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Drug Delivery Nov 2017The present work attempts to develop and statistically optimize transfersomes containing EGCG and hyaluronic acid to synergize the UV radiation-protective ability of... (Comparative Study)
Comparative Study
Skin delivery of epigallocatechin-3-gallate (EGCG) and hyaluronic acid loaded nano-transfersomes for antioxidant and anti-aging effects in UV radiation induced skin damage.
The present work attempts to develop and statistically optimize transfersomes containing EGCG and hyaluronic acid to synergize the UV radiation-protective ability of both compounds, along with imparting antioxidant and anti-aging effects. Transfersomes were prepared by thin film hydration technique, using soy phosphatidylcholine and sodium cholate, combined with high-pressure homogenization. They were characterized with respect to size, polydispersity index, zeta potential, morphology, entrapment efficiency, Fourier Transform Infrared Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC), X-ray Diffraction (XRD), in vitro antioxidant activity and ex vivo skin permeation studies. Cell viability, lipid peroxidation, intracellular ROS levels and expression of MMPs (2 and 9) were determined in human keratinocyte cell lines (HaCaT). The composition of the transfersomes was statistically optimized by Design of Experiments using Box-Behnken design with four factors at three levels. The optimized transfersome formulation showed vesicle size, polydispersity index and zeta potential of 101.2 ± 6.0 nm, 0.245 ± 0.069 and -44.8 ± 5.24 mV, respectively. FTIR and DSC showed no interaction between EGCG and the selected excipients. XRD results revealed no form conversion of EGCG in its transfersomal form. The optimized transfersomes were found to increase the cell viability and reduce the lipid peroxidation, intracellular ROS and expression of MMPs in HaCaT cells. The optimized transfersomal formulation of EGCG and HA exhibited considerably higher skin permeation and deposition of EGCG than that observed with plain EGCG. The results underline the potential application of the developed transfersomes in sunscreen cream/lotions for improvement of UV radiation-protection along with deriving antioxidant and anti-aging effects.
Topics: Administration, Cutaneous; Animals; Antioxidants; Calorimetry, Differential Scanning; Catechin; Cell Line; Cell Survival; Drug Carriers; Drug Compounding; Drug Synergism; Humans; Hyaluronic Acid; Keratinocytes; Lipid Peroxidation; Male; Matrix Metalloproteinases; Nanomedicine; Nanoparticles; Oxidative Stress; Particle Size; Permeability; Phosphatidylcholines; Rats, Wistar; Reactive Oxygen Species; Skin; Skin Absorption; Skin Aging; Sodium Cholate; Spectroscopy, Fourier Transform Infrared; Surface Properties; Technology, Pharmaceutical; Time Factors; X-Ray Diffraction
PubMed: 28155509
DOI: 10.1080/10717544.2016.1228718 -
Acta Pharmaceutica Sinica. B Jan 2019Liposomes mimic natural cell membranes and have long been investigated as drug carriers due to excellent entrapment capacity, biocompatibility and safety. Despite the... (Review)
Review
Liposomes mimic natural cell membranes and have long been investigated as drug carriers due to excellent entrapment capacity, biocompatibility and safety. Despite the success of parenteral liposomes, oral delivery of liposomes is impeded by various barriers such as instability in the gastrointestinal tract, difficulties in crossing biomembranes, and mass production problems. By modulating the compositions of the lipid bilayers and adding polymers or ligands, both the stability and permeability of liposomes can be greatly improved for oral drug delivery. This review provides an overview of the challenges and current approaches toward the oral delivery of liposomes.
