RESUMEN
Skin is the largest and outermost organ in the human body; it serves as a vital defense mechanism against various external threats. Therefore, it is crucial to maintain its health through protection against harmful substances and adequate moisture levels. This study investigates the anti-inflammatory, antioxidant, and moisturizing properties of Oxyceros horridus Lour. (Oh-EE) in human keratinocytes. Oh-EE demonstrates potent antioxidant activity and effectively protects against oxidative stress induced by external stimuli such as UVB radiation and H2O2. Additionally, it exhibits significant anti-inflammatory effects proven by its ability to downregulate the expression of pro-inflammatory cytokines, namely COX-2 and IL-6. The study also explores the involvement of the AP-1 pathway, highlighting the ability of Oh-EE to suppress the expression of p38 and its upstream regulator, MKK3/6, under UVB-induced conditions. Interestingly, Oh-EE can activate the AP-1 pathway in the absence of external triggers. Furthermore, Oh-EE enhances skin moisture by upregulating the expression of key genes involved in skin hydration, namely HAS3 and FLG. These findings underscore the potential of Oh-EE as a versatile ingredient in skincare formulations, providing a range of skin benefits. Further research is warranted to comprehensively understand the underlying mechanisms through which Oh-EE exerts its effects.
Asunto(s)
Antioxidantes , Etanol , Humanos , Antioxidantes/farmacología , Antioxidantes/metabolismo , Etanol/farmacología , Peróxido de Hidrógeno/farmacología , Factor de Transcripción AP-1/metabolismo , Factor de Transcripción AP-1/farmacología , Queratinocitos , Transducción de Señal , Antiinflamatorios/farmacología , Antiinflamatorios/metabolismoRESUMEN
Urban Particulate Matter (UPM) induces skin aging and inflammatory responses by regulating skin cells through the transient receptor potential vanilloid 1 (TRPV1). Although oleic acid, an unsaturated free fatty acid (FFA), has some functional activities, its effect on UPM-induced skin damage has not been elucidated. Here, we investigated signaling pathways on how oleic acid is involved in attenuating UPM induced cell damage. UPM treatment increased XRE-promoter luciferase activity and increased translocation of AhR to the nucleus, resulting in the upregulation of CYP1A1 gene. However, oleic acid treatment attenuated the UPM effects on AhR signaling. Furthermore, while UPM induced activation of TRPV1 and MAPKs signaling which activated the downstream molecules NFκB and AP-1, these effects were reduced by cotreatment with oleic acid. UPM-dependent generation of reactive oxygen species (ROS) and reduction of cellular proliferation were also attenuated by the treatment of oleic acid. These data reveal that cell damage induced by UPM treatment occurs through AhR signaling and TRPV1 activation which in turn activates ERK and JNK, ultimately inducing NFκB and AP-1 activation. These effects were reduced by the cotreatment of oleic acid on HaCaT cells. These suggest that oleic acid reduces UPM-induced cell damage through inhibiting both the AhR signaling and activation of TRPV1 and its downstream molecules, leading to a reduction of pro-inflammatory cytokine and recovery of cell proliferation.
Asunto(s)
Contaminantes Atmosféricos , Ácido Oléico , Material Particulado , Receptores de Hidrocarburo de Aril , Transducción de Señal , Canales Catiónicos TRPV , Humanos , Contaminantes Atmosféricos/toxicidad , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genética , Línea Celular , Proliferación Celular/efectos de los fármacos , Citocromo P-450 CYP1A1/metabolismo , Citocromo P-450 CYP1A1/genética , Células HaCaT , FN-kappa B/metabolismo , Ácido Oléico/farmacología , Ácido Oléico/toxicidad , Material Particulado/toxicidad , Especies Reactivas de Oxígeno/metabolismo , Receptores de Hidrocarburo de Aril/metabolismo , Transducción de Señal/efectos de los fármacos , Factor de Transcripción AP-1/metabolismo , Canales Catiónicos TRPV/metabolismo , Canales Catiónicos TRPV/genéticaRESUMEN
The immune system protects our body from bacteria, viruses, and toxins and removes malignant cells. Activation of immune cells requires the onset of a network of important signaling proteins. Methylation of these proteins affects their structure and biological function. Under stimulation, T cells, B cells, and other immune cells undergo activation, development, proliferation, differentiation, and manufacture of cytokines and antibodies. Methyltransferases alter the above processes and lead to diverse outcomes depending on the degree and type of methylation. In the previous two decades, methyltransferases have been reported to mediate a great variety of immune stages. Elucidating the roles of methylation in immunity not only contributes to understanding the immune mechanism but is helpful in the development of new immunotherapeutic strategies. Hence, we review herein the studies on methylation in immunity, aiming to provide ideas for new approaches.
