Ruiz Alcaraz, Antonio José

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Ruiz Alcaraz, Antonio José

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Ruiz Alcaraz, Antonio José

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Universidad de Murcia. Departamento de Bioquímica y Biología Molecular"B" e Inmunología

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Open Access
Therapeutic potential of pteridine derivatives: a comprehensive review
(Wiley, 2018-10-19) Carmona‐Martínez, Violeta; Vera, María; Guirado, Antonio; García-Peñarrubia, Pilar; Martínez-Esparza Alvargonzález, María Concepción; Ruiz Alcaraz, Antonio José; Bioquímica y Biología Molecular B e Inmunología
Pteridines are aromatic compounds formed by fused pyrazine and pyrimidine rings. Many living organisms synthesize pteridines, where they act as pigments, enzymatic cofactors, or immune system activation molecules. This variety of biological functions has motivated the synthesis of a huge number of pteridine derivatives with the aim of studying their therapeutic potential. This review gathers the state‐of‐the‐art of pteridine derivatives, describing their biological activities and molecular targets. The antitumor activity of pteridine‐based compounds is one of the most studied and advanced therapeutic potentials, for which several molecular targets have been identified. Nevertheless, pteridines are also considered as very promising therapeutics for the treatment of chronic inflammation‐related diseases. On the other hand, many pteridine derivatives have been tested for antimicrobial activities but, although some of them resulted to be active in preliminary assays, a deeper research is needed in this area. Moreover, pteridines may be of use in the treatment of many other diseases, such as diabetes, osteoporosis, ischemia, or neurodegeneration, among others. Thus, the diversity of the biological activities shown by these compounds highlights the promising therapeutic use of pteridine derivatives. Indeed, methotrexate, pralatrexate, and triamterene are Food and Drug Administration approved pteridines, while many others are currently under study in clinical trials.
Open Access
Potential of sulforaphane and broccoli membrane vesicles as regulators of M1/M2 human macrophage activity
(2022-09-22) García-Peñaranda, Andrea; García-Ibáñez, Paula; Yepes-Molina, Lucía; Carvajal, Micaela; Ruiz Alcaraz, Antonio José; Moreno, Diego A.; García Peñarrubia, María del Pilar; Martínez-Esparza Alvargonzález, María Concepción; Ramírez Pávez, Tamara Nadira; Bioquímica y Biología Molecular B e Inmunología; Facultad de Biología
Open Access
Brassica bioactives could ameliorate the chronic inflammatory condition of endometriosis
(MDPI, 2020-12-10) García-Ibañez, Paula; Yepes-Molina, Lucía; Ruiz Alcaraz, Antonio José; Martínez-Esparza Alvargonzález, María Concepción; Moreno, Diego A.; Carvajal, Micaela; García Peñarrubia, María del Pilar; Bioquímica y Biología Molecular B e Inmunología; Facultad de Biología
Endometriosis is a chronic, inflammatory, hormone-dependent disease characterized by histological lesions produced by the presence of endometrial tissue outside the uterine cavity. Despite the fact that an estimated 176 million women are affected worldwide by this gynecological disorder, risk factors that cause endometriosis have not been properly defined and current treatments are not efficient. Although the interaction between diet and human health has been the focus of many studies, little information about the correlation of foods and their bioactive derivates with endometriosis is available. In this framework, Brassica crops have emerged as potential candidates for ameliorating the chronic inflammatory condition of endometriosis, due to their abundant content of health-promoting compounds such as glucosinolates and their hydrolysis products, isothiocyanates. Several inflammation-related signaling pathways have been included among the known targets of isothiocyanates, but those involving aquaporin water channels have an important role in endometriosis. Therefore, the aim of this review is to highlight the promising effects of the phytochemicals present in Brassica spp. as major candidates for inclusion in a dietary approach aiming to improve the inflammatory condition of women affected with endometriosis. This review points out the potential roles of glucosinolates and sothiocyanates from Brassicas as anti-inflammatory compounds, which might contribute to a reduction in endometriosis symptoms. In view of these promising results, further investigation of the effect of glucosinolates on chronic inflammatory diseases, either as diet coadjuvants or as therapeutic molecules, should be performed. In addition, we highlight the involvement of aquaporins in the maintenance of immune homeostasis. In brief, glucosinolates and the modulation of cellular water by aquaporins could shed light on new approaches to improve the quality of life for women with endometriosis.
