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Matrix metalloproteinases 2 and 9 (MMP-2 and MMP-9) are regarded as important clinical targets due to their nodal-point role in inflammatory and oncological diseases. Here, we aimed at isolating and characterizing am MMP-2 and-9 inhibitor (MMPI) from Lupinus albus and at assessing its efficacy in vitro and in vivo. The protein was isolated using chromatographic and 2-D electrophoretic procedures and sequenced by using MALDI-TOF TOF and MS/MS analysis. In vitro MMP-2 and 9 inhibitions were determined on colon adenocarcinoma (HT29) cells, as well as by measuring the expression levels of genes related to these enzymes. Inhibitory activities were also confirmed in vivo using a model of experimental TNBS-induced colitis in mice, with oral administrations of 15 mg·kg-1. After chromatographic and electrophoretic isolation, the L. albus MMP-9 inhibitor was found to comprise a large fragment from δ-conglutin and, to a lower extent, small fragments of ß-conglutin. In vitro studies showed that the MMPI successfully inhibited MMP-9 activity in a dose-dependent manner in colon cancer cells, with an IC50 of 10 µg·mL-1 without impairing gene expression nor cell growth. In vivo studies showed that the MMPI maintained its bioactivities when administered orally and significantly reduced colitis symptoms, along with a very significant inhibition of MMP-2 and -9 activities. Overall, results reveal a novel type of MMPI in lupine that is edible, proteinaceous in nature and soluble in water, and effective in vivo, suggesting a high potential application as a nutraceutical or a functional food in pathologies related to abnormally high MMP-9 activity in the digestive system.
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Colitis/dietoterapia , Metaloproteinasa 2 de la Matriz/efectos de los fármacos , Metaloproteinasa 9 de la Matriz/efectos de los fármacos , Proteínas de Plantas/farmacología , Animales , Colitis/tratamiento farmacológico , Colitis/enzimología , Femenino , Células HT29 , Humanos , Lupinus/química , Lupinus/metabolismo , Masculino , Metaloproteinasa 2 de la Matriz/metabolismo , Metaloproteinasa 9 de la Matriz/metabolismo , Inhibidores de la Metaloproteinasa de la Matriz/aislamiento & purificación , Inhibidores de la Metaloproteinasa de la Matriz/farmacología , Ratones , Proteínas de Plantas/aislamiento & purificación , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción , Espectrometría de Masas en TándemRESUMEN
Our previous works produced a whey fermentation methodology that yielded antibacterial activity and potential inhibition of matrix metalloproteases (MMP)-2 and -9. Here, we evaluated if these activities were due to fermentation-produced peptides. Prolonged fermentation was carried out in the presence of our specific lactic acid bacteria (LAB) consortium. LAB fermentation yielded a total of 11 polypeptides, which were predominantly produced after 6 days of fermentation. One which was derived from beat casein presented a particularly high antibacterial activity against food pathogenic bacteria and was more effective than standard food disinfectants. This polypeptide was further studied and was also found to be active against several strains of pathogenic bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), in a dose-dependent manner. It also inhibited MMP-2 and MMP-9 whilst reducing HT29 cancer cell migration in vitro. Overall, this novel whey-derived polypeptide presents dual antibacterial and anti-inflammatory activity, revealing a strong potential to be used in functional foods or as a nutraceutical. Its identification and further characterization can open novel perspectives in the field of preventive/curative diets related to gut microbiota, gut inflammation, and cancer prevention, particularly if used in in vivo studies.