Asunto(s)
Metiltransferasas , Proteína Metiltransferasas , Anticuerpos , Linfocitos B , Diferenciación CelularRESUMEN
Hyperlipidemia, high levels of blood lipids including cholesterol and triglycerides, is a major risk factor for cardiovascular disease. Traditional treatments of hyperlipidemia often include lifestyle changes and pharmacotherapy. Recently, flaxseed has been approved as a nutrient that lowers blood lipids. Several metabolites of flaxseed lignan secoisolariciresinol diglucoside (SDG), have been identified that reduce blood lipids. SDG is present in flaxseed hull as an ester-linked copolymer with 3-hydroxy-3-methylglutaric acid (HMGA). However, purification processes involved in hydrolysis of the copolymer and enriching SDG are often expensive. The natural copolymer of SDG with HMGA (SDG polymer) is a source of bioactive compounds useful in prophylaxis of hypercholesterolemia. After consumption of the lignan copolymer, SDG and HMGA are released in the stomach and small intestines. SDG is metabolized to secoisolariciresinol, enterolactone and enterodiol, the bioactive forms of mammalian lignans. These metabolites are then distributed throughout the body where they accumulate in the liver, kidney, skin, other tissues, and organs. Successively, these metabolites reduce blood lipids including cholesterol, triglycerides, low density lipoprotein cholesterol, and lipid peroxidation products. In this review, the metabolism and efficacies of flaxseed-derived enriched SDG and SDG polymer will be discussed.
Asunto(s)
Lino , Proteínas HMGA , Hiperlipidemias , Lignanos , Animales , Humanos , Lino/metabolismo , Lípidos , Triglicéridos/metabolismo , Colesterol/metabolismo , Polímeros/metabolismo , Proteínas HMGA/metabolismo , Mamíferos/metabolismoRESUMEN
As one of the most prevalent post-transcriptional epigenetic modifications, N5-methylcytosine (m5C) plays an essential role in various cellular processes and disease pathogenesis. Therefore, it is important accurately identify m5C modifications in order to gain a deeper understanding of cellular processes and other possible functional mechanisms. Although a few computational methods have been proposed, their respective models have been developed using small training datasets. Hence, their practical application is quite limited in genome-wide detection. To overcome the existing limitations, we propose Deepm5C, a bioinformatics method for identifying RNA m5C sites throughout the human genome. To develop Deepm5C, we constructed a novel benchmarking dataset and investigated a mixture of three conventional feature-encoding algorithms and a feature derived from word-embedding approaches. Afterward, four variants of deep-learning classifiers and four commonly used conventional classifiers were employed and trained with the four encodings, ultimately obtaining 32 baseline models. A stacking strategy is effectively utilized by integrating the predicted output of the optimal baseline models and trained with a one-dimensional (1D) convolutional neural network. As a result, the Deepm5C predictor achieved excellent performance during cross-validation with a Matthews correlation coefficient and an accuracy of 0.697 and 0.855, respectively. The corresponding metrics during the independent test were 0.691 and 0.852, respectively. Overall, Deepm5C achieved a more accurate and stable performance than the baseline models and significantly outperformed the existing predictors, demonstrating the effectiveness of our proposed hybrid framework. Furthermore, Deepm5C is expected to assist community-wide efforts in identifying putative m5Cs and to formulate the novel testable biological hypothesis.