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Membrane vesicles for nanoencapsulated sulforaphane increased their anti-inflammatory role on an In vitro human macrophage model.
(MDPI, 2022-02-09) Yepes-Molina, Lucía; Pérez-Jiménez, María Isabel; Martínez-Esparza Alvargonzález, María Concepción; Teruel Puche, José Antonio; Ruiz Alcaraz, Antonio José; García Peñarrubia, María del Pilar; Carvajal, Micaela; Bioquímica y Biología Molecular B e Inmunología
At present, there is a growing interest in finding new non‐toxic anti‐inflammatory drugs to treat inflammation, which is a key pathology in the development of several diseases with considerable mortality. Sulforaphane (SFN), a bioactive compound derived from Brassica plants, was shown to be promising due to its anti‐inflammatory properties and great potential, though its actual clinical use is limited due to its poor stability and bioavailability. In this sense, the use of nanocarriers could solve stability‐related problems. In the current study, sulforaphane loaded into membrane vesicles derived from broccoli plants was studied to determine the anti‐inflammatory potential in a human‐macrophage‐like in vitro cell model under both normal and inflammatory conditions. On the one hand, the release of SFN from membrane vesicles was modeled in vitro, and two release phases were stabilized, one faster and the other slower due to the interaction between SFN and membrane proteins, such as aquaporins. Furthermore, the anti‐inflammatory action of sulforaphane‐loaded membrane vesicles was demonstrated, as a decrease in interleukins crucial for the development of nflammation, such as TNF‐α, IL‐1β and IL‐6, was observed. Furthermore, these results also showed that membrane vesicles by themselves had anti‐inflammatory properties, opening the possibility of new lines of research to study these vesicles, not only as carriers but also as active compounds.
Open Access
Anti-leukemia activity of 4-amino-2-aryl-6,9-dichlorobenzo[g]pteridines
(Springer, 2019-02) Carmona-Martínez, Violeta; Guirado, Antonio; Gálvez, Jesús; García-Peñarrubia, Pilar; Martínez-Esparza Alvargonzález, María Concepción; Ruiz Alcaraz, Antonio José; Bioquímica y Biología Molecular B e Inmunología
Open Access
Child head circumference and placental MFSD2a expression are associated to the level of MFSD2a in maternal blood during pregnancy
(Frontiers Media, 2020-02-05) Sánchez-Campillo, María; Ruiz-Palacios, María; Ruiz Alcaraz, Antonio José; Blanco Carnero, José Eliseo; Prieto Sánchez, María Teresa; Zornoza, Matilde; Ruiz-Pastor, María José; Demmelmair, Hans; Sánchez-Solís de Querol, Manuel; Koletzko, Berthold; Larqué Daza, Elvira; Bioquímica y Biología Molecular B e Inmunología; Facultad de Biología
Gestational diabetes mellitus (GDM) is a world-wide health challenge, which prevalence is expected to increase in parallel to the epidemic of obesity. Children born from GDM mothers have lower levels of docosahexaenoic acid (DHA) in cord blood, which might influence their neurodevelopment. Recently, the membrane transporter Major Family Super Domain 2a (MFSD2a) was associated with the selective transportation of DHA as lysophospholipids. The expression of the DHA membrane transporter MFSD2a is lower in GDM placentas, which could affect materno-fetal DHA transport. Humans with homozygous inactivating mutations in the MFSD2a gene present severe microcephalyand intellectual impairments. Herein, we intended to identify early blood biomarkers that maybeofuse during pregnancy to monitor the offspring development and the adequate nutritional interventions, such as nutritional supplementation, that may be selected to improve it. We evaluated MFSD2a expression in maternal blood at the third trimester of pregnancy, and its potential relationship with the expression of placental MFSD2a at delivery and child outcomes. Three groups of pregnant women were recruited: 25 controls, 23 GDM with dietary treatment, and 20 GDM with insulin treatment. Maternal and neonatal anthropometric and biochemical parameters were evaluated. MFSD2a was analyzed in placenta, blood and serum. MFSD2a protein expression in maternal blood was significantly lower in GDM groups and correlated with placental MFSD2a and Z-score neonatal head circumference during the first 6 months of life. The cord/maternal serum ratio of DHA, a solid indicator of materno-fetal DHA transport, was reduced in GDMgroups and correlated with MFSD2a in maternal blood at the third trimester and in placenta at delivery. This indicates that altered MFSD2a levels in maternal blood during pregnancy might influence placental nutrient transport and fetal neurodevelopment. Furthermore, MFSD2a levels in maternal blood on the third trimester were inversely correlated to DHA in maternal serum lyso-PL. Thus, the level of MFSD2a in maternal blood could be used as a potential biomarker for the early detection of disturbances of MFSD2a expression during pregnancy and the subsequent consequences for the neurodevelopment of the child, as well as it may help to choose the optimal treatment approach for the affected subjects.
