马里苷、黄诺玛苷对db/db小鼠肠道菌群的影响及相关性

目的探索两色金鸡菊中黄酮类成分马里苷、黄诺玛苷对db/db小鼠肠道菌群的影响。方法将db/m小鼠作为正常对照组,db/db小鼠分为db/db模型组、db/db+恩格列净(db/db+Empagliflozin)组、db/db+马里苷(db/db+Marein)组、db/db+黄诺玛苷(db/db+Flavanomarein)组,每组8只。采用实时荧光定量PCR(RT-qPCR)的方法检测小鼠粪样中Bacteroides ovatus、Ruminococcus gnavus的变化,并运用Pearson检验分析Bacteroides ovatus、Ruminococcus gnavus的变化与2型糖尿病相关表型的相关性。结果 (1)干预12周后与db/m组相比,db/db组小鼠粪样中Bacteroides ovatus水平显著降低(P0.010);恩格列净(P0.001)、马里苷(P0.050)、黄诺玛苷(P0.001)干预后能显著升高其含量,差异具有统计学意义。(2)与db/m组相比,db/db组小鼠粪样中Ruminococcus gnavus水平显著升高(P0.050);恩格列净(P0.050)、马里苷(P0.050)干预后能显著降低其含量,差异具有统计学意义。(3)Bacteroides ovatus水平与空腹血糖(FBG)、三酰甘油(TG)呈负相关(r=-0.420,P=0.021;r=-0.474,P=0.008);Ruminococcus gnavus水平与FBG、TG呈正相关(r=0.397,P=0.030;r=0.404,P=0.027)。结论马里苷、黄诺玛苷可以调节小鼠肠道菌群的变化,这可能是其抗糖尿病的重要机制。     

Marein protects against methylglyoxal-induced apoptosis by activating the AMPK pathway in PC12 cells

Diabetic encephalopathy, which is characterized by cognitive decline and dementia, commonly occurs in patients with long-standing diabetes. Previous studies have suggested that methylglyoxal (MG), an endogenous toxic compound, plays an important role in diabetic complications such as cognitive impairment. MG induces neuronal apoptosis. To clarify whether marein, a major compound from the hypoglycemic plant Coreopsis tinctoria, prevents PC12 cell damage induced by MG, we cultured PC12 cells in the presence of MG and marein. Marein attenuated MG-induced changes in the mitochondrial membrane potential (ΔΨm), mitochondrial permeability transition pores (mPTPs), intracellular Ca^2+?levels, the production of reactive oxygen species (ROS), glutathione (GSH)/glutathione disulfide (GSSG) and adenosine triphosphate (ATP), and the increase in the percentage of apoptotic cells. Marein also increased glyoxalase I (Glo1) activity, phospho-AMPKα (Thr172) and Bcl-2 expression and diminished the activation of Bax, caspase-3 and inhibitor of caspase-activated deoxyribonuclease (ICAD). Importantly, pretreatment of cells with marein diminished the compound C-induced inactivation of p-AMPK. Molecular docking simulation showed that marein interacted with the γ subunit of AMPK. In conclusion, we found for the first time that the neuroprotective effect of marein is due to a reduction of damage to mitochondria function and activation of the AMPK signal pathway. These results indicate that marein may be a potent compound for preventing/counteracting diabetic encephalopathy.