Asunto(s)
Aprendizaje Profundo , ARN , Algoritmos , Biología Computacional/métodos , Humanos , Aprendizaje Automático , ARN/genéticaRESUMEN
Flavonoids have been shown to have anti-oxidative effects, as well as other health benefits (e.g., anti-inflammatory and anti-tumor functions). Luteolin (3', 4', 5,7-tetrahydroxyflavone) is a flavonoid found in vegetables, fruits, flowers, and herbs, including celery, broccoli, green pepper, navel oranges, dandelion, peppermint, and rosemary. Luteolin has multiple useful effects, especially in regulating inflammation-related symptoms and diseases. In this paper, we summarize the studies about the immunopharmacological activity of luteolin on anti-inflammatory, anti-cardiovascular, anti-cancerous, and anti-neurodegenerative diseases published since 2018 and available in PubMed or Google Scholar. In this review, we also introduce some additional formulations of luteolin to improve its solubility and bioavailability.
Asunto(s)
Flavonoides , Luteolina , Humanos , Luteolina/farmacología , Luteolina/uso terapéutico , Flavonoides/farmacología , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Verduras , Enfermedad CrónicaRESUMEN
The skin is the main barrier between the body and the environment, protecting it from external oxidative stress induced by ultraviolet rays. It also prevents the entrance of infectious agents such as viruses, external antigens, allergens, and bacteria into our bodies. An overreaction to these agents causes severe skin diseases, including atopic dermatitis, pruritus, psoriasis, skin cancer, and vitiligo. Members of the flavonoid family include apigenin, quercetin, luteolin, and kaempferol. Of these, apigenin has been used as a dietary supplement due to its various biological activities and has been shown to reduce skin inflammation by downregulating various inflammatory markers and molecular targets. In this review, we deal with current knowledge about inflammatory reactions in the skin and the molecular mechanisms by which apigenin reduces skin inflammation.
Asunto(s)
Dermatitis Atópica , Neoplasias Cutáneas , Vitíligo , Humanos , Apigenina/farmacología , Apigenina/uso terapéutico , Piel , Dermatitis Atópica/tratamiento farmacológico , Inflamación/tratamiento farmacológicoRESUMEN
Nuclear factor kappa B (NF-κB) signaling pathways progress inflammation and immune cell differentiation in the host immune response; however, the uncontrollable stimulation of NF-κB signaling is responsible for several inflammatory illnesses regardless of whether the conditions are acute or chronic. Innate immune cells, such as macrophages, microglia, and Kupffer cells, secrete pro-inflammatory cytokines, such as TNF-α, IL-6, and IL-1ß, via the activation of NF-κB subunits, which may lead to the damage of normal cells, including neurons, cardiomyocytes, hepatocytes, and alveolar cells. This results in the occurrence of neurodegenerative disorders, cardiac infarction, or liver injury, which may eventually lead to systemic inflammation or cancer. Recently, ginsenosides from Panax ginseng, a historical herbal plant used in East Asia, have been used as possible options for curing inflammatory diseases. All of the ginsenosides tested target different steps of the NF-κB signaling pathway, ameliorating the symptoms of severe illnesses. Moreover, ginsenosides inhibit the NF-κB-mediated activation of cancer metastasis and immune resistance, significantly attenuating the expression of MMPs, Snail, Slug, TWIST1, and PD-L1. This review introduces current studies on the therapeutic efficacy of ginsenosides in alleviating NF-κB responses and emphasizes the critical role of ginsenosides in severe inflammatory diseases as well as cancers.
Asunto(s)
Antineoplásicos , Ginsenósidos , Panax , FN-kappa B/metabolismo , Ginsenósidos/farmacología , Ginsenósidos/uso terapéutico , Panax/metabolismo , Transducción de Señal , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Inflamación/tratamiento farmacológico , Antineoplásicos/farmacologíaRESUMEN
Muscle atrophy, also known as muscle wasting, is the thinning of muscle mass due to muscle disuse, aging, or diseases such as cancer or neurological problems. Muscle atrophy is closely related to the quality of life and has high morbidity and mortality. However, therapeutic options for muscle atrophy are limited, so studies to develop therapeutic agents for muscle loss are always required. For this study, we investigated how orally administered specific collagen peptides (CP) affect muscle atrophy and elucidated its molecular mechanism using an in vivo model. We treated mice with dexamethasone (DEX) to induce a muscular atrophy phenotype and then administered CP (0.25 and 0.5 g/kg) for four weeks. In a microcomputed tomography analysis, CP (0.5 g/kg) intake significantly increased the volume of calf muscles in mice with DEX-induced muscle atrophy. In addition, the administration of CP (0.25 and 0.5 g/kg) restored the weight of the gluteus maximus and the fiber cross-sectional area (CSA) of the pectoralis major and calf muscles, which were reduced by DEX. CP significantly inhibited the mRNA expression of myostatin and the phosphorylation of Smad2, but it did not affect TGF-ß, BDNF, or FNDC5 gene expression. In addition, AKT/mTOR, a central pathway for muscle protein synthesis and related to myostatin signaling, was enhanced in the groups that were administered CP. Finally, CP decreased serum albumin levels and increased TNF-α gene expression. Collectively, our in vivo results demonstrate that CP can alleviate muscle wasting through a multitude of mechanisms. Therefore, we propose CP as a supplement or treatment to prevent muscle atrophy.
