Designing amorphous formulations of polyphenols with naringin by spray-drying for enhanced solubility and permeability

Naringin (NAR), a major flavanone (FVA) glycoside, is a component of food mainly obtained from grapefruit. We used NAR as a food additive to improve the solubility and permeability of hydrophobic polyphenols used as supplements in the food industry. The spray-dried particles (SDPs) of NAR alone show an amorphous state with a glass transition temperature (T_g) at 93.2 °C. SDPs of hydrophobic polyphenols, such as flavone (FVO), quercetin (QCT), naringenin (NRG), and resveratrol (RVT) were prepared by adding varying amounts of NAR. All SDPs of hydrophobic polyphenols with added NAR were in an amorphous state with a single T_g, but SDPs of hydrophobic polyphenols without added NAR showed diffraction peaks derived from each crystal. The SDPs with NAR could keep an amorphous state after storage at a high humidity condition for one month, except for SDPs of RVT/NAR. SDPs with NAR enhanced the solubility of hydrophobic polyphenols, especially NRG solubility, which was enhanced more than 9 times compared to NRG crystal. The enhanced solubility resulted in the increased membrane permeability of NRG. The antioxidant effect of the hydrophobic NRG was also enhanced by the synergetic effect of NAR. The findings demonstrated that NAR could be used as a food additive to enhance the solubility and membrane permeability of hydrophobic polyphenols.     

单步溶胀聚合法制备单分散分子印迹聚合物微球

用无皂乳液聚合法制备了微米级粒径均匀的聚苯乙烯微球(PS).以制得的PS为种球,柚皮素为模板分子,通过单步溶胀聚合法制备了单分散分子印迹聚合物微球(MIPBs).研究了溶胀比及环己醇用量对MIPBs粒径及形态的影响,结果发现,采用粒径为1.50μm的PS作种球,且溶胀比控制在27～60时,可以制得粒径在4.5 μm～6.0 μ.m单分散的MIPBs;随着环己醇用量的增大,MIPBs球形更加规则、表面更加光滑.氮气吸附测量结果表明,制得的MIPBs是一种具有多孔结构、比表面积大的聚合物.Scatchard分析结果表明,在研究的浓度范围内,MIPBs存在一类等同的结合位点,其平衡离解常数Kd和最大表观吸附量Qmax分别为8.61 mmol·L-1和48.50μmol·g-1.制得的MIPBs对模板化合物柚皮素显示出较高的选择性,以槲皮素为竞争底物,其分离因子达1.96.     

牛血清白蛋白与柚皮素复合物的非变性质谱研究

血清白蛋白是血液中最丰富的蛋白,研究其与药物的结合情况对了解药物在体内的运输和分布具有重要意义。本研究以柚皮素为模型药物,采用非变性质谱法研究牛血清白蛋白（BSA）与柚皮素的相互作用情况。结果表明,BSA与柚皮素形成了化学计量比为1∶1和1∶2的非共价复合物,二者亲和力较强（平衡解离常数Kd1=（7.82±0.03） μmol/L,Kd2=（9.63±0.02） μmol/L),结合速度快,5 min左右即可达到饱和。该方法具有操作简便、检测快速、样品消耗量小、无需标记等优点,可为其他药物与血清白蛋白的相互作用研究提供参考。     

Antioxidant properties,radical scavenging activity and biomolecule protection capacity of flavonoid naringenin and its glycoside naringin: a comparative study

BACKGROUND: This study was designed to evaluate and compare antioxidant capacity and radical scavenging activity of naringin and its aglycone by different in vitro assays. The effects of flavanones on lipid peroxidation, glutathione (GSH) oxidation and DNA cleavage were also assessed. RESULTS: The results showed that naringenin exhibited higher antioxidant capacity and hydroxyl and superoxide radical scavenger efficiency than naringin. Our results evidenced that glycosylation attenuated the efficiency in inhibiting the enzyme xanthine oxidase and the aglycone could act like a more active chelator of metallic ions than the glycoside. Additionally, naringenin showed a greater effectiveness in the protection against oxidative damage to lipids in a dose‐dependent manner. Both flavanones were equally effective in reducing DNA damage. However, they show no protective effect on oxidation of GSH. CONCLUSION: The data obtained support the importance of characterizing the ratio naringin/naringenin in foods when they are evaluated for their health benefits. Copyright © 2010 Society of Chemical Industry     

