Efficacy and safety of Sancai powder in patients with type 2 diabetes mellitus: a randomized controlled trial

OBJECTIVE: To assess the efficacy and safety of Sancai powder in patients with type 2 diabetes mellitus(T2DM) inadequately controlled with single oral metformin in a randomized controlled trial(RCT).METHODS: A total of 132 patients with T2 DM were enrolled in the study, who only took metformin(500-1000 mg/day) for at least three months and with inadequate glycemic control(7.0% ≤ hemoglobin A1 c ≤ 9.0%) in the past three months.The patients stopped taking metformin with lifestyle interventions for three weeks, and 105 patients qualified for the program. They were randomly divided into the Sancai powder group and the metformin group(1500 mg/day). The follow-up period was for 12 weeks. Comparisons of several variables were analyzed.RESULTS: No significant differences were found between the two groups in hemoglobin A1c(Hb A1c),fasting plasma glucose(FPG) and 2 h post-meal glucose(2h PG), although they had decreased significantly(P < 0.01). Homeostasis model assessment of beta cell function index was significantly improved in Sancai powder group(P < 0.01), and there were significant differences in the changes of homeostasis model assessment of insulin resistance and insulin sensitivity index in the two groups(P < 0.05). Sancai powder significantly reduced triglyceride level(P < 0.05), although there was no significant difference in the body weight and body mass index in the two groups.CONCLUSION: In this 12-week study, Sancai powder could significantly reduce hemoglobin A1 c,FPG and 2h PG levels, improved beta-cell function and insulin resistance of the T2 DM inadequately controlled with metformin.

虫草菌丝抑制自噬相关AMPK/ULK1信号活性改善肾小管上皮细胞衰老的分子机制

为了探讨虫草菌丝(mycelium of Cordyceps sinensis,MCs)改善D-半乳糖(D-galactose,D-gal)诱导的肾小管上皮细胞衰老的作用和分子机制,将体外培养的大鼠近端肾小管上皮细胞(NRK-52E)分为正常组(normal group,N),模型组(D-gal model group,D),低剂量MCs组(low dose of MCs,L-MCs),中剂量MCs组(medium dose of MCs,M-MCs),高剂量MCs组(high dose of MCs,H-MCs),分别进行不同的干预。具体而言,N组加入1%胎牛血清(fetal bovine ser-um,FBS)1 m L;D组加入100 mmol·L^(-1)D-gal;L-MCs组加入100 mmol·L^(-1)D-gal+20 mg·L^(-1)MCs;M-MCs组加入100 mmol·L^(-1)D-gal+40 mg·L^(-1)MCs;H-MCs组加入100mmol·L^(-1)D-gal+80 mg·L^(-1)MCs。在干预后的24或48 h,首先,观察D-gal对NRK-52E细胞klotho,P27,P16蛋白表达水平,β-半乳糖苷酶(senescence-associatedβ-galactosidase,SA-β-gal)染色以及腺苷酸活化蛋白激酶(adenosine monophosphate activated protein kinase,AMPK)/不协调的51类激酶1(uncoordinated 51-like kinase 1,ULK1)信号活性的影响;其次,观察MCs对NRK-52E细胞增殖活性的影响;最后,观察MCs对D-gal诱导的NRK-52E细胞klotho,P27,P16蛋白表达水平,SA-β-gal染色以及哺乳动物同族物微管相关蛋白1轻链3(microtubule-associated protein 1 light chain 3,LC3)和AMPK/ULK1信号活性的影响。结果表明,对于NRK-52E细胞,D-gal能引起衰老,并诱导磷酸化AMPK(phosphorylated-AMPK,p-AMPK)和磷酸化ULK1(phosphorylated-ULK1,p-ULK1)蛋白高表达,激活AMPK/ULK1信号通路;中、高剂量MCs与D-gal联合干预能明显改善klotho,P27,P16蛋白表达水平和SA-β-gal染色程度,具有抗细胞衰老的作用;此外,中、高剂量MCs与D-gal联合干预能明显改善LC3,p-AMPK,p-ULK1蛋白表达水平,抑制AMPK/ULK1信号活性,提高自噬水平。总之,对于D-gal诱导的肾小管上皮细胞衰老模型,MCs在体外有抗衰老的作用,并且,通过抑制自噬相关AMPK/ULK1信号活性而干预其衰老进程。这可能是MCs抗肾小管上皮细胞衰老的新的分子机制。