Asunto(s)
Colágeno , Atrofia Muscular , Miostatina , Animales , Ratones , Dexametasona/efectos adversos , Fibronectinas/metabolismo , Músculo Esquelético/metabolismo , Atrofia Muscular/inducido químicamente , Atrofia Muscular/metabolismo , Microtomografía por Rayos X , Colágeno/farmacologíaRESUMEN
Flaxseed (Linum usitatissimum L.) has been associated with numerous health benefits. The flax plant synthesizes an array of biologically active compounds including peptides or linusorbs (LOs, a.k.a., cyclolinopeptides), lignans, soluble dietary fiber and omega-3 fatty acids. The LOs arise from post-translational modification of four or more ribosome-derived precursors. These compounds exhibit an array of biological activities, including suppression of T-cell proliferation, excessive inflammation, and osteoclast replication as well as induction of apoptosis in some cancer cell lines. The mechanisms of LO action are only now being elucidated but these compounds might interact with other active compounds in flaxseed and contribute to biological activity attributed to other flax compounds. This review focuses on both the biological interaction of LOs with proteins and other molecules and comprehensive knowledge of LO pharmacological and biological properties. The physicochemical and nutraceutical properties of LOs, as well as the biological effects of certain LOs, and their underlying mechanisms of action, are reviewed. Finally, strategies for producing LOs by either peptide synthesis or recombinant organisms are presented. This review will be the first to describe LOs as a versatile scaffold for the action of compounds to deliver physiochemically/biologically active molecules for developing novel nutraceuticals and pharmaceuticals.
RESUMEN
Inflammation is a critically important barrier found in innate immunity. However, severe and sustained inflammatory conditions are regarded as causes of many different serious diseases, such as cancer, atherosclerosis, and diabetes. Although numerous studies have addressed how inflammatory responses proceed and what kinds of proteins and cells are involved, the exact mechanism and protein components regulating inflammatory reactions are not fully understood. In this paper, to determine the regulatory role of mixed lineage kinase 3 (MLK3), which functions as mitogen-activated protein kinase kinase kinase (MAP3K) in cancer cells in inflammatory response to macrophages, we employed an overexpression strategy with MLK3 in HEK293 cells and used its inhibitor URMC-099 in lipopolysaccharide (LPS)-treated RAW264.7 cells. It was found that overexpressed MLK3 increased the mRNA expression of inflammatory genes (COX-2, IL-6, and TNF-α) via the activation of AP-1, according to a luciferase assay carried out with AP-1-Luc. Overexpression of MLK3 also induced phosphorylation of MAPKK (MEK1/2, MKK3/6, and MKK4/7), MAPK (ERK, p38, and JNK), and AP-1 subunits (c-Jun, c-Fos, and FRA-1). Phosphorylation of MLK3 was also observed in RAW264.7 cells stimulated by LPS, Pam3CSK, and poly(I:C). Finally, inhibition of MLK3 by URMC-099 reduced the expression of COX-2 and CCL-12, phosphorylation of c-Jun, luciferase activity mediated by AP-1, and phosphorylation of MAPK in LPS-treated RAW264.7 cells. Taken together, our findings strongly suggest that MLK3 plays a central role in controlling AP-1-mediated inflammatory responses in macrophages and that this enzyme can serve as a target molecule for treating AP-1-mediated inflammatory diseases.
