RESUMO
Liver injury is a life-threatening condition, and the hepatoprotective potential of cyanidin-3-glucoside (C3G) has been previously demonstrated. However, due to the low bioavailability, it has been doubtful that relatively low concentrations of intact C3G in vivo could account for these bioactivities. In this study, the hepatoprotective effects of intragastric and intravenous administration of C3G were investigated in a CCl4 induced liver injury model. Intragastric C3G administration was more effective than intravenous C3G injection in reducing serum damage biomarkers, oxidative stress, and inflammatory responses, indicating that absorption of C3G into the bloodstream does not fully account for its observed benefits in vivo. Furthermore, intragastric C3G administration modulated the gut microbiota structure and increased the contents of five metabolites in the feces and serum with high inter-individual variation, indicating the key role of the interaction between C3G and the gut microbiota. At equivalent doses, the metabolites cyanidin and protocatechuic acid exhibited greater efficacy than C3G in reducing apoptosis and ROS production by activating the Nrf2 pathway in an AAPH-induced oxidative stress model. To achieve the desired health effects via C3G-rich food intake, more attention should be paid to microbially derived catabolites. Screening of specific metabolite-producing strains will help overcome individual differences and enhance the health-promoting effects of C3G.
Assuntos
Antocianinas , Microbioma Gastrointestinal , Glucosídeos , Estresse Oxidativo , Microbioma Gastrointestinal/efeitos dos fármacos , Antocianinas/farmacologia , Antocianinas/administração & dosagem , Animais , Glucosídeos/farmacologia , Glucosídeos/administração & dosagem , Masculino , Estresse Oxidativo/efeitos dos fármacos , Fígado/metabolismo , Fígado/efeitos dos fármacos , Ratos , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Camundongos , Substâncias Protetoras/farmacologia , Substâncias Protetoras/administração & dosagem , Ratos Sprague-Dawley , Administração IntravenosaRESUMO
Liver fibrosis has proven to be the main predisposing factor for liver cirrhosis and liver cancer; however, an effective treatment remains elusive. Polysaccharides, with low toxicity and a wide range of bioactivities, are strong potential candidates for anti-hepatic fibrosis applications. For this study, a new low molecular weight neutral polysaccharide (B. striata glucomannan (BSP)) was extracted and purified from Bletilla striata. The structure of BSP was characterized and its activities for alleviating liver fibrosis in vivo were further evaluated. The results revealed that the structural unit of BSP was likely â4)-ß-D-Glcp-(1 â 4)-ß-D-Manp-(1 â 4)-ß-D-2ace-Manp-(1 â 4)-ß-D-Manp-(1 â 4)-ß-D-Glcp-(1 â 4)-ß-D-Manp-(1 â 4)-ß-D-Manp-(1 â 4)-ß-D-3ace-Manp-(1â, with a molecular weight of only 58.5 kDa. Additionally, BSP was observed to attenuate the passive impacts of liver fibrosis in a manner closely related to TLR2/TLR4-MyD88-NF-κB signaling pathway conduction. In summary, the results of this study provide theoretical foundations for the potential applications of BSP as an anti-liver fibrosis platform.
Assuntos
Orchidaceae , Polissacarídeos , Humanos , Polissacarídeos/farmacologia , Polissacarídeos/uso terapêutico , Polissacarídeos/química , Orchidaceae/química , Cirrose Hepática/induzido quimicamente , Cirrose Hepática/tratamento farmacológico , FibroseRESUMO
Acute liver injury has multiple causes and can result in liver failure. In this study, we evaluated the hepatoprotective ability of cyanidin (Cy) and investigated its associated mechanisms. Cy administration significantly and dose-dependently ameliorated acute liver injury induced by carbon tetrachloride (CCl4). High-dose Cy showed effects comparable to those achieved by the positive control (silymarin). Severe oxidative stress and inflammatory responses in the liver tissue induced by CCl4 were significantly mitigated by Cy supplementation. The total antioxidant capacity and the activity of superoxide dismutase, catalase, and glutathione peroxidase were increased and the content of malondialdehyde, lipid peroxide, tumor necrosis factor α, interleukin-1ß, and interleukin-6 were decreased. Additionally, the Nrf2 and NF-κB signaling pathways, which regulate antioxidative and inflammatory responses, were analyzed using quantitative real-time polymerase chain reaction and western blot assay. Cy treatment not only increased Nrf2 transcription and expression but also decreased NF-κB signaling. Moreover, molecular docking simulation indicated that Cy had high affinity for Keap1 and NF-κB/p65, which may promote nuclear translocation of Nrf2 and inhibit that of NF-κB. In summary, Cy treatment exerted antioxidative and anti-inflammatory effects and ameliorated liver injury by increasing Nrf2 and inhibiting the NF-κB pathway, demonstrating the potential of Cy as a therapeutic agent in liver injury.
