皂角刺化学成分及药理作用研究进展

皂角刺具有抗炎、免疫调节、抗肿瘤等多种药理活性,可用于消炎、镇痛、癌症等的治疗。其化学成分复杂,主要包括黄酮、酚酸、三萜等结构类型。对皂角刺的化学成分和药理作用研究现状作一综述。     

牛膝根结构特征与三萜皂苷的积累关系

三萜皂苷是牛膝根中主要的药用成分之一。利用皂苷定量分析与解剖学和组织化学定位方法对不同生长年限牛膝根的解剖结构及三萜皂苷的积累动态关系进行了研究。结果表明：牛膝根属于异常结构,三生结构发达。牛膝根的增粗生长主要依赖于额外形成层细胞的分裂活动,牛膝根中最多可以产生7～8圈额外形成层。次生韧皮部、栓内层和三生韧皮部是三萜皂苷的主要积累场所;三萜皂苷的积累动态随牛膝的生长年限增加呈现低→高的变化规律,3～4年生牛膝跟中三萜皂苷的积累达最大值。     

三萜皂苷生物合成相关糖基转移酶研究进展

三萜皂苷具有独特的化学性质和丰富的药理活性,在医药、保健品、化妆品、食品添加剂、农业等方面被广泛应用.尿苷二磷酸(UDP)依赖的糖基转移酶(UGTs)是催化三萜皂苷生成的关键酶,对三萜皂苷的结构及其药理活性多样性的形成有重要作用.文中基于UGTs来源及受体底物结构类型对参与植物三萜皂苷生物合成的UGTs进行了综述,并展...     

灵芝菌丝体三萜及其药理活性的研究进展

菌丝体作为灵芝生长发育过程中的一个特定生理阶段,会产生不同于子实体和孢子的特定结构的灵芝酸类三萜化合物。本文总结了灵芝菌丝体中已发现和鉴定的三萜化合物结构、生物活性及其构效关系的研究进展,以期为灵芝菌丝体三萜在生物合成、代谢调控等的基础研究及相关产品的开发应用提供科学参考。     

植物三萜皂苷生物合成途径及调控机制研究进展

三萜皂苷是一类天然存在的结构多样的三萜苷类化合物,广泛分布于植物中.三萜皂苷不仅是植物抵御病原微生物和食草动物的防御化合物,还具有多种药理活性,被广泛应用在医药、日化、食品、农业等领域.近年来,随着科学技术的发展和研究的深入,植物三萜皂苷生物合成途径的基本框架及调控机制研究已经取得了一定的进展.植物三萜皂苷种类繁多、结...     

13C核磁共振谱在三萜和三萜甙化学中的应用

本文简略地叙述了三萜和三萜甙的~(13)C NMR谱及其在研究生物合成、立体化学和阐明结构等方面的应用。     

空心莲子草营养器官结构与三萜皂苷动态积累的关系

采用组织化学定位、显微制片技术和三萜皂苷定量分析方法对空心莲子草营养器官结构与三萜皂苷类物质积累关系进行了研究。结果表明：空心莲子草宿根、根状茎、茎和叶中均有三萜皂苷物质的积累,叶和根状茎内含量十分丰富。在相同采收期内含量依次为：叶＞根状茎＞根＞茎,叶中主要积累于栅栏组织细胞内。空心莲子草的根和根状茎横切面均属于异常结构,具有成同心环状排列的三生维管束。在宿根和根状茎的次生韧皮部、栓内层、三生韧皮部和结合组织内均有三萜皂苷的分布,三生结构在宿根和根状茎中占有主要地位,是三萜皂苷积累的主要场所。在不同采收期内叶、根状茎和根中三萜皂苷的积累趋势基本一致,均随生长期的增加而递增。空心莲子草茎的横切面由表皮、皮层、维管束和髓腔组成,仅部分皮层细胞和初生韧皮部内有三萜皂苷分布。     

灵芝三萜的生物合成和发酵调控

灵芝作为一种名贵的药用真菌,在我国已有2 000多年的利用历史。灵芝三萜是灵芝的关键药效成分之一。从灵芝三萜的结构和构效关系、灵芝三萜的合成途径和相关关键酶,以及灵芝三萜的深层发酵调控策略和技术等方面,综述了灵芝三萜生物合成和发酵调控方面的新进展,进一步提出了当前存在的主要问题,并对今后的主要研究策略和研究方向进行了分析与展望。     

