Red blood cell permeabilization by hypotonic treatments, saponin, and anticancer avicins

Plasma membrane permeabilization by saponin and anticancer avicins was studied using light dispersion measurements, since high correlation between light dispersion changes and hemolysis has been demonstrated. Nevertheless, we observed that rat red blood cell swelling in moderately hypotonic media was accompanied by up to 20% decrease of light dispersion, when hemolysis was not yet detectable. Avicin G and avicin D were significantly more efficient than saponin in inducing cytotoxicity in PC3 human prostate cancer cells. We found that the preincubation of avicins with the plasma membrane, but not with the cytosolic fraction of previously lysed red blood cells, completely protected fresh cells against permeabilization. The data suggest that the plasma membrane can tightly bind the avicins, but not the saponin. Using the “osmotic protection” method with 100 mOsm PEGs of increasing molecular weight in isotonic media, the size of the pores generated by avicin G and avicin D in the plasma membrane was estimated to be higher than the hydrodynamic radius of PEG-8000. The obtained results indicate that the anticancer activity of avicin G and avicin D could be related, at least partially, to their high ability to permeabilize biological membranes. These data might represent interest for possible applications of these anticancer drugs in vivo.     

三七地下部分皂甙成分的HPLC比较研究

应用HPLC定量分析方法,对三七(Panax notoginseng)地下部位的皂甙成分进行分析,通过比较人参皂甙Rg1,Rb1,Re,Rd和三七皂甙R1等5种主要皂甙成分和总皂甙的含量变化,探讨不同部位和组织中皂甙成分的分布规律。结果表明在三七药材的不同商品等级中,人参皂甙Rg1和Rb1的含量以主根60头为最高,5个主要皂甙的总含量也明显高于其他的等级;根茎的生物产量只为全根的18%,皂甙含量占25%以上;主根和根茎中韧皮部的生物产量和总皂甙的含量均高于木质部;二年生三七的生物产量及皂甙含量均较三年生三七低得多。不同表型三七的皂甙组成也有区别。     

N-Aminoacyl and N-hydroxyacyl derivatives of diosgenyl 2-amino-2-deoxy-β-d-glucopyranoside: Synthesis,antimicrobial and hemolytic activities

Diosgenyl 2-amino-2-deoxy-β-d-glucopyranoside is a semisynthetic saponin with antimicrobial and antitumor activities. To search for more effective analogues, N-aminoacyl and N-hydroxyacyl derivatives of this saponin were synthesized conventionally and with microwave assistance, and tested against the human pathogenic fungi and Gram-positive and Gram-negative bacteria. None of the tested compounds exhibit activity against Gram-negative bacteria. Almost all of the synthesized N-aminoacyl saponins exhibit antifungal activity and act effectively against Gram-positive bacteria, some better than the parent compound. The best acting saponins are the same size and possess sarcosine or l- or d-alanine attached to the parent glucosaminoside. Shorter and longer aminoacyl residues are less advantageous. d-Alanine derivative is the most effective against Gram positive bacteria. Structure-activity relationship (SAR) analysis indicates that the free α-amino group in aminoacyl residue is necessary for antimicrobial activities of the tested saponins. (N-Acetyl)aminoacyl and N-hydroxyacyl analogs are inactive. Measurements of the hemolytic activities demonstrate that the best acting saponins are not toxic towards human red blood cells.     

Anticancer saponin OSW-1 is a novel class of selective Golgi stress inducer

OSW-1 is a plant-derived natural product proposed to selectively kill cancer cells by binding to members of the oxysterol binding protein family, thereby disrupting lipid/sterol homeostasis. However, how these protein-ligand interactions mediate cell death signaling has remained elusive. Here, we discovered that OSW-1 selectively activates the Golgi stress response leading to apoptosis, providing a mechanistic basis for the anticancer activity of OSW-1.     

姜状三七根茎的皂苷类化学成分研究

为了解姜状三七(Panax zingiberensis)根茎的皂苷类化学成分,采用正相硅胶、反相硅胶和凝胶等色谱方法从其根茎的乙醇提取物中得到9个皂苷类化合物,根据理化性质和波谱数据,其结构分别鉴定为人参皂苷SL₁ (1)、人参皂苷Rh₁ (2)、三七皂苷R₈ (3)、竹节参皂苷IVa (4)、越南人参皂苷R₁₀ (5)、人参皂苷Rg₁ (6)、菠菜皂苷A 28-O-β-d-葡萄糖苷 (7)、齐墩果酸28-O-β-d-葡萄糖苷 (8)和姜状三七苷R₁ (9)。化合物1、3、5、7和8为首次从该植物中分离得到, 其中化合物5为奥克梯隆醇型皂苷,此类皂苷在该植物中未见报道。     

