桂枝汤对发热大鼠下丘脑蛋白质组影响初探

目的：初步观察桂枝汤对发热大鼠下丘脑组织中蛋白质的差异表达，为进一步探讨桂枝汤的解热分子机制奠定基础。方法：应用蛋白质组技术，对酵母发热大鼠模型和桂枝汤治疗组下丘脑组织中蛋白质表达进行比较，观察其差异点。结果：发现模型和治疗大鼠下丘脑蛋白表达有明显差异，主要是蛋白表达量的增加和减少以及个别蛋白等电点的改变，其中在给予桂枝汤后有8种蛋白（Mr/pI：28.9kD/4.47，24.4kD/6.28，25.4kD/6.39，25.9kD/6.39,17.6中7.38,17.2kD/7.43，24.9kD/7.39，26.9kD/7.59）表达增强，6种蛋白Mr/pI：14.3kD/4.83，28.5kD/4.39，16.2kD/4.11，15.3kD/6.7，30.5kD/7.09，30.5kD/7.13）表达降低，1种蛋白（Mr/pI：14.8kD/5.4）等电点发生了改变，差异蛋白数量约占可分辨蛋白点的2.3％，本次实验未发现新的差异蛋白点。结论：桂枝汤的解热作用可能与改变下丘脑组织中某些蛋白质的表达及修饰有关。     

桂枝汤有效成分苯丙烯类化合物干预IL-1β刺激小鼠脑微血管内皮细胞释放PGE2的构效关系

前期研究发现,桂枝汤解热有效部位A(Fr.A)在很小剂量(3.8~7.6mg.kg-1,po)即显示了明显的解热活性,并可降低发热动物下丘脑PGE2含量[1],经LC/MS,GC/MS和化学分离确证,其含十余种苯丙烯类化合物,此类化合物为该部位的主要成分。由于Fr.A中除桂皮醛、桂皮醇、2-甲氧基桂皮醛、香豆     

Structure-activity relationships for inhibition of human 5alpha-reductases by polyphenols

The enzyme steroid 5 alpha-reductase (EC 1.3.99.5) catalyzes the NADPH-dependent reduction of the double bond of a variety of 3-oxo-Delta(4) steroids including the conversion of testosterone to 5 alpha-dihydrotestosterone. In humans, 5 alpha-reductase activity is critical for certain aspects of male sexual differentiation, and may be involved in the development of benign prostatic hyperplasia, alopecia, hirsutism, and prostate cancer. Certain natural products contain components that are inhibitors of 5 alpha-reductase, such as the green tea catechin (-)-epigallocatechin gallate (EGCG). EGCG shows potent inhibition in cell-free but not in whole-cell assays of 5 alpha-reductase. Replacement of the gallate ester in EGCG with long-chain fatty acids produced potent 5 alpha-reductase inhibitors that were active in both cell-free and whole-cell assay systems. Other flavonoids that were potent inhibitors of the type 1 5alpha-reductase include myricetin, quercitin, baicalein, and fisetin. Biochanin A, daidzein, genistein, and kaempferol were much better inhibitors of the type 2 than the type 1 isozyme. Several other natural and synthetic polyphenolic compounds were more effective inhibitors of the type 1 than the type 2 isozyme, including alizarin, anthrarobin, gossypol, nordihydroguaiaretic acid, caffeic acid phenethyl ester, and octyl and dodecyl gallates. The presence of a catechol group was characteristic of almost all inhibitors that showed selectivity for the type 1 isozyme of 5 alpha-reductase. Since some of these compounds are consumed as part of the normal diet or in supplements, they have the potential to inhibit 5 alpha-reductase activity, which may be useful for the prevention or treatment of androgen-dependent disorders. However, these compounds also may adversely affect male sexual differentiation.     

Phytochemical and analytical studies of Panax notoginseng (Burk.) F.H. Chen

Panax notoginseng (Burk.) F.H. Chen is distributed throughout the southwest of China, Burma and Nepal. The root of this plant, called notoginseng or sanchi, has a long history of use as a remedy in Oriental traditional medicine. Modern studies have found that extracts and compounds from notoginseng exert various physiological effects. The active constituents are mainly recognized as saponins. In this review, we summarized the discovery and analysis of chemical constituents in notoginseng. Fifty-six saponins from notoginseng were isolated and elucidated. All of them are dammarane saponins, 35 of which can be classified as belonging to the protopanaxadiols group, and 21 as belonging to the protopanaxatriols group. Evidence from phytochemical studies on notoginseng demonstrated that no oleanane-type saponin, which exists in Asian ginseng (Panax ginseng) and American ginseng (Panax quinquefolius), was found. Other types of compounds such as non-protein amino acids, polyacetylenes, phytosterols, flavonoids, and polysaccharides, many of which have pharmacological activities, were also isolated from notoginseng. Analytical studies on notoginseng were carried out based on botanical and phytochemical advances. In the qualitative studies, identification of the herbal materials and extracts was the main objective. The utilization of high-performance liquid chromatography (HPLC) fingerprint and molecular biological methods made the identification accurate and efficient. Spectral, chromatographic and immunoassay methods were used for the quantitative analysis. HPLC methods are the main authority regarding the determination of saponins and other types of constituents. The chromatographic conditions and detectors employed in the HPLC are discussed.     