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Queso , Fermentación/fisiología , Inhibidores de la Metaloproteinasa de la Matriz/metabolismo , Animales , Antibacterianos/metabolismo , Antibacterianos/farmacología , Caseínas/metabolismo , Caseínas/farmacología , Bovinos , Movimiento Celular/efectos de los fármacos , Queso/análisis , Queso/microbiología , Microbiología de Alimentos , Gelatinasas/antagonistas & inhibidores , Gelatinasas/metabolismo , Cabras , Células HT29 , Humanos , Metaloproteinasa 2 de la Matriz/metabolismo , Metaloproteinasa 9 de la Matriz/metabolismo , Inhibidores de la Metaloproteinasa de la Matriz/química , Inhibidores de la Metaloproteinasa de la Matriz/farmacología , Pruebas de Sensibilidad Microbiana , Neoplasias/patología , Péptidos/metabolismo , Péptidos/farmacología , Ovinos , Suero Lácteo/química , Suero Lácteo/metabolismo , Suero Lácteo/microbiología , Proteína de Suero de Leche/metabolismo , Proteína de Suero de Leche/farmacologíaRESUMEN
Bacterial nanocellulose (BNC) membranes have enormous potential as systems for topical drug delivery due to their intrinsic biocompatibility and three-dimensional nanoporous structure, which can house all kinds of active pharmaceutical ingredients (APIs). Thus, the present study investigated the long-term storage stability of BNC membranes loaded with both hydrophilic and lipophilic APIs, namely, caffeine, lidocaine, ibuprofen and diclofenac. The storage stability was evaluated under accelerated testing conditions at different temperatures and relative humidity (RH), i.e., 75% RH/40 °C, 60% RH/25 °C and 0% RH/40 °C. All systems were quite stable under these storage conditions with no significant structural and morphological changes or variations in the drug release profile. The only difference observed was in the moisture-uptake, which increased with RH due to the hydrophilic nature of BNC. Furthermore, the caffeine-loaded BNC membrane was selected for in vivo cutaneous compatibility studies, where patches were applied in the volar forearm of twenty volunteers for 24 h. The cutaneous responses were assessed by non-invasive measurements and the tests revealed good compatibility for caffeine-loaded BNC membranes. These results highlight the good storage stability of the API-loaded BNC membranes and their cutaneous compatibility, which confirms the real potential of these dermal delivery systems.
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Materiales Biocompatibles/farmacología , Celulosa/farmacología , Sistemas de Liberación de Medicamentos , Nanopartículas/química , Administración Tópica , Bacterias/química , Materiales Biocompatibles/química , Cafeína/química , Cafeína/farmacología , Celulosa/química , Diclofenaco/química , Diclofenaco/farmacología , Portadores de Fármacos , Liberación de Fármacos , Estabilidad de Medicamentos , Humanos , Ibuprofeno/química , Ibuprofeno/farmacología , Lidocaína/química , Lidocaína/farmacologíaRESUMEN
The abietane 7α-acetoxy-6ß-hydroxyroyleanone (AHR), obtained from plant extracts, is an attractive lead for drug development, given its known antimicrobial properties. Two basic requirements to establish any compound as a new drug are the development of a convenient extraction process and the characterization of its structural and thermal properties. In this work seven different methods were tested to optimize the extraction of AHR from Plectranthus grandidentatus. Supercritical fluid extraction (SFE) proved to be the method of choice, delivering an amount of AHR (57.351 µg·mg-1) approximately six times higher than the second best method (maceration in acetone; 9.77 µg·mg-1). Single crystal X-ray diffraction analysis of the ARH molecular and crystal structure carried out at 167 ± 2 K and 296 ± 2 K showed only a single phase, here dubbed form III (orthorhombic space group P21212), at those temperatures. The presence of two other polymorphs above room temperature was, however, evidenced by differential scanning calorimetry (DSC). The three forms are enantiotropically related, with the form III â form II and form II â form I transitions occurring at 333.5 ± 1.6 K and 352.0 ± 1.6 K, respectively. The fact that the transitions are reversible suggests that polymorphism is not likely to be an issue in the development pharmaceutical formulations based on ARH. DSC experiments also showed that the compound decomposes on melting at 500.8 ± 0.8 K. Melting should therefore be avoided if, for example, strategies to improve solubility based on the production of glassy materials or solid dispersions are considered.
