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丹参酮IIA的抗炎和抗吸收活性减轻实验性牙周炎小鼠的牙槽骨破坏。

Anti-inflammatory and antiresorptive activities of tanshinone-IIA mitigate alveolar bone destruction in mice with experimental periodontitis.

作者信息

Pavanelli Angelica Leticia Reis, Vieira Sâmmea Martins, Marcantonio Camila Chierici, Faria Gisele, Tetradis Sotirios, de Souza Pedro Paulo Chaves, Cirelli Joni Augusto, de Molon Rafael Scaf

机构信息

Department of Diagnosis and Surgery, São Paulo State University, School of Dentistry at Araraquara, Araraquara, São Paulo, Brazil.

Department of Restorative Dentistry, São Paulo State University, School of Dentistry at Araraquara, Araraquara, São Paulo, Brazil.

出版信息

J Periodontol. 2025 Jul 15. doi: 10.1002/JPER.24-0618.

Abstract

BACKGROUND

Periodontitis is a chronic inflammatory condition that leads to progressive destruction of the alveolar bone. Currently, there is a lack of effective adjuvant treatments to nonsurgical periodontal therapy offering strong antiresorptive properties. Tanshinone IIA (T-IIA), a lipophilic compound derived from Salvia miltiorrhiza, exhibits various biological properties. This study investigates the antiresorptive activity of tanshinone as an adjuvant therapy for periodontitis.

METHODS

Forty 8-week-old male C57BL6/J mice were randomly assigned to four experimental groups: control (C), periodontitis (P), T-IIA, and sodium tanshinone IIA sulfonate (STS). The C group did not undergo experimental periodontitis, while the P, T-IIA, and STS groups were induced with periodontitis by placing ligatures around the first maxillary molars bilaterally. Tanshinones (40 mg/kg) were administered daily via oral gavage immediately following ligature placement for 10 days. The P group received only the vehicle solution. Microcomputed tomography (micro-CT) and histological, immunohistochemical, and real-time quantitative polymerase chain reaction (RT-qPCR) analyses were performed.

RESULTS

T-IIA and STS significantly reduced the infiltration of inflammatory cells in the connective tissue and increased the percentage of fibroblasts. This treatment also mitigated alveolar bone loss caused by ligature placement compared to the P group, enhancing bone mineral density and improving bone architectural parameters. The T-IIA and STS groups effectively lowered the number of osteoclasts and significantly downregulated the production of IL-1β, IL-17, and MMP-13. The mRNA level of cathepsin K was significantly reduced in the STS group compared to the P and T-IIA groups, whereas IL-1β, TNF-α, and RANKL were not statistically different among groups.

CONCLUSION

Our findings demonstrate that T-IIA and STS prevent periodontitis-induced bone loss by controlling inflammation and inhibiting osteoclastogenesis. This suggests that these compounds possess dual antiresorptive and anti-inflammatory properties, making them promising novel therapeutic agents for treating periodontitis.

PLAIN LANGUAGE SUMMARY

Periodontitis is a serious gum disease that damages the bone supporting teeth, often leading to tooth loss. While current treatments aim to clean the affected areas, they do not always prevent further bone damage. In this study, we explored whether tanshinone IIA, a natural compound from a traditional medicinal plant, could offer extra protection against bone loss. We worked with mice to mimic human gum disease by placing small threads around their teeth to cause inflammation and bone loss. The mice were divided into four groups: one received no treatment, another had untreated periodontitis, and two groups were given different forms of tanshinone IIA for 10 days. We then examined their bones, tissues, and key markers of inflammation and bone damage. Mice treated with tanshinone IIA showed less inflammation, improved bone structure, and fewer cells that break down bone. The treatments also reduced harmful proteins linked to inflammation and tissue damage. These findings suggest that tanshinone IIA helps protect the bone by reducing inflammation and preventing excessive bone breakdown. Our research highlights tanshinone IIA as a potential new therapy for periodontitis. By targeting both inflammation and bone loss, this compound could be an interesting alternative to manage experimental periodontitis.

摘要

背景

牙周炎是一种慢性炎症性疾病,会导致牙槽骨的渐进性破坏。目前,非手术牙周治疗缺乏具有强大抗吸收特性的有效辅助治疗方法。丹参酮IIA(T-IIA)是一种从丹参中提取的亲脂性化合物,具有多种生物学特性。本研究调查了丹参酮作为牙周炎辅助治疗的抗吸收活性。

方法

将40只8周龄雄性C57BL6/J小鼠随机分为四个实验组:对照组(C)、牙周炎组(P)、T-IIA组和丹参酮IIA磺酸钠(STS)组。C组未进行实验性牙周炎,而P组、T-IIA组和STS组通过双侧在上颌第一磨牙周围放置结扎丝诱导牙周炎。在放置结扎丝后立即每天通过口服灌胃给予丹参酮(40mg/kg),持续10天。P组仅接受赋形剂溶液。进行了微型计算机断层扫描(micro-CT)以及组织学、免疫组织化学和实时定量聚合酶链反应(RT-qPCR)分析。

结果

T-IIA和STS显著减少了结缔组织中炎性细胞的浸润,并增加了成纤维细胞的百分比。与P组相比,这种治疗还减轻了结扎丝放置引起的牙槽骨丧失,提高了骨矿物质密度并改善了骨结构参数。T-IIA组和STS组有效降低了破骨细胞的数量,并显著下调了IL-1β、IL-17和MMP-13的产生。与P组和T-IIA组相比,STS组组织蛋白酶K的mRNA水平显著降低,而IL-1β、TNF-α和RANKL在各组之间无统计学差异。

结论

我们的研究结果表明,T-IIA和STS通过控制炎症和抑制破骨细胞生成来预防牙周炎引起的骨质流失。这表明这些化合物具有双重抗吸收和抗炎特性,使其成为治疗牙周炎的有前景的新型治疗药物。

通俗易懂的总结

牙周炎是一种严重的牙龈疾病,会损害支撑牙齿的骨骼,常常导致牙齿脱落。虽然目前的治疗旨在清洁受影响的区域,但它们并不总是能防止进一步的骨损伤。在这项研究中,我们探讨了一种来自传统药用植物的天然化合物丹参酮IIA是否能提供额外的抗骨质流失保护。我们用小鼠通过在它们的牙齿周围放置细线来模拟人类牙龈疾病,以引起炎症和骨质流失。小鼠被分为四组:一组不接受治疗,另一组患有未经治疗的牙周炎,两组给予不同形式的丹参酮IIA,持续10天。然后我们检查了它们的骨骼、组织以及炎症和骨损伤的关键标志物。用丹参酮IIA治疗的小鼠炎症较少,骨结构改善,分解骨骼的细胞较少。这些治疗还减少了与炎症和组织损伤相关的有害蛋白质。这些发现表明,丹参酮IIA通过减少炎症和防止过度的骨质分解来帮助保护骨骼。我们的研究突出了丹参酮IIA作为牙周炎潜在新疗法的地位。通过针对炎症和骨质流失,这种化合物可能是治疗实验性牙周炎的一个有趣的替代方法。

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