Notopterol, an active component isolated from the
traditional Chinese medicine Notopterygium incisum
Ting ex H.T. Chang, exerts anti-inflammatory activity in
rheumatoid arthritis. However, its roles in suppression of inflammatory insults and halting progression of tissue destruction in
periodontitis remain elusive. In this study, we reveal that
notopterol can inhibit osteoclastogenesis, thereby limiting
alveolar bone loss in vivo. In vitro results demonstrated that
notopterol administration inhibited synthesis of inflammatory mediators such as IL-1β, IL-32, and
IL-8 in LPS-stimulated human gingival fibroblasts. Mechanistically,
notopterol inhibits activation of the NF-κB signaling pathway, which is considered a prototypical proinflammatory signaling pathway.
RNA sequencing data revealed that
notopterol activates the PI3K/
protein kinase B (Akt)/
NF-E2-related factor 2 (Nrf2) signaling pathway in LPS-stimulated human gingival fibroblasts, a phenomenon validated via Western blot assay. Additionally,
notopterol treatment suppressed
reactive oxygen species levels by upregulating the expression of
antioxidant genes, including
heme oxygenase 1 (HO-1),
NAD(P)H
quinone oxidoreductase 1 (NQO1),
catalase (CAT), and
glutathione reductase (GSR), indicating that
notopterol confers protection against oxidative stress. Notably, inhibition of Akt activity by the potent inhibitor,
MK-2206, partially attenuated both anti-inflammatory and
antioxidant effects of
notopterol. Collectively, these results raise the possibility that
notopterol relieves periodontal
inflammation by suppressing and activating the NF-κB and PI3K/AKT/Nrf2 signaling pathways in periodontal tissue, respectively, suggesting its potential as an efficacious treatment
therapy for
periodontitis.