芒果苷衍生物的合成及其PTP1B酶抑制活性研究

目的设计合成一系列芒果苷衍生物并进行体外蛋白酪氨酸磷酸酶1B（PTP1B）抑制活性实验。方法利用亲核取代反应在芒果苷上引入疏水苄基,设计合成8个新化合物4~11,采用比色法对化合物进行PTP1B抑制活性研究。结果设计合成的8个化合物对PTP1B酶都有一定的抑制作用。结论芒果苷衍生物的活性明显好于芒果苷本身的活性,苄基的对位取代活性要优于邻位和间位取代,且苄基上氯原子取代的衍生物要高于其它原子取代的化合物活性。     

芒果苷的药理作用研究进展

芒果苷又称知母宁、芒果素,主要存在于漆树科和龙胆科植物中。因其是多酚酸类化合物,具有较强的抗氧化活性和多种药理作用。近年来,国内外大量研究报道芒果苷的各种药理学活性,包括抗糖尿病及其并发症、调节脂代谢异常、抗肿瘤、心血管保护、抗高尿酸血症、神经保护、抗氧化、抗炎、解热和镇痛、抗菌、抗病毒、抗辐射、保肝、促进骨骼发育、抗过敏和免疫调节等广泛的药理作用,具有进一步研究和开发的可能性。该文对近年来国内外芒果苷药理学作用的研究进展归纳、分析和总结,为进一步的药物研究和开发提供参考。     

知母提取物的降血糖作用

目的对知母进行系统提取分离,筛选提取物的降血糖作用活性组分。方法用四氧嘧啶及链脲佐菌素诱导的糖尿病小鼠和大鼠模型,以空腹血糖值为指标研究知母各提取物的降糖作用;从其活性部位知母总酚中继续分离得3个化合物(拔契皂苷元、芒果苷、新芒果苷),并探讨知母总酚及其成分对α-葡萄糖苷酶活性的影响。结果知母总酚能显著降低四氧嘧啶和链脲佐菌素引起的糖尿病动物的空腹血糖,从中分离得到的芒果苷体外有较好的抑制α-葡萄糖苷酶活性的作用。结论知母总酚对糖尿病动物有较好的降糖作用,其中芒果苷对α-葡萄糖苷酶活性的抑制可能是其降糖作用机制之一。     

小檗碱与芒果苷及其配伍对L6成纤维细胞葡萄糖摄取的影响及机制

<正>小檗碱与芒果苷皆为来源于植物的天然产物,具有抗糖尿病等多种药理活性。李学坚等[1-3]曾报道小檗碱与芒果苷配伍具有抗炎、抑菌、镇痛、降糖的药理活性,但二者配伍后在细胞水平的研究尚未见报道。该文以葡萄糖摄取为切入点,观察二者配伍对葡萄糖摄取的影响,并进而研究二者配伍对葡萄糖摄取信号通路的影响。     

大豆苷元氨基甲酸酯类衍生物的合成及其抗缺氧活性

采用三光气与吗啉、二甲胺、哌啶及乙基哌嗪等反应生成相应的氨基甲酰氯,再与大豆苷元反应成酯,合成了4个新的大豆苷元氨基甲酸酯类衍生物,结构均经1H-NMR、13C-NMR和MS确证.采用常压耐缺氧试验对目标化合物的药理活性进行评价,化合物Ⅰ、Ⅲ的抗缺氧作用等价于母体化合物,化合物Ⅱ和Ⅳ具有优于母体化合物的抗缺氧活性.     

桑叶抗糖尿病活性成分研究

目的 研究桑叶抗糖尿病的活性成分。方法 桑叶用80%乙醇和水提取。利用硅胶、凝胶等柱色谱及制备液相色谱进行分离,并根据理化性质和有机波谱技术鉴定了化合物的结构,进一步通过测定生物碱类化合物和黄酮苷类化合物对胰岛素抵抗的HepG2细胞葡萄糖消耗量来评价其抗糖尿病活性。结果 从桑叶中分离鉴定了8个化合物,分别为:1-脱氧野尻霉素(1),1,4-dideoxy-1,4-imino-D-arabinitol(2),山奈酚-3-O-β-D-吡喃葡萄糖苷(3),β-谷甾醇(4), 正三十四烷醇(5),oxyresveratrol(6),熊果酸(7),葡萄糖乙醇苷(8),此外化合物3能够显著提高胰岛素抵抗HepG2细胞葡萄糖消耗量。结论 化合物3具有较强的抗糖尿病活性。     

