Phytochemical Screening, Study of Acute Toxicity and Hypoglycemic and Antihyperglycemic Activities of Silver Nanoparticles from Guibourtia tessmannii (Harms) J. Leonard (Caesalpiniaceae)

According to the World Health Organization, diabetes affects approximately 347 million people worldwide. Its management is not within the reach of all social classes, therefore medicinal plants are still the first resort for many populations in Africa. The biological material used in this study was the trunk bark of Guibourtia tessmannii. 50 g of trunk bark powder were decocted in 500 ml of distilled water for 5 minutes were carried out. The method used for the synthesis of silver nanoparticles (AgNps) was an organometallic bio-reduction of silver nitrate salts mediated by various secondary metabolites contained in the plant extract. The study of the toxicity acute was conducted according to guideline 423 of the OECD protocol. The pharmacological activities were each carried out with 28 female rats divided into 7 groups of four rats. It was a question for the hypoglycemic activity of administering various doses of silver nanoparticles and other substances to the rats thirty minutes after the carbohydrate intake and for the anti-hyperglycemic activity of administering the same substances to the rats thirty minutes before the carbohydrate intake. The extraction yield was 8.76%. Only the alkaloid test was negative. After acute toxicity study, the LD50 was greater than 2000 mg/kg. Blood sugar tests revealed that glibenclamide 5 mg/kg, which is the reference molecule, lowered blood sugar more than the other treatments applied in the other batches. It was followed by treatment with silver nanoparticles at a dose of 400 μg/kg in both tests. It was therefore concluded that silver nanoparticles from G. tessmannii are good for the formulation of improved traditional medicines and bring up their afficacity .

新型甜味剂塔格糖的应用及生产

D-塔格糖是一种新型低热量甜味剂,用于食品和药品领域,有抗高血糖和益生保健等多种功能。本文综述了其基本性质和功能,抗高血糖的机制,食品和药品应用情况及生产技术开发的进展,重点阐述了塔格糖生产的工具酶——L-阿拉伯糖异构酶的基因克隆与筛选、酶工程化改造及固定化等方面的研究进展。

灵菊七水提物的降糖作用及促胰岛素分泌作用研究

目的观察灵菊七水提物的降糖作用及对胰岛细胞分泌胰岛素的影响。方法采用四氧嘧啶(70 mg.kg-1)诱导的糖尿病模型小鼠和正常小鼠,连续给药7 d后,观察灵菊七水提物(2.5 mg.kg-1、5 mg.kg-1和10 mg.kg-1)对血糖、血清胰岛素水平和糖耐量的影响;采用M IN6胰岛细胞株,观察灵菊七水提物对胰岛素分泌的影响。结果在给药7 d后,灵菊七水提物可明显降低糖尿病小鼠的血糖水平,并可明显降低正常小鼠和糖尿病小鼠的糖耐量,促进胰岛素的分泌;灵菊七水提物对葡萄糖(16.7 mmol.L-1)刺激下胰岛素的分泌明显具有促进作用。结论灵菊七水提物可通过促进胰岛素分泌来降低血糖。

Screening ofα-glucosidase inhibitors in large-leaf yellow tea by offline bioassay coupled with liquid chromatography tandem mass spectrometry

Larger-leaf yellow tea(LYT)is a characteristic type of Chinese tea produced in Huoshan County,Anhui Province,which is made by mature leaves with stems.According to recent report,LYT showed competitive effects in anti-hyperglycemia in comparison to other teas such as green or black tea.However,the bioactive compounds of LYT are still undiscovered so far.For this purpose,5 fractions of LYT were prepared by sequential extraction.The in vitro bioassay results indicated that the ethyl acetate fraction of LYT had the strongest inhibitory effects onα-glucosidase andα-amylase.Fluorescence-quenching analysis and proteinbinding test revealed that the compounds of ethyl acetate fraction could inhibitα-glucosidase andα-amylase activities through binding to enzymes or other mechanisms.All chromatographic peaks of high-performance liquid chromatography(HPLC)of ethyl acetate fraction were separated and collected.The purified compounds were identified by liquid chromatography-mass spectrometry(LC-MS),and subsequently screened by calculating their inhibition ratio onα-glucosidase at the real concentration in LYT infusion.The results showed that(-)-epigallocatechin gallate,(-)-gallocatechin gallate,caffeine,N-ethyl-2-pyrrolidone-substituted flavan-3-ols were effective inhibitors forα-glucosidase.

