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1.
Int Immunopharmacol ; 134: 112261, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38761783

RESUMO

BACKGROUND: Psoriasis, a chronic inflammatory condition of the skin, is characterized by an atypical proliferation of epidermal keratinocytes and immune cell infiltration. Orientin is a flavonoid monomer with potent anti-inflammatory activities. However, the therapeutic effects of orientin on psoriasis and the underlying mechanisms have not been elucidated. OBJECTIVE: To investigate the therapeutic effect of orientin on psoriasis and the underlying mechanisms using network pharmacology and experimental studies. METHODS: A psoriasis-like mouse model was established using imiquimod (IMQ). Lipopolysaccharide (LPS) was used to stimulate the RAW264.7 and HaCaT cells in vitro. The therapeutic effects of orientin and the underlying mechanism were analyzed using histopathological, immunohistochemical, quantitative real-time polymerase chain reaction, enzyme-linked immunosorbent assay, flow cytometry, and western blotting analyses. RESULTS: Orientin ameliorated skin lesions and suppressed keratinocyte proliferation and immune cell infiltration in the IMQ-induced psoriasis-like mouse model. Additionally, orientin inhibited the secretion of the pro-inflammatory factors interleukin (IL)-1ß, tumor necrosis factor (TNF)-α, IL-6, IL-8, IL-17, and IL-23 in the psoriasis-like mouse model and LPS-induced RAW264.7 and HaCaT cells. Furthermore, orientin mitigated the LPS-induced upregulation of reactive oxygen species and downregulation of IL-10 and glutathione levels. Orientin alleviated inflammation by downregulating the MAPK signaling pathway. CONCLUSION: Orientin alleviated psoriasis-like dermatitis by suppressing the MAPK signaling pathway, suggesting that orientin is a potential therapeutic for psoriasis.


Assuntos
Anti-Inflamatórios , Citocinas , Modelos Animais de Doenças , Flavonoides , Glucosídeos , Células HaCaT , Imiquimode , Queratinócitos , Lipopolissacarídeos , Sistema de Sinalização das MAP Quinases , Camundongos Endogâmicos BALB C , Psoríase , Animais , Psoríase/tratamento farmacológico , Psoríase/imunologia , Psoríase/induzido quimicamente , Psoríase/patologia , Camundongos , Humanos , Células RAW 264.7 , Anti-Inflamatórios/uso terapêutico , Anti-Inflamatórios/farmacologia , Flavonoides/farmacologia , Flavonoides/uso terapêutico , Citocinas/metabolismo , Queratinócitos/efeitos dos fármacos , Glucosídeos/uso terapêutico , Glucosídeos/farmacologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Pele/patologia , Pele/efeitos dos fármacos , Pele/imunologia , Proliferação de Células/efeitos dos fármacos , Masculino , Espécies Reativas de Oxigênio/metabolismo , Dermatite/tratamento farmacológico , Dermatite/patologia , Dermatite/imunologia , Linhagem Celular
2.
Int J Pharm ; 655: 124047, 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38531434

RESUMO

In this study, nanoparticles loaded with active components from Polygonum orientale L. (PO), a traditional Chinese herb known for its anti-myocardial ischemic properties, were investigated for cardio-protective properties. Specifically, OVQ-Nanoparticles (OVQ-NPs) with Orientin (Ori), Vitexin (Vit), and Quercetin (Que) was obtained by double emulsion-solvent evaporation method. The OVQ-NPs exhibited a spherical shape, with a uniform size distribution of 136.77 ± 3.88 nm and a stable ζ-potential of -13.40 ± 2.24 mV. Notably, these nanoparticles exhibited a favorable sustained-release characteristic, resulting in an extended circulation time within the living organism. Consequently, the administration of these nanoparticles resulted in significant improvements in electrocardiograms and heart mass index of myocardial ischemic rats induced by isoproterenol, as well as decreased serum levels of CK, LDH, and AST. Furthermore, the results of histopathological examination, such as H&E staining and TUNEL staining, confirmed a reduced level of cardiac tissue pathology and apoptosis. Moreover, the quantification of biochemical indicators (SOD, MDA, GSH, NO, TNF-α, and IL-6) demonstrated that OVQ-NPs effectively mitigated myocardial ischemia by regulating oxidative stress and inflammatory pathways. In conclusion, OVQ-NPs demonstrate promising therapeutic potential as an intervention for myocardial ischemia, providing a new perspective on traditional Chinese medicine treatment in this area.