黄芩苷衍生物的合成及其生物活性研究

目的为改善黄芩苷的溶解性,设计合成系列黄芩苷衍生物,并评价其抗脂质过氧化活性和抗肿瘤活性。方法以黄芩苷和环氧乙(丙)烷为原料,通过羟乙基化、羟丙基化、酯化反应合成了一系列黄芩苷衍生物;分别采用生化法和台盼蓝染色法测试目标化合物对小鼠脑脂质过氧化产物丙二醛(MDA)的体外抑制作用及对白血病细胞HL-60的生长抑制活性。结果合成了13个黄芩苷衍生物,其结构经1H-NMR和MS确证。其中,化合物3⁶、116、11¹3为未见文献报道的新化合物。化合物1、6对MDA的抑制作用显著,化合物713为未见文献报道的新化合物。化合物1、6对MDA的抑制作用显著,化合物7¹0、12具有中等强度的抑制HL-60生长作用。结论黄芩苷结构中的酚羟基是其抑制脂质过氧化产物MDA的活性基团,葡萄糖醛酸的6位游离羧基是能够增强化合物抗肿瘤活性的有效基团。     

芒果苷单钠盐的制备及其与芒果苷的药效比较

目的 制备芒果苷单钠盐,并与芒果苷的药效进行比较.方法 芒果苷与NaHCO3,反应制备芒果苷单钠盐,用ESIMS及元素分析对其结构进行表征,并比较其镇咳、祛痰和抗炎的作用.结果 芒果苷单钠盐的镇咳、化痰和抗炎作用比芒果苷强.结论 本合成方法简单可行,收率高.芒果苷单钠盐有望开发成呼吸系统药物.     

芒果苷药理作用研究概况

芒果苷（mangiferin）是一种四羟基吡酮的碳糖苷，属双苯吡酮类黄酮类化合物，在多种植物中存在，如漆树科芒果树（Manifera indica）。扁桃树（Mangifera perisciformis）的叶、果实、树皮，龙胆科植物（Canscora-decussate），百合科植物知母（Anemarrhena asphodeloids Bunge）及水龙骨科植物光石韦（Foliaum Pyrrosiae）等。现代药理研究表明，芒果苷具有抗氧化、抗细菌、抗病毒、免疫调节及抗肿瘤等多方面的生理活性和药理作用。现就国内外有关芒果苷的药理作用的研究现状进行综述。[第一段]     

2-(E)-(4-甲磺酰氨基)亚苄基环戊酮Mannich碱类化合物的合成及抗炎活性

目的设计合成2-(E)-(4-甲磺酰氨基)亚苄基环戊酮Mannich碱类化合物,并对其抗炎活性进行初步评价.方法以环戊酮、4-硝基苯甲醛及胺类化合物为原料,经多步反应合成目标化合物,并以二甲苯致小鼠耳肿胀模型测试目标化合物的抗炎活性.结果与结论共合成11个新化合物,经IR、1H-NMR和MS确证其结构.初步药理实验结果显示,化合物6f、6i具有一定的抗炎活性.     

Mangiferin and its aglycone,norathyriol, improve glucose metabolism by activation of AMP-activated protein kinase

Context: Mangiferin has been reported to possess antidiabetic activities. Norathyriol, a xanthone aglycone, has the same structure as mangiferin, except for a C-glucosyl bond. To our best knowledge, no study has been conducted to determine and compare those two compounds on glucose consumption in vitro.

Objective: In this study, the effects of norathyriol and mangiferin on glucose consumption in normal and insulin resistance (IR) L6 myotubes were evaluated. Simultaneously, the potential mechanism of this effect was also investigated.

Materials and methods: Normal or IR L6 myotubes were incubated with norathyriol (2.5?～?10?μM, 0.625?～?2.5?μM), mangiferin (10?～?40?μM, 2.5?～?10?μM) or rosiglitazone (20?μM) and/or 0.05?nM insulin for 24?h, respectively. The glucose consumption was assessed using the glucose oxidase method. Immunoblotting was performed to detect protein kinase B (PKB/Akt) and AMP-activated protein kinase (AMPK) phosphorylation in L6 myotubes cells.

Results: Norathyriol and mangiferin treatment alone increased the glucose consumption 61.9 and 56.3%, respectively, in L6 myotubes and made additional increasing with 0.05?nM insulin. In IR L6 myotubes, norathyriol treatment made increasing with or without insulin, mangiferin treatment also made increasing but only when co-treated with insulin. Immunoblotting results showed that norathyriol and mangiferin produced an increase of 1.9?- and 1.8-fold in the phosphorylation levels of the AMPK, but not in Akt.