RESUMO
Aging, a natural and inevitable physiological process, is the primary risk factor for all age-related diseases; it severely threatens the health of individuals and places a heavy burden on the public health-care system. Thus, strategies to extend the lifespan and prevent and treat age-related diseases have been gaining increasing scientific interest. Anthocyanins (ACNs) are a subclass of flavonoids widely distributed in fruits and vegetables. Growing evidence suggests that ACNs delay aging and relieve age-related diseases. However, owing to the low bioavailability of ACNs, their gut metabolites have been proposed to play a critical role in mediating health benefits. In this review, we introduce the biological fate of ACNs after consumption and highlight ACNs metabolites (phenolic acids) from intestinal microorganisms. Additionally, ACNs and gut metabolites exhibit outstanding anti-aging ability in Caenorhabditis elegans, Drosophila melanogaster, and mouse models, probably associated with increasing antioxidation, anti-inflammation, protein homeostasis, antiglycation, mitochondrial function, and inhibition of insulin/IGF-1 signaling (IIS). ACNs and gut metabolites have great application prospects as functional foods and drugs to delay aging and manage age-related diseases. Further investigation should focus on the interaction between ACNs and gut microbiota, including clarifying the complex metabolic pathway and maximizing the health effects of ACNs.
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Polysaccharide is one of the main active components of Polygonatum sibiricum. For this study, P. sibiricum polysaccharides (PSP) were obtained through purification using DEAE-Cellulose52 and Sephacryl G-150 column chromatography. The obtained samples were named PSP1, PSP2 and PSP3. The PSP1 sample was found to have the highest content and the best solubility, and a subsequent. So, its structure and characterization were analyzed. The main sugar residue linkages were found to be â 1)-ß-D-Fruf-(2 â 1)-ß-D-Fruf-(2 â 1), 1 â -ß-D-Fruf-(2 â 6)α-D-Glcp (1â, â4)-ß-D-Manp-(1 â 4)-ß-D-Manp-(1â and â6)-ß-D-Glcp-(1 â 4)-ß-D-Manp-(1â link existed. Branch chain analysis indicated â1,6)-ß-D-Fruf-(2â, ß-D-Fruf-(2â, â1,6)-ß-D-Fruf-(2â, â6)-ß-D- Fruf-(2â link existed, and the link site was at position C-6. In vitro antioxidant activity tests showed that PSP1 had a certain scavenging effect on DPPH, hydroxyl radical, superoxide anion radical and a particular effect on the chelating ability of ferrous. This suggested that P. sibiricum polysaccharides may be a potential antioxidant.
Assuntos
Polygonatum , Antioxidantes/química , Antioxidantes/farmacologia , Configuração de Carboidratos , Polygonatum/química , Polissacarídeos/químicaRESUMO
Living organisms tend to evolve various naturally photoprotective mechanisms to avoid photodamage. Among them, polydopamine (PDA) is an effective sunscreen, a mimic of melanin, which is the main functional component of the photoprotective system of human skin. However, the concerns of its dark color, skin penetration and photoprotective efficiency remain yet to be solved. Herein, we have constructed melanin-inspired nanocomposite hydrogels (CS-PDAh-GP-HA) for photoprotection, in which PDA was prepared as hollow nanoparticles (PDAh NPs) and entrapped in a physically cross-linked hydrogel (CS-GP-HA) formed by chitosan (CS) and hyaluronic acid (HA) using ß-glycerophosphate (ß-GP) as a modulator. The CS-PDAh-GP-HA hydrogels exhibit a shear-thinning flow behavior with an elastic modulus of 300 Pa with the gel-sol transition temperature maintained at about 37 °C simply by adjusting the ß-GP content in the hydrogels. The CS-PDAh-GP-HA hydrogels also possess excellent resistance toward skin penetration. The photoprotective performances of CS-PDAh-GP-HA hydrogels were evaluated by the determination of sun protection factor (SPF) and in vitro UVA protection efficacy (UVAPE) along with UV-Vis spectroscopy. Compared with the TiO2 nanoparticles in CS-GP-HA hydrogel, the CS-PDAh-GP-HA hydrogels show stronger shielding ability in both UVA and UVB regions. When protected by the CS-PDAh-GP-HA hydrogels, the cell viability of NIH-3T3 fibroblasts increases to 96% while it was only 14% in the case of non-protecting group. These results suggest that the CS-PDAh-GP-HA hydrogels could efficiently shield the UV irradiation and protect the skin from photodamage. This work introduces PDA-based nanocomposite hydrogels with safe, biocompatible and photoprotective properties, and provides a melanin-mimicking photoprotection system for the application in sunscreens.
