唇兰属 3 种植物总膏的降血糖活性研究简

目的 研究开唇兰属3种药用植物齿唇兰、艳丽齿唇兰和西南齿唇兰的总膏对高糖高脂饮食联合链脲佐菌素(STZ)诱导的大鼠模型血糖相关指标的影响.方法 高血糖实验组大鼠分别灌胃给予3种总膏,测定给药后大鼠血糖、胰岛素敏感性、抗氧化活性及一氧化氮(NO)水平等相关指标.胰腺切片,进行病理学检查.结果 与模型组比较,西南齿唇兰总膏组的随机血糖明显降低,由给药前19.3降至8.5 mmol.L^-1(P<0.05),而且该组大鼠的体质量明显高于模型组,同时能提高胰岛素敏感性,改善高糖负荷以后的糖耐量.开唇兰属3种植物提取物给药组的超氧化物歧化酶(SOD)活性增加,NO含量均显著降低.结论 西南齿唇兰总膏具有良好的降血糖作用,其作用机制可能与改善胰岛素抵抗、增强机体抗氧化活性和降低血浆NO等机制有关.     

吲哚衍生物的设计、合成及胰岛素增敏活性

目的设计合成具胰岛素增敏活性的系列化合物。方法以具备胰岛素增敏活性的化合物为基础，运用拼合设计原理，设计合成了10个目标化合物，用3T3-L1前脂肪细胞对这些化合物进行了胰岛素增敏活性筛选。结果发现其中化合物4在3T3-L1前脂肪细胞模型上表现出较强的胰岛素增敏活性。结论该化合物可能在体内具有降糖活性，拟选送进行体内降糖活性测试。     

门冬胰岛素30、格列美脲对初诊2型糖尿病患者胰岛功能的影响研究

目的:探讨不同强化治疗方案对初诊2型糖尿病患者胰岛B细胞功能的影响。方法:将初诊的54例2型糖尿病患者随机分为2组,分别给予门冬胰岛素30、格列美脲联合二甲双胍治疗,对比观察治疗前后患者血糖、糖化血红蛋白(HbA1c)、胰岛B细胞功能的变化情况。结果:治疗前后2组患者血糖、HbA1c均显著降低(P<0.01),胰岛B细胞功能明显恢复,胰岛素治疗组较口服降糖药组血糖达标时间更早,观察24周后前者进入"蜜月期"的人数和时间高于后者(P<0.05)。结论:胰岛素和口服降糖药强化治疗初诊2型糖尿病均能有效地控制血糖,显著降低HbA1c,胰岛B细胞功能明显恢复,但前者血糖达标时间更快,诱导出血糖正常的"蜜月期"持续时间更长。     

胰岛素抵抗和脑血管病关系的研究

目的：探讨胰岛素抵抗与脑梗死、脑出血的关系，为针对胰岛素抵抗的治疗可以有效地预防脑血管疾病提供理论依据。方法：选取42例脑梗死（脑梗死组）、40例脑出血（脑出血组）及30例非脑血管病患者（对照组），分别测定空腹胰岛素（FINS）、空腹血糖（FBG），计算胰岛素敏感指数（ISI），各组间进行比较。结果：脑梗死组和脑出血组患者ISI低于对照组（P〈0.05），而FINS高于对照组（P〈0．05），FBG与对照组差异无统计学意义（P〉0．05）。结论：胰岛素抵抗可能是脑血管病的一个重要危险因素。     

1,3-二羰基衍生物的合成及胰岛素增敏活性研究

目的合成1．3-二羰基衍生物并检测其胰岛素增敏活性。方法在化合物1的基础上合成了5个目标化合物,用3T3-L1前脂肪细胞对这些化合物进行了胰岛素增敏活性筛选。结果化合物3在3T3-L1脂肪细胞模型上表现出较强的胰岛素增敏活性。结论化合物3可能在体内具有降糖活性,拟选送进行体内降糖活性测试。     