抗TNF-α抗体减轻创伤感染应激高血糖大鼠急性胰岛素抵抗的实验研究

目的:研究抗肿瘤坏死因子α抗体(anti-TNF-αantibody)对腹部创伤合并感染脓毒血症大鼠的急性胰岛素抵抗的影响机制。方法:建立大鼠创伤脓毒症导致高血糖的动物模型,并随机分为4组,分别给予大剂量和小剂量抗TNF-α治疗;通过血糖、血清胰岛素水平、葡萄糖耐量试验以及高胰岛素正葡萄糖钳夹试验等方法比较各组大鼠的差异。结果:采用抗TNF-α抗体治疗可显著降低术后血清胰岛素水平、葡萄糖耐量、葡萄糖输注率和肝组织Akt磷酸化水平,提高mTOR磷酸化水平。结论:抗TNF-α抗体治疗可调节肝组织胰岛素信号通路Akt和mTOR的磷酸化水平,进而减轻创伤感染应激后大鼠急性胰岛素抵抗程度。

In vitro,in vivo and in silico anti-hyperglycemic inhibition by sinigrin

Objective:To evaluate the anti-hyperglycemic potential of sinigrin using in ritro.in silico and in riro streptozotocin(STZ) induced hyperglycemic zebrafish model.Methods:The in vitro enzyme inhibition assay was carried out to determine the IC_(50) value against α-glucosidase and α-amylase.in silico molecular docking was performed against both enzymes with PyRx tool and simulations were performed using GROMACS tool.Hyperglycemia was induced in zebrafishes using three intraperitoneal injections on alternating days for one week at 350mg/kg of STZ.Hyperglycemic fishes were treated intraperitoncally with 50.100 and 150 mg of sinigrin/kg of body weight for 24 h and glucose levels were measured.Results:The sinigrin showed very strong inhibition against α-glucosidase and α-amylase with 0.248 and0.00124 μM while reference drug acarbose showed IC_(50) value of 73.0700 and 0.0017 μM against α-glucosidase and α-amylase,respectively.Kinetic analysis revealed that sinigrin has the mixed type mode of inhibition against α-glucosidase.Molecular docking results revealed its strong binding affinity with α-glucosidase(-10.00 Kcal/mol) and α-amylase(-8.10 Kcal/mol).Simulations graphs confirmed its stability against both enzymes.Furthermore.in hyperglycemic zebrafishes most significant(P<0.001) reduction of glucose was occurred at150 mg/kg.moderate significant reduction of glucose was observed at 100 mg/kg and no any significant reduction of glucose was measured at 50 mg/kg.Conclusions:It can be evident from the present results that sinigrin has potent anti-hyperglycemic activity and it may prove to be effective treatment for the hyperglycemia.

Effects of Single Administered Bofutsushosan-Composed Crude Drugs on Diabetic Serum Parameters in Streptozotocin-Induced Diabetic Mice

The 18 crude drugs in Bofutsushosan (BOF: Pulvis ledebouriellae compositae: 防風通聖散) are separated into 6 groups such as diaphoretic, cathartic, antidote, antipyretic, neutralizer and diuretic groups. The effects of single administered BOF and composed crude drugs in 6 groups were investigated on the levels of diabetic parameters (serum glucose, insulin, triglyceride and cholesterol) in streptozotocin-induced diabetic mice. The anti-hyperglycemic action of BOF was depended on Ephedrae Herba, Saposhnikoviae Radix and Schizonepetae Spica in diaphoretic group, Forsythiae Fructus, Saposhnikoviae Radix, Schizonepetae Spica and Cnidii Rhizoma in antidote group, Scutellariae Radix, Gardeniae Fructus and Gypsum Fibrosum in antipyretic group and Paeoniae Radix in neutralizer group. In these crude drugs, Ephedrae Herba, Saposhnikoviae Radix, Schizonepetae Spica, Forsythiae Fructus, Scutellariae Radix, Gypsum Fibrosum and Paeoniae Radix increased serum insulin level, but Cnidii Rhizoma and Gardeniae Fructus did not affect serum insulin level. From these results, it suggested that anti-hyperglycemic action of BOF was through insulin-dependent and insulin independent manners. The lowering effect of BOF on serum triglyceride level was dependent on actions of Platycodi Radix in antidote and diuretic groups and Gardeniae Fructus in antipyretic group. The lowering effect of Gardeniae Fructus was parallel with its anti-hyperglycemic action. The lowering effect of BOF on high serum triglyceride level also included both direct action and indirect action. The reducing effect of BOF on serum cholesterol level was observed together with the actions of Ephedrae Herba and Zingiberis Rhizoma in diaphoretic group, Schizonepetae Spica in diaphoretic and antidote groups and Paeoniae Radix in neutralizer group. The lowering effects of Ephedrae Herba, Schizonepetae Spica and Paeoniae Radix on serum cholesterol level were parallel with their anti-hyperglycemic actions. Zingiberis Rhizoma in diaphoretic group might be direct reducing effect on serum cholesterol level but no serum glucose level. The Ephedrae Herba in diaphoretic group, Schizonepetae Spica in diaphoretic and antidote groups and Paeoniae Radix in neutralizer group might have reduced serum cholesterol level by reducing blood glucose level. From these results, composed crude drugs in 6 groups show various mechanisms in the action of BOF.