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Abietanos/química , Antibacterianos/química , Extractos Vegetales/química , Rastreo Diferencial de Calorimetría/métodos , Química Farmacéutica/métodos , Cristalización/métodos , Cristalografía por Rayos X/métodos , Plectranthus/química , Solubilidad , Temperatura , Difracción de Rayos X/métodosRESUMEN
BACKGROUND: Poor drug solubility represents a problem for the development of topical formulations. Since ionic liquids (ILs) can be placed in either lipophilic or hydrophilic solutions, they may be advantageous vehicles in such delivery systems. Nonetheless, it is vital to determine their usefulness when used at concentrations were cell viability is maintained, which was considered herein. METHOD: Five different ILs were prepared-three imidazole-based ILs: [C2mim][Br], [C4mim][Br], and [C6mim][Br]; and two choline-based ILs: [Cho][Phe] and [Cho][Glu]. Their cytotoxicity in human keratinocytes (HaCat cells), their influence in drug solubility and in percutaneous permeation, using pig skin membranes, was evaluated. RESULTS: Caffeine and salicylic acid were used as model actives. Choline-based ILs proved to be more suitable as functional ingredients, since they showed higher impact on drug solubility and a lower cytotoxicity. The major solubility enhancement was observed for caffeine and further solubility studies were carried out with this active in several concentrations of the choline-based ILs (0.1; 0.2; 0.5; 1.0; 3.0 and 5.0%, w/w) at 25 °C and 32 °C. Solubility was greatly influenced by concentrations up to 0.5%. The choline-based ILs showed no significant impact on the skin permeation, for both actives. The size of the imidazole-based ILs alkyl chain enhances the caffeine solubility and permeation, but also the ILs cytotoxicity. Stable O/W emulsions and gels were prepared containing the less toxic choline-based ILs and caffeine. CONCLUSIONS: Our results indicate that the choline-based ILs were effective functional ingredients, since, when used at nontoxic concentrations, they allowed a higher drug loading, while maintaining the stability of the formulations.
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Cafeína/metabolismo , Colina/administración & dosificación , Colina/química , Sistemas de Liberación de Medicamentos/métodos , Emulsiones/metabolismo , Geles/farmacología , Imidazoles/administración & dosificación , Imidazoles/química , Líquidos Iónicos/administración & dosificación , Piel/metabolismo , Administración Cutánea , Animales , Química Farmacéutica , Emulsiones/química , Geles/química , Humanos , Interacciones Hidrofóbicas e Hidrofílicas , Líquidos Iónicos/química , Absorción Cutánea , Solubilidad , PorcinosRESUMEN
Milk thistle (Silybum marianum) is well-known for its antioxidant activity due to the presence of silymarin. Albeit some studies show a potential for skin inflammation, its activity against dermal MMP-9 and MMP-2 remains to be studied. Silymarin isolated from an S. marianum herbal extract was tested for gelatinase inhibition in the presence of isolated MMP-9 and in dermal adenocarcinome HaCaT cells. Silymarin was then further tested in vivo, using a cutaneous inflammation mice model mediated by reactive oxygen species. Silymarin was able to significantly inhibit gelatinolytic activity in vitro without impairing cell growth and viability. Furthermore, inhibition was more pronounced in cells than with the isolated gelatinase, suggesting an additional effect upon metabolic pathways. In vivo, silymarin was able to reduce ear edema up to 74% and attenuated histological lesions. Results highlight silymarin potential for application in skin inflammatory disorders via gelatinase inhibition.
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The role of capsule endoscopy and enteroscopy in managing various small-bowel pathologies is well-established. However, their broader application has been hampered mainly by their lengthy reading times. As a result, there is a growing interest in employing artificial intelligence (AI) in these diagnostic and therapeutic procedures, driven by the prospect of overcoming some major limitations and enhancing healthcare efficiency, while maintaining high accuracy levels. In the past two decades, the applicability of AI to gastroenterology has been increasing, mainly because of the strong imaging component. Nowadays, there are a multitude of studies using AI, specifically using convolutional neural networks, that prove the potential applications of AI to these endoscopic techniques, achieving remarkable results. These findings suggest that there is ample opportunity for AI to expand its presence in the management of gastroenterology diseases and, in the future, catalyze a game-changing transformation in clinical activities. This review provides an overview of the current state-of-the-art of AI in the scope of small-bowel study, with a particular focus on capsule endoscopy and enteroscopy.
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Microbial foodborne diseases are a major health concern. In this regard, one of the major risk factors is related to consumer preferences for "ready-to-eat" or minimally processed (MP) fruits and vegetables. Essential oil (EO) is a viable alternative used to reduce pathogenic bacteria and increase the shelf-life of MP foods, due to the health risks associated with food chlorine. Indeed, there has been increased interest in using EO in fresh produce. However, more information about EO applications in MP foods is necessary. For instance, although in vitro tests have defined EO as a valuable antimicrobial agent, its practical use in MP foods can be hampered by unrealistic concentrations, as most studies focus on growth reductions instead of bactericidal activity, which, in the case of MP foods, is of utmost importance. The present review focuses on the effects of EO in MP food pathogens, including the more realistic applications. Overall, due to this type of information, EO could be better regarded as an "added value" to the food industry.