非编码RNA调控自噬的分子机制及中药的干预作用

在哺乳动物细胞内,以长链非编码RNA(long non-coding RNA,lncRNA)和微小RNA(microRNA,miRNA)为代表的非编码RNA在调控自噬的上游发挥着重要作用。lncRNA和miRNA参与了自噬过程的各个阶段,包括起始、囊泡成核、自噬体成熟以及自噬体融合等。具有双向调控自噬作用的非编码RNA包括母系表达基因3(maternally expressed gene 3,MEG3),H19和miRNA-21(miR-21);具有抑制自噬作用的非编码RNA包括生长阻滞特异转录本5(growth arrest-specific transcript 5,GAS5),miRNA-34a(miR-34a)和miRNA-30a(miR-30a);具有促进自噬作用的非编码RNA包括转移相关的肺腺癌转录本1(metastasis associated lung adenocarcinoma transcript 1,MALAT1),miRNA-152(miR-152)和miRNA-24(miR-24)。非编码RNA调控自噬的作用具有条件性、多样性和复杂性的特点。近年来,国内外学者相继发现,白蔹素、丹酚酸B、丹皮酚等单味中药提取物和加味八珍方可以在体内外干预非编码RNA而调控自噬。最新的研究表明,植物源性短链非编码RNA(small non-coding RNA,sncRNA)作为中药的有效成分之一可以直接进入循环血液和内脏而跨界调控人类基因表达。此外,大黄酸、金丝桃苷以及虫草菌丝均能在体内外通过调控自噬相关信号通路而干预肾小管上皮细胞自噬,减轻肾脏损伤和肾脏衰老,其部分药理机制可能与miR-34a通路介导有关。总之,针对肿瘤、免疫性疾病、代谢性疾病以及神经退行性疾病等临床常见疾病而揭示非编码RNA(lncRNA和miRNA)调控自噬的分子机制,这是建立精准治疗策略和阐明中药药理作用的必由之路。

Salvianolic acid B decreases interleukin-1b-induced colitis recurrence in mice

Background:Degree of mucosal recovery is an important indicator for evaluating the therapeutic effects of drugs in treatment of inflammatory bowel disease(IBD).Increasing evidences has proved that tight junction(TJ)barrier dysfunction is one of the pathological mechanisms of IBD.The aim of this study was to observe whether enhancement of TJ can decrease colitis recurrence.Methods:Eighty C57BL/6 mice were randomly divided into four groups including normal group,colitis group,sulfasalazine(SASP)treated group,and traditional Chinese drug salvianolic acid B(Sal B)treated group.Colitis was established in mice by free drinking water containing dextran sulfate sodium,after treatments by SASP and Sal B,recombinant human interleukin-1b(IL-1b)was injected intraperitoneally to induce colitis recurrence.Results:Compared with sham control,cell apoptosis in colitis group was increased from 100.85±3.46%to 162.89±11.45%(P=0.0038),and TJ dysfunction marker myosin light chain kinase(MLCK)was also significantly increased from 99.70±9.29%to 296.23±30.78%(P=0.0025).The increased cell apoptosis was reversed by both SASP(125.99±8.45%vs.162.89±11.45%,P=0.0059)and Sal B(104.27±6.09%vs.162.89±11.45%,P=0.0044).High MLCK expression in colitis group was reversed by Sal B(182.44±89.42%vs.296.23±30.78%,P=0.0028)but not influenced by SASP(285.23±41.04%vs.296.23±30.78%,P>0.05).The recurrence rate induced by recombinant human IL-1b in Sal B-treated group was significantly lower than that in SASP-treated group.Conclusions:These results suggested a link between intestinal mucosal barrier dysfunction,especially TJ barrier dysfunction,and colitis recurrence.The TJ barrier dysfunction in remission stage of colitis increased the colitis recurrence.This study might provide potential treatment strategies for IBD recurrence.