PPARγ激动剂的设计、合成及其胰岛素增敏活性

目的寻找新的高效、低毒的PPARγ激动剂。方法以JTT-501和JTT-20993为先导化合物，设计并合成新的丙二酸类和异恶唑类化合物，并测定其胰岛素增敏活性。结果共合成了8个新化合物,用核磁共振、质谱和红外光谱进行结构确证，并用胰岛素筛选模型初步评价了这些化合物的胰岛素增敏活性。化合物1A-4A显示胰岛素增敏活性,其中化合物1A和3A有较强活性。结论化合物1A和3A值得进一步评价。     

滇黄芩茎叶乙醇提取物及其不同溶剂萃取部位的抗氧化和降脂活性研究

目的:研究滇黄芩茎叶乙醇提取物及其不同溶剂萃取部位的抗氧化活性和降脂活性.方法:取滇黄芩茎叶用95％乙醇回流提取,得乙醇提取物;取上述提取物,依次用石油醚、乙酸乙酯、正丁醇萃取,回收溶剂得到不同溶剂萃取部位.以维生素C(Vc)为阳性对照,采用羟基自由基、超氧阴离子自由基、1,1-二苯基-2-三硝基苯肼(DPPH)自由基...     

严重烧伤患者血浆TNFα与乳酸含量、胰岛素抵抗指数和胰岛素分泌指数变化的相关性研究

目的:探讨严重烧伤患者血浆肿瘤坏死因子(TNFα)与胰岛素抵抗指数、胰岛素分泌指数和乳酸含量的相关性。方法:2013年1月—2015年1月间本院共收治严重烧伤患者68例,其中一般烧伤者36例(Ⅰ组),烧伤致功能不全者32例(Ⅱ组)。另选36例健康体检者作为Ⅲ组。对三组患者TNFα,胰岛素和乳酸进行测定,评估检测结果。结果:单因素分析显示患者TNFα,胰岛素抵抗指数、乳酸水平随着患者病情加重而上升,胰岛素分泌指数随着患者病情加重而降低。多因素分析显示烧伤患者TNFα水平与胰岛素抵抗指数及乳酸水平成正比例关系,与胰岛素分泌指数成反比例关系。结论:TNFα水平是判断烧伤患者胰岛素抵抗功能和胰岛素分泌功能的重要指标,其在烧伤患者胰岛素抵抗及胰岛素分泌障碍中发挥了举足轻重的作用。     

高血糖人群血清脂联素、胰岛素抵抗指数和血管内皮功能变化及相关性研究

目的探讨高血糖人群血清脂联素、胰岛素抵抗(IR)指数和血管内皮功能变化及相关性。方法从35～55岁健康体检人群经口服葡萄糖耐量试验(OGTT)筛选出糖耐量正常(NGT)43例,空腹血糖调节受损(IFG)47例,糖耐量受损(IGT)52例,糖尿病(DM)41例,检测并比较血糖、血清脂联素水平、IR指数及血管内皮功能。结果空腹胰岛素水平在IFG、IGT、DM3组均高于NGT组(P0.05);餐后2h胰岛素水平从DM、IGT、IFG组到NGT组依次降低,且差异有统计学意义(P0.05)。IFG、IGT、DM组IR指数明显高于NGT组,DM组IR指数高于IFG和IGT组(P0.05)。血清脂联素水平及血管内皮功能在NGT、IFG、IGT、DM组依次降低(P0.05)。脂联素与空腹血糖、IR指数呈负相关(P0.01)。结论血清脂联素水平、IR指数和血管内皮功能可作为OGTT异常人群动脉硬化的早期监测指标。     

高血糖人群血清脂联素、胰岛素抵抗指数和血管内皮功能变化及相关性研究

目的探讨高血糖人群血清脂联素、胰岛素抵抗（IR）指数和血管内皮功能变化及相关性。方法从35。55岁健康体检人群经口服葡萄糖耐量试验（OGTT）筛选出糖耐量正常（NGT）43例,空腹血糖调节受损（IFG）47例,糖耐量受损（IGT）52例,糖尿病（DM）41例,检测并比较血糖、血清脂联素水平、IR指数及血管内皮功能。结果空腹胰岛素水平在IFG、IGT、DM3组均高于NGT组（P〈0．05）;餐后2h胰岛素水平从DM、IGT、IFG组到NGT组依次降低,且差异有统计学意义（P〈0．05）。IFG、IGT、DM组IR指数明显高于NGT组,DM组IR指数高于IFG和IGT组（P〈0．05）。血清脂联素水平及血管内皮功能在NGT、IFG、IGT、DM组依次降低（P〈0．05）。脂联素与空腹血糖、IR指数呈负相关（P〈0．01）。结论血清脂联素水平、IR指数和血管内皮功能可作为OGTT异常人群动脉硬化的早期监测指标。     