PubMed: 30766776
DOI: 10.1016/j.apsb.2018.06.005 -
Current Opinion in Gastroenterology May 2015It is our opinion that there is an unmet need in hepatology for a minimally or noninvasive test of liver function and physiology. Quantitative liver function tests... (Review)
Review
PURPOSE OF REVIEW
It is our opinion that there is an unmet need in hepatology for a minimally or noninvasive test of liver function and physiology. Quantitative liver function tests define the severity and prognosis of liver disease by measuring the clearance of substrates whose uptake or metabolism is dependent upon liver perfusion or hepatocyte function. Substrates with high-affinity hepatic transporters exhibit high 'first-pass' hepatic extraction and their clearance measures hepatic perfusion. In contrast, substrates metabolized by the liver have low first-pass extraction and their clearance measures specific drug metabolizing pathways.
RECENT FINDINGS
We highlight one quantitative liver function test, the dual cholate test, and introduce the concept of a disease severity index linked to clinical outcome that quantifies the simultaneous processes of hepatocyte uptake, clearance from the systemic circulation, clearance from the portal circulation, and portal-systemic shunting.
SUMMARY
It is our opinion that dual cholate is a relevant test for defining disease severity, monitoring the natural course of disease progression, and quantifying the response to therapy.
Topics: Cholates; Health Services Needs and Demand; Hepatocytes; Humans; Liver; Liver Diseases; Liver Function Tests; Metabolic Clearance Rate; Predictive Value of Tests; Severity of Illness Index
PubMed: 25714706
DOI: 10.1097/MOG.0000000000000167 -
Advanced Nanobiomed Research Jan 2021A method is developed for membrane labeling of erythrocytes with porphyrin-phospholipid (PoP). To generate a concentrated PoP solution for labeling human red blood cells...
A method is developed for membrane labeling of erythrocytes with porphyrin-phospholipid (PoP). To generate a concentrated PoP solution for labeling human red blood cells (RBCs), various surfactants and solvents are screened to identify conditions that avoid hemolysis, while minimizing non-specific PoP co-precipitation with RBCs in the pellet during centrifugation washes. Cholate, Tween 80 and Tween 40 are identified as useful surfactants for this purpose. When labeled RBCs are mixed with unlabeled ones, substantial non-specific PoP exchange is observed. Egg-yolk lecithin is included in a washing buffer to remove loosely bound PoP and reduce PoP exchange with unlabeled erythrocytes, based on flow cytometry and photodynamic hemolysis assays. Murine RBCs that are labeled with Cu-chelated PoP displayed altered biodistribution with longer blood circulation relative to directly administered Cu-chelated PoP.
PubMed: 34212160
DOI: 10.1002/anbr.202000013 -
Molecules (Basel, Switzerland) Dec 2022Pomelo peel is a natural plant product with numerous pharmacological effects and is used in traditional Chinese medicine. In the present study, we extracted naringin...
Pomelo peel is a natural plant product with numerous pharmacological effects and is used in traditional Chinese medicine. In the present study, we extracted naringin from pomelo peel and aimed to decipher its therapeutic potential against hyperlipidemia. We used ultrasonic-assisted extraction to obtain naringin prior to identifying its structure, to evaluate its ability in binding sodium glycine cholate and sodium bovine cholate in vitro by simulating the gastrointestinal environment, so as to evaluate its blood lipid-lowering activity. The hyperlipidemia mouse model was established. Following the intragastric administration of naringin for 5 weeks, we measured the weight change, organ index, high-density lipoprotein cholesterol (HDL-C), serum total cholesterol (TC), serum triglycerides (TG), liver superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), low-density lipoprotein cholesterol (LDL-C) level, malondialdehyde (MDA), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) level of mice in the normal control and high-fat diet groups in addition to the high-, medium-, and low-dose naringin groups. The pathological changes in the liver were observed under a light microscope. The total RNA of the liver was extracted, and the mRNA expression level of lipid metabolism-related factors in mouse liver was detected via a fluorescence quantitative polymerase chain reaction (PCR). Naringin significantly (p < 0.01) reduced the body weight, organ index, serum TG, LDL-C, and TC levels of hyperlipidemic mice, but increased the serum HDL-C levels (p < 0.01). Furthermore, naringin increased GSH Px and SOD activity (p < 0.01), while decreasing MDA, ALT, and AST levels, as well as the liver index (p < 0.01). There was no statistically significant difference in the brain, heart, spleen, kidney, and other indicators (p > 0.05). A histopathological analysis of mouse liver showed that naringin could alleviate the degenerative damage of fatty liver cells in hyperlipidemic mice. Naringin could significantly (p < 0.01) reduce the expression of FAS and SREBP-1c mRNA, and simultaneously increase PPARα mRNA expression. This study shows that naringin has the strong effect of lowering lipids and protecting the liver in hyperlipidemic mice. Our findings underscore the anti-hyperlipidemia potential of naringin and increase the scientific understanding of its anti-hyperlipidemia effects, that may lead to its potential application as a dietary strategy for hyperlipidemia management in the future.