Assuntos
Quitosana , Nanopartículas , Humanos , Hidrogéis/farmacologia , Indóis/farmacologia , PolímerosRESUMO
Atractylodes lancea is a type of typical traditional Chinese medicinal (TCM) herb that is economically important in China. The traditional planting method of A. lancea is to plant in situ continuously for many years, which often leads to impediments for its growth and development and soil-borne diseases. The root-associated microbiome is believed to play an important role in plant resistance and the quality of products from the plant. This study aims to reveal detailed changes in the populations of rhizosphere microorganisms, and providing theoretical guidance for the prevention and control of soil-borne diseases in A. lancea. A high-throughput sequencing approach was utilized to illustrate changes in the microbial community from different planting years. Results and conclusions: The results show that the diversity and composition of the root-associated microbiome was significantly impacted by the consecutive monoculture of A. lancea. At the level of the comparisons of the phyla, Bacteroidetes, Proteobacteria, Ascomycota, and Basidiomycota declined significantly. In contrast, the relative abundance of Actinobacteria, Acidobacteria, and Mortierellomycota distinctly increased. Comparisons at the genus level indicated that Sphingomonas, Flavobacterium, Pseudomonas, Pedobacter, and Tausonia decreased significantly, whereas Mortierella, Cylindrocarpon, Dactylonectria, and Mucor distinctly increased. In conclusion, this study helps to develop an understanding of the impediments involved in the consecutive monoculture of A. lancea.
Assuntos
Atractylodes/microbiologia , Atractylodes/fisiologia , Flavobacterium/patogenicidade , Pedobacter/patogenicidade , Pseudomonas/patogenicidade , Rizosfera , Microbiologia do Solo , Sphingomonas/patogenicidadeRESUMO
BACKGROUP: Superfine grinding (SG) technology has attracted considerable attention in food and medicine researcher fields. METHODS: Polysaccharides in superfine powder of Gynostemma pentaphyllum Makino (GPP) were extracted using three methods, including hot water extraction (HWE), ultrasound-assisted hot extraction (UAE), and microwave-assisted hot extraction (MAE), and the purified polysaccharides were specially denoted as GPWP, GPUP, and GPMP, respectively. The possible structures of polysaccharides were investigated by FT-IR, HPLC and SEM. In addition, the antioxidative and immunomodulatory activities were evaluated by in vitro radical-scavenging activity assay and immune cell functional evaluation. RESULTS: We observed that the yield of GPUP (20.31%) was relatively higher than that of GPWP (15.34%) and GPMP (16.96%). Among all products, GPWP exhibited the highest antioxidative activities against DPPH, hydroxyl, and superoxide anion radicals. GPWP could also preferably chelate Fe2+ and protect against the oxidative damage by increasing the cellular levels of antioxidant enzymes (SOD, CAT and GSH-PX) and decreasing the content of oxidation product (MDA). Three polysaccharides presented some extent of immunoregulatory activity by promoting the phagocytosis of mononuclear macrophages and elevating the levels of NO, TNF-É, and IL-6, and among which GPWP showed the best. CONCLUSION: These results indicate that the HWE method is an excellent technique for extracting GPP with high bioactivities that would be suitable for various industrial applications. Graphical Abstract.
