Rapid identification of triterpenoid saponins in the roots of <Emphasis Type="Italic">Codonopsis lanceolata</Emphasis> by liquid chromatography–mass spectrometry

Liquid chromatography coupled with sequential mass spectrometry (LC–MS ⁿ ) has been used to identify 3,28-bidesmosidic triterpenoid saponins, lancemaside A (1), foetidissimoside A (2), aster saponin Hb (3), lancemaside E (4), lancemaside B (5), lancemaside F (6), lancemaside G (7), lancemaside C (8), and lancemaside D (9) in the roots of Codonopsis lanceolata. Structural information about both the aglycone and the sugar moiety at the C-3 position of saponins was obtained in the negative-ion mode. On the other hand, positive-ion spectra mainly provide structural information about the sugar chains of saponins, especially the oligosaccharide moiety at the C-28 position. During subsequent fragmentation of the product ions derived from the oligosaccharide moiety at the C-28 position, fragments produced by sequential loss of a monosaccharide unit were observed. Furthermore, the structural features of two unknown saponins in the roots of C. lanceolata were assigned on the basis of the fragmentation patterns of the known saponins. These studies demonstrate that LC–MS ⁿ analysis has great potential for the identification and characterization of triterpenoid saponins in plant extracts.     

A novel oligosaccharide ester from Syringa pubescens

Pubescenside A (1), a novel oligosaccharide ester, has been isolated from the flowers of Syringa pubescens, together with five known compounds d-mannitol (2), meso-inositol (3), hydrostytosol (4), glucose (5), and sucrose (6). The structure of 1 was elucidated as 1-O-[β-d-glucopyranosyl-(1–6)-β-d-galactopyranosyl-(1–1)-β-d-galactopyranosyl-6]-4,4-dimethylpelargonicate by chemical and spectroscopic means. The water extract of the flowers and leaves of S. pubescens showed cytotoxicity against L2215 cell line (IC₅₀ = 78 μg/ml).     

Patent Evaluation: An Adhesin-Oligosaccharide Conjugate Vaccine for Haemophilus Influenzae

Summary

Novelty: Vaccines against H. influenzae are described which utilize an immunogenic conjugate comprizing a synthetic oligosaccharide, corresponding to a fragment of the capsule of H. influenzae type b, coupled to an H. influenzae adhesion protein. The adhesion protein mediates attachment by bonding bacteria to host cells.

Biology: Adhesion is said to be immunogenic in BALB/c mice, and antibodies to adhesin appear to neutralize the adhesin binding to its receptor. No biological data are presented for the conjugate.

Chemistry: Fourteen synthetic ribosylribitol phosphates are described. together with chain elongation details using solid phase synthesis. The identification, preparation and purification of a 47kDa adhesion molecule, and its coupling to the oligosaccharide is described. The 47kDa adhesion molecule is shown to be conserved in non-typable, type b and non-typed clinical isolates using western blot techniques. A typical conjugate is shown.

Structure:      

Novel nanostructured lipid carrier-based inserts for controlled ocular drug delivery: evaluation of corneal bioavailability and treatment efficacy in bacterial keratitis

Objectives: The aim of the present study was to develop novel ofloxacin (OFX)-loaded nanostructured lipid carrier (NLC)-based inserts for ocular application for treatment of bacterial keratitis.

Methods: NLC loaded with 0.3% OFX was prepared by means of high shear homogenization and 0.75% chitosan oligosaccharide lactate (COL) was added. Glycerin or PEG 400 at the range of 1 – 15% was added to NLCs as plasticizers and inserts were developed by solvent casting evaporation. Characterization, in vitro release, microbiological, ex vivo and in vivo studies were performed.

Results: The inserts developed with the addition of glycerin (Ins3_OFX) was found as optimal. The kinetic studies revealed that the release of Ins3_OFX was a combination of diffusion and swelling. Ins3_OFX was more bioadhesive in texture profile analysis studies. In the in vivo studies performed with rabbits, the pre-ocular retention time was enhanced up to 24 h and C_max was increased almost six times in comparison with commercial. The rabbits were infected with Staphylococcus aureus and keratitis was confirmed. This group was treated with Ins3_OFX and they recovered in 7 days with no significant sign of conjunctival redness and corneal opacity.

