Oral Ecology Research Group, Faculty of Dentistry, Laval University, Quebec City, QC, Canada.
J Periodontol. 2013 May;84(5):704-11. doi: 10.1902/jop.2012.120118. Epub 2012 Aug 16.
Collinin is a secondary plant metabolite belonging to the class of geranyloxycoumarins. We explored the potential beneficial impact of collinin on periodontal health by investigating its effect on Porphyromonas gingivalis (P. gingivalis), lipopolysaccharide (LPS)-induced inflammatory response of macrophages, and osteoclastogenesis.
Collinin was synthesized from pyrogallol and propiolic acid. A microdilution assay was used to determine antibacterial activity of collinin. The effect of collinin on collagenase activity of P. gingivalis was determined using fluorescent collagen. Macrophages were treated with collinin before being stimulated with LPS. The secretion of interleukin-6, chemokine (C-C motif) ligand 5, and prostaglandin E2 was assessed by enzyme-linked immunosorbent assays (ELISA). The inhibitory effect of collinin on differentiation of human preosteoclastic cells was assessed by tartrate-resistant acid phosphatase staining, whereas the secretion of matrix metalloproteinase-9 (MMP-9) was measured by ELISA. Bone resorption activity was investigated by using a human bone plate coupled with an immunoassay that detected the release of collagen fragments.
Collinin inhibited the growth of P. gingivalis. The effect was more pronounced under iron-restricted conditions. Collinin dose dependently inhibited the degradation of type I collagen by P. gingivalis. It was also a potent inhibitor of the LPS-induced inflammatory response in macrophages and completely inhibited receptor activator of nuclear factor κB ligand-dependent osteoclast differentiation and MMP-9 secretion. Last, collinin affected bone degradation mediated by mature osteoclasts by significantly decreasing the release of collagen helical peptides.
Although clinical trials are required, data from these in vitro analyses support the potential of collinin as a therapeutic agent for treating inflammatory periodontitis associated with bone breakdown.
Collinin 是一种次级植物代谢物，属于香叶氧基香豆素类。我们通过研究其对牙龈卟啉单胞菌（P. gingivalis）、脂多糖（LPS）诱导的巨噬细胞炎症反应和破骨细胞形成的影响，探索了 Collinin 对牙周健康的潜在有益影响。
Collinin 由焦儿茶酚和丙炔酸合成。采用微量稀释法测定 Collinin 的抗菌活性。荧光胶原法测定 Collinin 对牙龈卟啉单胞菌胶原酶活性的影响。用 LPS 刺激巨噬细胞前用 Collinin 处理。通过酶联免疫吸附试验（ELISA）评估白细胞介素-6、趋化因子（C-C 基序）配体 5 和前列腺素 E2 的分泌。通过抗酒石酸酸性磷酸酶染色评估 Collinin 对人前破骨细胞分化的抑制作用，通过 ELISA 测量基质金属蛋白酶-9（MMP-9）的分泌。通过与免疫测定相结合的人骨板检测胶原片段释放来研究骨吸收活性。
Collinin 抑制牙龈卟啉单胞菌的生长。在缺铁条件下效果更为明显。Collinin 浓度依赖性地抑制牙龈卟啉单胞菌对 I 型胶原的降解。它也是 LPS 诱导的巨噬细胞炎症反应的有效抑制剂，完全抑制核因子 κB 受体激活剂配体依赖性破骨细胞分化和 MMP-9 分泌。最后，Collinin 通过显著减少胶原螺旋肽的释放来影响成熟破骨细胞介导的骨降解。
尽管需要临床试验，但这些体外分析的数据支持 Collinin 作为治疗与骨破坏相关的炎症性牙周炎的治疗剂的潜力。