Assuntos
Doença da Artéria Coronariana , Isquemia Miocárdica , Polygonum , Ratos , Animais , Isoproterenol/uso terapêutico , Polygonum/química , Isquemia Miocárdica/induzido quimicamente , Isquemia Miocárdica/tratamento farmacológico , Isquemia Miocárdica/prevenção & controle , Miocárdio/patologia
3.
J Agric Food Chem ; 72(12): 6226-6235, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38492240

RESUMO

The sleep-breathing condition obstructive sleep apnea (OSA) is characterized by repetitive upper airway collapse, which can exacerbate oxidative stress and free radical generation, thereby detrimentally impacting both motor and sensory nerve function and inducing muscular damage. OSA development is promoted by increasing proportions of fast-twitch muscle fibers in the genioglossus. Orientin, a water-soluble dietary C-glycosyl flavonoid with antioxidant properties, increased the expression of slow myosin heavy chain (MyHC) and signaling factors associated with AMP-activated protein kinase (AMPK) activation both in vivo and in vitro. Inhibiting AMPK signaling diminished the effects of orientin on slow MyHC, fast MyHC, and Sirt1 expression. Overall, orientin enhanced type I muscle fibers in the genioglossus, enhanced antioxidant capacity, increased mitochondrial biogenesis through AMPK signaling, and ultimately improved fatigue resistance in C2C12 myotubes and mouse genioglossus. These findings suggest that orientin may contribute to upper airway stability in patients with OSA, potentially preventing airway collapse.


Assuntos
Proteínas Quinases Ativadas por AMP , Glucosídeos , Apneia Obstrutiva do Sono , Humanos , Camundongos , Animais , Proteínas Quinases Ativadas por AMP/metabolismo , Antioxidantes/metabolismo , Biogênese de Organelas , Músculo Esquelético/metabolismo , Fibras Musculares Esqueléticas/metabolismo , Fibras Musculares de Contração Lenta/metabolismo , Flavonoides/metabolismo , Apneia Obstrutiva do Sono/metabolismo
4.
J Mol Histol ; 55(1): 109-120, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38165567

RESUMO

Endothelial cells are a crucial component of the vessel-tissue wall and exert an important role in atherosclerosis (AS). To explore the role of Orientin in AS, human vascular endothelial cells (HUVECs) were induced by oxidized low-density lipoprotein (ox-LDL) to simulate the vascular endothelial injury during AS. Cell viability was detected by CCK-8 assay. Oxidative stress and inflammation related markers were measured using kits, RT-qPCR or western blot. Besides, cell apoptosis was assessed with TUNEL staining and cell autophagy was evaluated by LC3 immunofluorescent staining. Additionally, western blot was utilized to evaluate the expression of Sestrin 1 (SESN1) and proteins in AMPK/mTOR signaling. Afterwards, SESN1 was silenced to determine the expression of autophagy-related proteins. The further application of autophagy inhibitor 3-methyladenine (3-MA) was used to clarify the regulatory mechanism of Orientin on autophagy. Results showed that the decreased viability of HUVECs caused by ox-LDL induction was elevated by Orientin. Oxidative stress and inflammation were also attenuated after Orientin addition in HUVECs under ox-LDL condition. Moreover, Orientin suppressed apoptosis and induced autophagy of HUVECs stimulated by ox-LDL, accompanied by enhanced level of phospho (p)-AMPK and declined level of p-mTOR. Interestingly, SESN1 level was elevated by Orientin, and SESN1 depletion alleviated autophagy and reduced p-AMPK expression but enhanced p-mTOR expression. The further experiments indicated that SESN1 silencing or 3-MA addition reversed the inhibitory effects of Orientin on the oxidative stress, inflammation and apoptosis of HUVECs. Collectively, Orientin could induce autophagy by activating SESN1 expression, thereby regulating AMPK/mTOR signaling in ox-LDL-induced HUVECs.