Asunto(s)
Lipopolisacáridos , Factor de Transcripción AP-1 , Animales , Ciclooxigenasa 2/metabolismo , Células HEK293 , Humanos , Inflamación , Interleucina-6 , Lipopolisacáridos/farmacología , Quinasas Quinasa Quinasa PAM/genética , Quinasas Quinasa Quinasa PAM/metabolismo , Ratones , Quinasas de Proteína Quinasa Activadas por Mitógenos , Células RAW 264.7 , ARN Mensajero , Factor de Transcripción AP-1/metabolismo , Factor de Necrosis Tumoral alfa/genética , Proteina Quinasa Quinasa Quinasa 11 Activada por MitógenoRESUMEN
Anti-inflammatory therapies have been shown to be effective in the prevention of various cardiovascular diseases, tumors, and cancer complications. Thymoquinone (TQ), the main active constituent of Nigella sativa, has shown promising therapeutic properties in many in vivo and in vitro models. However, TQ has poor bioavailability and is hydrophobic, prohibiting clinical trials with TQ alone. Studies have explored the combination of TQ with biological nanomaterials to improve its bioavailability. The TQ nanoparticle formulation shows better bioavailability than free TQ, and these formulations are ready for clinical trials to determine their potential as therapeutic agents. In this paper, we review current knowledge about the interaction between TQ and the inflammatory response and summarize the research prospects in Korea and abroad. We discuss the different biological activities of TQ and various combination therapies of TQ and nanomaterials in clinical trials.
Asunto(s)
Benzoquinonas , Nigella sativa , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Benzoquinonas/farmacología , Benzoquinonas/uso terapéutico , Enfermedad Crónica , Humanos , Nigella sativa/químicaRESUMEN
Since chronic inflammation can be seen in severe, long-lasting diseases such as cancer, there is a high demand for effective methods to modulate inflammatory responses. Among many therapeutic candidates, lignans, absorbed from various plant sources, represent a type of phytoestrogen classified into secoisolariciresionol (Seco), pinoresinol (Pino), matairesinol (Mat), medioresinol (Med), sesamin (Ses), syringaresinol (Syr), and lariciresinol (Lari). Lignans consumed by humans can be further modified into END or ENL by the activities of gut microbiota. Lignans are known to exert antioxidant and anti-inflammatory activities, together with activity in estrogen receptor-dependent pathways. Lignans may have therapeutic potential for postmenopausal symptoms, including cardiovascular disease, osteoporosis, and psychological disorders. Moreover, the antitumor efficacy of lignans has been demonstrated in various cancer cell lines, including hormone-dependent breast cancer and prostate cancer, as well as colorectal cancer. Interestingly, the molecular mechanisms of lignans in these diseases involve the inhibition of inflammatory signals, including the nuclear factor (NF)-κB pathway. Therefore, we summarize the recent in vitro and in vivo studies evaluating the biological effects of various lignans, focusing on their values as effective anti-inflammatory agents.
Asunto(s)
Enfermedades Cardiovasculares , Lignanos , Neoplasias , Humanos , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Lignanos/farmacología , Lignanos/uso terapéutico , Lignanos/metabolismo , FN-kappa B , FitoestrógenosRESUMEN
Loratadine is an anti-histamine routinely used for treating allergies. However, recent findings have shown that Loratadine may also have anti-inflammatory functions, while their exact mechanisms have not yet been fully uncovered. In this paper, we investigated whether Loratadine can be utilized as an anti-inflammatory drug through a series of in vitro and in vivo experiments using a murine macrophage cell line and an acute gastritis mouse model. Loratadine was found to dramatically reduce the expression of pro-inflammatory genes, including MMP1, MMP3, and MMP9, and inhibit AP-1 transcriptional activation, as demonstrated by the luciferase assay. Therefore, we decided to further explore its role in the AP-1 signaling pathway. The expression of c-Jun and c-Fos, AP-1 subunits, was repressed by Loratadine and, correspondingly, the expression of p-JNK, p-MKK7, and p-TAK1 was also inhibited. In addition, Loratadine was able to reduce gastric bleeding in acute gastritis-induced mice; Western blotting using the stomach samples showed reduced p-c-Fos protein levels. Loratadine was shown to effectively suppress inflammation by specifically targeting TAK1 and suppressing consequent AP-1 signaling pathway activation and inflammatory cytokine production.