An UPLC-MS/MS application to investigate the chemical composition of the ethanol extract from Anoectochilus chapaensis and its hypoglycemic activity in insulin-resistant HepG2 cells

Anoectochilus chapaensis Gagnep. (Orchidaceae) was named as the “king of medicine” because of its excellent efficacy for the treatment of diabetes. However, the bioactive constituents are unknown. An ethanol extract from A. chapaensis showed significant stimulating effect on glucose consumption in HepG2 cells. The chemical composition was investigated by UPLC-MS/MS in negative electrospray ionization (ESI) mode, and 63 compounds including flavonoids, triterpenoids, and aliphatic acids were tentatively identified by accurate mass and characteristic fragments. Moreover, the method of hypoglycemic screening with insulinresistant HepG2 cells and UPLC-MS/MS might be potentially useful in rapid and efficient characterization and primary prediction of natural products prior to traditional isolation.     

Pharmacologically active compounds in the Anoectochilus and Goodyera species

The extract of Anoectochilus formosanus showed significant activity in decreasing the levels of the cytosolic enzymes LDH, GOT, and GPT, and the result demonstrated that A. formosanus possessed prominent hepatoprotective activity against CCl₄-induced hepatotoxicity. Moreover, in the results of the test using aurothioglucose-induced obese mice, the extract showed a significant antihyperliposis effect. A. formosanus grown in the wild and propagated by tissue culture contain ten compounds, including a major known component, (3R)-3-(β-d-glucopyranosyloxy)butanolide (kinsenoside; 1), and two new components, (3R)-3-(β-d-glucopyranosyloxy)-4-hydroxybutanoic acid (2) and 2-[(β-d-glucopyranosyloxy)methyl]-5-hydroxymethylfuran (3), along with the known compounds, isopropyl-β-d-glucopyranoside (4), (R)-3,4-dihydroxybutanoic acid γ-lactone (5), 4-(β-d-glucopyranosyloxy) benzyl alcohol (6), (6R,9S)-9-(β-d-glucopyranosyloxy)megastigma-4,7-dien-3-one (7), and (3R)-3-(β-d-glucopyranosyloxy)-4-hydroxybutanolide (8). Since a higher concentration of kinsenoside (1) was detected in the crude drugs A. formosanus and A. koshunensis by high-performance liquid chromatography (HPLC) analysis, we proved a simple purification system for kinsenoside (1), giving 180 mg of kinsenoside (1) from 1 g of dried samples for further pharmacological experiments. In an anti-hyperliposis assay using high-fat-diet rats, 1 significantly reduced the weights of the body and the liver, and also decreased the triglyceride level in the liver compared to those of control rats. On the other hand, the epimer of 1, (3S)-3-(β-d-glucopyranosyloxy)butanolide, goodyeroside A (9), which was isolated from the Goodyera species, had no effect for anti-hyperliposis. In aurothioglucose-induced obese mice, 1 suppressed the body and liver weight increase, significantly ameliorated the triglyceride level in the liver, and also reduced the deposition of uterine fat pads. The anti-hepatoxic activities of 9 and goodyerosides B (10) were studied on injury induced by CCl₄ in primary cultured rat hepatocytes by measuring the levels of LDH, GOT, and GPT. In the CCl₄-treated control group, there were marked increases in LDH, GOT, and GPT activities compared with the normal group. In contrast, these levels were suppressed in 9- and 10-treated groups. Goodyerin (11), a new typical flavone glycoside, exhibited a significant and dose-dependent sedative and anticonvulsant effect.     