Assuntos
Proteínas Quinases Ativadas por AMP , Flavonoides , Glucosídeos , Sestrinas , Humanos , Sestrinas/metabolismo , Células Endoteliais da Veia Umbilical Humana , Proteínas Quinases Ativadas por AMP/metabolismo , Estresse Oxidativo , Lipoproteínas LDL/farmacologia , Serina-Treonina Quinases TOR/metabolismo , Apoptose , Autofagia , Inflamação/metabolismo
5.
Neurochem Res ; 49(6): 1577-1587, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38276990

RESUMO

Parkinson's disease (PD) is characterized by oxidative stress and neuroinflammation as key pathological features. Emerging evidence suggests that nuclear factor erythroid 2 related factor 2-antioxidant response element (Nrf2-ARE), phosphatidylinositol 3­kinase-protein kinase B (PI3K-Akt), c-Jun N-terminal kinase-extracellular signal-regulated kinase 1/2 (JNK-ERK1/2), and toll-like receptor 4/nuclear factor-kappa B (TLR4/NF-kB) pathways play pivotal roles in PD pathogenesis. Orientin, a phenolic phytoconstituent, has demonstrated modulatory potential on these pathways in various experimental conditions other than PD. In this study, we aimed to evaluate the neuroprotective effects of Orientin against rotenone-induced neurodegeneration in SH-SY5Y cell lines and the Swiss albino mice model of PD. Orientin was administered at doses 10 and 20 µM in cell lines and 10 and 20 mg/kg in mice, and its effects on rotenone-induced neurodegeneration were investigated. Oxidative stress markers including mitochondrial membrane potential (ΔΨm), reactive oxygen species (ROS), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx), as well as inflammatory markers including interleukin-1ß (IL-1ß), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), were measured. The expression levels of genes related to Nrf2-ARE (Nrf2), PI3K/Akt (Akt), JNK-ERK1/2 (TNF-α), and TLR4/NF-kB (TNF-α) pathways were measured to understand the modulatory effect of Orientin on these pathways. Additionally, behavioral studies assessing locomotor activity, muscle coordination, and muscle rigidity were conducted with mice. Our results indicate that Orientin dose-dependently attenuated rotenone-induced changes in oxidative stress markers, inflammatory markers, gene expression levels, and behavioral parameters. Therefore, our study concludes that Orientin exhibits significant neuroprotective benefits against rotenone-induced PD by modulating Nrf2-ARE, PI3K-Akt, JNK-ERK1/2, and TLR4/NF-kB pathways.


Assuntos
Flavonoides , Glucosídeos , Fator 2 Relacionado a NF-E2 , NF-kappa B , Fármacos Neuroprotetores , Doença de Parkinson , Receptor 4 Toll-Like , Animais , Humanos , Camundongos , Linhagem Celular Tumoral , Flavonoides/farmacologia , Flavonoides/uso terapêutico , Glucosídeos/farmacologia , Glucosídeos/uso terapêutico , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/fisiologia , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Fator 2 Relacionado a NF-E2/efeitos dos fármacos , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/efeitos dos fármacos , NF-kappa B/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Doença de Parkinson/metabolismo , Doença de Parkinson/tratamento farmacológico , Fosfatidilinositol 3-Quinases/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Rotenona/toxicidade , Transdução de Sinais/efeitos dos fármacos , Receptor 4 Toll-Like/efeitos dos fármacos , Receptor 4 Toll-Like/metabolismo
6.
Photochem Photobiol ; 100(4): 923-935, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38148662

RESUMO

Rich in antioxidants with a variety of flavones and anthocyanins, passionflower/fruit has been extensively used in food, beverage, medicinal, and natural dyes industries. The individual components present in passionflower are identified by extracting them in methanol, partitioning them between ethyl acetate and aqueous layers, and recording their ESI mass spectrometric data. The steady-state absorption and fluorescence spectra of the extract in methanol and dimethyl sulfoxide are recorded and the lifetime of the fluorescing species is reported. The pH dependence of the absorption spectrum confirms the presence of the anthocyanins.