Clerodane Diterpenoids with Anti-hyperglycemic Activity from Tinospora crispa

Four new clerodane diterpenoids,tinosporols A–C(2–4)and tinosporoside A(5),together with six known analogues were isolated from the vines of Tinospora crispa.Their structures were established by extensive spectroscopic analysis.The relative configuration at C-12 in the known diterpenoid borapetoside E(1),the major component of the plant,was firstly established with the aid of molecular model.Compound 1 significantly reduced serum glucose levels at dosedependent manners in alloxan-induced hyperglycemic mice and db/db type 2 diabetic mice.

抗炎合剂治疗脓毒症患者应激性高血糖临床观察

目的观察中药抗炎合剂对脓毒症应激性高血糖的疗效。方法将脓毒症并应激性高血糖符合热毒内盛患者74例随机分为两组,对照组采用强化胰岛素疗法控制应激性高血糖,治疗组应用抗炎合剂联合胰岛素非强化治疗,疗程均为7 d。结果治疗组总有效率为74.36%,显著高于对照组的65.71%(P<0.05);治疗后治疗组空腹血糖高于对照组(P<0.05),低血糖的发生率显著低于对照组(P<0.01),胰岛素敏感性改善治疗组优于对照组(P<0.05);治疗组TNF-α、CRP水平均低于治疗组(P<0.01)。结论抗炎合剂对改善脓毒症患者应激性高血糖有效。

交泰丸中小檗碱联合cinnamtannin D1的降血糖作用

目的研究交泰丸中小檗碱联合cinnamtannin D1的降血糖作用。方法 40只db/db小鼠随机分为对照组(0. 5%CMC-Na)、二甲双胍组(150 mg/kg)、小檗碱组(200 mg/kg)、小檗碱+cinnamtannin D1组(200 mg/kg+30 mg/kg),每组10只; 10只db/m小鼠作为正常组。灌胃给药5周后,进行口服葡萄糖耐量、胰岛素耐量试验,检测空腹血糖及甘油三酯(TG)、总胆固醇(TC)、游离脂肪酸(NEFA)、谷丙转氨酶(ALT)、天门冬氨酸转氨酶(AST)水平。结果与对照组比较,小檗碱组、小檗碱+cinnamtannin D1组口服葡萄糖耐量、胰岛素耐量有所改善,空腹血糖及血清TG、NEFA水平显著降低(P <0. 05,P <0. 01,P <0. 001),但仅后一组肝脏TG水平显著降低(P <0. 01);与小檗碱组比较,小檗碱+cinnamtannin D1组空腹血糖、胰岛素耐量AUC显著降低(P <0. 05)。结论交泰丸中小檗碱联合cinnamtannin D1可有效改善2型糖尿病小鼠症状,可能具有协同作用。

荷叶碱药理作用的研究进展

荷叶碱是来源于睡莲科植物莲干燥叶中的一种阿朴啡类生物碱,也是《中国药典》收载荷叶这味中药的质控成分。现代研究表明,荷叶碱具有降脂、降糖、抗肿瘤、抗脑缺血等多种药理作用,具有广阔的开发前景。但荷叶碱自身存在水溶性差、药物安全性数据缺失、生物利用度争议较大等成药性缺陷,极大地影响了荷叶碱的深入研究与开发。因此,如何从众多药理活性中获得启发,进而选择最适合荷叶碱产品开发的临床适应症,依据制剂或化学手段改善其溶解性和生物利用度,同时降低毒副作用的发生,是当前迫切需要解决的问题。该文在回顾荷叶碱的理化性质及药动学研究报道的基础上,系统总结了其药理活性及作用机制,以期为荷叶碱药理作用的深入研究及创新品种的开发提供参考。