Conclusion: NLC-based inserts developed with COL and glycerin may be offered as appropriate vehicles for ocular delivery.     

One-pot synthesis of a 3,6-branched hexaarabinogalactan using galactopyranosyl thioglycoside diol as a key glycosylating agent

We present in this paper the efficient four-component one-pot synthesis of a fully protected hexaarabinogalactan 2 with di-branched structure by using d-thiogalactopyranoside 3,6-diol 3 as the central glycosylating agent. After global deprotection, 2 was converted into the 3-aminopropyl linker-containing free oligosaccharide 1 that is structurally related to ALR-5IIa-1-1, an arabino-3,6-galactan with intestinal immune system modulating activity.     

鬼臼毒素聚合物胶团对人胶质瘤细胞的抑制作用

目的 合成鬼臼毒素聚合物胶团,评价其对人胶质瘤细胞的增殖抑制作用。方法 制备鬼臼毒素聚合物胶团,考察其理化性质,通过肿瘤细胞摄取实验,噻唑蓝（MTT）法检测其对U87细胞的增殖抑制作用。结果 鬼臼毒素聚合物胶团比游离药物鬼臼毒素对人胶质瘤细胞有更大的增殖抑制作用,显著增加肿瘤细胞内的药物浓度。结论 鬼臼毒素聚合物胶团对人脑胶质瘤细胞增殖有明显的抑制作用。     

礞石滚痰丸联合哌罗匹隆对精神分裂症患者血清生化指标的影响

目的 研究礞石滚痰丸联合哌罗匹隆对精神分裂症患者血清生化指标的影响。方法 选择2015年1月-2017年12月南阳市第四人民医院收治的300例精神分裂症患者,随机分为两组。对照组单纯口服哌罗匹隆,观察组联合口服礞石滚痰丸。两组均治疗6周。比较两组治疗前后的阳性和阴性症状量表评分（PANSS）和血清生化指标改变情况。结果 与对照组临床有效率78.00%比较,观察组临床有效率92.67%显著高于对照组（P<0.05）。治疗后,两组PANSS评分均显著降低（P<0.05）;且观察组PANSS评分显著低于对照组（P<0.05）。治疗后,两组血清皮质醇（Cor）、神经生长因子（NGF）、脑源性神经营养因子（BDNF）水平均显著降低（P<0.05）,血清5-羟色胺（5-HT）水平均显著升高（P<0.05）;且观察组血清Cor、NGF、BDNF水平显著低于对照组,5-HT水平显著高于对照组（P<0.05）。对照组不良反应的发生率为36.0%,观察组为35.3%,对比无明显的差异。结论 礞石滚痰丸联合哌罗匹隆对精神分裂症患者具有较为显著的治疗效果,其作用机制可能与降低血清Cor、NGF、BDNF水平,提高血清5-HT水平有关。     

Preparation and In Vivo. Antitumor Activity of κ-Carrageenan Oligosaccharides

Abstract

Carrageenan oligosaccharides were produced from the final products of commercial extractions of gelling carrageenan and thickening carrageenan, which were specifically depolymerized by κ-carrageenase extracted from the marine bacterium Cytophaga. MCA-2. The weight-average molecular weights of the two oligosaccharides produced were 681 and 798 Da. The sulfate contents were assayed as 17.2% and 21.8%. Antitumor activities of the oligosaccharides were tested on Sarcoma 180 tumor transplanted in mice. The carrageenan oligosaccharide from the thickening carrageenan product showed much higher tumor inhibition (70.8%) and catalase activity at a dosage of 100 mg kg^?1 compared with the control group. The gelling and thickening carrageenan oligosaccarides could also significantly increase the weight of immune organs such as the thymus, which suggests that the antitumor mechanism of the carrageenan oligosaccharides may be initiated via organ-mediated defense reactions.     