Assuntos
Antocianinas , Flavonas , Passiflora , Antocianinas/química , Passiflora/química , Flavonas/química , Espectrometria de Massas por Ionização por Electrospray , Concentração de Íons de Hidrogênio , Espectrometria de Fluorescência , Antioxidantes/química , Extratos Vegetais/química
7.
J Agric Food Chem ; 71(46): 17842-17851, 2023 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-37941337

RESUMO

Glycosylation can enhance the solubility and stability of flavonoids. The main limitation of the glycosylation process is low intracellular uridine diphosphate glucose (UDPG) availability. This study aimed to create a glycosylation platform strain in Escherichia coli BL21(DE3) by multiple metabolic engineering of the UDPG supply. Glycosyltransferase TcCGT1 was introduced to synthesize vitexin and orientin from apigenin and luteolin, respectively. To further expand this glycosylation platform strain, not only were UDP rhamnose and UDP galactose synthesis pathways constructed, but rhamnosyltransferase (GtfC) and galactosyltransferase (PhUGT) were also introduced, respectively. In a 5 L bioreactor with apigenin, luteolin, kaempferol, and quercetin as glycosyl acceptors, vitexin, orientin, afzelin, quercitrin, hyperoside, and trifolin glycosylation products reached 17.2, 36.5, 5.2, 14.1, 6.4, and 11.4 g/L, respectively, the highest titers reported to date for all. The platform strain has great potential for large-scale production of glycosylated flavonoids.


Assuntos
Apigenina , Uridina Difosfato Glucose , Glicosilação , Uridina Difosfato Glucose/metabolismo , Apigenina/metabolismo , Escherichia coli/genética , Escherichia coli/metabolismo , Luteolina/metabolismo , Flavonoides/metabolismo
8.
Food Sci Nutr ; 11(9): 5582-5595, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37701239

RESUMO

The aberrant differentiation of osteoclasts is a key feature of the pathogenesis of osteoporosis, which has a devastating impact on human health. While the effects of Orientin (Ori) on osteoporosis, particularly on RANKL-stimulated osteoclast production and activation, remain still unclear, Ori has been found to display several biological activities, including antioxidant and anti-inflammatory. In this work, we investigated the possible pathways through which Ori suppressed RANKL-induced osteoclast development and showed for the first time that it does so. The macrophages from the bone marrow (BMMs) were cultivated and then treated with Ori after being stimulated with RANKL. Then, TRAP-positive multinucleated cells were counted, and F-actin ring analysis was used to assess Ori's impact on mature osteoclast development. In addition, dihydroethidium (DHE) staining was used to evaluate the impact of Ori on RANKL-induced reactive oxygen species (ROS). In addition, we performed western blotting and quantitative RT-PCR analysis to investigate probable causes of these downregulation effects. We discovered that Ori inhibits the creation of osteoclasts, the gene and protein expressions unique to osteoclasts, and the ROS production. By activating Nrf2 and other ROS-scavenging enzymes, Ori reduces intracellular ROS levels. The expression of the main transcription factor of osteoclast development, c-Fos, was downregulated together with NFATc1, CTSK, and NFATc2, thanks to Ori's inhibition of RANKL-induced NF-κB. Consistent with its in vitro antiosteoclastogenic action, Ori therapy in the ovariectomized (OVX) rat model was also able to restore bone mass and improve microarchitecture in the distal femurs. Together, our results demonstrate that Ori is a flavonoid molecule with therapeutic promise for bone illnesses associated with osteoclasts, such as osteoporosis.

9.
Naunyn Schmiedebergs Arch Pharmacol ; 396(10): 2519-2528, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37178274

RESUMO

Orientin is a flavone isolated from medicinal plants used in traditional Chinese medicine (TCM) that suppresses the growth of cancer cells in vitro. The effects of orientin in hepatoma carcinoma cells remain unknown. The aim of this paper is to investigate the effects of orientin on the viability, proliferation, and migration of hepatocellular carcinoma cells in vitro. In this study, we found that orientin could inhibit the proliferation, migration, and the activation of NF-κB signaling pathway in hepatocellular carcinoma cells. An activator of NF-κB signaling pathway, PMA, could abolish the inhibitory effect of orientin on NF-κB signaling pathway and proliferation and migration of Huh7 cells. These findings raise the possibility that orientin can be used in the treatment of hepatocellular carcinoma.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patologia , NF-kappa B/metabolismo , Neoplasias Hepáticas/patologia , Proliferação de Células , Linhagem Celular Tumoral
10.
J Orthop Res ; 41(11): 2405-2417, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37186383