Topics: Mice; Animals; Cattle; Cholesterol, LDL; Hyperlipidemias; Lipids; Liver; Diet, High-Fat; Superoxide Dismutase; Triglycerides
PubMed: 36558166
DOI: 10.3390/molecules27249033 -
Arteriosclerosis, Thrombosis, and... Nov 2023SR-B1 (scavenger receptor class B type 1)/LDLR (low-density lipoprotein receptor) double knockout mice fed a high-fat, high-cholesterol diet containing cholate exhibit...
BACKGROUND
SR-B1 (scavenger receptor class B type 1)/LDLR (low-density lipoprotein receptor) double knockout mice fed a high-fat, high-cholesterol diet containing cholate exhibit coronary artery disease characterized by occlusive coronary artery atherosclerosis, platelet accumulation in coronary arteries, and myocardial fibrosis. Platelets are involved in atherosclerosis development, and PAR (protease-activated receptor) 4 has a prominent role in platelet function in mice. However, the role of PAR4 on coronary artery disease in mice has not been tested.
METHODS
We tested the effects of a PAR4 inhibitory pepducin (RAG8) on diet-induced aortic sinus and coronary artery atherosclerosis, platelet accumulation in atherosclerotic coronary arteries, and myocardial fibrosis in SR-B1/LDLR double knockout mice. SR-B1/LDLR double knockout mice were fed a high-fat, high-cholesterol diet containing cholate and injected daily with 20 mg/kg of either the RAG8 pepducin or a control reverse-sequence pepducin (SRQ8) for 20 days.
RESULTS
Platelets from the RAG8-treated mice exhibited reduced thrombin and PAR4 agonist peptide-mediated activation compared with those from control SRQ8-treated mice when tested ex vivo. Although aortic sinus atherosclerosis levels did not differ, RAG8-treated mice exhibited reduced coronary artery atherosclerosis, reduced platelet accumulation in atherosclerotic coronary arteries, and reduced myocardial fibrosis. These protective effects were not accompanied by changes in circulating lipids, inflammatory cytokines, or immune cells. However, RAG8-treated mice exhibited reduced VCAM-1 (vascular cell adhesion molecule 1) protein levels in nonatherosclerotic coronary artery cross sections and reduced leukocyte accumulation in atherosclerotic coronary artery cross sections compared with those from SRQ8-treated mice.
CONCLUSIONS
The PAR4 inhibitory RAG8 pepducin reduced coronary artery atherosclerosis and myocardial fibrosis in SR-B1/LDLR double knockout mice fed a high-fat, high-cholesterol diet containing cholate. Furthermore, RAG8 reduced VCAM-1 in nonatherosclerotic coronary arteries and reduced leukocyte and platelet accumulation in atherosclerotic coronary arteries. These findings identify PAR4 as an attractive target in reducing coronary artery disease development, and the use of RAG8 may potentially be beneficial in cardiovascular disease.