Anti-diabetic effect of a novel oligosaccharide isolated from Rosa canina via modulation of DNA methylation in Streptozotocin-diabetic rats

BackgroundDiabetes mellitus (DM) is a well-known clinical entity with various late complications. There is a surge of research aiming to use the medical herb in the management of DM.ObjectiveThis study aimed to investigate whether the alleviation of DM by an isolated compound from Rosa canina is mediated by DNA methylation in STZ-diabetic rats.MethodsSixty adult Wistar male rats were classified into control, diabetic and treatment groups. Rats were treated with STZ (40 mg/kg), metformin (500 mg/kg), and oligosaccharide fraction (OF; 10, 20 and 30 mg/kg) isolated from Rosa canina. DNA was extracted from the blood and pancreas to determine DNA methylation using the Global DNA Methylation kit. The expressions of DNA methyltransferases (Dnmts), PDX1, Ins1, GCK and PTP1B2 were determined by using qRT-PCR.ResultsThe significant blood glucose-lowering potential of OF was associated with a reduced level of global DNA methylation (p < 0.05). The expression levels of Dnmts 1 and 3α increased in the pancreas and blood from diabetic rats compared to control group which declined by OF treatment (p < 0.05). Paradoxically, the expression of Dnmt 3β augmented in the pancreas and blood of OF group compared to diabetic ones (p < 0.05). Besides, the expressions of Pdx1, PTP1B2, Ins1 and GCK increased in OF-treated rats compared to diabetic groups.ConclusionResults revealed that DNA methylation plays a causal role in the effectiveness of the isolated OF. Furthermore, the possible regenerative potential of oligosaccharide in diabetic rats may have contributed to the modulation of DNA methylation.Graphical abstractElectronic supplementary materialThe online version of this article (10.1007/s40199-020-00363-8) contains supplementary material, which is available to authorized users.     

Further derivatives of 4-benzoyl-1,5-diphenyl-1H-pyrazole-3-carboxylic acid and their antibacterial activities

Compound 4, 5, 6, 7, and 8 were synthesized from 4-benzoyl-1,5-diphenyl-1H-pyrazole-3-carboxylic acid 1 as a starting material. The pyrazolo[4,3-d]oxazinone 4 was obtained from direct reaction of the acid 1 with hydroxylamine hydrochloride. Acid chloride 2 was converted easily into the new derivatives consisting of 1-(4-benzoyl-1,5-diphenyl-1H-pyrazol-3-oyl)-sulfamide 5 and 3,4-dibenzoyl-1,5-diphenyl-1H-pyrazole 6. The nitrile derivative 7 was obtained by dehydration of the amide 3 in a mixture of SOCl₂ and Dimethylformamide (DMF). Cyclocondensation reaction of 7 with anhydrous hydrazine led to the formation of 7-aminopyrazolo[3,4-d]pyridazine 8 derivative. These new synthesized compounds evaluated for their antibacterial activities against Gram-positive and Gram-negative bacteria using the tube dilution method. The finding of antibacterial activity study showed that the sulfamide derivative 5 was the best compound of the series, exhibiting antibacterial activity against both Gram-positive and Gram-negative bacteria.     

Chemical constituents of Cistanche sinensis

One new phenylethanoid glycoside, cistansinenside A and one new oligosaccharide, cistansinensose A₁/A₂, were isolated from the stems of Cistanche sinensis, together with six known compounds. The structures of the new compounds were elucidated on the basis of spectral data.     

Promoting the effect of chemical constituents from the flowers of <Emphasis Type="Italic">Poacynum</Emphasis><Emphasis Type="Italic">hendersonii</Emphasis> on adipogenesis in 3T3-L1 cells

A novel sugar ester poacynose (1) was isolated from the flowers of Poacynum hendersonii together with 31 known compounds. The structure of 1 was established mainly on the basis of 1D and 2D NMR spectral data. Among the isolates, several constituents, such as kaempferol 3-O-sophoroside (5), picein (16), and 4-hydroxybenzoic acid 4-O-β-d-glucopyranoside (17) moderately promoted adipogenesis of 3T3-L1 cells. In addition, simultaneous quantitative analysis of eight flavonoid constituents from the flower and leaf parts of P. hendersonii was developed.     