Assuntos
Antioxidantes/química , Gynostemma/química , Fatores Imunológicos/química , Polissacarídeos/química , Antioxidantes/isolamento & purificação , Antioxidantes/farmacologia , Compostos de Bifenilo/química , Radical Hidroxila/química , Fatores Imunológicos/isolamento & purificação , Fatores Imunológicos/farmacologia , Micro-Ondas , Picratos/química , Polissacarídeos/isolamento & purificação , Polissacarídeos/farmacologia , Pós/química , Superóxidos/químicaRESUMO
In this study, a water-soluble polysaccharide (BSP) was extracted and purified from pseudobulb of Bletilla striata. The preliminary structure and gastroprotective activity of BSP were analyzed. Results indicate that BSP is a glucomannan with a molar ratio of 7.45:2.55 (Man:Glc), and its molecular weight is approximately 1.7 × 105 Da. BSP displayed outstanding protective action against ethanol-induced GES-1 cell injury in vitro, as well as, excellent gastroprotective activity in vivo. Especially, a high-dose of BSP (100 mg/kg) could reduce the ulcer index of the gastric mucosa and increase the percentage of ulcer inhibition, which possibly caused by enhancing the antioxidant capacity and inhibiting the apoptotic pathway in gastric tissue. Interestingly, BSP exhibited a comparative gastroprotective activity to that of positive control (omeprazole). In summary, our results indicated that BSP could be considered as a potential supplement for the prevention of gastric injury.
Assuntos
Antioxidantes/farmacologia , Mucosa Gástrica/efeitos dos fármacos , Fármacos Gastrointestinais/farmacologia , Mananas/farmacologia , Orchidaceae/química , Úlcera Gástrica/prevenção & controle , Animais , Antioxidantes/química , Antioxidantes/isolamento & purificação , Catalase/metabolismo , Linhagem Celular , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Etanol/antagonistas & inibidores , Etanol/toxicidade , Mucosa Gástrica/metabolismo , Mucosa Gástrica/patologia , Fármacos Gastrointestinais/química , Fármacos Gastrointestinais/isolamento & purificação , Vida Livre de Germes , Glutationa Peroxidase/metabolismo , Humanos , Masculino , Malondialdeído/antagonistas & inibidores , Malondialdeído/metabolismo , Mananas/química , Mananas/isolamento & purificação , Camundongos , Peso Molecular , Omeprazol/farmacologia , Solubilidade , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/metabolismo , Úlcera Gástrica/patologia , Superóxido Dismutase/metabolismo , Água/químicaRESUMO
Burn wound healing remains a challenging health problem worldwide due to the lack of efficient and precise therapy. Inherent oxidative stress following burn injury is importantly responsible for prolonged inflammation, fibrotic scar, and multiple organ failure. Herein, a bioinspired antioxidative defense system coupling with in situ forming hydrogel, namely, multiresponsive injectable catechol-Fe3+ coordination hydrogel (MICH) matrix, is engineered to promote burn-wound dermal repair by inhibiting tissue oxidative stress. This MICH matrix serves as the special traits of "Fe-superoxide dismutases," small molecular antioxidant (vitamin E), and extracellular matrix (ECM) in alleviating cellular oxidative damage, which demonstrates precise scavenging on reactive oxygen species (ROS) of different cellular locations, blocking lipid peroxidation and cell apoptosis. In in vivo burn-wound treatment, this MICH promptly integrates with injured surrounding tissue to provide hydration microenvironment and physicochemical ECM for burn wounds. Importantly, the MICH matrix suppresses tissue ROS production, reducing the inflammatory response, prompting re-epithelization and neoangiogenesis during wound healing. Meanwhile, the remodeling skin treated with MICH matrix demonstrates low collagen deposition and normal dermal collagen architecture. Overall, the MICH prevents burn wound progression and enhances skin regeneration, which might be a promising biomaterial for burn-wound care and other disease therapy induced by oxidative stress.
