烟酸和烟酰胺的现状与前景

叙述了烟酸和烟酰胺的性状、用途、制法和发展前景。     

β-烟酰胺单核苷酸对生理机能影响的研究进展

我国处于亚健康状态的超重或肥胖人群与老龄化人口数量都在逐年上升。在衰老和肥胖过程中,细胞内烟酰胺腺嘌呤二核苷酸（nicotinamide adenine dinucleotide,NAD＋）水平会发生系统性下降。NAD＋是细胞能量代谢、调节细胞机能、影响衰老的关键靶点,因此,通过补充NAD＋前体以改善生理机能、延缓衰老已经成为目前研究热点。β-烟酰胺单核苷酸（nicotinamide mononucleotide,NMN）是动物体内NAD＋代谢的中间产物,也是目前最直接高效的NAD＋补充前体。但是NMN对生理机能存在多方面多器官的复杂影响,而且人体临床试验与动物实验结果并不一致,服用量也尚未确定。本文综述到目前为止NMN的动物实验和人体临床试验结果,旨在探究补充NMN对动物、人体生理机能的影响、机制及其适宜剂量和不良反应,以期为未来NMN研究与应用提供思路。     

Thermodynamics and Intermolecular Interactions of Nicotinamide in Neat and Binary Solutions: Experimental Measurements and COSMO-RS Concentration Dependent Reactions Investigations

In this study, the temperature-dependent solubility of nicotinamide (niacin) was measured in six neat solvents and five aqueous-organic binary mixtures (methanol, 1,4-dioxane, acetonitrile, DMSO and DMF). It was discovered that the selected set of organic solvents offer all sorts of solvent effects, including co-solvent, synergistic, and anti-solvent features, enabling flexible tuning of niacin solubility. In addition, differential scanning calorimetry was used to characterize the fusion thermodynamics of nicotinamide. In particular, the heat capacity change upon melting was measured. The experimental data were interpreted by means of COSMO-RS-DARE (conductor-like screening model for realistic solvation–dimerization, aggregation, and reaction extension) for concentration dependent reactions. The solute–solute and solute–solvent intermolecular interactions were found to be significant in all of the studied systems, which was proven by the computed mutual affinity of the components at the saturated conditions. The values of the Gibbs free energies of pair formation were derived at an advanced level of theory (MP2), including corrections for electron correlation and zero point vibrational energy (ZPE). In all of the studied systems the self-association of nicotinamide was found to be a predominant intermolecular complex, irrespective of the temperature and composition of the binary system. The application of the COSMO-RS-DARE approach led to a perfect match between the computed and measured solubility data, by optimizing the parameter of intermolecular interactions.     

高效液相色谱法同时测定保健食品中泛酸、烟酰胺、维生素B1、维生素B2、维生素B6的含量

目的建立高效液相色谱法同时测定保健食品中泛酸、烟酰胺、维生素B_1、维生素B_2、维生素B_6的含量。方法样品经0.2%磷酸溶液超声提取,经Alltima-C18柱分离,以乙腈-5 mmol/L庚烷磺酸钠溶液为流动相进行梯度洗脱,采用二极管阵列检测器(diode array detector,DAD)同时在200 nm、280 nm波长处进行检测。结果泛酸、烟酰胺、维生素B_1、维生素B_2、维生素B_6能实现较好的分离,在各自线性范围内线性关系良好,平均回收率为93.9%~103.2%,相对标准偏差(relative standard deviation,RSD)为0.4%~1.8%。结论该方法操作快速简便、精密度和重复性好,可适用于保健食品中泛酸、烟酰胺、维生素B_1、维生素B_2、维生素B_6含量的同时测定。     

Different Effects of RNAi-Mediated Downregulation or Chemical Inhibition of NAMPT in an Isogenic IDH Mutant and Wild-Type Glioma Cell Model

The IDH1^R132H mutation in glioma results in the neoenzymatic function of IDH1, leading to the production of the oncometabolite 2-hydroxyglutarate (2-HG), alterations in energy metabolism and changes in the cellular redox household. Although shifts in the redox ratio NADPH/NADP⁺ were described, the consequences for the NAD⁺ synthesis pathways and potential therapeutic interventions were largely unexplored. Here, we describe the effects of heterozygous IDH1^R132H on the redox system in a CRISPR/Cas edited glioblastoma model and compare them with IDH1 wild-type (IDH1^wt) cells. Besides an increase in 2-HG and decrease in NADPH, we observed an increase in NAD⁺ in IDH1^R132H glioblastoma cells. RT-qPCR analysis revealed the upregulation of the expression of the NAD⁺ synthesis enzyme nicotinamide phosphoribosyltransferase (NAMPT). Knockdown of NAMPT resulted in significantly reduced viability in IDH1^R132H glioblastoma cells. Given this dependence of IDH1^R132H cells on NAMPT expression, we explored the effects of the NAMPT inhibitors FK866, GMX1778 and GNE-617. Surprisingly, these agents were equally cytotoxic to IDH1^R132H and IDH1^wt cells. Altogether, our results indicate that targeting the NAD⁺ synthesis pathway is a promising therapeutic strategy in IDH mutant gliomas; however, the agent should be carefully considered since three small-molecule inhibitors of NAMPT tested in this study were not suitable for this purpose.     

