The use of a high quercetin dose to demonstrate its absorption and bioavailability does not reflect the real dietary situation because quercetin glycosides are usually present in small amounts in the human diet. This study aimed to demonstrate the absorption and bioavailability of quercetin in mulberry leaves that represents a more physiologic dietary situation. Mulberry leaf ethanol extract was prepared similar to tea infusion, which is the way the tea leaves are generally prepared for consumption. Accordingly, rats were fed by oral intubation the mulberry leaf ethanol extract (15 g%/rat per day) or pure rutin (135 microg/rat per day) for 2 weeks. The control group received a similar volume of the vehicle, 10% ethanol. There was a significant increase in total antioxidant activity (TAA) in the urine and feces of the antioxidants-fed rats. Phenylacetic acid, a microbial metabolite of quercetin, was detected in the urine of the test animals, and quercetin was present in the fecal samples. By using an in situ intestinal preparation, 3-hydroxyphenylacetic acid, another microbial metabolite of quercetin, was detected in the plasma when the duodenal segment was instilled with 2 mg of rutin. This microbial metabolite retained 50% of the TAA of quercetin. The results of this study indicate that in a more realistic dietary situation, an increase in TAA in the body after consumption of quercetin-containing foods is contributed mainly by the microbial metabolites.
Airway inflammation and infections are the primary causes of damage in the airway epithelium, that lead to hypersecretion of mucus and airway hyper-responsiveness. The role of reactive oxygen species (ROS) and their components in the pathophysiological mechanisms of airway inflammation have been well-studied and emphasized for the past several decades. Rutin, a potent bioflavonoid, is well-known for its antioxidant, anti-inflammatory, especially in bronchial inflammation. However, poor solubility and rapid metabolism have led to its low bioavailability in biological systems, and hence limit its application. The present study aims to investigate the beneficial effects of rutin-loaded liquid crystalline nanoparticles (LCNs) against lipopolysaccharide (LPS) induced oxidative damage in human bronchial epithelial cell line (BEAS-2-B) cells in vitro. LPS was used to stimulate BEAS-2-B cells, causing the generation of nitric oxide (NO) and other reactive oxygen species (ROS) that had led to cellular apoptosis. The levels of NO and ROS were detected by, Griess reagent kit and dichlorodihydrofluorescein diacetate (DCFH-DA) respectively, whereas, cell apoptosis was studied by Annexin V-FITC and PI staining. The findings revealed that rutin-loaded LCNs significantly reduced NO, ROS levels and prevented apoptosis in BEAS-2B cells. The observations and findings provide a mechanistic understanding of the effectiveness of rutin-loaded LCNs in protecting the bronchial cells against airway inflammation, thus possessing a promising therapeutic option for the management of airway diseases.
Non-small cell lung cancer (NSCLC) is one of the major causes of cancer-related mortality globally. Despite the availability of therapeutic options, the improvement in patient survival is yet to be achieved. Recent advances in natural product (e.g., Rutin) research, therapeutic nanotechnology and especially the combination of both could aid in achieving significant improvements in the treatment or management of NSCLC. In this study, we explore the anti-cancer activity of Rutin-loaded liquid crystalline nanoparticles (LCNs) in an in vitro model where we have employed the A549 human lung epithelial carcinoma cell line. The anti-proliferative activity was determined by MTT and Trypan blue assays, whereas, the anti-migratory activity was evaluated by the scratch wound healing assay and a modified Boyden chamber assay. We also evaluated the anti-apoptotic activity by Annexin V-FITC staining, and the colony formation activity was studied using crystal violet staining. Here, we report that Rutin-LCNs showed promising anti-proliferative and anti-migratory activities. Furthermore, Rutin-LCNs also induced apoptosis in the A549 cells and inhibited colony formation. The findings warrant further detailed and in-depth anti-cancer mechanistic studies of Rutin-LCNs with a focus towards a potential therapeutic option for NSCLC. LCNs may help to enhance the solubility of Rutin used in the treatment of lung cancer and hence enhance the anticancer effect of Rutin.
The influence of optical parameters, additional techniques (e.g. PIDS technology) and the importance of light microscopy were investigated by comparing laser diffraction data obtained via the conventional method and an optimized analysis method. Also the influence of a possible dissolution of nanocrystals during a measurement on the size result obtained was assessed in this study. The results reveal that dissolution occurs if unsaturated medium or microparticle saturated medium is used for the measurements. The dissolution is erratic and the results are not reproducible. Dissolution can be overcome by saturating the measuring medium prior to the measurement. If nanocrystals are analysed the dispersion medium should be saturated with the nanocrystals, because the solubility is higher than for coarse micro-sized drug material. The importance of using the optimized analysis method was proven by analysing 40 different nanosuspensions via the conventional versus the optimized sizing method. There was no large difference in the results obtained for the 40 nanosuspensions using the conventional method. This would have led to the conclusion, that all the 40 formulations investigated are physically stable. However, the analysis via the optimized method revealed that from 40 formulations investigated only four were physically stable. In conclusion an optimized analysis saves time and money and avoids misleading developments, because discrimination between "stable" and "unstable" can be done reliably at a very early stage of the development.