Topics: Animals; Mice; Atherosclerosis; Cholates; Cholesterol; Coronary Artery Disease; Fibrosis; Mice, Inbred C57BL; Mice, Knockout; Receptors, LDL; Vascular Cell Adhesion Molecule-1
PubMed: 37675637
DOI: 10.1161/ATVBAHA.123.319767 -
Chemical Research in Toxicology Jul 2022Applications of reduced graphene oxide (rGO) in many different areas have been gradually increasing owing to its unique physicochemical characteristics, demanding more...
Applications of reduced graphene oxide (rGO) in many different areas have been gradually increasing owing to its unique physicochemical characteristics, demanding more understanding of their biological impacts. Herein, we assessed the toxicological effects of rGO in mammary epithelial cells. Because the as-synthesized rGO was dissolved in sodium cholate to maintain a stable aqueous dispersion, we hypothesize that changing the cholate concentration in the dispersion may alter the surface property of rGO and subsequently affect its cellular toxicity. Thus, four types of rGO were prepared and compared: rGO dispersed in 4 and 2 mg/mL sodium cholate, labeled as rGO and concentrated-rGO (c-rGO), respectively, and rGO and c-rGO coated with a protein corona through 1 h incubation in culture media, correspondingly named pro-rGO and pro-c-rGO. Notably, c-rGO and pro-c-rGO exhibited higher toxicity than rGO and pro-rGO and also caused higher reactive oxygen species production, more lipid membrane peroxidation, and more significant disruption of mitochondrial-based ATP synthesis. In all toxicological assessments, pro-c-rGO induced more severe adverse impacts than c-rGO. Further examination of the material surface, protein adsorption, and cellular uptake showed that the surface of c-rGO was coated with a lower content of surfactant and adsorbed more proteins, which may result in the higher cellular uptake observed with pro-c-rGO than pro-rGO. Several proteins involved in cellular redox mediation were also more enriched in pro-c-rGO. These results support the strong correlation between dispersant coating and corona formation and their subsequent cellular impacts. Future studies in this direction could reveal a deeper understanding of the correlation and the specific cellular pathways involved and help gain knowledge on how the toxicity of rGO could be modulated through surface modification, guiding the sustainable applications of rGO.
Topics: Graphite; Protein Corona; Reactive Oxygen Species; Sodium Cholate
PubMed: 35706338
DOI: 10.1021/acs.chemrestox.2c00042 -
MBio Mar 2016Steroids are ubiquitous in natural environments and are a significant growth substrate for microorganisms. Microbial steroid metabolism is also important for some... (Comparative Study)
Comparative Study
UNLABELLED
Steroids are ubiquitous in natural environments and are a significant growth substrate for microorganisms. Microbial steroid metabolism is also important for some pathogens and for biotechnical applications. This study delineated the distribution of aerobic steroid catabolism pathways among over 8,000 microorganisms whose genomes are available in the NCBI RefSeq database. Combined analysis of bacterial, archaeal, and fungal genomes with both hidden Markov models and reciprocal BLAST identified 265 putative steroid degraders within only Actinobacteria and Proteobacteria, which mainly originated from soil, eukaryotic host, and aquatic environments. These bacteria include members of 17 genera not previously known to contain steroid degraders. A pathway for cholesterol degradation was conserved in many actinobacterial genera, particularly in members of the Corynebacterineae, and a pathway for cholate degradation was conserved in members of the genus Rhodococcus. A pathway for testosterone and, sometimes, cholate degradation had a patchy distribution among Proteobacteria. The steroid degradation genes tended to occur within large gene clusters. Growth experiments confirmed bioinformatic predictions of steroid metabolism capacity in nine bacterial strains. The results indicate there was a single ancestral 9,10-seco-steroid degradation pathway. Gene duplication, likely in a progenitor of Rhodococcus, later gave rise to a cholate degradation pathway. Proteobacteria and additional Actinobacteria subsequently obtained a cholate degradation pathway via horizontal gene transfer, in some cases facilitated by plasmids. Catabolism of steroids appears to be an important component of the ecological niches of broad groups of Actinobacteria and individual species of Proteobacteria.