纤维素纳米晶体提升柚皮素抗氧化活性的研究

柚皮素是一种黄酮类化合物,具有广泛的药理活性,具有抗炎、抗氧化、抗癌、降血脂等药理作用。然而,柚皮素在水中溶解性能差,生物利用度低,限制了其在临床中的应用。本研究以纤维素纳米晶体(Cellulose nanocrystals,CNCs)为载体,以柚皮素为疏水药物模型,利用反溶剂重结晶法成功制备了CNCs/柚皮素纳米复合物,并表征了所得纳米复合物的性能,分析了纳米复合物中柚皮素的溶出性能和抗氧化活性。结果表明,形成CNCs/柚皮素纳米复合物后,柚皮素得到充分的纳米化和稳定分散,从结晶态转变为无定型态。负载CNCs的柚皮素在水中的溶出性能得到显著提升,120min时累积溶出度达到93.4%;经CNCs负载后,当柚皮素浓度为50μg/mL时,羟基自由基清除率达44.3%,柚皮素的体外抗氧化活性显著提高。     

The Gastroprotective Effect of Naringenin against Ethanol-Induced Gastric Ulcers in Mice through Inhibiting Oxidative and Inflammatory Responses

Naringenin is a major flavanone found in grapes, tangelos, blood oranges, lemons, pummelo, and tangerines. It is known to have anti-inflammatory, antioxidant, anticancer, antimutagenic, antifibrogenic, and antiatherogenic pharmacological properties. This study aims to investigate the anti-inflammatory effects of naringenin in ethanol-induced gastric damage in vivo and ethanol-stimulated KATO III cells in vitro. Our results showed that pretreatment with naringenin significantly protected mice from ethanol-induced hemorrhagic damage, epithelial cell loss, and edema with leucocytes. It reduced gastric ulcers (GU) by suppressing ethanol-induced nuclear factor-κB (NF-κB) activity and decreasing the levels of nitric oxide (NO), malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-8 (IL-8), and myeloperoxidase (MPO). In addition, pretreatment with naringenin might inhibit the secretion of TNF-α, IL-6, and IL-8, as well as the proteins cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) via the suppression of NF-κB and mitogen-activated protein kinase (MAPK) signaling in ethanol-stimulated stomach epithelial KATO III cells. Together, the results of this study highlight the gastroprotective effect of naringenin in GU of mice by inhibiting gastric secretion and acidity, reducing inflammation and oxidative stress, suppressing NF-κB activity, and restoring the histological architecture. These findings suggested that naringenin has therapeutic potential in the alleviation of ethanol-induced GU.     

The Effects of Naringenin on miRNA-mRNA Profiles in HepaRG Cells

Naringenin, a natural flavonoid widely found in citrus fruits, has been reported to possess anti-oxidant, anti-inflammatory, and hepatoprotective properties as a natural dietary supplement. However, the regulatory mechanism of naringenin in human liver remains unclear. In the present study, messenger RNA sequencing (mRNA-seq), microRNA sequencing (miRNA-seq), and real-time qPCR were used to distinguish the expression differences between control and naringenin-treated HepaRG cells. We obtained 1037 differentially expressed mRNAs and 234 miRNAs. According to the target prediction and integration analysis in silico, we found 20 potential miRNA-mRNA pairs involved in liver metabolism. This study is the first to provide a perspective of miRNA–mRNA interactions in the regulation of naringenin via an integrated analysis of mRNA-seq and miRNA-seq in HepaRG cells, which further characterizes the nutraceutical value of naringenin as a food additive.     

Dissolution rate and stability study of flavanone aglycones,naringenin and hesperetin,by drug delivery systems based on polyvinylpyrrolidone (PVP) nanodispersions

Objective: To study the dissolution behavior, the release mechanism and the stability of nanodispersion system of aglycones with PVP. Methods: The nanodispersion system of polyvinylpyrrolidone (PVP)/naringenin–hesperetin was prepared using the solvent evaporation method. The chemical stability (compatibility) of naringenin and hesperetin in the prepared dispersions was studied under accelerated conditions for 3 months. The evaluation of physical stability was performed by X-ray diffraction analysis (XRD) and by comparing the dissolution profile before and after storage at high temperature and moisture (40ºC, RH 75%). Results: The dissolution rate of naringenin and hesperetin released was dramatically increased in the nanodispersion system of PVP/naringenin–hesperetin (80/20, w/w). The release mechanism of both flavanone aglycones was better described by the diffusion model (Higuchi model). Also it was found that the rate-limiting step that controlled the release of naringenin and hesperetin in the nanodispersion system was dissolution of the carrier (PVP). Conclusions: During accelerated degradation analysis, for 3 months at high temperature and moisture, PVP nanodispersion system showed enhanced chemical compatibility and physical stability. The physical evaluation (obtained from XRD analysis) of PVP/naringenin–hesperetin (80/20, w/w) in the selected storage conditions did not show any crystallization of flavanone aglycones in the PVP nanodispersion system or any change in their release profile.