RESUMO

Effects of Orientin on murine chondrocytes treated with interleukin-1ß (IL-1ß) were evaluated using qPCR, western blot analysis, ELISA, and immunofluorescent staining in vitro. In vivo, We established a standard OA model by performing the destabilized medial meniscus (DMM) surgery on C57BL/6 mice, and assessed healing effect of Orientin by X-ray imaging, histopathological analysis, immunohistochemical staining. Osteoarthritis (OA) is the most common form of degenerative joint disease in clinic and the chondrocyte inflammation plays the most important role in OA development. The natural flavonoid compound (Orientin) has anti-inflammatory bioactive properties in the treatment of various diseases. But studies have not explored whether Orientin modulates OA progression. In this study, a significant suppression in IL-1ß-mediated pro-inflammatory mediators and the degradation of cartilage extracellular matrix (ECM) was observed in vitro through qPCR, western blot analysis, ELISA, and immunofluorescent staining after the treatment with Orientin. In addition, Orientin abrogated DMM surgery induced cartilage degradation in mice, which was assessed by X-ray imaging, histopathological analysis, immunohistochemical staining. Mechanistic studies showed that Orientin suppressed OA development by downregulating activation of NF-κB by activating Nrf2/HO-1 axis and SIRT6 signaling pathway. These results provide evidence that Orientin serves as a potentially viable compound for the treatment of OA.


Assuntos
Osteoartrite , Sirtuínas , Camundongos , Animais , Condrócitos/metabolismo , NF-kappa B/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Fator 2 Relacionado a NF-E2/farmacologia , Osteoartrite/metabolismo , Camundongos Endogâmicos C57BL , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Flavonoides/farmacologia , Flavonoides/uso terapêutico , Meniscos Tibiais/patologia , Sirtuínas/metabolismo , Sirtuínas/farmacologia , Interleucina-1beta/metabolismo , Células Cultivadas
11.
Struct Chem ; : 1-11, 2023 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-36721714

RESUMO

Nanocarriers allow the connection between biomolecules and other structures to enhance the treatment efficacy, through the biomolecule's properties to an existing drug, or to allow a better and specific delivery. Apigenin and orientin are biomolecules with excellent therapeutic properties that are proposed in the fight against COVID-19. Besides that, graphene oxide is a nanomaterial that exhibits antiviral activity and is used as a nanocarrier of several drugs. We evaluated in this work, through molecular docking, the binding affinity between these structures to the receptor-binding domain of spike protein of two coronavirus variants, Delta and Omicron. The results indicate that all the structures exhibit affinity with the two protein targets, with binding affinity values of -11.88 to -6.65 kcal/mol for the Delta variant and values of -9.58 to -13.20 kcal/mol for the Omicron variant, which is a successful value as found in the literature as a potential inhibitor of SARS-CoV-2 infection. Also, through first-principles calculations based on Density Functional Theory, the interaction of graphene oxide with the biomolecules apigenin and orientin occurred. The results exhibit weak binding energy, which indicates that physical adsorption occurs, with better results when the biomolecule is set in parallel to the nanomaterial due to attractive π-π staking. These results are conducive to the development of a nanocarrier.

12.
Biomed Pharmacother ; 159: 114244, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36638594

RESUMO

Obesity is a disorder with an increasing prevalence, which impairs the life quality of patients and intensifies societal health care costs. The development of safe and innovative prevention strategies and therapeutic approaches is thus of great importance. The complex pathophysiology of obesity involves multiple signaling pathways that influence energy metabolism in different tissues. The phosphatidylinositol 3-kinases (PI3K)/protein kinase B (AKT) pathway is critical for the metabolic homeostasis and its function in insulin-sensitive tissues is described in the context of health, obesity and obesity-related complications. The PI3K family participates in the regulation of diverse physiological processes including but not limited to cell growth, survival, differentiation, autophagy, chemotaxis, and metabolism depending on the cellular context. AKT is downstream of PI3K in the insulin signaling pathway, and promotes multiple cellular processes by targeting a plethora of regulatory proteins that control glucose and lipid metabolism. Natural products are essential for prevention and treatment of many human diseases, including obesity. Anti-obesity natural compounds effect multiple pathophysiological mechanisms involved in obesity development. Numerous recent preclinical studies reveal the advances in using plant secondary metabolites to target the PI3K/AKT signaling pathway for obesity management. In this paper the druggability of PI3K as a target for compounds with anti-obesity potential is evaluated. Perspectives on the strategies and limitations for clinical implementation of obesity management using natural compounds modulating the PI3K/AKT pathway are suggested.