Efficient synthesis of glycyrrhetinic acid glycoside/glucuronide derivatives using silver zeolite as promoter

3-O-Glycopyranosides of glycyrrhetinic acid have been synthesized in good to high yields and excellent stereoselectivity using glycosyl bromide donors and silver zeolite as promoter. In addition to the preparation of glycosides containing β-linked glucosyl, 2-deoxy-2-trichloroacetamido-glucosyl, galactosyl, cellobiosyl and lactosyl residues, also the deactivated acetylated methyl glucopyranosyluronate bromide donor could be coupled to triterpene aglycon ester derivatives in good yields. The ester protecting group located at C-30 of the oleanolic acid scaffold exerted an influence on the overall yield, with the methylester-protected glycosyl acceptor giving better yields compared to the allyl, benzyl as well as diphenylmethyl ester aglycon. The acetyl-protected glucuronides were differently deblocked in high yields via Zemplén deacetylation or via hydrogenolysis followed by Zemplén deacetylation, and alkaline hydrolysis, respectively, to allow for a selective liberation of the ester groups from either the glucuronide or the glycyrrhetinic acid unit, respectively. The target glycosides/glucuronides serve as probes for pharmaceutical studies aimed at defining structure-activity relationships of glycoside/glucuronide triterpenes.     

三七(Panax notoginseng)根残体化感自毒效应研究

为研究三七(Panax notoginseng(Burk)F.H.Chen)采收过程中残留须根的化感自毒效应,采用土培和水培2种方法,按不同比例添加三七须根粉碎物,检测根残体作用下土培三七土壤中皂苷的动态变化及水培三七根部形态结构变化。结果显示,土培条件下,随着须根粉碎物处理时间的延长,土壤中皂苷成分种类增加、总皂苷含量减少。水培条件下,随着处理时间的延长,添加须根粉碎物处理后的三七根尖细胞壁增厚,细胞中出现菌丝体;随着处理时间及处理浓度的增加,细胞开始皱缩甚至破碎,细胞中无完整细胞器结构,三七根部细胞结构差异明显。研究表明三七采收过程中残留在土壤中的须根腐解释放的化学物质可能是导致三七自毒效应的因素之一。     

Synthesis of L-arabinose-containing fragments of the oat root saponin Avenacin A-1

Chemical syntheses of two disaccharides, benzyl beta-D-glucopyranosyl-(1-->2)-alpha-L-arabinopyranoside (1) and benzyl beta-D-glucopyranosyl-(1-->4)-alpha-L-arabinopyranoside (2), and a trisaccharide, benzyl beta-D-glucopyranosyl-(1-->2)-3-O-acetyl-4-O-(beta-D-glucopyranosyl)-alpha-L-arabinopyranoside (3), related to oat root triterpenoid saponin Avenacin A-1 are reported.     

Enzymatic liberation of lycotetraose from the Solanum glycoalkaloid alpha-tomatine

The branched tetrasaccharide, O-β-d-glucopyranosyl-(1 → 2)-O-[β-d-xylopyranosyl-(1 → 3)]-O-β-d-glucopyranosyl-(1 → 4)-d-galactose (lycotetraose) is a key constituent of many biologically interesting natural products. Described herein is a convenient enzymatic preparation of lycotetraose from the readily available Solanum glycoalkaloid α-tomatine. The preparation makes use of the recombinant endo-glycosidase, tomatinase, from the plant pathogen Fusarium oxysporum f. sp. lycopersici.     

Plant bioactives for ruminant health and productivity

Plants have been used throughout history for their medicinal properties. This use has often focused on human health but plants have also been, and still are, applied in ethnoveterinary practice and animal health management. In recent times, the use of synthetic chemicals has become prevalent. Public awareness of the potential environmental and health risks associated with heavy chemical use has also increased. This has put pressure on regulatory bodies to reduce the use of chemicals in agriculture. The most striking example is the 2006 banning of antibiotics in animal feed by the European Union. Moves such as this have increased the drive to find alternatives to synthetic chemicals and research has again turned to the use of plant bioactives as a means of improving animal health. Current scientific evidence suggests there is significant potential to use plants to enhance animal health in general and that of ruminants (cattle, deer, sheep, etc.) in particular. Active areas of research for plant bioactives (particularly saponin and tannin containing plants) include reproductive efficiency, milk and meat quality improvement, foam production/bloat control and methane production. Nematode control is also a significant area of research and the evidence suggests a much broader range of phytochemicals may be effective. This review presents a summary of the literature and examines international research efforts towards the development of plant bioactives for animal health.