Kintoko Kintoko, Xu Xiaohui, Lin Xing, Jiao Yang, Wen Qingwei, Chen Zhaoni, Wei Jinbin, Liang Tao, Huang Renbin
Pharmaceutical College, Guangxi Medical University, Guangxi, China.
Arch Med Sci. 2018 Aug;14(5):1163-1172. doi: 10.5114/aoms.2016.63285. Epub 2016 Oct 26.
Diabetes mellitus is characterized by hyperglycaemia causing changes in plasma lipoproteins, which leads to insulin resistance, secretion defects or both. The present study aimed to evaluate the ability of 2-dodecyl-6-methoxy-cyclohexa-2,5-diene-1,4-dione (DMDD) isolated from L. roots to lower hyperglycaemia and to investigate its potential mechanism in diabetic mice.
DMDD was isolated using a column chromatographic technique. Experimental mice were fed with a high-fat diet for a month and were intravenously injected with streptozotocin (80 mg/kg, single dose). Diabetic mice were orally administered DMDD (12.5, 25, 50 mg/kg) and 50 mg/kg pioglitazone for 15 days. Fasting blood glucose (FBG), fasting blood insulin (FINS), pancreatic insulin content, interleukin-6 (IL-6), tumour necrosis factor-α (TNF-α), as well as serum total cholesterol (TC), triglyceride (TG) and free fatty acid (FFA) were determined. Adipose tissue was assessed by histological examination, immunohistochemistry, western blot and reverse transcription-polymerase chain reaction methods.
DMDD significantly increased the insulin level (all < 0.05). In contrast, FBG, IL-6, TNF-α, TC, TG and FFA were significantly decreased (all < 0.05). However, DMDD induced the activation of adipocyte peroxisome proliferator-activated receptor γ (PPAR-γ), confirmed by increased protein and mRNA expression of PPAR-γ.
DMDD possessed hypoglycaemic activity due to its potential mechanism involving PPARγ-mediated adipocyte endocrine regulation.
糖尿病的特征是高血糖,可导致血浆脂蛋白发生变化,进而引发胰岛素抵抗、分泌缺陷或两者皆有。本研究旨在评估从L.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(DMDD)降低高血糖的能力,并研究其在糖尿病小鼠中的潜在作用机制。
采用柱色谱技术分离DMDD。实验小鼠喂食高脂饮食一个月,然后静脉注射链脲佐菌素(80mg/kg,单次剂量)。糖尿病小鼠口服给予DMDD(12.5、25、50mg/kg)和50mg/kg吡格列酮,持续15天。测定空腹血糖(FBG)、空腹血胰岛素(FINS)、胰腺胰岛素含量、白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)以及血清总胆固醇(TC)、甘油三酯(TG)和游离脂肪酸(FFA)。通过组织学检查、免疫组织化学、蛋白质印迹和逆转录-聚合酶链反应方法评估脂肪组织。
DMDD显著提高了胰岛素水平(均P<0.05)。相比之下,FBG、IL-6、TNF-α、TC、TG和FFA显著降低(均P<0.05)。然而,DMDD诱导了脂肪细胞过氧化物酶体增殖物激活受体γ(PPAR-γ)的激活,PPAR-γ的蛋白质和mRNA表达增加证实了这一点。
DMDD具有降血糖活性,其潜在机制涉及PPARγ介导的脂肪细胞内分泌调节。