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Matrix metalloproteinases (MMPs) are proteolytic enzymes that play a crucial role in tumor microenvironment remodeling, contributing to inflammatory and angiogenic processes, and ultimately promoting tumor maintenance and progression. Several studies on bioactive polypeptides isolated from legumes have shown anti-migratory, anti-MMPs, and anti-tumor effects, potentially constituting novel strategies for both the prevention and progression of cancer. In this work, we investigated the anti-tumor role of deflamin, a protein oligomer isolated from white lupine seeds (Lupinus albus) reported to inhibit MMP-9 and cell migration in colorectal cancer (CRC) cell lines. We found that deflamin exerts an inhibitory effect on tumor growth and metastasis formation, contributing to increased tumor apoptosis in the xenotransplanted zebrafish larvae model. Furthermore, deflamin resulted not only in a significant reduction in MMP-2 and MMP-9 activity but also in impaired cancer cell migration and invasion in vitro. Using the xenograft zebrafish model, we observed that deflamin inhibits collagen degradation and angiogenesis in the tumor microenvironment in vivo. Overall, our work reveals the potential of deflamin as an agent against CRC development and progression.
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There is a strong demand for plant-based milk substitutes, often low in protein content (<1.5% w/v). Protein-rich pulse seeds and the right processing technologies make it possible to make relevant choices. The major objective of this study was to assess the impact of processing on the nutritional characteristics of beverages with a high impact on health, in particular on digestibility and specific bioactivities. The results suggest that pulse beverages are as high in protein content (3.24% w/v for chickpea and 4.05% w/v for lupin) as cow's milk. The anti-nutrient level characteristics of pulses have been considerably reduced by strategic processing. However, when present in small quantities, some of these anti-nutritional factors may have health benefits. Controlling processing conditions play a crucial role in this fine balance as a tool to take advantage of their health benefits. There is evidence of protein hydrolysis by in vitro digestion and limited bioaccessibility of minerals. In addition to being highly digestible, lupin and chickpea beverages have anti-inflammatory and anti-carcinogenic potential evaluated through the inhibition of metalloproteinase MMP-9.
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Food fortification with bioactive compounds may constitute a way to ameliorate inflammatory bowel diseases (IBDs). Lupin seeds contain an oligomer named deflamin that can reduce IBD's symptoms via MMP-9 inhibition. Here, our goal was to develop a lupin protein concentrate (LPC) enriched in deflamin and to test its application as a food additive to be used as a functional food against colitis. The nutritional profile of the LPC was evaluated, and its efficacy in vivo was tested, either alone or as added to wheat cookies. The LPC presented high protein and carbohydrate contents (20.09 g/100 g and 62.05/100 g, respectively), as well as antioxidant activity (FRAP: 351.19 mg AAE/10 mg and DPPH: 273.9 mg AAE/10 mg). It was also effective against TNBS-induced colitis in a dose dependent-manner, reducing DAI scores by more than 50% and concomitantly inhibiting MMP-9 activity. When added to cookies, the LPC activities were maintained after baking, and a 4-day diet with LPC cookies induced a significant protective effect against acetic acid-induced colitis, overall bringing lesions, oxidative stress and DNA damage levels to values significantly similar to controls (p < 0.001). The results show that the LPC is an efficient way to deliver deflamin in IBD-targeted diets.