钠葡萄糖协同共转体2抑制剂的临床研究进展

钠葡萄糖协同共转体2抑制剂主要作用于肾小管近端,抑制葡萄糖在肾小管的重吸收,从而增加葡萄糖的排出,起到降低血糖的作用,为糖尿病患者的治疗提供了新的选择。近年来临床研究显示,其可以降糖、降血脂、减轻体质量、降血压等,同时也有发生低血糖、泌尿系感染、生殖器感染等不良反应的可能。该文对其近年的临床研究结果及应用前景进行综述。

高血糖与衰老相关性研究进展

随着生活水平的提高,我国处于高血糖"亚健康"状态人群比例日益增加,且趋于年轻化。持续高血糖状态会导致机体内稳态紊乱,加速各器官、系统的衰老,威胁健康。衰老是生命过程的必然规律,社会老龄化进程的加快使人们对健康长寿更加关注。近年来国内外学者在衰老生物学机制研究方面已取得系列进展,本文通过对高血糖与衰老相关性的文献研究进行综述与分析,以期为后续抗衰老相关研究提供理论参考。

抗肿瘤靶向药物及免疫制剂对血糖的影响

正常机体常以多种方式来调节机体的血糖水平,以促血糖水平维持在一定范围内,达到稳态。血糖稳态遭到破坏时可导致血糖的波动如高血糖或低血糖,进而影响患者的生活质量,威胁人类健康。抗肿瘤靶向及免疫治疗通过抑制促癌信号靶点和通路,通常可以改善患者的预后,靶向及免疫疗法为患者带来了重要的和实质性的益处。IGF-1R、EGFR、PI3K-AKT-mTOR等靶点及信号通路与驱动肿瘤细胞增殖、存活、代谢转化和转移等密切相关。这些药物的使用,可能会使患者处于血糖波动的风险当中。为了更好地使患者从这些抗肿瘤靶向药物、免疫制剂中获益。本文将对抗肿瘤靶向药物、免疫制剂对血糖代谢的影响、可能发生机制及处理方法作一文献综述。

肠外营养致高血糖对重型颅脑损伤患者血清HSP27抗体的影响

目的:研究重型颅脑损伤患者肠外营养致高血糖对血清热休克蛋白27(HSP27)抗体表达的影响。方法:将2013年9月到2014年12月我科ICU收治的重型颅脑损伤行肠外营养致高血糖的31例患者随机分为胰岛素强化治疗组(IIT组,n=16)及常规血糖控制组(CGC组,n=16),其至少50%的估计能量需要量(EER)由肠外营养获得。比较两组入ICU时、第7 d和第14 d血清抗HSP27抗体浓度。结果:IIT组血清HSP27抗体浓度第14d较GCG组明显下降(P<0.05)。结论 :胰岛素强化治疗可通过降低血清中HSP27抗体而减轻接受肠外营养的重型颅脑损伤患者的神经元应激。

厚朴酚及和厚朴酚防治高血糖、高脂血症及其并发症的药理机制研究进展

厚朴酚及和厚朴酚是来自于中药厚朴的同分异构体,具有相同的药理活性。它们都可通过保护胰腺β-细胞,促进胰岛素分泌,提高血中胰岛素水平及细胞对葡萄糖的摄取和利用,从而降低胰岛素抵抗和血糖水平;还能通过抑制脂质合成和促进脂质分解,产生调血脂作用。厚朴酚及和厚朴酚可通过降血糖、调血脂及抗氧化作用,从源头上减少氧化低密度脂蛋白(ox-LDL)和晚期糖基化终末产物(AGEs)的生成,还可通过抗氧化、抗炎及细胞保护作用,保护心血管系统、肾脏、肝脏、胰腺等组织器官对抗高血糖、高脂血症诱导并发症的发生和发展。因此厚朴酚及和厚朴酚有开发成为治疗代谢综合征新药的潜力。

Anti-hyperglycemic effect of the polysaccharide fraction isolated from mactra veneriformis

