首页> 美国卫生研究院文献>Acta Pharmacologica Sinica >Plumbagin suppresses chronic periodontitis in rats via down-regulation of TNF-α IL-1β and IL-6 expression
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Plumbagin suppresses chronic periodontitis in rats via down-regulation of TNF-α IL-1β and IL-6 expression

机译:Plumbagin通过下调TNF-αIL-1β和IL-6表达抑制大鼠慢性牙周炎

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摘要

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−1·d−1, 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−1·d−1 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.
机译:慢性牙周炎(CP)是最常见的口腔疾病之一,它会导致成年人的牙槽骨吸收和牙齿脱落。在这项研究中,我们旨在研究plumbagin(PL)的潜力,plumbagin(PL)是一种从中草药Plumbago zeylanica L中提取的活性化合物,用于治疗CP。使用人牙周膜干细胞(PDLSC)进行体外研究,而通过结扎+牙龈卟啉单胞菌(Pg)刺激在SD大鼠中建立CP的动物模型。给大鼠静脉注射PL(2、4和6 mg·kg -1 ·d -1 ,ip)。用TNF-α(10 ng / mL)处理PDLSCs可以明显刺激促炎细胞因子TNF-α,IL-1β和IL-6以及趋化因子CCL-2和CCL-5的表达,这些剂量分别为-通过与PL(1.25-5μmol/ L)共同治疗可显着抑制。此外,PL(3.75μmol/ L)显着抑制了TNF-α诱导的PDLSCs中MAPK,NF-κB和JAK / STAT信号通路的激活。与体外研究一致,剂量为4 mg·kg -1 时,PL给药可明显降低CP大鼠牙龈中TNF-α,IL-1β和IL-6的表达。 ·d −1 显示最佳的抗炎作用。此外,PL给药可降低CP大鼠的骨质破坏,其表现为肺泡骨丢失(ABL)和H&E染色结果。总之,PL通过下调TNF-α,IL-1β和IL-6的表达并抑制MAPK,NF-κB和JAK / STAT信号通路来抑制大鼠CP的进展。

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