A Novel Modified-Curcumin Promotes Resolvin-Like Activity and Reduces Bone Loss in Diabetes-Induced Experimental Periodontitis.
A Novel Modified-Curcumin Promotes Resolvin-Like Activity and Reduces Bone Loss in Diabetes-Induced Experimental Periodontitis.
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DOI：
10.2147/jir.s330157
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发表时间：
2021
影响因子：
4.5
通讯作者：
Gu Y
中科院分区：
文献类型：
--
作者：
Deng J;Golub LM;Lee HM;Raja V;Johnson F;Kucine A;Lee W;Xu TM;Gu Y
临床上，糖尿病患者合并牙周炎的治疗具有挑战性。从生物化学角度来看，两者都涉及范围广泛的炎症/胶原溶解疾病，并以“双向方式”相互加剧。然而，这类牙周炎的标准治疗依赖于减少细菌负担，而不是控制过度炎症/过度胶原溶解。因此，迫切需要新的治疗策略来调节这种过度的宿主反应并促进炎症的消退。本研究的目的是评价一种新型化学修饰的姜黄素2.24 （CMC2.24）对糖尿病大鼠宿主炎症反应的影响。链脲佐菌素诱导1型糖尿病；牙周损伤是高血糖不受控制的并发症。非糖尿病大鼠作为对照。糖尿病患者每日口服灌胃CMC2.24或单独给药3周。Micro-CT用于分析形态学变化和量化骨质流失。明胶酶谱法分析MMPs。细胞迁移法检测细胞功能，酶联免疫吸附法检测细胞因子和溶解蛋白。在这个严重炎症疾病模型中，多效性CMC2.24被发现使腹膜渗出液中巨噬细胞的过度积累和趋化活性受损正常化，显著降低MMP-9和促炎细胞因子至接近正常水平，并显著增加巯基乙酸盐诱导的腹膜渗出液（tPE）中的溶解蛋白D1 （RvD1）水平。在非诱导腹膜常驻冲洗（rPW）中，观察到对MMPs和RvD1的类似影响。在临床相关性方面，CMC2.24显著抑制牙槽骨高度、体积和矿物质密度的损失（即糖尿病引起的牙周炎和骨质疏松症）。综上所述，CMC2.24（一种三酮苯胺羰基姜黄素）治疗高血糖糖尿病大鼠，除了抑制胶原溶解MMPs和促炎细胞因子外，还能促进局部和全身炎症的消退，减少骨质流失，为治疗牙周炎合并其他慢性疾病提供了一种新的治疗策略。
Clinically, it is challenging to manage diabetic patients with periodontitis. Biochemically, both involve a wide range of inflammatory/collagenolytic conditions which exacerbate each other in a “bi-directional manner.” However, standard treatments for this type of periodontitis rely on reducing the bacterial burden and less on controlling hyper-inflammation/excessive-collagenolysis. Thus, there is a crucial need for new therapeutic strategies to modulate this excessive host response and to promote enhanced resolution of inflammation. The aim of the current study is to evaluate the impact of a novel chemically-modified curcumin 2.24 (CMC2.24) on host inflammatory response in diabetic rats. Type I diabetes was induced by streptozotocin injection; periodontal breakdown then results as a complication of uncontrolled hyperglycemia. Non-diabetic rats served as controls. CMC2.24, or the vehicle-alone, was administered by oral gavage daily for 3 weeks to the diabetics. Micro-CT was used to analyze morphometric changes and quantify bone loss. MMPs were analyzed by gelatin zymography. Cell function was examined by cell migration assay, and cytokines and resolvins were measured by ELISA. In this severe inflammatory disease model, administration of the pleiotropic CMC2.24 was found to normalize the excessive accumulation and impaired chemotactic activity of macrophages in peritoneal exudates, significantly decrease MMP-9 and pro-inflammatory cytokines to near normal levels, and markedly increase resolvin D1 (RvD1) levels in the thioglycolate-elicited peritoneal exudates (tPE). Similar effects on MMPs and RvD1 were observed in the non-elicited resident peritoneal washes (rPW). Regarding clinical relevance, CMC2.24 significantly inhibited the loss of alveolar bone height, volume and mineral density (ie, diabetes-induced periodontitis and osteoporosis). In conclusion, treating hyperglycemic diabetic rats with CMC2.24 (a tri-ketonic phenylaminocarbonyl curcumin) promotes the resolution of local and systemic inflammation, reduces bone loss, in addition to suppressing collagenolytic MMPs and pro-inflammatory cytokines, suggesting a novel therapeutic strategy for treating periodontitis complicated by other chronic diseases.