Asunto(s)
Colitis , Enfermedades Inflamatorias del Intestino , Colitis/inducido químicamente , Colitis/tratamiento farmacológico , Colitis/patología , Aditivos Alimentarios/efectos adversos , Alimentos Funcionales , Humanos , Inflamación , Enfermedades Inflamatorias del Intestino/metabolismo , Metaloproteinasa 9 de la Matriz/metabolismo , Estrés OxidativoRESUMEN
BACKGROUND: The risk of coronary heart disease (CHD) is related to environmental factors and genetic variants. Apolipoprotein E (apoE) polymorphisms are heritable determinants of total and low-density lipoprotein cholesterol, with some authors suggesting an association between the ε4 allele and CHD. We investigated the relationship between apoE genotype and age at referral to a specialized lipid clinic by the primary care physician and whether the benefits of treatment with statin differed between genotypes. METHODS: We assessed individual apoE genotypes and lipid blood profile in a total of 463 patients followed at a specialized lipid clinic due to dyslipidemia, with a 3-year median follow-up time. The primary care physician at the time of the referral had no access to the apoE genotyping results. Carriers of apoE ε4/ε2 genotype were excluded. RESULTS: The frequencies of ε2, ε3 and ε4 alleles were 7.8, 78.9 and 13.3%, respectively. There were no significant differences between genders. Although with similar lipid profiles and antidyslipidemic drug usage at baseline, ε4-carriers were referred to the clinic at a younger age (44.2 ± 14.7 years) compared with non-ε4 carriers (50.6 ± 13.8 years) (p < 0.001), with a substantially younger age of referral for homozygous E4/4 and for all genotypes with at least one copy of the ε4 allele (p < 0.001 for trend). Although both ε4 and non-ε4 carriers achieved significant reductions in total cholesterol during follow-up (p < 0.001 vs. baseline), the mean relative decrease in total cholesterol levels was higher in non-ε4 carriers (-19.9 ± 2.3%) compared with ε4 carriers (-11.8 ± 2.3%), p = 0.003. CONCLUSION: Our findings support the concept that there is a reduced response to anti-dyslipidemic treatment in ε4 carriers; this can be a contributing factor for the earlier referral of these patients to our specialized lipid clinic and reinforces the usefulness of apoE genotyping in predicting patients response to lipid lowering therapies.
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Apolipoproteína E4/genética , Dislipidemias/tratamiento farmacológico , Dislipidemias/genética , Polimorfismo Genético/genética , Adulto , Femenino , Genotipo , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Masculino , Persona de Mediana Edad , Factores de RiesgoRESUMEN
Previous reports have shown that lupin protein extracts (LE) contain a polypeptide named deflamin with a potent matrix metalloproteinase (MMP)-9 inhibitory activity. The aim of our study was to develop an efficient delivery method for incorporating deflamin into cookies using different alternative flours. A lupin protein concentrate (10 g protein/100 g cookie dough) was added to gluten and gluten-free flours to produce savoury cookies, and its impacts on the physical properties of doughs and cookies, as well on the maintenance of deflamin's anti-MMP-9 activity, were analysed. The results showed that the biochemical compositions of all cookies with LE presented higher protein and ash contents when compared to the control cookies. Rice, buckwheat and oat doughs were firmer than the others, whereas the addition of LE to kamut and buckwheat flours made cookies significantly firmer than the controls. Additionally, strong interactions between LE and several flours were observed, yielding different impacts on the MMP-9 bioactivity. Overall, the only flour that did not interfere with the desired nutraceutical activities was buckwheat, with 60% MMP-9 inhibitory activity and a concomitant reduction of colon cancer migration; hence, buckwheat flour was revealed to be a good vehicle to deliver bioactive deflamin, showing strong potential as a functional food to be used in preventive or curative approaches to gastrointestinal diseases.
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One of the most challenging problems with food-borne bioactive compounds is that there are commonly no cost-effective, generally recognized as safe (GRAS) methods for obtaining gram quantities of their purified forms. Here we aimed at developing a method to isolate deflamin, an oligomeric protein from lupin seeds with anti-inflammatory and anticancer activity through matrix metalloprotease (MMP)-9 inhibition. Our goal was to develop a GRAS method that could be easily up-scalable whilst maintaining deflamin's activity. A sequential precipitation methodology was developed, using an aqueous extraction, followed by heat denaturation, acid precipitation and solubilization in ethanol. A final precipitation with 90% ethanol yielded a purified protein which was sequenced through mass spectrometry and tested for its MMP inhibitory activity using the Dye-quenched (DQ) gelatin assay and the standard wound healing assay in HT29 cells. The developed method yielded a purified oligomer, which represented 0.1% (w/w) of total dry seed weight and was positively confirmed to be deflamin. It further showed to effectively reduce MMP-9 gelatinolytic activity as well as colon cancer cell migration, hence corroborating the effectiveness of our method. Overall, this is the first reported method for isolating an MMP-9 inhibitor from legume seeds, which is up-scalable to an industrial level, in a cost-effective manner.