Assuntos
Antioxidantes , Queimaduras/tratamento farmacológico , Derme/metabolismo , Hidrogéis , Estresse Oxidativo/efeitos dos fármacos , Cicatrização/efeitos dos fármacos , Animais , Antioxidantes/química , Antioxidantes/farmacocinética , Antioxidantes/farmacologia , Queimaduras/metabolismo , Queimaduras/patologia , Derme/patologia , Feminino , Hidrogéis/química , Hidrogéis/farmacocinética , Hidrogéis/farmacologia , Camundongos , Camundongos Endogâmicos BALB C , Células NIH 3T3RESUMO
The polysaccharide fraction of Bletilla ochracea (BOP) was isolated from its tubers, and purified by DEAE-52 Cellulose and Sephadex G-200 column chromatography. The structural features of BOP were analyzed by GC-MS, HPLP, FT-IR, methylation and NMR. The average molecular weight of BOP was approximately 4.9 × 105 Da, and the monosaccharide composition was 7.88:2.12 mix of mannose and glucose. The FT-IR and NMR analyses revealed the following linkage: [â(4-ß-D-Man-1)4 â (4-ß-D-Glc-1)2 â 4-2-O-acetyl-ß-D-Man-1 â 4-ß-D-Man-1 â 4-3-O-acetyl-ß-D-Man-1 â 4-2-O-acetyl-ß-D-Man-1â]. Although BOP had no effect on the proliferation rate of CT26 colon carcinoma cells, it significantly inhibited tumor xenograft growth in vivo by stimulating CD4+ T cell expansion in the spleen of the tumor-bearing mice. Taken together, BOP is a potent immunomodulatory agent that can be considered for anti-tumor therapy.
Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , Orchidaceae/química , Polissacarídeos/química , Polissacarídeos/farmacologia , Animais , Sequência de Carboidratos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Humanos , Metilação , Camundongos , Peso Molecular , Monossacarídeos , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Polylactic acid (PLA) is one of the biodegradable materials that has been used in the areas of surgical healing lines, cancer treatment, and wound healing. However, the application of PLA is still rather limited due to its high hydrophobicity and poor antibacterial activity. In order to enhance the antifouling and antibacterial performances of PLA, here we modified the surface of PLA with various sizes of hydrogel micropatterns in negative or positive mode using plasma treatment, the photomask technique, and UV-graft polymerization. The hydrogel micropatterns consist of poly(ethylene glycol) diacrylate (PEGDA), poly(2-methacryloyloxyethylphosphorylcholine) (PMPC), and poly(methacryloyloxyethyltrimethylammonium chloride) (PDMC). Compared to PLA, the patterned PLA (PLA-PMPC/PDMC/PEGDA) shows obviously enhanced antifouling and antibacterial activities. For PLA-PMPC/PDMC/PEGDA with either positive or negative micropatterns, the antifouling and antibacterial properties are gradually increasing with decreasing the size of micropatterns. Compared with PLA-PMPC/PDMC/PEGDA bearing positive and negative micropatterns in the same size, the PLA-PMPC/PDMC/PEGDA with negative micropatterns exhibits slightly better biological activity and the PLA-PMPC/PDMC/PEGDA with 3 µm negative hydrogel micropatterns shows the best hydrophilicity, antifouling, and antibacterial properties. Combining the in vitro hemolysis assay, cytotoxicity, water absorption test, and degradation test results, it is suggested that the fabrication of hydrogel micropatterns onto the PLA surface could significantly improve biological activities of PLA. We expect that this work would provide a new strategy to potentially develop PLA as a promising wound dressing.
Assuntos
Hidrogéis , Poliésteres , Interações Hidrofóbicas e Hidrofílicas , PolietilenoglicóisRESUMO
In this study, LLP-1, LLP-2, and LLP-3 three novel polysaccharide fractions were purified from the leaves of Lilium lancifolium, and their physicochemical characterizations and antioxidant properties were investigated by chemical methods, high performance gel permeation chromatography (HPGPC), high performance liquid chromatography (HPLC), fourier transform infrared spectrometry (FT-IR), scanning electron microscopy (SEM), and DPPH radical assay, hydroxyl radical assay, superoxide radical assay and ferrous ion chelating assay, respectively. Results showed that LLP-1, LLP-2, and LLP-3 had low protein and uronic acid contents, meanwhile, their weight-average molecular weight were estimated to be 2.25×106, 2.02×106, and 2.08×106Da, respectively. Mannose, rhamnose, glucuronic acid, galacturonic acid, glucose, galactose, arabinose glucose and galactose were the major monosaccaherides components presenting in the polysaccharide fractions. Three polysaccharide fractions were not observed triple-helical conformation, while possessed variant surface structure. In addition, three polysaccharide fractions all exhibited significantly scavenging activities against free radical and chelate Fe2+in vitro.