植物三萜皂苷生物合成中关键后修饰酶研究进展

三萜皂苷是由三萜苷元、糖基、糖醛酸等组成的C30萜类化合物,是许多药用植物的主要活性成分,具有广泛的药理作用。三萜皂苷的生物合成包括前体和三萜皂苷骨架的形成以及调控皂苷结构多样性的后修饰。三萜皂苷的后修饰包括三萜骨架的氧化/羟基化和糖基化,分别由不同超基因家族编码的细胞色素P450单加氧酶和糖基转移酶进行催化。三萜皂苷通过后修饰最终可形成多种单体皂苷。目前,已在少数植物中识别和确认了个别与三萜皂苷生物合成相关的关键后修饰酶,发现了部分很可能参与后修饰过程的候选基因。该文就近年来国内外有关三萜皂苷生物合成途径关键后修饰酶的研究进行综述,为进一步开展相关研究和对合成精细途径的解析提供参考。     

灵芝羊毛甾烷型三萜抗肿瘤构效关系初探

多篇文献报道灵芝三萜具有良好的抗肿瘤活性,但其构效关系和作用靶点尚未系统比较。本研究以45种灵芝三萜为研究对象,通过对小鼠白血病细胞L1210的增殖抑制测定,来评价化合物抗肿瘤的能力。结果表明,灵芝菌丝体三萜和子实体中性三萜的活性较强。进一步采用Discovery Studio分子对接技术探讨了12种活性较强的灵芝三萜与5种抗肿瘤作用相关蛋白p53、Bcl-xl、EGFR、IL-2和VEGFR2之间可能的作用靶点,推测三萜化合物抗肿瘤能力与其结构上的乙酰氧基和母环上的共轭双键有关。其中,具有这一特征的含有3个乙酰氧基的ganoderic acid T,其抗肿瘤活性最强。本研究为灵芝三萜活性位点的寻找和结构改造提供了参考。     

A comparison of the fatty acid esters of estradiol and corticosterone synthesized by tissues of the rat

The biosynthesis of the fatty acid esters of the corticoid (corticosterone) and estrogen (estradiol) was compared in parallel incubations of corticosterone and estradiol with several tissues of the rat. The fatty acid composition of the esters of the two steroids was characterized in mammary and uterine tissue. In both of these tissues, the esters of estradiol were extremely heterogeneous. To the contrary, in the same tissues only one predominant ester of corticosterone, corticosterone-21-oleate, was formed. It comprised 70-80% of the total. The oleate ester of estradiol accounted for only 20% of the esters of this estrogen. In addition, fatty acid esters of an A-ring reduced metabolite of corticosterone, 5 beta-dihydrocorticosterone, was also identified. Its fatty acid composition is identical to that of corticosterone. In other experiments the fatty acid esters of both steroids were isolated from several tissues and quantified. When the amount of steroidal ester formed was compared, there was over a 100-fold difference among the various tissues in the ratio of estradiol to corticosterone ester synthesized. Thus, the rate of synthesis of the fatty acid esters of each class of steroid varies dramatically from tissue to tissue, and their fatty acid composition differs markedly as well. If the same enzyme synthesized both the estrogen and corticoid esters, then it would be expected that the relative amount of both esters synthesized in various tissues should be constant and likewise that their composition should be the same. Since neither occurred, these results suggest that the enzyme which produces the C-17 fatty acid esters of the estrogens may be different from the one which synthesizes the C-21 esters of the corticoids. The existence of separate enzyme systems for the synthesis of the fatty acid esters of these steroid hormones opens the possibility of specific physiological controls of each of these unusual steroidal metabolites.     

3, 4-Dihydroxyphenylalanine is oxidized by phenoxyl radicals of hydroxycinnamic acid esters in leaves ofVicia faba L

Mechanisms of oxidation of 3,4-dihydroxyphenylalanine (dopa) in leaves ofVicia faba have not yet been elucidated in details. The author hypothesized its oxidation by radicals of hydroxycinnamic acid esters that were generated by a peroxidase-dependent reaction in vacuoles. The results obtained in this study were followings. 1) Vacuolar peroxidase isolated from the leaves oxidized dopa more slowly than 4-coumaric and caffeic acid esters isolated from the leaves. 2) The hydroxycinnamic acid esters enhanced peroxidase-dependent oxidation of dopa and dopa suppressed their oxidation. 3) Degree of the enhancement was roughly correlated with rates of the oxidation of hydroxycinnamic acid esters. 4) The hydroxycinnamic acid esters increased levels of dopa radical in the presence of peroxidase. 5) In protoplasts of mesophyll cells ofV. faba, hydrogen peroxide-induced oxidation of dopa was faster than that of 4-coumaric acid and caffeic acid esters. These results support the above hypothesis that dopa in vacuoles is oxidized by phenoxyl radicals of hydroxycinnamic acid esters that are generated by vacuolar peroxidase.     

