Department of Periodontology, Hospital of Stomatology, Jilin University, 1500 Tsinghua Road, Chaoyang District, Changchun 130021, China.
Department of Prosthodontics, Hospital of Stomatology, Jilin University, Changchun 130021, China.
Int J Mol Sci. 2023 Mar 28;24(7):6364. doi: 10.3390/ijms24076364.
Periodontitis is a long-term inflammatory illness and a leading contributor to tooth loss in humans. Due to the influence of the anatomic parameters of teeth, such as root bifurcation lesions and the depth of the periodontal pocket, basic periodontal treatment on its own often does not completely obliterate flora microorganisms. As a consequence, topical medication has become a significant supplement in the treatment of chronic periodontitis. Berberine (BBR) has various pharmacological effects, such as hypoglycemic, antitumor, antiarrhythmic, anti-inflammatory, etc. The target of our project is to develop a safe and non-toxic carrier that can effectively release berberine, which can significantly reduce periodontal tissue inflammation, and to investigate whether berberine thermosensitive hydrogel can exert anti-inflammatory and osteogenic effects by modulating phosphatifylinositol-3-kinase/Protein Kinase B (PI3K/AKT) signaling pathway. Consequently, firstly berberine temperature-sensitive hydrogel was prepared, and its characterizations showed that the mixed solution gelated within 3 min under 37 °C with a hole diameter of 10-130 µm, and the accumulation of berberine release amounted to 89.99% at 21 days. CCK-8 and live-dead cell staining results indicated that this hydrogel was not biotoxic, and it is also presumed that the optimum concentration of berberine is 5 µM, which was selected for subsequent experiments. Real-time polymerase chain reaction (qRT-PCR) and Western blotting (WB)results demonstrated that inflammatory factors, as well as protein levels, were significantly reduced in the berberine-loaded hydrogel group, and LY294002 (PI3K inhibitor) could enhance this effect ( < 0.05). In the berberine-loaded hydrogel group, osteogenesis-related factor levels and protein profiles were visibly increased, along with an increase in alkaline phosphatase expression, which was inhibited by LY294002 ( < 0.05). Therefore, berberine thermosensitive hydrogel may be an effective treatment for periodontitis, and it may exert anti-inflammatory and osteogenic effects through the PI3K/AKT signaling pathway.
牙周炎是一种长期的炎症性疾病，也是导致人类牙齿脱落的主要原因。由于牙齿解剖参数的影响，如根分叉病变和牙周袋深度，单纯的基础牙周治疗往往不能完全消灭菌群微生物。因此，局部用药已成为慢性牙周炎治疗的重要补充。小檗碱（BBR）具有降血糖、抗肿瘤、抗心律失常、抗炎等多种药理作用。我们项目的目标是开发一种安全无毒的载体，能够有效释放小檗碱，显著减轻牙周组织炎症，并研究小檗碱温敏水凝胶是否可以通过调节磷酸肌醇-3-激酶/蛋白激酶 B（PI3K/AKT）信号通路发挥抗炎和成骨作用。因此，首先制备了小檗碱温敏水凝胶，其特性表明，混合溶液在 37°C 下 3 分钟内凝胶化，孔径为 10-130µm，21 天内小檗碱累积释放量达到 89.99%。CCK-8 和死活细胞染色结果表明，该水凝胶无细胞毒性，推测小檗碱的最佳浓度为 5µM，用于后续实验。实时聚合酶链反应（qRT-PCR）和 Western blot（WB）结果表明，载小檗碱水凝胶组炎症因子和蛋白水平明显降低，PI3K 抑制剂 LY294002 可增强这种作用（<0.05）。在载小檗碱水凝胶组中，成骨相关因子水平和蛋白谱明显增加，碱性磷酸酶表达增加，LY294002 可抑制这种作用（<0.05）。因此，小檗碱温敏水凝胶可能是治疗牙周炎的一种有效方法，它可能通过 PI3K/AKT 信号通路发挥抗炎和成骨作用。