GSTP1、GSTM1基因多态性与顺铂导致骨髓抑制的相关性研究

目的考察顺铂致骨髓抑制与谷胱甘肽硫转移酶P1(GSTP1)和谷胱甘肽硫转移酶M1(GSTM1)基因多态性的关系。方法用病例对照研究的方法考察以顺铂为主要化疗方案的100例癌症初治肿瘤化疗患者基因多态性与骨髓移植的相关性,白细胞计数和血小板的数量为指标判断是否发生了骨髓抑制以及骨髓抑制程度。提取DNA扩增测序法判断GSTP1、GSTM1基因型。结果 GSTP1的3种基因型AA、AG、GG型均存在,并且在62例发生骨髓抑制的病例中,GSTP1 AG/GA型的患者的分布明显高于GSTP1 AA型患者。GSTM1包含缺失(-)和非缺失(+)2种基因型,100例病例中GSTM1(+)少于GSTM1(-)。Logistic分析结果表明GSTP1 AG/GG型是顺铂致骨髓抑制的独立危险因素,GSTM基因缺失虽不是顺铂致骨髓抑制的独立危险因素,但能促进GSTP1 AG/GG型的作用,导致顺铂致骨髓抑制进一步加重。结论顺铂导致的骨髓抑制程度与GSTP1基因多态性相关。     

A new picrotoxane-type sesquiterpene from Dendrobium findlayanum

A new picrotoxane-type sesquiterpene, findlayanin (1), was isolated from Dendrobium findlayanum with crystallinin (2). The structure of compound 1 was established to be (1R,2S,3R,4S,5R,6S,9R)-2,3,11,12-tetrahydroxypicrotoxan-12(15)-lactone by spectroscopic methods.     

Antioxidant activity of oligosaccharide ester extracted from Polygala tenuifolia roots in senescence-accelerated mice

The constituents of the ethanol extract from the root of Polygala tenuifolia Willd. (Polygalaceae) were investigated for antioxidant activity in senescence-accelerated mice. Consequently, two relevant samples were obtained, a fraction separated by macroporous resin (YZ-OE), and a major pure crystal of 3,6′-disinapoyl sucrose (DISS). Based on HPLC-ESI-MS analysis, the most constituents in the YZ-OE fraction from the extract of P. tenuifolia were oligosaccharide esters. The antioxidant activities of these two samples were evaluated using the accelerated senescence-prone, short-lived mice (SAMP) in vivo. The activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) were increased significantly in SAMP mice fed oligosaccharide esters (YZ-OE 50?mg/kg) and its constituents (DISS 50?mg/kg). However, the content of malondialdehyde (MDA) was increased in the blood and liver of SAMP mice. But when given YZ-OE, it could be decreased, by 44.3% and 47.5%, respectively, compared with the SAMP model. Results from the analyses indicated that the oligosaccharide esters (YZ-OE) from roots of P. tenuifolia had a high in vivo antioxidant activity.     

Concise synthesis and PTP1B inhibitory activity of (R)- and (S)-dihydroresorcylide

The present study was designed to develop a concise synthetic route for macrolide, with the purpose of confirming the absolute configuration of natural dihydroresorcylide (1) and making it more easily accessible for biological evaluation. The absolute configuration of C-3 in natural 1 was revised to be R by comparison of the rotation sign of synthetic (R)- and (S)-1. The synthetic (R)-1 was found to be a novel highly specific PTP1B inhibitor with an IC₅₀ value of 17.06 μM.     

Stereochemical Characterization of the Diastereomers of the Amobarbital N-Glucosides Excreted in Human Urine

The stereochemistry associated with the amobarbital N-glucoside diastereomers (1a and 1b) that are excreted by humans in urine is unknown. Using X-ray crystallography, the absolute configuration of 1b was determined to be S (C-5 position of the barbiturate ring). Following oral administration of amobarbital to Caucasians and Orientals, from 5 to 25% of the dose of amobarbital was excreted in the urine as 1b. The other diastereomer, 1a, accounted for less than 0.1 to 0.2% of the dose in four individuals, with none detected in nine individuals. The rate constants, k _{f ,1b}, determined from the urinary excretion of lb were lower than those previously reported for unresolved amobarbital N-glucosides. However, based on the urinary excretion of lb, the rate constants, K, for elimination of amobarbital in Caucasians and Orientals were similar to those previously determined from the serum levels of amobarbital and the urinary excretion of unresolved amobarbital N-glucosides. In previous studies of the N-glucosylation of amobarbital, it is likely that a single N-glucose diastereomer, lb, was being observed.     