Open Access
Inherited epigenetic hallmarks of childhood obesity derived from prenatal exposure to obesogens
(MDPI, 2023-03-07) Núñez-Sánchez, María Á.; Jiménez-Méndez, Almudena; Suárez Cortés, María; Martínez-Sánchez, María A.; Sánchez-Solís de Querol, Manuel; Blanco Carnero, José Eliseo; Ruiz Alcaraz, Antonio José; Ramos-Molina, Bruno; Bioquímica y Biología Molecular B e Inmunología; Facultad de Biología
Childhood obesity has reached epidemic levels in developed countries and is becoming a major cause for concern in the developing world. The causes of childhood obesity are complex and multifactorial, involving the interaction between individual genetics and environmental and developmental factors. Among the environmental factors, there is a growing interest in understanding the possible relationship between the so-called environmental obesogens and the development of obesity in children. Exposure to these obesogens such as phthalates, bisphenol A, or parabens, has been identified as a promoter of obesity through different mechanisms such as the alteration of adipocyte development from mesenchymal progenitors, the interference with hormone receptors, and induced inflammation. However, less attention has been paid to the inheritance of epigenetic modifications due to maternal exposure to these compounds during pregnancy. Thus, the aim of this review is to summarize the current knowledge of epigenetic modifications due to maternal exposure to those obesogens during pregnancy as well as their potential implication on long-term obesity development in the offspring and transgenerational inheritance of epiphenotypes.
Open Access
Inflammatory status in human hepatic cirrhosis
(Baishideng publishing Group, 2015-11-07) Tristán-Manzano, María; García-Peñarrubia, Pilar; Martínez-Esparza Alvargonzález, María Concepción; Ruiz Alcaraz, Antonio José; Bioquímica y Biología Molecular B e Inmunología
This review focuses on new findings about the inflammatory status involved in the development of human liver cirrhosis induced by the two main causes, hepatitis C virus (HCV) infection and chronic alcohol abuse, avoiding results obtained from animal models. When liver is faced to a persistent and/or intense local damage the maintained inflammatory response gives rise to a progressive replacement of normal hepatic tissue by non-functional fibrotic scar. The imbalance between tissue regeneration and fibrosis will determine the outcome toward health recovery or hepatic cirrhosis. In all cases progression toward liver cirrhosis is caused by a dysregulation of mechanisms that govern the balance between activation/homeostasis of the immune system. Detecting differences between the inflammatory status in HCV-induced vs alcohol-induced cirrhosis could be useful to identify specific targets for preventive and therapeutic intervention in each case. Thus, although survival of patients with alcoholic cirrhosis seems to be similar to that of patients with HCV-related cirrhosis (HCV-C), there are important differences in the altered cellular and molecular mechanisms implicated in the progression toward human liver cirrhosis. The predominant features of HCV-C are more related with those that allow viral evasion of the immune defenses, especially although not exclusively, inhibition of interferons secretion, natural killer cells activation and T cell-mediated cytotoxicity. On the contrary, the inflammatory status of alcohol-induced cirrhosis is determined by the combined effect of direct hepatotoxicity of ethanol metabolites and increases of the intestinal permeability, allowing bacteria and bacterial products translocation, into the portal circulation, mesenteric lymph nodes and peritoneal cavity. This phenomenon generates a stronger pro-inflammatory response compared with HCV-related cirrhosis. Hence, therapeutic intervention in HCV-related cirrhosis must be mainly focused to counteract HCV-immune system evasion, while in the case of alcohol-induced cirrhosis it must try to break the inflammatory loop established at the gut-mesenteric lymph nodes-peritoneal-systemic axis.