Assuntos
Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Humanos , Insulina , Fosfatidilinositol 3-Quinase/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Obesidade/metabolismo
13.
Food Chem X ; 16: 100515, 2022 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-36519092

RESUMO

In thermally processed foods, several heat-induced toxicants are potentially formed due to the Maillard reaction, such as α-dicarbonyls and advanced glycation end products (AGEs). In the present work, we found that the methylglyoxal (MGO)-trapping and antiglycative activities of the herbal tea samples correlated strongly with their total phenolic and flavonoid contents. Among the tested herbal tea samples, rooibos exhibited the strongest MGO-trapping and antiglycative activities against AGEs formation. Aspalathin, orientin and isoorientin were further identified as the major bioactive compounds of rooibos that scavenged MGO to form the corresponding mono-MGO adducts. Moreover, the contents of dicarbonyls and AGEs in the cookie were remarkably reduced by fortification with rooibos. Altogether, our current findings suggested that rooibos might serve as a functional ingredient to reduce intake of dietary reactive carbonyl species (RCS) and AGEs from thermally processed foods, especially bakery products.

14.
Allergol Immunopathol (Madr) ; 50(6): 154-162, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36335459

RESUMO

BACKGROUND: Natural compounds are found to play an essential role in diverse inflammatory diseases, including rheumatoid arthritis (RA). Orientin, a flavonoid compound, is closely related to diverse pathological processes. Nevertheless, the role of orientin in RA is still unknown. METHODS: The cell viability was tested through cell counting kit 8 (CCK-8) assay, and the number of cell colonies was calculated via colony formation assay. In addition, flow cytometry assay was employed to detect apoptosis rate in human RA fibroblast-like synoviocytes (RA-FLS). Besides, Transwell assay was introduced to determine cell migratory and invasive abilities. Moreover, the level of cytokines (IL-8, IL-1ß, and IL-6) was estimated with quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent serologic assay. Furthermore, western blotting analysis was used to test the protein levels of cleaved-caspase-3, Bax, BCL-2, matrix metalloproteinase (MMP)-2, MMP-9, phosphorylated c-Jun N-terminal kinase, p-P38, and phospho-extracellular signal-related kinase. RESULTS: Orientin inhibited cell viability, migration as well as invasion in a concentration- dependent manner in human RA-FLS. Additionally, treatment of orientin facilitated apoptosis and decreased the secretion of cytokines induced by tumor necrosis factor alpha (TNF-α) in human RA-FLS. Moreover, orientin inactivated mitogen-activated protein kinase (MAPK)-related signaling pathway, notably in human RA-FLS. CONCLUSION: These findings confirmed that orientin inhibited human RA-FLS development and decreased TNF-α-induced inflammatory factors, at least partly, by modulating MAPK-signaling pathway, which implied that orientin might be an effective agent for treating RA.


Assuntos
Artrite Reumatoide , Sinoviócitos , Humanos , Sinoviócitos/metabolismo , Sinoviócitos/patologia , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Proteínas Quinases Ativadas por Mitógeno/farmacologia , Membrana Sinovial/metabolismo , Membrana Sinovial/patologia , Fator de Necrose Tumoral alfa/metabolismo , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/metabolismo , Fibroblastos , Flavonoides/farmacologia , Transdução de Sinais , Citocinas/metabolismo , Células Cultivadas , Proliferação de Células
15.
Microb Cell Fact ; 21(1): 210, 2022 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-36242071

RESUMO

BACKGROUND: Flavonoid C-glycosides have many beneficial effects and are widely used in food and medicine. However, plants contain a limited number of flavonoid C-glycosides, and it is challenging to create these substances chemically. RESULTS: To screen more robust C-glycosyltransferases (CGTs) for the biosynthesis of flavonoid C-glycosides, one CGT enzyme from Stenoloma chusanum (ScCGT1) was characterized. Biochemical analyses revealed that ScCGT1 showed the C-glycosylation activity for phloretin, 2-hydroxynaringenin, and 2-hydroxyeriodictyol. Structure modeling and mutagenesis experiments indicated that the glycosylation of ScCGT1 may be initiated by the synergistic action of conserved residue His26 and Asp14. The P164T mutation increased C-glycosylation activity by forming a hydrogen bond with the sugar donor. Furthermore, when using phloretin as a substrate, the extracellular nothofagin production obtained from the Escherichia coli strain ScCGT1-P164T reached 38 mg/L, which was 2.3-fold higher than that of the wild-type strain. Finally, it is proved that the coupling catalysis of CjFNS I/F2H and ScCGT1-P164T could convert naringenin into vitexin and isovitexin. CONCLUSION: This is the first time that C-glycosyltransferase has been characterized from fern species and provides a candidate gene and strategy for the efficient production of bioactive C-glycosides using enzyme catalysis and metabolic engineering.


