5-hydroxymethyl-2-furfural prolongs survival and inhibits oxidative stress in a mouse model of forebrain ischemia

In the present study, we hypothesized that 5-hydroxymethyl-2-furfural could attenuate ischemic brain damage by reducing oxidative injury. Thus, mice were subjected to bilateral common carotid artery occlusion to establish a model of permanent forebrain ischemia. The mice were intraperitoneally injected with 5-hydroxymethyl-2-furfura130 minutes before ischemia or 5 minutes after ischemia. The survival time of mice injected with 5-hydroxymethyl-2-furfural was longer compared with untreated mice. The mice subjected to ischemia for 30 minutes and reperfusion for 5 minutes were intraperitoneally injected with 5-hydroxymethyl-2-furfural 5 minutes prior to reperfusion, which increased superoxide dismutase content and reduced malondialdehyde content, similar to the effects of Edaravone, a hydroxyl radical scavenger used for the treatment of stroke. These findings indicate that intraperitoneal injection of 5-hydroxymethyl-2-furfural can prolong the survival of mice with permanent forebrain ischemia. This outcome may be mediated by its antioxidative effects.

Thermoresponsive block copolymer supported Pt nanocatalysts for base-free aerobic oxidation of 5-hydroxymethyl-2-furfural

A base-free catalytic system for the aerobic oxidation of 5-hydroxymethyl-2-furfural was exploited by using Pt nanoparticles immobilized onto a thermoresponsive poly(acrylamide-co-acrylonitrile)-b-poly(N-vinylimidazole)block copolymer,with an upper critical solution temperature of about 45°C.The Pt nanocatalysts were well-dispersed and highly active for the base-free oxidation of 5-hydroxymethyl-2-furfural by molecular oxygen in water,affording high yields of 2,5-furandicarboxylic acid(up to>99.9%).The imidazole groups in the block copolymer were conducive to the improvement of catalytic performance.Moreover,the catalysts could be easily separated and recovered based on their thermosensitivity by cooling the reaction system below the upper critical solution temperature.Good stability and reusability were observed over these copolymer-immobilized catalysts with no obvious decrease in catalytic activity in the five consecutive cycles.

SYNTHESIS AND ANTITUMOR ACTIVITY OF PEPTIDYL-N^2-HYDROXYMETHYL-5-FLUOROURACIL

Six hydrophobic peptidyl and four amino acid (L-Val, L-Leu, L-Phe, L-Gly) derivatives of 5-fluorouracil(5-FU) were synthesized. The structure of these compounds were characterized by ~1H-NMR, IR, UV spectra and elemental analysis. The antitumor activity was test- ed against EAC cells in vitro.

正交实验法优选熟地黄中5-HMF的提取工艺

目的:以5-羟甲基糠醛(5-HMF)含量和熟地黄干膏收得率为指标,探讨熟地黄中5-HMF的提取工艺.方法:采用正交试验法考察加水量、提取时间、提取次数及醇沉浓度4个因素对5-HMF含量和干膏收得率的影响,并运用高效液相法测定5-HMF的含量.结果:通过对正交试验结果的极差分析,得出提取次数和提取时间两个因素对干膏收得率和含量影响最大,参考两种主要影响因素,最终确定8倍量水、提取3次、每次1.5h,700mL/L乙醇沉淀的提取工艺,并对该工艺进行三次重复性小试实验.5-HMF收得率可达58%以上.结论:通过对上述提取条件的重复性考察,该方法重复性好,5-HMF收得率稳定,为进一步中试实验提供了参考依据.

HPLC法同时测定丹参注射液中8种成分

目的建立HPLC法,同时测定丹参注射液中杂质5-羟甲基糠醛、原儿茶醛、丹酚酸B等8种成分的含量。方法采用Waters Symmetry C_(18)(4.6mm×250 mm,5μm)色谱柱,以乙腈-0.05%三氟乙酸为流动相梯度洗脱,流速0.8 mL/min,检测波长288 nm,柱温25℃。结果 5-羟甲基糠醛、丹参素钠、原儿茶酸、原儿茶醛、香草酸、阿魏酸、迷迭香酸、丹酚酸B浓度与峰面积在一定范围内线性关系良好。加样回收率、精密度、重复性、稳定性试验的考察结果均符合中国药典要求。应用该方法检测150批样品并对测定结果统计分析,进一步阐明了杂质5-羟甲基糠醛含量与丹参注射液中7种水溶性成分含量的关系。结论 HPLC方法简便准确,重复性和稳定性良好,分析效率较高。