Discussion and conclusion: Our findings suggest that norathyriol and mangiferin could improve the glucose utilization and insulin sensitivity by up-regulation of the phosphorylation of AMPK. Norathyriol may be considered as an active metabolite responsible for the antidiabetic activity of mangiferin.     

Reducing effect of mangiferin on serum uric acid levels in mice

Context: Mangiferin, a natural bioactive xanthone C-glycoside, is widely present in medicinal plants like the leaf of Mangifera indica L. (Anacardiaceae). It has been reported that mangiferin possesses a variety of biological activities, including antidiabetic, hepatoprotective, anti-inflammatory, antioxidant, and anticarcinogenic. Objective: The hypouricemic effect and xanthine oxidoreductase (XOR) inhibitory activity of mangiferin were investigated here for the first time. Materials and methods: The hypouricemic effect of mangiferin was investigated in normal and hyperuricemic mice induced by potassium oxonate. Mangiferin at a dose of 0.75-100.0 mg/kg was given intragastrically to mice. The serum urate levels were determined using the phosphotungstic acid method. The hepatic activities of xanthine dehydrogenase (XDH) and xanthine oxidase (XOD) in hyperuricemic mice were assayed using commercially available kits. Results: The results showed that mangiferin at a dose of 1.5, 3.0, and 6.0 mg/kg significantly reduced the serum urate levels (148.7 ± 37.8, 142.2 ± 44.5, 121.7 ± 21.7 μmmol/L) in hyperuricemic mice, compared with untreated hyperuricemic mice (201.8 ± 71.2 μmmol/L). However, mangiferin did not decrease the serum urate levels in normal mice until mangiferin was up to 100 mg/kg. In addition, the hepatic activities of XDH in hyperuricemic mice were significantly decreased by mangiferin, while no changes of XOD were observed. Acute toxicity study in mice showed that mangiferin was very safe at a dose of up to 25 g/kg. Discussion and conclusion: These findings demonstrate that mangiferin has the potential to be developed as a new therapeutic agent for the treatment of hyperuricemia and gout.     

Flavone-based novel antidiabetic and antidyslipidemic agents

The hybrid congeners 62-90 of 6- and 7-hydroxyflavones with aminopropanol have been synthesized and evaluated for their antidiabetic activity in sucrose-challenged low-dosed streptozotocin (STZ)-induced diabetic rats and db/db mice. The optical enantiomers 70a, 70b, 90a, and 90b of two congeners 70 and 90 exhibiting consistent antidiabetic and antidyslipidemic activities were also prepared, and their antidiabetic activity results indicate its association mainly with S isomers. These compounds also lower cholesterol and TG profiles while improving high-density lipoprotein cholesterol to CHOL ratio in db/db mice. The bioavailability of compound 70 and its isomer varies between 27 and 29% whereas that of the more polar compound 90a is poor as determined in rat by oral and intraperitoneal administrations.     

Reducing effect of mangiferin on serum uric acid levels in mice

Context: Mangiferin, a natural bioactive xanthone C-glycoside, is widely present in medicinal plants like the leaf of Mangifera indica L. (Anacardiaceae). It has been reported that mangiferin possesses a variety of biological activities, including antidiabetic, hepatoprotective, anti-inflammatory, antioxidant, and anticarcinogenic.

Objective: The hypouricemic effect and xanthine oxidoreductase (XOR) inhibitory activity of mangiferin were investigated here for the first time.

Materials and methods: The hypouricemic effect of mangiferin was investigated in normal and hyperuricemic mice induced by potassium oxonate. Mangiferin at a dose of 0.75–100.0 mg/kg was given intragastrically to mice. The serum urate levels were determined using the phosphotungstic acid method. The hepatic activities of xanthine dehydrogenase (XDH) and xanthine oxidase (XOD) in hyperuricemic mice were assayed using commercially available kits.

Results: The results showed that mangiferin at a dose of 1.5, 3.0, and 6.0 mg/kg significantly reduced the serum urate levels (148.7 ± 37.8, 142.2 ± 44.5, 121.7 ± 21.7 µmmol/L) in hyperuricemic mice, compared with untreated hyperuricemic mice (201.8 ± 71.2 µmmol/L). However, mangiferin did not decrease the serum urate levels in normal mice until mangiferin was up to 100 mg/kg. In addition, the hepatic activities of XDH in hyperuricemic mice were significantly decreased by mangiferin, while no changes of XOD were observed. Acute toxicity study in mice showed that mangiferin was very safe at a dose of up to 25 g/kg.

