IL1B and periodontal disorder: Furthermore, during the treatment of apigenin on this cell models, LPS (1 μg/ml) and nicotine (5 mM) induced HO-1 protein expression and activities, further upregulating iNOS, COX-2, NO, PGE2, IL-1β, TNF-α, IL-6, and IL-12 by the PI3K/MAPK (P38, JNK, ERK)/PKC signaling pathway, indicating that apigenin possesses anti-inflammatory activity for the prevention and treatment of periodontal diseases associated with smoking and dental plaque (84).