Synthesis and biological activity studies of new hybrid molecules containing tryptamine moiety

The synthesis of N′-(4-substitutedphenylsulfonyl)-2-{4-[2-(1H-indol-yl)ethyl]-3-(4-chlorobenzyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl}acetohydrazides (3a–c), 2-{4-[2-(1H-indol-3-yl)ethyl]-3-(4-chlorobenzyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl}-N′-aryl methylidene acetohydrazides (4a–f) and 4-[2-(1H-indol-3-yl)ethyl]-5-(4-substitutedbenzyl)-2-[(5-sulfanyl-1,3,4-oxadiazol-2-yl)methyl]-2,4-dihydro-3H-1,2,4-triazol-3-ones (5a, b) was performed starting from the corresponding acid hydrazides (2a, b) which was reported earlier. The treatment of 1,3,4-oxadiazole derivatives (5a, b) with hydrazine hydrate produced 4-amino-5-sulfanyl-4H-1,2,4-triazol-3-yl derivatives (6a, b). Then, compound 6b was converted to the corresponding Schiff base (7) by the treatment with anisaldehyde. The synthesis of 5-(4-chlorobenzyl)-4-[2-(1H-indol-3-yl)ethyl]-2-[(4-benzyl-5-oxo-4,5-dihydro-1H-1,2,4-triazol-3-yl)methyl]-2,4-dihydro-3H-1,2,4-triazol-3-one (8) and 5-(4-methylbenzyl)-4-[2-(1H-indol-3-yl)ethyl]-2-[(4-benzyl-5-oxo-4,5-dihydro-1H-1,2,4-triazol-3-yl)methyl]-2,4-dihydro-3H-1,2,4-triazol-3-one (10) was carried out by the reaction of acid hydrazides (2a, b) with aryl iso(thio)cyanates either via the formation of the intermediates (9a, b) (for 10) or direct cyclization (for 8). 1,3-Oxa(thia)zol-2(3H)-ylidene]acetohydrazide derivatives (11a, b) were obtained by the reaction of 9a, b with 4-chlorophenacyl bromide. All newly synthesized compounds were screened for their antimicrobial activities and some of which was found to be active against the test microorganisms.     

Anti-inflammatory lupane triterpenoids from Menyanthes trifoliata

A new lupane triterpenoid, 23-O-trans-feruloylcylicodiscic acid (1), as well as four known analogues (2?5), was isolated from the EtOAc fraction of Menyanthes trefoliata. The structure of compound 1 was elucidated on the basis of extensive spectroscopic analysis, including 2D NMR data. The structures of the known compounds were established by comparison of their spectroscopic data with that in the literature. Compounds 1, 2, and 4 exhibited certain anti-NO production activities.     

Cytotoxic activity of flavonoids from the flowers of Chrysanthemum morifolium on human colon cancer Colon205 cells

A new p-hydroxyphenylacetyl flavonoid, diosmetin 7-(6″-O-p-hydroxyphenylacetyl)-O-β-d-glucopyranoside (1), was isolated from the flowers of Chrysanthemum morifolium Ramat. ‘huaiju’ cv. nov. (Compositae), together with five known flavonoids, luteolin (2), diosmetin (3), diosmetin 7-O-β-d-glucopyranoside (4), diosmin (5), and scolimoside (6), and four known caffeoylquinic acid derivatives, macranthoin F (7), 3,5-dicaffeoylquinic acid (8), 1,3-dicaffeoyl-epi-quinic acid (9), and chlorogenic acid (10). The structure of 1 was elucidated by UV, IR, ESI-TOF-MS, 1D, and 2D NMR spectroscopic methods. Cytotoxic activity of compounds 1–5 against human colon cancer cell Colon205 was investigated using MTT assays. Compounds 2 and 3 showed significant cytotoxicities against Colon205, with their IC₅₀ values being 96.9 and 82.9 μM, respectively. However, compounds 1, 4, and 5 showed little cytotoxic activity.