不同炮制方法对熟地黄中7种化学成分含量的影响

目的:通过建立熟地黄中梓醇、益母草苷、地黄苷A、地黄苷D、毛蕊花糖苷、异毛蕊花糖苷和5-羟甲基糠醛(5-HMF)7种化学成分同时分析的方法,测定清蒸熟地黄、酒炖熟地黄、九蒸九晒熟地黄3种不同炮制品中7种化学成分的含量,探讨不同炮制方法对熟地黄中化学成分的影响。方法:采用超声提取法处理熟地黄3种不同炮制品,赛默飞C18色谱柱(250 mm×4.6 mm,5μm);流动相:0.1%磷酸(A)-乙腈(B),梯度洗脱,程序为:0~8 min,1%B;8~9 min,1%~4%B;9~25 min,4%B;25~35 min,4%~20%B;35~50 min,20%B;50~50.01 min,20%~1%B;50.01~55 min,1%B。柱温:30℃,检测波长:203 nm、332 nm,测定3种样品中7种化学成分的含量。结果:生地黄中未检出5-HMF。清蒸熟地黄和酒炖熟地黄中,环烯醚萜单糖苷梓醇和益母草苷几乎全部降解;环烯醚萜双糖苷地黄苷A、地黄苷D和苯丙素苷毛蕊花糖苷、异毛蕊花糖苷的含量较生地黄中含量降低;可以检测到5-HMF。九蒸九晒熟地黄中环烯醚萜单糖苷梓醇和益母草苷、环烯醚萜双糖苷地黄苷A、地黄苷D和苯丙素苷毛蕊花糖苷、异毛蕊花糖苷几乎全部降解;可以检测到5-HMF。结论:不同炮制方法对熟地黄成分的影响较大,该方法可用于熟地黄不同炮制品的质量控制。

Significantly improved oxidation of bio-based furans into furan carboxylic acids using substrate-adapted whole cells

Furan carboxylic acids are important building blocks in polymer and fine chemical industries. In this work, a simple substrate adaptation strategy was applied to improve the catalytic performances of Comamonas testosteroni SC1588 cells for the synthesis of various furan carboxylic acids. It was found that biocatalytic synthesis of 5-hydroxymethyl-2-furancarboxylic acid(HMFCA) was substantially promoted by adding histidine and increasing cell concentrations. HMFCA was produced in a quantitative yield from200 m M HMF in 24 h. Besides, the HMFCA yields of 71%–81% were achieved with the substrate concentrations up to 250–300 m M. It was firstly found that 4-tert-butylcatechol(TBC), as the stabilizer present in HMF, exerted a significantly detrimental effect on whole-cell catalytic synthesis of HMFCA at high substrate concentrations(more than 130 m M). In addition, a variety of furan carboxylic acids such as2-furoic acid, 5-methyl-2-furancarboxylic acid and 5-methoxymethyl-2-furancarboxylic acid were synthesized with the yields up to 98%.

Pan-cancer analysis of DNA epigenetic modifications by hydrophilic interaction liquid chromatography-tandem mass spectrometry

Accumulating evidence in recent years indicates that DNA methylation(5-methyl-2-deoxycytidine,5-mdC) and hydroxymethylation(5-hydroxymethyl-2-deoxycytidine, 5-hmd C) have been implicated in various biological processes, and the aberrations of these DNA cytosine modifications is tightly associated with cancer. N6-methyl-2-deoxyadenosine(m~6dA), as a newly discovered epigenetic modification in genome of mammals, has been demonstrated to play vital regulatory roles in tumorigenesis. However, the content information of m~6dA in human tumor tissues is still limited and pan-cancer analysis of these DNA epigenetic modifications is lacked. Herein, we developed a sensitive and robust stable isotopediluted hydrophilic interaction liquid chromatography-tandem mass spectrometry(HILIC-MS/MS) method for accurate quantification of m~6dA, 5-mdC and 5-hmdC in genomic DNA from 82 pairs of human tumor tissues and matched tumor-adjacent normal tissues. The types of tumors included esophagus cancer, lung cancer, breast cancer, liver cancer, pancreatic cancer, gastric cancer, stromal tumor and colorectal cancer.Compared to the normal tissues, we revealed the level of m6dA was increased in tumor tissues of esophagus cancer, lung cancer and liver cancer, whereas the level of m~6dA was diminished in tumor tissues of pancreatic cancer and gastric cancer;while the contents of 5-mdC and 5-hmdC exhibited significant decrease in tumor tissues of most types of cancer. It is worth noting that we revealed, for the first time,the content of genomic m~6dA in pancreatic cancer, stromal tumor and colorectal cancer. The significant changes of these DNA epigenetic modifications indicate they may serve as indicators of cancers. In addition, this study will benefit for better understanding of the regulatory roles of these DNA epigenetic modifications in cancers.