台湾金线莲多糖的分离纯化及其体外抑瘤活性研究

目的研究台湾金线莲(Anoectochilus formosanus)的水溶性多糖(AFP)分离纯化条件,检测单一组分多糖的细胞活性及其结构。方法采用DEAE-Cellulose Fast Flow阴离子交换色谱和Sephadex G-200分离AFP,得到AFP-1和AFP-2两个水溶性单一多糖组分;采用红外光谱检测结构;检测AFP、AFP-1和AFP-2对SMMC-7721肝癌细胞,Hela宫颈癌细胞,spc-A1肺腺癌细胞和Bcap37人乳癌细胞进行细胞杀伤活性。结果AFP-1和AFP-2均为β-D型的吡喃糖环。AFP、AFP-1和AFP-2对癌细胞均具有较好的杀伤作用。结论台湾金线莲多糖(AFP、AFP-1和AFP-2)是非常有前景的抗肿瘤药物或辅助抗肿瘤药物。     

金线莲多糖的分离纯化与含量测定

目的：从金线莲中分离纯化多糖，并建立金线莲多糖含量测定方法。方法：用水提醇沉法提取金线莲多糖，用SephadexG-100凝胶柱色谱纯化多糖；并用改良的苯酚-硫酸法测定多糖含量。结果：测得金线莲粗多糖生药量为37．45％，精制金线莲多糖（AFPS）含量为72．84％，AFPS生药量为27．14％，测定平均回收率为100．40％。结论：金线莲中多糖含量较高，具有开发利用价值。     

金线莲多糖抗糖尿病作用的研究

目的研究全线莲多糖对糖尿病小鼠的降血糖作用,并初步探讨其作用机制。方法采用超声波辅助水提法分离得到金线莲多糖（PSA）;用四氧嘧啶诱导建立糖尿病小鼠模型,以不同剂量的PSA连续灌胃给药14d后,测定血糖、甘油三酯（TG）、总胆固醇（TC）、低密度脂蛋白（LDL-C）高密度脂蛋白（HDL-C）及丙二醛（MDA）含量,谷胱甘肽过氧化物酶（GSH—Px）、超氧化物歧化酶（SOD）活力及总抗氧化能力（T-AOC）。结果PSA的中、高剂量组均显著降低糖尿病小鼠的血糖值（P〈0．05）;高剂量组显著降低血清中的TG（P〈0．01）和TC（P〈0．05）,并显著降低LDL-C含量（P〈0．05）;低、中、高剂量组均可极显著提高血清中的SOD活性（P〈0．01）,中、高剂量组能不同程度地提高肝肾组织的T-AOC及SOD、GSH—Px活性,并显著降低MDA含量。结论金线莲多糖能显著降低糖尿病小鼠的血糖,其降血糖功能可能与调节脂代谢,抑制脂质过氧化作用,并提高体内抗氧化酶活性,抑制高血糖引发的氧化应激有关。     

Antihyperglycemic,antihyperlipidemic and antioxidant activities of polysaccharides from Catathelasma ventricosum in streptozotocin-induced diabetic mice

It is the first time to extract polysaccharides (CVPs) from Catathelasma ventricosum. The antihyperglycemic and antioxidant activity of CVPs in streptozotocin-induced diabetic mice were examined. Compared with untreated diabetic mice, the administration of CVPs for 30 days caused a significant decrease in the concentrations of blood glucose, total cholesterol (TC), triglycerides (TGs), low-density lipoprotein-cholesterol (LDL-C) and maleic dialdehyde (MDA), and a significant increase in the concentrations of high density lipoprotein-cholesterol (HDL-C) and the activities of antioxidant enzymes. Specially, when normal mice were treated with CVPs, all detection indexes and pathologic morphologies of liver, kidney and pancreas are similar to untreated normal mice, which indicated CVPs are safe for normal mice. In addition, the average molecular weight of CVPs was estimated to be from 3.7 × 10³ to 1.7 × 10⁷ Da and they were mainly composed of glucose (93.5%) with the conformation of α-d-Glucopyranose.     

