2-dodecyl-6-methoxycyclohexa-2,5-diene-1,4-dione isolated from Averrhoa carambola L. root ameliorates diabetic nephropathy by inhibiting the TLR4/MyD88/NF-κB pathway
2-dodecyl-6-methoxycyclohexa-2,5-diene-1,4-dione isolated from Averrhoa carambola L. root ameliorates diabetic nephropathy by inhibiting the TLR4/MyD88/NF-κB pathway
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从杨桃根中分离出的 2-十二烷基-6-甲氧基环己-2,5-二烯-1,4-二酮通过抑制 TLR4/MyD88/NF-kappa B 通路改善糖尿病肾病
DOI：
10.2147/dmso.s209436
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发表时间：
2019-01-01
期刊：
影响因子：
--
通讯作者：
Huang, Renbin
中科院分区：
文献类型：
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作者：
Lu, Shunyu;Zhang, Hongliang;Huang, Renbin
背景：杨桃是一种传统中药材，长期以来一直用于治疗糖尿病。我们以前的研究发现杨桃根中提取的2-dodecyl-6-methoxycyclohexa-2，5-diene-1，4-dione能改善糖尿病肾病，但其确切机制尚不清楚。方法：用链脲佐菌素100 mg/kg体重建立糖尿病肾病模型。糖尿病小鼠灌胃给予DMDD(12.5、25、50 mg/kg体重/d)后，测定体重和血糖。用生化分析仪检测血脂，包括总胆固醇、甘油三酯、高密度脂蛋白、低密度脂蛋白及肾功能指标血肌酐、尿素氮。用双抗体夹心法测定IL-6、TNF-α等炎性细胞因子水平。用电子显微镜观察肾脏超微结构的变化。Western印迹分析和RT-PCR检测TLR4、MyD88和NF-kappa B的蛋白表达和mRNA水平。结果：DMDD治疗可减轻糖尿病肾病大鼠的血糖、血肌酐和尿氮水平，增加足细胞的数量和密度，并改善血脂异常。DMDD可抑制糖尿病小鼠的炎症反应，下调TLR4/MyD88/NF-kappa B信号通路的表达，与TLR4-/-小鼠相比差异显著。结论：DMDD通过抑制TLR4/MyD88/NF-kappa B信号通路减轻糖尿病肾病的肾脏损害和炎症反应。
Background: Averrhoa carambola L. is a traditional medicinal herb that has long been used to treat diabetes. Our previous studies found that 2-dodecyl-6-methoxycyclohexa-2,5-diene-1,4-dione (DMDD) isolated from A. carambola L. roots could ameliorate diabetic nephropathy (DN), but its exact mechanism remains unclear.Methods: A DN model was established by streptozotocin (STZ, 100 mg/kg body weight) in TLR4 knockout (TLR4-/-, KO) mice and wild-type (WT) mice. Body weight and blood glucose were evaluated after oral administration of DMDD (12.5, 25, 50 mg/kg body weight/d) in diabetic mice. The levels of serum lipids, including TC, TG, HDL, and LDL and kidney function indexes Scr and BUN, were detected by biochemical equipment. The levels of inflammatory cytokines including IL-6 and TNF-alpha, were determined by ELISA kits. Furthermore, changes in renal ultrastructure were observed by electron microscopy. Western blot analysis and RT-PCR were used to assess the protein expression and mRNA levels of TLR4, MyD88 and NF-kappa B.Results: DMDD treatment attenuated diabetic nephropathy, as a result of a decline in blood glucose, serum creatinine, and blood urine nitrogen levels and an increase in the quantity and density of podocytes, combined with improved dyslipidaemia. DMDD treatment inhibited the inflammatory response and downregulated the expression of the TLR4/MyD88/NF-kappa B pathway in diabetic mice, and these changes were significantly different in TLR4-/- mice.Conclusion: DMDD alleviates diabetic nephropathy by mitigating kidney damage and inflammation via the inhibition of the TLR4/MyD88/NF-kappa B signalling pathway.