Asunto(s)
Gastritis , Factor de Transcripción AP-1 , Animales , Antiinflamatorios/efectos adversos , Gastritis/inducido químicamente , Antagonistas de los Receptores Histamínicos/uso terapéutico , Loratadina/farmacología , Loratadina/uso terapéutico , Ratones , Células RAW 264.7 , Factor de Transcripción AP-1/metabolismoRESUMEN
Linosorbs (Los) are cyclic peptides from flaxseed oil composed of the LO mixture (LOMIX). The activity of LO has been reported as being anti-cancer and anti-inflammatory. However, the study of skin protection has still not proceeded. In particular, there are poorly understood mechanisms of melanogenesis to LO. Therefore, we investigated the anti-melanogenesis effects of LOMIX and LO, and its activity was examined in mouse melanoma cell lines. The treatment of LOMIX (50 and 100 µg/mL) and LO (6.25-50 µM) suppressed melanin secretion and synthesis, which were 3-fold increased, in a dose-dependent manner, up to 95%. In particular, [1-9-NαC]-linusorb B3 (LO1) and [1-9-NαC]-linusorb B2 (LO2) treatment (12.5 and 25 µM) highly suppressed the synthesis of melanin in B16F10 cell lines up to 90%, without toxicity. LOMIX and LOs decreased the 2- or 3-fold increased mRNA levels, including the microphthalmia-associated transcription factor (MITF), Tyrosinase, tyrosinase-related protein 1 (TYRP1), and tyrosinase-related protein 2 (TYRP2) at the highest concentration (25 µM). Moreover, the treatment of 25 µM LO1 and LO2 inhibited the expression of MITF and phosphorylation of upper regulatory proteins such as CREB and PKA. Taken together, these results suggested that LOMIX and its individual LO could inhibit melanin synthesis via downregulating the CREB-dependent signaling pathways, and it could be used for novel therapeutic materials in hyperpigmentation.
Asunto(s)
Lino , Melanoma Experimental , Melanoma , Animales , Ratones , Melaninas , Monofenol Monooxigenasa/metabolismo , Lino/metabolismo , Péptidos Cíclicos/farmacología , Melanoma/metabolismo , Factor de Transcripción Asociado a Microftalmía/genética , Factor de Transcripción Asociado a Microftalmía/metabolismo , Línea Celular Tumoral , Melanoma Experimental/tratamiento farmacológico , Melanoma Experimental/metabolismo , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/metabolismoRESUMEN
There is a growing demand for hair loss treatments with minimal side effects and recurrence potential. Connarus semidecandrus Jack has been used as a folk medicine for fever in tropical regions, but its anti-alopecia effects remain unclear. In this study, the anti-androgenic alopecia effect of an ethanol extract of Connarus semidecandrus Jack (Cs-EE) was demonstrated in a testosterone-induced androgenic alopecia (AGA) model, in terms of the hair-skin ratio, hair type frequency, and hair thickness. The area of restored hair growth and thickened hair population after Cs-EE treatment showed the hair-growth-promoting effect of Cs-EE. Histological data support the possibility that Cs-EE could reduce hair loss and upregulate hair proliferation in mouse skin by shifting hair follicles from the catagen phase to the anagen phase. Western blotting indicated that Cs-EE reduced the expression of the androgenic receptor. Cs-EE treatment also inhibited programmed cell death by upregulating Bcl-2 expression at the mRNA and protein levels. The anti-alopecia effect of Cs-EE was confirmed by in vitro experiments showing that Cs-EE had suppressive effects on 5-α reductase activity and lymph node carcinoma of the prostate proliferation, and a proliferative effect on human hair-follicle dermal papilla (HDP) cells. Apoptotic pathways in HDP cells were downregulated by Cs-EE treatment. Thus, Cs-EE could be a potential treatment for AGA.