拳参黄酮的分离纯化及其抗氧化活性部位的筛选

目的 通过大孔吸附树脂筛选拳参黄酮抗氧化的最佳活性部位.方法 以静态吸附率和解吸率为指标,从中筛选出富集拳参黄酮的最佳树脂,通过黄酮液pH、浓度等性能来确定动态吸附和洗脱的条件,并采用DPPH和ABTS+清除实验来筛选拳参黄酮抗氧化最佳活性部位.结果 X-5大孔吸附树脂对拳参黄酮有较好的吸附分离性能,其静态吸附平衡时间为2h,吸附条件为(上样液pH3、流速1 mL· min-1),黄酮浓度为0.4477 mg· mL-1,分别以40％、60％、80％、95％乙醇洗脱,得A～D部位.各洗脱部位均有一定的抗氧化能力,其中C部位(80％乙醇洗脱部位)清除·DPPH与ABTS+的活性最强,是拳参黄酮抗氧化的最佳活性部位.结论 拳参黄酮是一种很好的天然抗氧化剂.     

壮骨止痛胶囊有效部位在大鼠体内肠襻吸收状态的研究

目的 通过对壮骨止痛胶囊有效部位在体肠吸收状态的研究,为壮骨止痛胶囊的质量控制及有效成分的分离提供依据.方法 利用高效液相色谱法(HPLC)构建有效部位的HPLC图谱,然后采用SD大鼠在体肠襻吸收实验,构建大鼠在体肠襻吸收后的HPLC图谱,通过各时点的HPLC图谱比较,确定被小肠吸收的差异峰.结果 壮骨止痛胶囊无水乙醇部位中有5个主要化学成分可通过肠襻吸收.结论 壮骨止痛胶囊有效部位体内肠襻吸收实验可指导壮骨止痛胶囊化学成分的分离.     

Effect of Anoectochilus formosanus on fibrosis and regeneration of the liver in rats

1. The present study examined the effects of an aqueous extract of Anoectochilus formosanus (AFE) on both hepatic fibrosis and regeneration in rats. 2. Fibrosis was induced by intraperitoneal injection of dimethylnitrosamine (DMN) for 3 consecutive days per week for 4 weeks. 3. In DMN-treated rats, liver cirrhosis-associated complications, such as liver atrophy, low concentrations of serum albumin and the accumulation of hepatic collagen, were observed. The AFE protected the liver against DMN-induced fibrosis, as determined by morphological and biochemical observations. 4. In addition, AFE was administered to two-thirds hepatectomized normal and DMN-injured rats. Three and 5 days after hepatectomy, AFE increased the extent of liver weight regeneration and the number of S-phase cells in DMN-injured rats, but not in normal rats. 5. These results show that AFE seems to be useful in the repair of liver injury, improvement of fibrotic changes and promotion of liver regeneration.     

Potent protein tyrosine phosphatase 1B (PTP1B) inhibiting constituents from Anoectochilus chapaensis and molecular docking studies

Abstract

Context: Anoectochilus chapaensis Gagnep. (Orchidaceae), an indigenous and valuable Chinese folk medicine, has been used as an antidiabetic remedy. However, the bioactive constituents have not been reported.

Objective: To explore potent protein tyrosine phosphatase 1B (PTP1B) inhibitors from the whole herbs of A. chapaensis for the treatment of diabetes.

Materials and methods: The compounds were obtained by PTP1B bioactivity-guided isolation from the active fraction of ethonal extract of A. chapaensis, and elucidated by extensive spectroscopic methods and evaluated for their potential to inhibit PTP1B with a series of doses in dimethyl sulphoxide by a colorimetric assay in vitro. The Autodock program was used to dock the active compounds into the binding sites.

Results: Fifteen compounds were identified; epifriedelanol, friedelane, 2α, 3β-dihydroxyolean-12-en-23, 28, 30-trioic acid, dibutyl-phthalate, and 7-hydroxy-2-methoxy-9,10-dihydrophenanthrene-1,4-dione were isolated from the genera Anoectochilus for the first time. All 15 compounds were tested for their inhibitory activity against PTP1B in vitro. Nine active compounds exhibited potent inhibitory effect with IC₅₀ values of 1.16–6.21?μM, which were comparable with the positive control suramin. The 3D-docking simulations showed negative binding energies of ?7.4 to ?8.5?kcal/mol and supported a high affinity to PTP1B residues in the pocket site, indicating that they may stabilize the open form and generate tighter binding to the catalytic sites of PTP1B.

Discussion and conclusion: The results clearly demonstrated that the potential active constituents from A. chapaensis could inhibit PTP1B, which may be mainly attributed to a combination of triterpenoids and flavonoids.