Plumbagin suppresses chronic periodontitis in rats via down-regulation of TNF-α, IL-1β and IL-6 expression

Abstract

Chronic periodontitis (CP) is one of the most common oral diseases, which causes alveolar bone absorption and tooth loss in adults. In this study we aimed to investigate the potential of plumbagin (PL), a widely-investigated active compound extracted from the traditional Chinese herb Plumbago zeylanica L in treating CP. Human periodontal ligament stem cells (PDLSCs) were used for in vitro studies, whereas an animal model of CP was established in SD rats by ligation+Porphyromonas gingivalis (Pg) stimulation. The rats were injected with PL (2, 4, and 6 mg·kg·d, ip) for 4 weeks. Treatment of PDLSCs with TNF-α (10 ng/mL) markedly stimulated the expression of the proinflammatory cytokines TNF-α, IL-1β and IL-6, as well as the chemokines CCL-2 and CCL-5, which were dose-dependently suppressed by co-treatment with PL (1.25-5 μmol/L). Furthermore, PL (3.75 μmol/L) markedly suppressed TNF-α-induced activation of the MAPK, NF-κB and JAK/STAT signaling pathways in PDLSCs. In consistence with the in vitro studies, PL administration significantly decreased the expression of TNF-α, IL-1β and IL-6 in gingiva of the rat with CP, with the dosage 4 mg·kg·d showing the best anti-inflammatory effect. Moreover, PL administration decelerated bone destruction in the rat with CP, evidenced by the aveolar bone loss (ABL) and H&E staining results. In conclusion, PL suppresses CP progression in rats by downregulating the expressions of TNF-α, IL-1β and IL-6 and inhibiting the MAPK, NF-κB and JAK/STAT signaling pathways.

Caspase-11 promotes renal fibrosis by stimulating IL-1β maturation via activating caspase-1

“…IL-1β is originally synthesized as an inactive precursor, pro-IL-1β [35,36]. The activation of pro-IL-1β relies on caspase-1, formerly called IL-1β-converting enzyme, which cleaves inactive pro-IL-1β into mature IL-1β [37].…”

Interleukin-1β is a potential therapeutic target for periodontitis: a narrative review

“…155 Plumbagin is extracted from the roots of Plumbago zeylanica L. It significantly decreases the expression of TNF-α, IL-1β and IL-6 and decelerates bone destruction in rats with chronic periodontitis. 156 Compared to the systemic antimicrobial agents or the chemical agent chlorhexidine gluconate, plant-derived substances partly avoid the problems of drug resistance, overdoses and a number of adverse effects. 157,158 Plant-derived substances have great potential as adjuvant therapy for periodontal diseases.…”

Treatment with Luteolin Improves Lipopolysaccharide-Induced Periodontal Diseases in Rats

“…Furthermore, TNF-α, together with IL-6, plays a crucial role in establishing the inflammatory state in periodontitis; therefore, they can be considered specific markers of the disease [ 23 ]. All of these considerations led us to investigate the levels of cytokines previously mentioned.…”