Asunto(s)
Connaraceae , Alopecia/inducido químicamente , Animales , Apoptosis , Colestenona 5 alfa-Reductasa , Folículo Piloso , Masculino , RatonesRESUMEN
CONTEXT: Cordycepin (COR), from Cordyceps militaris L., (Cordycipitaceae), is a valuable agent with immense health benefits. OBJECTIVE: The protective effects of COR in ageing-associated oxidative and apoptosis events in vivo and hydrogen peroxide (H2O2)-exposed spermatogenesis gene alterations in TM3 Leydig cells was investigated. MATERIALS AND METHODS: Male Sprague-Dawley rats were divided into young control (YC), aged control (AC) and COR treated (COR-20) aged groups. COR-20 group received daily doses of COR (20 mg/kg) for 6 months. Cell viability and hormone levels were analysed by MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] and enzyme immunoassay kits with COR treated at 1, 5, and 10 µg/mL. Oxidative enzymes, spermatogenic, and apoptotic expression in testis tissues were evaluated by Western blotting and real-time RT-PCR. RESULTS: COR treatment (1, 5, and 10 µg/mL) significantly (p < 0.05 â¼ p < 0.001) inhibited the H2O2-induced decrease in the percentage of viable cells (from 63.27% to 71.25%, 85.67% and 93.97%, respectively), and reduced the malondialdehyde (MDA) content (from 4.28 to 3.98, 3.14 and 1.78 nM MDA/mg protein, respectively). Further, the decreased antioxidant enzymes (glutathione-S-transferase mu5, glutathione peroxidase 4 and peroxiredoxin 3), spermatogenesis-related factors (nectin-2 and inhibin-α) and testosterone levels in H2O2-exposed TM3 cells were significantly (p < 0.05 â¼ p < 0.001) ameliorated by COR. In aged rats, COR (20 mg/kg) restored the altered enzymatic and non-enzymatic antioxidative status and attenuated the apoptotic p53 and Bax/Bcl-2 expression significantly (p < 0.05). CONCLUSION: COR might be developed as a potential agent against ageing-associated and oxidative stress-induced male infertility.
Asunto(s)
Desoxiadenosinas/farmacología , Células Intersticiales del Testículo/efectos de los fármacos , Espermatogénesis/efectos de los fármacos , Testículo/efectos de los fármacos , Envejecimiento , Animales , Antioxidantes/metabolismo , Apoptosis/efectos de los fármacos , Línea Celular , Supervivencia Celular/efectos de los fármacos , Cordyceps/química , Desoxiadenosinas/aislamiento & purificación , Peróxido de Hidrógeno , Células Intersticiales del Testículo/metabolismo , Masculino , Ratones , Oxidación-Reducción/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Transducción de Señal/efectos de los fármacosRESUMEN
Kahweol is a diterpene present in coffee. Until now, several studies have shown that kahweol has anti-inflammatory and anti-angiogenic functions. Due to the limited research available about skin protection, this study aims to discern the potential abilities of kahweol and the possible regulation targets. First, the cytotoxicity of kahweol was checked by 3-4-5-dimethylthiazol-2-yl)-2-5-diphenyltetrazolium bromide assay, while 2,20-azino-bis (3ethylbenzothiazoline-6-sulphonic acid) diammonium salt and 1-diphenyl-2-picryl-hydrazyl were used to examine the radical scavenging ability. Polymerase chain reaction analysis was performed to explore the proper time points and doses affecting skin hydration and barrier-related genes. Luciferase assay and Western blotting were used to explore the possible transcription factors. Finally, fludarabine (a STAT1 inhibitor) was chosen to discern the relationship between skin-moisturizing factors and STAT1. We found that HaCaT cells experienced no toxicity from kahweol, and kahweol displayed moderate radical scavenging ability. Moreover, kahweol increased the outcome of HAS1, HAS2, occludin, and TGM-1 from six hours in a dose-dependent manner as well as the activation of STAT1 from six hours. Additionally, kahweol recovered the suppression of HAS2, STAT1-mediated luciferase activity, and HA secretion, which was all downregulated by fludarabine. In this study, we demonstrated that kahweol promotes skin-moisturizing activities by upregulating STAT1.