Synthesis and biological activities of 4-chloroindole-3-acetic acid and its esters

4-Chloroindole-3-acetic acid (4-Cl-IAA) and its esters were synthesized from 2-chloro-6-nitrotoluene as the starting material. The biological activities of 4-CI-IAA and its esters were determined by four bioassays. Except for the tert-butyl ester, 4-Cl-IAA and its esters had stronger elongation activity toward Avena coleoptiles than had indole-3-acetic acid. The biological activities of the methyl, ethyl and allyl esters were as strong as the activity of the free acid. All the esters, except for the tert-butyl, inhibited Chinese cabbage hypocotyl growth more than the free acid did, and all the esters induced severe swelling and formation of numerous lateral roots in black gram seedlings even at a low concentration. Furthermore, adventitious root formation was strongly promoted in Serissa japonica cuttings by all the esters. The root formation-promoting activities of the ethyl and allyl esters were about three times the value for indole-3-butyric acid which is used to promote and accelerate root formation in plant cuttings.     

Hydroxycinnamic acid esters enhance peroxidase-dependent oxidation of 3, 4-dihydroxyphenylalanine. differences in the enhancement among the esters

Horseradish peroxidase (HRP)-dependent oxidation of 3, 4-dihydroxyphenylalanine (dopa) was studied to elucidate the mechanism of its oxidation. The oxidation of dopa was enhanced by hydroxycinnamic acid esters and dopa supressed HRP-dependent oxidation of the esters. These results indicate that phenoxyl radicals of hydroxycinnamic acid esters that are formed at first, can oxidize dopa. Among hydroxycinnamic acid esters used, affinity of the phenoxyl radicals for dopa was in order 4-coumaric>caffeic>ferulic acid ester radicals.     

Separation of polyunsaturated fatty acids by selective inclusion in guanidinium-1,5-naphthalenedisulfonate-2-methoxyethanol host networks

Hydrogen-bonded networks composed of guanidinium (G) and 1,5-naphthalenedisulfonate (NDS) have been developed for the selective inclusion and separation of fatty acid esters based on their degree of unsaturation. Porous crystalline networks have been synthesized and include fatty acid esters during crystallization from both methanol and 2-methoxyethanol. Crystalline networks formed in methanol are selective for the inclusion of saturates in preference to polyunsaturated fatty acid methyl esters, but their applicability is limited by the competing inclusion of the solvent methanol. In 2-methoxyethanol, a three-component host structure is formed that provides 4.1 x 4.7 A2 pores which are also selective for saturated fatty acid ester inclusion. These networks do not suffer from the competing inclusion of the solvent 2-methoxyethanol as is the case with methanol, and thus complete removal of initial saturated fatty acid 2-methoxyethyl esters is possible. Binary selectivity experiments on mixtures of the 2-methoxyethyl esters of saturated stearic acid and the omega-3 fatty acid alpha-linolenic acid reveal that this three-component network structure provides nearly complete resolution of these two guests in the crystal and filtrate fractions. Separation of the 2-methoxyethyl esters of alpha-linolenic acid from the monounsaturated oleic acid is also possible, although with decreased efficiency in comparison to removal of the saturated fatty acid ester.     

Synthesis and degradation of fatty acid ethyl esters by cultured hepatoma cells exposed to ethanol

Fatty acid ethyl esters are a family of neutral lipids that are the products of esterification of fatty acids with ethanol. Unlike other pathways of ethanol metabolism, ethyl esters are present in numerous human organs which are the targets of ethanol-induced damage. In the present study, we have shown that fatty acid ethyl esters are synthesized by a hepatoma cell line in tissue culture when exposed to ethanol concentrations easily attained by man during social drinking. Unlike alcohol dehydrogenase, the enzyme(s) responsible for synthesis of ethyl esters are membrane-bound and concentrated in the microsomal fraction of rat hepatocytes. In addition, fatty acid ethyl esters are hydrolyzed to free fatty acids and ethanol by membrane-bound enzyme(s) that are enriched in the microsomal and mitochondrial-lysosomal fractions. Intracellular hydrolysis of fatty acid ethyl esters release free fatty acids which are preferentially incorporated into cellular cholesterol esters. Thus, we have shown that a hepatocellular line exposed to concentrations of ethanol easily achieved in man by social drinking utilize endogenous fatty acids to form long-lived ethanol metabolites, fatty acid ethyl esters. Importantly, this family of neutral lipids may act as biochemical mediators of ethanol-induced cell damage, including the changes in cholesterol metabolism noted in chronic alcoholics.     