Discussion and conclusion: These findings demonstrate that mangiferin has the potential to be developed as a new therapeutic agent for the treatment of hyperuricemia and gout.     

Therapeutic and cosmetic applications of mangiferin: a patent review

Introduction: Mangiferin, a natural C-glucoside xanthone [2-C-β-D-glucopyranosyl-1, 3, 6, 7-tetrahydroxyxanthone], is abundantly present in young leaves and stem bark of the mango tree. The xanthonoid structure of mangiferin with C-glycosyl linkage and polyhydroxy components contributes to its free radical-scavenging ability, leading to a potent antioxidant effect as well as multiple biological activities.

Areas covered: An extensive search was carried out to collect patent information on mangiferin and its derivatives using various patent databases spanning all priority years to date. The patents claiming therapeutic and cosmetic applications of mangiferin and its derivatives were analyzed in detail. The technology areas covered in this article include metabolic disorders, cosmeceuticals, multiple uses of the same compound, miscellaneous uses, infectious diseases, inflammation, cancer and autoimmune disorders, and neurological disorders.

Expert opinion: Mangiferin has the potential to modulate multiple molecular targets including nuclear factor-kappa B (NF-κB) signaling and cyclooxygenase-2 (COX-2) protein expression. Mangiferin exhibits antioxidant, antidiabetic, antihyperuricemic, antiviral, anticancer and antiinflammatory activities. The molecular structure of mangiferin fulfils the four Lipinski's requisites reported to favor high bioavailability by oral administration. There is no evidence of adverse side effects of mangiferin so far. Mangiferin could thus be a promising candidate for development of a multipotent drug.     

Synthesis of novel beta-aminoalcohols containing nabumetone moiety with potential antidiabetic activity

Twenty five new beta-aminoalcohols containing nabumetone moiety were prepared via the reduction of potassium borohydride with a convenient and efficient procedure, starting from beta-aminoketones that have been synthesized by our group. Their chemical structures were determined by IR, MS, 1H NMR, 13C NMR, HR-MS and antidiabetic activities were screened in vitro. Preliminary results revealed that the antidiabetic activity of most beta-aminoalcohols were better than that of the corresponding beta-aminoketones. Although most compounds showed weak antidiabetic activity, the alpha-glucosidase inhibitory activity of compounds 5hd(1) and 5id(2) reached 74.37% and 90.15%, respectively, which were superior to the positive control. The relative peroxisome proliferator-activated receptor response element (PPRE) activity of five compounds were more than 60%, among them compound 5ca possessed the highest activity (112.59%). As lead molecules of antidiabetic agents, compounds 5hd(1), 5id(2) and 5ca deserve further study.     

Semi-synthesis of mangiferin-7-O-β-D-glucuronide

Mangiferin is a natural plant polyphenol with a structure of xanthone C-glycoside and it displays a wide spectrum of pharmacological activities. Investigation of the metabolites of mangiferin is valuable in studying the mechanisms of its various pharmacological properties and developing novel drugs from the mangiferin derivatives. Among the metabolites of mangiferin, mangiferin-7-O-β-D-glucuronide has been reported as the phase II metabolite of mangiferin. Herein we described the first semi-synthesis of mangiferin-7-O-β-D-glucuronide with the natural product mangiferin as the starting material. In this work, we adopted several regioselective protection procedures to distinguish the different hydroxyl groups in the structure of mangiferin, and we accomplished the glycosylation under the phase-transfer catalysis conditions. In this method, we efficiently synthesized the glucuronide derivative of mangiferin in 10 steps with highly regioselective protection.     

Benzimidazole: a medicinally important heterocyclic moiety

Benzimidazole nucleus is a constituent of many bioactive heterocyclic compounds that are of wide interest because of their diverse biological and clinical applications. Moreover, benzimidazole derivatives are structural isosters of naturally occurring nucleotides, which allows them to interact easily with the biopolymers of the living system. This created interest in researchers who have synthesized variety of benzimidazole derivatives and screened them for their various biological activities, viz., anticancer, hormone antagonist, antiviral, anti-HIV, anthelmintic, antiprotozoal, antimycobacterial, antihypertensive, anti-inflammatory, analgesic, anxiolytic, antiallergic, coagulant, anticoagulant, antioxidant as well antidiabetic activities.