IMPORTANCE
Steroids are ubiquitous growth substrates for environmental and pathogenic bacteria, and bacterial steroid metabolism has important pharmaceutical and health applications. To date, the genetics and biochemistry of microbial steroid degradation have mainly been studied in a few model bacteria, and the diversity of this metabolism remains largely unexplored. Here, we provide a bioinformatically derived perspective of the taxonomic distribution of aerobic microbial steroid catabolism pathways. We identified several novel steroid-degrading bacterial groups, including ones from marine environments. In several cases, we confirmed bioinformatic predictions of metabolism in cultures. We found that cholesterol and cholate catabolism pathways are highly conserved among certain actinobacterial taxa. We found evidence for horizontal transfer of a pathway to several proteobacterial genera, conferring testosterone and, sometimes, cholate catabolism. The results of this study greatly expand our ecological and evolutionary understanding of microbial steroid metabolism and provide a basis for better exploiting this metabolism for biotechnology.
Topics: Actinobacteria; Aerobiosis; Biotransformation; Genomics; Metabolic Networks and Pathways; Proteobacteria; Steroids
PubMed: 26956583
DOI: 10.1128/mBio.00166-16 -
Cells Jun 2021Cytochrome c oxidase (CytOx), the oxygen-accepting and rate-limiting enzyme of mitochondrial respiration, binds with 10 molecules of ADP, 7 of which are exchanged by ATP...
Cytochrome c oxidase (CytOx), the oxygen-accepting and rate-limiting enzyme of mitochondrial respiration, binds with 10 molecules of ADP, 7 of which are exchanged by ATP at high ATP/ADP-ratios. These bound ATP and ADP can be exchanged by cholate, which is generally used for the purification of CytOx. Many crystal structures of isolated CytOx were performed with the enzyme isolated from mitochondria using sodium cholate as a detergent. Cholate, however, dimerizes the enzyme isolated in non-ionic detergents and induces a structural change as evident from a spectral change. Consequently, it turns off the "allosteric ATP-inhibition of CytOx", which is reversibly switched on under relaxed conditions via cAMP-dependent phosphorylation and keeps the membrane potential and ROS formation in mitochondria at low levels. This cholate effect gives an insight into the structural-functional relationship of the enzyme with respect to ATP inhibition and its role in mitochondrial respiration and energy production.
Topics: Adenosine Diphosphate; Animals; Cattle; Cholates; Electron Transport Complex IV; Mitochondria, Heart; Rats; Spectrophotometry, Ultraviolet
PubMed: 34201437
DOI: 10.3390/cells10071579 -
The Journal of Experimental Medicine Oct 1914Solutions of the bodies of pneumococci, obtained by dissolving them in dilute solutions of sodium cholate, by permitting them to undergo autolysis, or by first freezing,...
Solutions of the bodies of pneumococci, obtained by dissolving them in dilute solutions of sodium cholate, by permitting them to undergo autolysis, or by first freezing, drying, and then grinding in salt solution, are actively hemolytic for rabbit, sheep, guinea pig, and human red blood corpuscles. The substance on which this hemolytic property depends is very labile, much of its activity is lost on passing through a filter, and it is destroyed by the action of trypsin. In its properties it corresponds to the substance contained in such solutions which causes the death of guinea pigs on intravenous injection. Its activity is prevented by the presence of minute amounts of cholesterin. Following the injection of this solution into rabbits and sheep, the sera of these animals acquire increased power of inhibiting its hemolytic action. It therefore possesses antigenic properties. It may therefore be concluded that the bodies of pneumococci contain a toxin that is hemolytic for red blood corpuscles. This substance is not simply a product of autolysis but undoubtedly exists preformed in the bacterial cell. However, it is not given up to the surrounding fluid as long as the bodies of the bacteria are intact. It may therefore be considered a hemolytic endotoxin.
PubMed: 19867825
DOI: 10.1084/jem.20.4.346