury. Sipeimine is mainly used in the study of anti-inflammatory and degenerative diseases^[1][2]. In Vitro:Sipeimine (100 μM, 200 μM; 24-48 h) significantly reduces cell viability in mouse chondrocytes^[1].
Sipeimine (10-50 μM; 24 h) dose-dependently inhibits lipopolysaccharide (LPS)-induced cytotoxicity in the LDH release assay^[1].
Sipeimine (25 μM, 50 μM; 24 h) inhibits the mRNA and protein expression of proinflammatory factors (COX-2, iNOS, IL-1β, IL-18) in 1 μg/mL LPS-induced mouse chondrocytes and reduces PGE2 and nitrite production^[1].
Sipeimine (25 μM, 50 μM; 4 h) increases the extracellular matrix components (collagen-II, aggrecan) and reduces the protein expression of degradative enzymes (MMP-13, ADAMTS-5) in mouse chondrocytes in WB experiments^[1].
Sipeimine (50 μM; 2-24 h) inhibits LPS-induced NF-κB pathway activation (reduced p-IκBα, p-p65 phosphorylation and p65 nuclear translocation) and NLRP3 inflammasome-mediated cell pyroptosis (reduced NLRP3, ASC, cleaved-caspase-1, cleaved-GSDMD protein expression) in mouse chondrocytes^[1].
In Vivo:Sipeimine (30 mg/kg; intra-articular injection; once daily; 14 days) can reduce cartilage degradation, subchondral bone remodeling, synovial inflammation and extracellular matrix (ECM) degradation in the DMM-induced osteoarthritis (OA) mouse model^[1].
Sipeimine (15, 30 mg/kg; intraperitoneal injection; once daily; 3 days) can reduce lung tissue damage, pulmonary edema, inflammatory response, inhibit ferroptosis-related indicators (4-HNE, MDA, tissue iron) and upregulate antioxidant factors (GSH, Nrf2, GPX4, HO-1) in the PM2.5-induced lung injury Sprague-Dawley rat model^[1].