Maria José Rodríguez-Lagunas

Flavonoids affect host-microbiota crosstalk through TLR modulation

Interaction between host cells and microbes is known as crosstalk. Among other mechanisms, this takes place when certain molecules of the micro-organisms are recognized by the toll-like receptors (TLRs) in the body cells, mainly in the intestinal epithelial cells and in the immune cells. TLRs belong to the pattern-recognition receptors and represent the first line of defense against pathogens, playing a pivotal role in both innate and adaptive immunity. Dysregulation in the activity of such receptors can lead to the development of chronic and severe inflammation as well as immunological disorders. Among components present in the diet, flavonoids have been suggested as antioxidant dietary factors able to modulate TLR-mediated signaling pathways. This review focuses on the molecular targets involved in the modulatory action of flavonoids on TLR-mediated signaling pathways, providing an overview of the mechanisms involved in such action. Particular flavonoids have been able to modify the composition of the microbiota, to modulate TLR gene and protein expression, and to regulate the downstream signaling molecules involved in the TLR pathway. These synergistic mechanisms suggest the role of some flavonoids in the preventive effect on certain chronic diseases.

Human skin permeation studies with PPARγ agonist to improve its permeability and efficacy in inflammatory processes

Rosacea is the most common inflammatory skin disease. It is characterized by erythema, inflammatory papules and pustules, visible blood vessels, and telangiectasia. The current treatment has limitations and unsatisfactory results. Pioglitazone (PGZ) is an agonist of peroxisome proliferator-activated receptors (PPARs), a nuclear receptor that regulates important cellular functions, including inflammatory responses. The purpose of this study was to evaluate the permeation of PGZ with a selection of penetration enhancers and to analyze its effectiveness for treating rosacea. The high-performance liquid chromatography (HPLC) method was validated for the quantitative determination of PGZ. Ex vivo permeation experiments were realized in Franz diffusion cells using human skin, in which PGZ with different penetration enhancers were assayed. The results showed that the limonene was the most effective penetration enhancer that promotes the permeation of PGZ through the skin. The cytotoxicity studies and the Draize test detected cell viability and the absence of skin irritation, respectively. The determination of the skin color using a skin colorimetric probe and the results of histopathological studies confirmed the ability of PGZ-limonene to reduce erythema and vasodilation. This study suggests new pharmacological indications of PGZ and its possible application in the treatment of skin diseases, namely rosacea.

Second International Congress on Chocolate and Cocoa in Medicine Held in Barcelona, Spain, 25-26th September 2015

Cocoa powder is a product derived from the beans of the Theobroma cacao tree, which is considered a good source of fiber (26%–40%), proteins (15%–20%), carbohydrates (about 15%) and lipids (10%–24%; generally, 10%–12%).[...]

TGF-β2, EGF, and FGF21 Growth Factors Present in Breast Milk Promote Mesenteric Lymph Node Lymphocytes Maturation in Suckling Rats

Breast milk, due to its large number of nutrients and bioactive factors, contributes to optimal development and immune maturation in early life. In this study, we aimed to assess the influence of some growth factors present in breast milk, such as transforming growth factor-β2 (TGF-β2), epidermal growth factor (EGF), and fibroblast growth factor 21 (FGF21), on the immune response development. Newborn Wistar rats were supplemented daily with TGF-β2, EGF, or FGF21, throughout the suckling period. At day 14 and 21 of life, lymphocytes from mesenteric lymph nodes (MLNs) were isolated, immunophenotyped, and cultured to evaluate their ability to proliferate and release cytokines. The main results demonstrated that supplementation with TGF-β2, EGF, or FGF21 modified the lymphocyte composition in MLNs. At day 14, all supplementations were able to induce a lower percentage of natural killer (NK) cells with the immature phenotype (CD8+), and they reduced the CD8αα/CD8αβ ratio at day 21. Moreover, the cytokine pattern was modified by the three treatments, with a down regulation of interleukin (IL)-13 secretion. These results showed the contribution of these growth factors in the lymphocytes MLNs immune maturation during the neonatal period.

Skin-controlled release lipid nanosystems of pranoprofen for the treatment of local inflammation and pain

AIM The design and development of pranoprofen (PF) nanostructured lipid carriers (NLCs) for topical treatment of local inflammation and pain. MATERIALS & METHODS PF-NLCs were designed and optimized by central rotatable composite design. A physicochemical characterization was addressed. Release and skin permeation were performed in Franz diffusion cells. In vivo anti-inflammatory efficacy was assayed in mice and tolerance study in humans. RESULTS PF-NLCs F7 and F10 provided sustained release, good stability and optimal skin retention avoiding systemic undesired side effects. Anti-inflammatory activity was enhanced, suggesting an improved efficacy as compared with standard formulation. No skin irritancy was detected. CONCLUSION Topical PF-NLCs F7 and F10 could be effective and safe new therapeutic tools for the treatment of local inflammation and pain. [Formula: see text].

Supplementation With 2′-FL and scGOS/lcFOS Ameliorates Rotavirus-Induced Diarrhea in Suckling Rats

Rotavirus (RV) is considered to be the most common cause of gastroenteritis among infants aged less than 5 years old. Human milk bioactive compounds have the ability to modulate the diarrheic process caused by several intestinal pathogens. This study aimed to evaluate the potential protective role of a specific human milk oligosaccharide, 2′-fucosyllactose (2′-FL), a mixture of the prebiotic short-chain galacto-oligosaccharides and long-chain fructo-oligosaccharides 9:1 (GOS/FOS) and their combination (2′-FL+GOS/FOS) on RV-induced diarrhea in suckling rats. The nutritional intervention was performed from the second to the sixteenth day of life by oral gavage and on day 5 an RV strain was orally administered to induce infection. Fecal samples were scored daily to assess the clinical pattern of severity, incidence and duration of diarrhea. Blood and tissues were obtained at day 8 and 16 in order to evaluate the effects on the epithelial barrier and the mucosal and systemic immune responses. In the assessment of severity, incidence and duration of diarrhea, both 2′-FL and GOS/FOS displayed a beneficial effect in terms of amelioration. However, the mechanisms involved seemed to differ: 2′-FL displayed a direct ability to promote intestinal maturation and to enhance neonatal immune responses, while GOS/FOS induced an intestinal trophic effect and an RV-blocking action. The combination of 2′-FL and GOS/FOS showed additive effects in some variables. Therefore, it could be a good strategy to add these compounds in combination to infant formulas, to protect against human RV-induced diarrhea in children.