Asunto(s)
Antiinflamatorios/farmacología , Diterpenos/farmacología , Regulación de la Expresión Génica/efectos de los fármacos , Queratinocitos/fisiología , Factor de Transcripción STAT1/metabolismo , Piel/efectos de los fármacos , Apoptosis , Proliferación Celular , Células Cultivadas , Humanos , Queratinocitos/citología , Queratinocitos/efectos de los fármacos , Factor de Transcripción STAT1/genéticaRESUMEN
Quercetin 3-O-ß-D-glucuronide (Q-3-G), the glucuronide conjugate of quercetin, has been reported as having anti-inflammatory properties in the lipopolysaccharide-stimulated macrophages, as well as anticancer and antioxidant properties. Unlike quercetin, which has been extensively described to possess a wide range of pharmacological activities including skin protective effects, the pharmacological benefits and mechanisms Q-3-G in the skin remained to be elucidated. This study focused on characterizing the skin protective properties, including anti-inflammatory and antioxidant properties, of Q-3-G against UVB-induced or H2O2-induced oxidative stress, the hydration effects, and antimelanogenesis activities using human keratinocytes (HaCaT) and melanoma (B16F10) cells. Q-3-G down-regulated the expression of the pro-inflammatory gene and cytokine such as cyclooxygenase-2 (COX-2) and tumor necrosis factor (TNF)-α in H2O2 or UVB-irradiated HaCaT cells. We also showed that Q-3-G exhibits an antioxidant effect using free radical scavenging assays, flow cytometry, and an increased expression of nuclear factor erythroid 2- related factor 2 (Nrf2). Q-3-G reduced melanin production in α-melanocyte-stimulating hormone (α-MSH)-induced B16F10 cells. The hydration effects and mechanisms of Q-3-G were examined by evaluating the moisturizing factor-related genes, such as transglutaminase-1 (TGM-1), filaggrin (FLG), and hyaluronic acid synthase (HAS)-1. In addition, Q-3-G increased the phosphorylation of c-Jun, Jun N-terminal kinase (JNK), Mitogen-activated protein kinase (MAPK) kinase 4 (MKK4), and TAK1, involved in the MAPKs/AP-1 pathway, and the phosphorylation of IκBα, IκB kinase (IKK)-α, Akt, and Src, involved in the NF-κB pathway. Taken together, we have demonstrated that Q-3-G exerts anti-inflammatory, antioxidant, moisturizing, and antimelanogenesis properties in human keratinocytes and melanoma cells through NF-κB and AP-1 pathways.
Asunto(s)
Antiinflamatorios/farmacología , Antioxidantes/farmacología , Queratinocitos/patología , Melaninas/metabolismo , Melanoma Experimental/patología , FN-kappa B/metabolismo , Quercetina/análogos & derivados , Factor de Transcripción AP-1/metabolismo , Células HEK293 , Células HaCaT , Humanos , Peróxido de Hidrógeno/toxicidad , Queratinocitos/efectos de los fármacos , Queratinocitos/efectos de la radiación , Modelos Biológicos , Quercetina/química , Quercetina/farmacología , Transducción de Señal/efectos de los fármacos , Transducción de Señal/efectos de la radiación , Activación Transcripcional/efectos de los fármacos , Activación Transcripcional/genética , Activación Transcripcional/efectos de la radiación , Rayos UltravioletaRESUMEN
Theasinensin A (TSA) is a major group of catechin dimers mainly found in oolong tea and black tea. This compound is also manufactured with epigallocatechin gallate (EGCG) as a substrate and is refined after the enzyme reaction. In previous studies, TSA has been reported to be effective against inflammation. However, the effect of these substances on skin melanin formation remains unknown. In this study, we unraveled the role of TSA in melanogenesis using mouse melanoma B16F10 cells and normal human epidermal melanocytes (NHEMs) through reverse transcription polymerase chain reaction (RT-PCR), Western blotting analysis, luciferase reporter assay, and enzyme-linked immunosorbent assay analysis. TSA inhibited melanin formation and secretion in α-melanocyte stimulating hormone (α-MSH)-induced B16F10 cells and NHEMs. TSA down-regulated the mRNA expression of tyrosinase (Tyr), tyrosinase-related protein 1 (Tyrp1), and Tyrp2, which are all related to melanin formation in these cells. TSA was able to suppress the activities of certain proteins in the melanocortin 1 receptor (MC1R) signaling pathway associated with melanin synthesis in B16F10 cells: cyclic adenosine monophosphate (cAMP) response element-binding protein (CREB), protein kinase A (PKA), tyrosinase, and microphthalmia-associated transcription factor (MITF). We also confirmed α-MSH-mediated CREB activities through a luciferase reporter assay, and that the quantities of cAMP were reduced by TSA in the enzyme linked immunosorbent assay (ELISA) results. Based on these findings, TSA should be considered an effective inhibitor of hyperpigmentation.