Assuntos
Gleiquênias , Glicosiltransferases , Escherichia coli/metabolismo , Gleiquênias/metabolismo , Flavonoides/metabolismo , Glicosídeos , Glicosiltransferases/genética , Glicosiltransferases/metabolismo , Floretina , Açúcares
16.
Apoptosis ; 27(11-12): 1031-1048, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36125665

RESUMO

Although considered as a major contributor to low back pain (LBP), intervertebral disc degeneration (IVDD) has poor medical and surgical treatments. Various studies have revealed that endoplasmic reticulum (ER) stress and extracellular matrix (ECM) degeneration play a vital role in initiating and developing the progression of IVDD. Moreover, restoration of SIRT1/AMPK was confirmed to prevent IVDD and damage via maintaining ER and extracellular homeostasis. In addition, orientin (Ori) has been shown to upregulate SIRT1. However, the effect of Ori in nucleus pulposus cells (NPCs) is not determined. Hence, in this study we aim to explore the function of Ori in IVDD pathological model. The results demonstrate that Ori treatment in vitro increased SIRT1/AMPK in NPCs, maintained ECM and ER balance and decreased oxidative stress (OS) response. Ori rescued the disordered homeostasis stimulated by tert-butyl hydroperoxide (TBHP), and its function can be inhibited by thapsigargin (TG). Compound C and EX-527, inhibitors of AMPK and SIRT1 counteracted the Ori-mediated ER stress elimination. These results confirm that Ori exerts its effects by upregulating AMPK and SIRT1. Puncture-stimulated IVDD rats were used to show that Ori attenuates the pathological development in vivo. In all, we partly unveil the underlying mechanisms of Ori in IVDD.


Assuntos
Degeneração do Disco Intervertebral , Disco Intervertebral , Núcleo Pulposo , Ratos , Animais , Núcleo Pulposo/metabolismo , Degeneração do Disco Intervertebral/genética , Degeneração do Disco Intervertebral/patologia , Sirtuína 1/genética , Sirtuína 1/metabolismo , Estresse do Retículo Endoplasmático , Proteínas Quinases Ativadas por AMP/genética , Proteínas Quinases Ativadas por AMP/metabolismo , Ratos Sprague-Dawley , Apoptose , Estresse Oxidativo , Mitocôndrias , Disco Intervertebral/metabolismo , Disco Intervertebral/patologia
17.
Molecules ; 27(11)2022 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-35684542

RESUMO

Recent studies on the ethnomedicinal use of Clinacanthus nutans suggest promising anti-inflammatory, anti-tumorigenic, and antiviral properties for this plant. Extraction of the leaves with polar and nonpolar solvents has yielded many C-glycosyl flavones, including schaftoside, isoorientin, orientin, isovitexin, and vitexin. Aside from studies with different extracts, there is increasing interest to understand the properties of these components, especially regarding their ability to exert anti-inflammatory effects on cells and tissues. A major focus for this review is to obtain information on the effects of C. nutans extracts and its phytochemical components on inflammatory signaling pathways in the peripheral and central nervous system. Particular emphasis is placed on their role to target the Toll-like receptor 4 (TLR4)-NF-kB pathway and pro-inflammatory cytokines, the antioxidant defense pathway involving nuclear factor erythroid-2-related factor 2 (NRF2) and heme oxygenase 1 (HO-1); and the phospholipase A2 (PLA2) pathway linking to cyclooxygenase-2 (COX-2) and production of eicosanoids. The ability to provide a better understanding of the molecular targets and mechanism of action of C. nutans extracts and their phytochemical components should encourage future studies to develop new therapeutic strategies for better use of this herb to combat inflammatory diseases.