钟声蛋白样受体的研究及现状

目的:整理钟声蛋白样受体(Toll样受体,TLRs)研究资料,为中药抗炎免疫药物的作用靶点研究提供思路与方法.资料来源:主要搜集近10年来国内外学者公开发表的对Toll样受体的研究成果,对其进行整理与分析.资料选择:综述Toll样受体的发现、分布、结构特征,尤其是其效应细胞配体、信号转导途径及功能研究资料,综合分析其研究现状.结果:目前的研究主要集中在对Toll样受体信号转导通路的基础研究上,而对药物的研究却极为匮乏.结论:对Toll样受体信号转导通路的进一步研究可能会为某些疾病的防治提供科学依据,同时为中药抗炎免疫药物作用靶点的研究提供新的思路与方法.     

桂枝汤对发热大鼠下丘脑组织PKA,PKC活性的影响

目的:研究前列腺素受体Ⅲ型(EP3)受体激动剂硫前列酮(Sul)致热大鼠下丘脑蛋白激酶A(PKA)、蛋白激酶C(PKC)活性的变化及桂枝汤的解热作用机制。方法:选用Sul 1 mg.kg^-1脑室注射(icv)致大鼠发热,观察H-89(特异性PKA抑制剂)1 mg.kg^-1(icv),calphostin C(特异性PKC抑制剂)1 mg.kg^-1(icv)和桂枝汤10 g.kg^-1(ig)对模型大鼠发热的影响,继而采用放射性同位素法,测定给予桂枝汤后EP3受体激动剂致热大鼠下丘脑组织中PKA,PKC的活性变化。结果:Sul脑室注射后,呈现单峰的发热曲线,峰值时在注射后0.5 h左右,并伴有下丘脑组织中PKA活性显著增高和PKC活性的降低倾向。PKA,PKC抑制剂及桂枝汤均可使模型大鼠的发热曲线下移;口饲桂枝汤能显著抑制造模动物下丘脑PKA的活性,大剂量桂枝汤还能显著降低PKC的活性。结论:下丘脑组织中的PKA,PKC参与了EP₃致大鼠发热的病理过程,桂枝汤可抑制EP₃激动诱致的PKA活性增高,这可能是桂枝汤解热作用靶点之一。     

Extracellular detection of delayed afterdepolarization of cardiac fibers using signal averaging technique

AIM: To detect delayed after depolarizations (DAD) in extracellular electrograms using signal averaging technique. METHODS: DAD were induced by acetylstrophanthidin (0.25 mumol.L-1, n = 9) and resibufogenin (0.52 mumol.L-1, n = 5) in sheep cardiac Purkinje fibers. Intracellular voltage was recorded with a conventional microelectrode, and simultaneous extracellular electrograms were recorded differentially from widely spaced electrodes placed in the tissue bath. Noise of electrograms was reduced using signal averaging technique. RESULTS: Acetylstrophanthidin and resibufogenin both induced DAD in the intracellular recording and extracellular DAD (DAD-E) in the extracellular electrogram in sheep heart Purkinje fibers. Acetylstrophanthidin and resibufogenin induced typical changes in the action potential including decrease in action potential amplitude, resting potential, maximum diastolic potential, and action potential duration. Similar shortening occurred in the "Q-T interval" recorded by the extracellular electrogram. With either acetylstrophanthidin or resibufogenin, shortening of stimulation cycle length from 990 ms to 690 ms reduced the coupling interval between action potential upstroke and peak voltage of the DAD (P < 0.01), and the coupling interval between the "QRS" and DAD-E recorded extracellularly (P < 0.01). CONCLUSION: DAD can be detected using the extracellular electrograms combined with the high resolution, signal averaging technique.     

Alternative therapies for male and female sexual dysfunction

Sexual dysfunction is prevalent in both men and women. Although new pharmaceutical agents have been identified for male erectile problems, sexual desire and orgasm disorders, individuals with sexual dysfunction often seek alternative therapies, including traditional Chinese medicine. This article reviews currently used alternative therapies, such as herbal medications, L-arginine, acupuncture, biofeedback and others. Potential herb-drug interactions are also presented.     

Synergistic effect of Scutellaria baicalensis and grape seed proanthocyanidins on scavenging reactive oxygen species in vitro

Scutellaria baicalensis (SbE) is a commonly used Chinese herb medicine and grape seed proanthocyanidins is a popular herbal supplement in the United States. Both herbs have been shown to possess potent antioxidant effects. Using an in vitro model to produce the reactive oxygen species (ROS) generation (H2O2/FeSO4 for hydroxyl radicals, xanthine/xanthine oxidase for suproxide), we observed that Scutellaria baicalensis and grape seed proanthocyanidins acted synergistically to scavenge ROS. Our data suggest that a combination of these two herbs can potentially enhance their antioxidant efficacy, allowing lower dosages of each drug to be used. This has the advantage of avoiding possible side effects that may arise when higher doses of a single herb are used in an attempt to achieve a maximum degree of antioxidant activity.