Combined Therapy with Simvastatin- and Coenzyme-Q10-Loaded Nanoparticles Upregulates the Akt-eNOS Pathway in Experimental Metabolic Syndrome

In addition to their LDL-cholesterol-lowering effect, statins have pleiotropic beneficial effects on the cardiovascular system. However, long-term treatment with statins may be associated with serious side effects. With the aim to make statin therapy more effective, we studied the effects of simvastatin- and coenzyme-Q10-loaded polymeric nanoparticles on the lipid profile and nitric oxide (NO)/reactive oxygen species (ROS) balance in the heart and aorta of adult male obese Zucker rats. The rats were divided into an untreated group, a group treated with empty nanoparticles, and groups treated with simvastatin-, coenzyme Q10 (CoQ10)-, or a combination of simvastatin- and CoQ10-loaded nanoparticles (SIMV+CoQ10). After 6 weeks, the lipid profile in the plasma and the concentration of conjugated dienes in the liver were determined. Nitric oxide synthase (NOS) activity, Akt, endothelial NOS (eNOS), phosphorylated eNOS (p-eNOS), nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, and nuclear factor kappaB (NF-kappaB) protein expressions were measured in the heart and aorta. All simvastatin, CoQ10, and SIMV+CoQ10 treatments decreased plasma LDL levels, but only the combined SIMV+CoQ10 treatment increased NOS activity and the expression of Akt, eNOS, and p-eNOS in both the heart and the aorta. Interestingly, NADPH oxidase in the heart and NF-kappaB protein expression in the aorta were decreased by all treatments, including nanoparticles alone. In conclusion, only combined therapy with SIMV- and CoQ10-loaded nanoparticles increased NOS activity and upregulated the Akt-eNOS pathway in obese Zucker rats, which may represent a promising tool for the treatment of cardiometabolic diseases.     

Unbalance between Pyridine Nucleotide Cofactors in The SOD1 Deficient Yeast Saccharomyces cerevisiae Causes Hypersensitivity to Alcohols and Aldehydes

Alcohol and aldehyde dehydrogenases are especially relevant enzymes involved in metabolic and detoxification reactions that occur in living cells. The comparison between the gene expression, protein content, and enzymatic activities of cytosolic alcohol and aldehyde dehydrogenases of the wild-type strain and the Δsod1 mutant lacking superoxide dismutase 1, which is hypersensitive to alcohols and aldehydes, shows that the activity of these enzymes is significantly higher in the Δsod1 mutant, but this is not a mere consequence of differences in the enzymatic protein content nor in the expression levels of genes. The analysis of the NAD(H) and NADP(H) content showed that the higher activity of alcohol and aldehyde dehydrogenases in the Δsod1 mutant could be a result of the increased availability of pyridine nucleotide cofactors. The higher level of NAD⁺ in the Δsod1 mutant is not related to the higher level of tryptophan; in turn, a higher generation of NADPH is associated with the upregulation of the pentose phosphate pathway. It is concluded that the increased sensitivity of the Δsod1 mutant to alcohols and aldehydes is not only a result of the disorder of redox homeostasis caused by the induction of oxidative stress but also a consequence of the unbalance between pyridine nucleotide cofactors.     

猪肉助色剂的研究及配方优化

研究不同异抗坏血酸钠、烟酰胺、茶多酚添加量对猪肉色差、发色率、肌红蛋白存在形式比例及亚硝酸钠残留量的影响,并通过正交交互分析方法来确定减少亚硝酸钠用量的最佳发色配方。结果表明,亚硝酸钠的添加量为100mg/kg时,最佳助色剂配方为:异抗坏血酸钠400mg/kg、烟酰胺500mg/kg、茶多酚300mg/kg。在此条件下,a*为12.78,发色率为56.67%,经过腌制,猪肉在感官上表现为鲜艳的玫瑰红色,发色均匀,且在保藏期间长期不退色。