Total macromolecule extract was obtained from the soft body of Mactra veneriformis by the coupling techniques of decoction and alcohol precipitation.The extract was deproteinized with an ion exchange column,and resulted in the purifying of the crude polysaccharide fraction.It was found by chemical analysis that the crude polysaccharide part is composed of abundant polysacchar-ides(>95%)and few proteins(<1%).Furthermore,only one type of monosaccharide,glucose,was detected from its hydrolytes by thin-layer chromatography,indicating that the polysaccharides might be analogs of glucosan.The anti-hyperglycemia effects of the crude polysaccharide part were preliminarily investigated using several pharmacolo-gical methods in normal and diabetic mice.Animal experimental results showed that the crude polysaccharide fraction exhibited proper glycemia inhibition activity,and 300 mg/kg-weight dose has the optimal effect among all the studied doses.It is concluded that the crude polysaccharide fraction can be explored as a novel health product that possesses potential as an anti-hyperglycemic agent.

盐酸二甲双胍中基因毒杂质N-亚硝基二甲胺检测方法的建立

目的:建立高效液相色谱-三重四极杆质谱(HPLC-MS/MS)法测定盐酸二甲双胍原料药和制剂中N-亚硝基二甲胺(NDMA)。方法:采用Phenomenex ACE Excel 3 C_(18)-AR色谱柱(100 mm×4.6 mm,3μm),以0.1%甲酸水-0.1%甲酸甲醇为流动相,梯度洗脱,流速0.5 mL·min^(-1),柱温40℃,进样量5μL;质谱离子化方式为APCI,正离子模式,多反应监测(MRM),NDMA的定量离子对为m/z 75.0→43.0,定性离子对为m/z 75.0→58.0。结果:NDMA质量浓度在1~100 ng·mL^(-1)范围内,线性关系良好;检测限为0.25 ng·mL^(-1);30批样品的测定结果NDMA的含量为0~0.46μg·g^(-1)。结论:本方法可用于测定盐酸二甲双胍原料药和制剂中NDMA含量。

尖萼金丝桃中抗人脐静脉内皮细胞高糖损伤活性组分的筛选及其作用机制

目的筛选抗人脐静脉内皮细胞(HUVEC)高糖损伤的活性物质,并研究其机制。方法建立高糖损伤HUVEC模型,筛选提取自尖萼金丝桃的多个样品;检测已知结构活性样品对高糖损伤HUVEC细胞的增殖活性、细胞凋亡和细胞坏死、超氧化物歧化酶(SOD)活性、活性氧(ROS)及肿瘤坏死因子-α(TNF-α)、白细胞介素-4(IL-4)含量的影响。结果获得1个已知结构的活性样品hypercohone G,其可提高HUVEC细胞的增殖活性,减少细胞凋亡,对细胞坏死无影响;能增加SOD的活性,降低ROS、TNF-α、IL-4的含量。结论尖萼金丝桃中hypercohone G能抗高糖所致HUVEC细胞损伤,其机制可能与提高细胞抗氧化能力,减轻炎症反应,减少细胞凋亡有关。

植物性发酵乳杆菌对免疫系统的生理活性、抗高血糖和促进肠蠕动的影响

研究植物源性发酵乳杆菌对免疫系统生理活性、抗高血糖和促进肠蠕动的影响。β-内啡肽对免疫系统有重要作用,阿片-促黑素细胞皮质素原(POMC)是β-内啡肽的前体物质,为了探讨发酵乳杆菌对免疫功能的影响,检测小鼠下丘脑和脑垂体中POMC的基因表达水平。通过喂食发酵乳杆菌时间和浓度的不同及测量β-内啡肽表达水平的方式,来分析血液中β-内啡肽的变化情况。此外,测定了三种小鼠模型的血糖变化,即常规的WT小鼠模型、D-葡萄糖诱导的急性高血糖模型和链唑霉素(STZ)诱导的糖尿病模型,以证实发酵乳杆菌的降血糖效果,并对降血糖效果进行了验证。通过检测血糖随喂食发酵乳杆菌浓度和时间而变化的情况,已证实给药浓度和时间对血糖浓度有很好的影响。另外,为证实发酵乳杆菌对肠蠕动的影响测定了胃肠通过时间,证明发酵乳杆菌对肠蠕动有极好的促进作用。通过此项研究,证实发酵乳杆菌对提高人体免疫系统的生理活性、抗高血糖和促进小肠蠕动有极佳的效果。