Open Access
In vitro study of the differential anti-inflammatory activity of dietary phytochemicals upon human macrophage-like cells as a previous step for dietary intervention
(MDPI, 2024-10-05) Ruiz Alcaraz, Antonio José; Baquero, Lorena; Martínez Pérez-Munar, Paula; Oliva-Bolarín, Alba; Sánchez-Martínez, María A.; Ramos-Molina, Bruno; Núñez-Sánchez, María A.; Moreno, Diego A.; Bioquímica y Biología Molecular B e Inmunología; Facultad de Biología
Chronic inflammatory diseases pose a substantial health challenge globally, significantly contributing to morbidity and mortality. Addressing this issue requires the use of effective anti-inflammatory strategies with fewer side effects than those provoked by currently used drugs. In this study, a range of phytochemicals (phenolic di-caffeoylquinic acid (Di-CQA), flavonoid cyanidin-3,5-diglucoside (Cy3,5DiG), aromatic isothiocyanate sinalbin (SNB) and aliphatic isothiocyanate sulforaphane (SFN)) sourced from vegetables and fruits underwent assessment for their potential anti-inflammatory activity. An in vitro model of human macrophage-like cells treated with a low dose of LPS to obtain a low degree of inflammation that emulates a chronic inflammation scenario revealed promising results. Cell viability and production of the key pro-inflammatory cytokines were assessed in the presence of various phytochemicals. The compounds Di-CQA and Cy-3,5-DiG, within low physiologically relevant doses, demonstrated notable anti-inflammatory effects by significantly reducing the production of key pro-inflammatory cytokines TNF-α and IL-6 without affecting cell viability. These findings underscore the potential of plant-derived bioactive compounds as valuable contributors to the prevention or treatment of chronic inflammatory diseases. These results suggest that these compounds, whether used individually or as part of natural mixtures, hold promise for their inclusion in nutritional interventions designed to mitigate inflammation in associated pathologies.
Embargo
Quinoxalines Potential to Target Pathologies
(Bentham Science Publishers, 2015) Tristán-Manzano, María; Guirado, Antonio; Gálvez, Jesús; García-Peñarrubia, Pilar; Martínez-Esparza Alvargonzález, María Concepción; Ruiz Alcaraz, Antonio José; Bioquímica y Biología Molecular B e Inmunología
The study of quinoxalines has increased immeasurably during the last two decades, due firstly to their relatively simple chemical synthesis, which has generated a vast variety of compounds with diverse structural modifications, and secondly, to the wide therapeutic potential and biological activities exhibited by this family of compounds. Quinoxalines constitute a rising biomedical class of low-molecular weight heterocyclic compounds with potential functions as antitumour, anti-inflammatory, antibacterial, antiviral, antifungal, antiparasitic and antidiabetic agents, as well as being of interest for the potential treatment of glaucoma, insomnia, cardiovascular and neurological diseases, among others. However, a deeper knowledge of the molecular targets of quinoxalines that fulfil a key role in certain pathologies is required for the development of new and more specific drugs through a rational design strategy to avoid undesirable side effects. In the present review, we summarize the most important molecular targets of the quinoxaline derivatives discovered to date, thus providing a first reference index for researchers to identify the potential targets of their quinoxalines derived collections, which could facilitate the development of new quinoxaline- based therapies.