Assuntos
Acanthaceae , Extratos Vegetais , Acanthaceae/química , Anti-Inflamatórios/análise , Anti-Inflamatórios/farmacologia , Compostos Fitoquímicos/análise , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/química , Folhas de Planta/química
18.
Food Chem (Oxf) ; 4: 100097, 2022 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-35769401

RESUMO

Anthocyanin-rich strawberry model solutions were co-pigmented with rooibos phenolics to enhance color and heat stability. The addition of green and fermented rooibos extracts at pigment-to-co-pigment molar ratios of 1:10, 1:50, and 1:100 pelargonidin-3-glucoside equivalents: orientin equivalents induced hyper- and bathochromic shifts at room temperature and during thermal processing at 80 °C for an hour. Co-pigmentation effects on hyperchromic shift were up to 96%, and bathochromic shift reached 19 nm when adding flavonoid-rich fractions of green rooibos phenolics. Following the co-pigmentation tests with rooibos extracts, selected pure phenolic co-pigments were tested for their monomeric contribution to the observed co-pigmentation effects. Orientin was identified as a potent co-pigment for pelargonidin-3-glucoside, showing stronger co-pigmentation effects than that of its aglycon luteolin. Additionally, orientin had the most pronounced bathochromic shift in heat-treated solutions. Rooibos extracts, particularly flavonoid-rich fractions composed of luteolin, apigenin, and quercetin glycosides, are suggested as color enhancers and stabilizers for strawberry products.

19.
J Agric Food Chem ; 70(26): 7953-7967, 2022 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-35729734

RESUMO

Oxidative stress is involved in the pathogenesis of liver diseases, including liver injury, a serious health problem worldwide. Natural polyphenols have attracted increasing attention as potential agents for the prevention and treatment of liver diseases. Orientin, a flavonoid component with antioxidant capacity, has been regarded as a promising nutraceutical for patients with liver damage. This study aimed to investigate the amelioration effect of orientin on d-galactosamine and lipopolysaccharides (d-GalN/LPS) induced liver injury in mice, with a focus on its underlying mechanisms by using the H2O2-induced oxidative damage model of HepG2 cells. Results indicated that orientin alleviated d-GalN/LPS-induced liver damage by improving the hepatic histological changes and reducing the levels of hepatic and serum alanine aminotransferase and aspartic acid aminotransferase. Additionally, supplementation of orientin improved the antioxidant ability in mice by decreasing the levels of hepatic malondialdehyde, protein carbonyl, myeloperoxidase, nitric oxide, glutathione, glutathione peroxidase, gluathione reductase, and superoxide dismutase. Orientin treatment significantly elevated both the protein and mRNA expressions of nuclear factor erythroid 2-related factor 2, Kelch-like ECH-associated protein-1, heme oxygenase-1, and nicotinamide quinone oxidoreductase 1 in liver and HepG2 cells. The management of orientin also elevated the protein expression of glutathione S-transferase and Maf in HepG2 cells. Taken together, it suggested that orientin played an amelioration effect on liver injury by suppressing oxidative stress, which might be strongly related to the activation of Nrf2/ARE through PI3K/Akt and P38/MAPK signal pathways.


Assuntos
Doença Hepática Crônica Induzida por Substâncias e Drogas , Doença Hepática Induzida por Substâncias e Drogas , Animais , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Doença Hepática Induzida por Substâncias e Drogas/genética , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Crônica Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Crônica Induzida por Substâncias e Drogas/patologia , Flavonoides/metabolismo , Flavonoides/farmacologia , Galactosamina/efeitos adversos , Glucosídeos , Peróxido de Hidrogênio/farmacologia , Proteína 1 Associada a ECH Semelhante a Kelch/genética , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Lipopolissacarídeos/farmacologia , Fígado/metabolismo , Camundongos , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo
20.
Arch Microbiol ; 204(6): 310, 2022 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-35536516

RESUMO

Glycosidic bond of C-glycosides is difficult to be broken due to its chemical stability. Screening specific microbe from microbiota is a practical way to deglycosylate these compounds. In this study, a new strain W974-1 which is capable of cleaving C-glycosidic bonds was isolated from human gut microbiota by spread plate method. It deglycosylates flavonoid 8-C-glycosides such as orientin and vitexin to their aglycones with the enzymes secreted outside the bacterial cells. This strain was identified as Enterococcus avium by 16S rDNA sequencing, physiological and biochemical characterization.


Assuntos
Microbioma Gastrointestinal , Glicosídeos , Flavonoides , Humanos , Intestinos/microbiologia
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