Lanthanide-induced hydrolysis of 4,7-diphenyl-1,10-phenanthroline-2,9-dicarboxylic acid esters

The hydrolysis of 4,7-diphenyl-1,10-phenanthroline-2,9-dicarboxylic acid (DPPDA) esters is induced by lanthanide(III) ions. As the related 2,6-pyridinedicarboxylic acid esters are not cleaved, the effect is traced back on improved complexation of the lanthanides by the DPPDA esters. Time-resolved fluorescence spectroscopic and electrospray mass spectrometric investigations on the esters provide information on the progress of the reactions.     

Identification and quantitation of fatty acid ethyl esters in biological specimens

Fatty acid ethyl esters, recently described as enzymatic products of nonoxidative ethanol metabolism in the heart, may represent a mediator or marker of ethanol-induced organ pathology such as alcoholic cardiomyopathy. This study was designed to develop a method for the extraction, quantitation, and definitive identification of fatty acid ethyl esters formed both in biological specimens and during enzymatic incubations. First, several potential sources of error were identified and characterized. Tissue extraction with alcohols led to the time, temperature, and concentration-dependent nonenzymatic formation of fatty acid alcohol esters. Contamination of both substrates, [14C]ethanol and 14C-fatty acid, used to measure enzymatically mediated fatty acid ethyl ester synthesis, could be removed by purification. Accurate quantitation of fatty acid ethyl esters in tissue was achieved using acetone as an extraction solvent, after which isolated lipids were thin-layer chromatographed on silica gel developed with an apolar solvent system (petroleum ether:diethyl ether:acetic acid, 75:5:1). Gas chromatography and mass spectroscopy identified individual fatty acid ethyl esters. The reproducibility of this assay was high, as assessed by quintuplicate determinations of fatty acid ethyl esters formed in liver and heart homogenates, a method with standard deviations 4 to 11% of the mean.     

Mechanism of toxicity of esters of caffeic and dihydrocaffeic acids

Ten esters each of caffeic acid and dihydrocaffeic acid have recently been synthesized. Cytotoxicity evaluations of these esters versus L1210 leukemia and MCF-7 breast cancer cells in culture have led to the delineation of substantially different QSAR for each series. The L1210 QSAR for dihydrocaffeic acid esters resembles the QSAR obtained for simple phenols and estrogenic phenols. However, the QSAR pertaining to the caffeic acid esters differs considerably from its sister QSAR. This difference may be attributed to the presence of the olefinic linkage in the side chain. The octyl ester of caffeic acid is nearly ten times as toxic to the leukemia cells than the widely studied phenethyl ester, CAPE.     

Steroidal fatty acid esters

Several years ago we discovered an unexpected family of steroidal metabolites, steroidal fatty acid esters. We found that fatty acid esters of 5-ene-3β-hydroxysteroids, pregnenolone and dehydroisoandrosterone are present in the adrenal. Subsequently, others have shown the existence of these non-polar 5-ene-3β-hydroxysteroidal esters in blood, brain and ovaries. Currently, almost every family of steroid hormone is known to occur in esterified form. We have studied the esters of the estrogens and glucocorticoids in some detail, and have found that these two steroidal families are esterified by separate enzymes. In a biosynthetic experiment performed simultaneously with estrodiol and corticosterone, we established that the fatty acid composition of the steroidal esters is quite different. The corticoid is composed predominantly of one fatty acid, oleate, while the estradiol esters are extremely heterogeneous. Our studies have demonstrated that the estrogens are extremely long-lived hormones, that they are protected by the fatty acid from metabolism. They are extremely potent estrogens, with prolonged activity. Esterification appears to be the only form of metabolism that does not deactivate the biological effects of estradiol. We have demonstrated the biosynthesis of fatty acid esters of estriol, monoesters at both C-16 and C-17β. They too are very potent estrogens. These fatty acid esters of the estrogens are the endogenous analogs of estrogen esters, like benzoate, cypionate, etc., which have been used for decades, pharmacologically because of their prolonged therapeutic potency. We have found that the estradiol esters are located predominantly in hydrophobic tissues, such as fat. Sequestered in these tissues, they are an obvious reservoir of estrogenic reserve, requiring only an esterase for activation. To the contrary the biological activity of the fatty acid esters of the glucocorticoid, corticosterone, is not different from that of its free parent steroid. We have shown that the rapid kinetics of its induction of gluconeogenic responses is caused by its labile C-21 ester which is rapidly hydrolyzed by esterase enzymes. While it appears that the physiological role of the estrogen esters may be related to their long-lived hormonal activity, the role of the other families of steroidal esters is not yet apparent. They, and perhaps the estrogen esters as well, must serve other purposes. Indeed they may serve important biological functions beyond those which we ordinarily associate with steroid hormones.