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Lipidic implants are valuable controlled delivery systems that present good biocompatibility and are useful for long-lasting therapies. However, these promising systems can present inflexible drug release profiles that limit their performance. Thus, finding new materials to overcome this drawback is crucial. Herein, lipidic implants containing caffeine and poorly soluble salicylic acid and rutin were developed. The inclusion of Gelucire® 50/02, sucrose, and two biobased ionic liquids, [Cho][Phe] and [Cho][Glu], were evaluated as a mean to improve the performance of the systems. The formulation procedure, dye content distribution, drug content, drug release, water content, and lipidic erosion of the developed systems were assessed. AFM analysis of the implants containing ILs was also performed. The results demonstrated that neither Gelucire® 50/02 nor sucrose were suitable tools to improve the drug release profile. In contrast, the ILs proved to be promising materials for multiple reasons; not only did they facilitate the formulation and incorporation of the studied drugs into the implants, but they also allowed a more suitable release profile, with [Cho][Glu] allowing a higher drug release due to its ability to increase surface wrinkling. Hence, this study showcases ILs as multitalented materials in lipid-based drug implants.
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Legume proteins can be successfully used in bakery foods, like cookies, to obtain a protein-enriched product. A lupin extract (10 g/100 g) was added to gluten and gluten-free flours from different sources: rice, buckwheat, oat, kamut and spelt. The impact on the physical properties of the dough and cookies was evaluated for the different systems. Rice and buckwheat doughs were 20% firmer and 40% less cohesive than the others. The incorporation of lupin extract had a reduced impact on the shape parameters of the cookies, namely in terms of area and thickness. The texture differed over time and after eight weeks, the oat and buckwheat cookies enriched with lupin extract were significantly firmer than the cookies without lupin. The incorporation of lupin extract induced a certain golden-brown coloring on the cookies, making them more appealing: lightness (L*) values decreased, generally, for the cookies with lupin extract when compared to the controls. The aw and moisture content values were very low for all samples, suggesting a high stability food product. Hence, the addition of lupin extract brought some technological changes in the dough and cookies in all the flours tested but improved the final product quality which aligns with the trends in the food industry.
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The influence of flour replacement by yogurt or curd-cheese additions (from 10% to 20%, w/w) on the glycemic response and bioactivity improvements of gluten-free bread was evaluated. Starch digestibility, measured by an in vitro digestion model, was applied to determine the effect on starch fractions. The bread glycemic index was calculated. Bread antioxidant capacity (2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH) and ferric-ion-reducing antioxidant power (FRAP) methods) and total phenolic compounds were assessed. Anti-inflammatory properties according to enzymatic matrix metalloproteinase (MMP)-9 inhibitory activity were also studied. Considering the higher level of both dairy products tested (20%, w/w) and comparing with control bread results, a reduction of around 35% in the glycemic response of curd cheese bread was achieved, resulting in intermediate index level (glycemic index (GI) 55-69), with yogurt bread still showing a high glycemic index (GI > 70). In terms of bread bioactivity, curd cheese bread expressed better reducing power effects, whereas yogurt bread showed more effective radical-scavenging capacity. An increase in bread phenolic compounds by yogurt (55.3%) and curd cheese (73.0%) additions (at 20%) were also registered. MMP-9 inhibition activity was higher in the dairy bread than in control bread, suggesting an improvement in terms of anti-inflammatory properties. The supplementation of the gluten-free bread by yogurt or curd cheese was shown to be a promising strategy to reduce the glycemic response and to improve the bioactive properties of the bread, that which can contribute to preventive diets of celiac patients and irritable bowel syndrome individuals.
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Plectranthus ecklonii Benth. has widespread ethnobotanical use in African folk medicine for its medicinal properties in skin conditions. In this study, two different basic formulations containing P. ecklonii extracts were prepared, one in an organic solvent and the other using water. The aqueous extract only contained rosmarinic acid (RA) at 2.02 mM, and the organic extract contained RA and parvifloron D at 0.29 and 3.13 mM, respectively. RA in aqueous solution permeated skin; however, in P. ecklonii organic extract, this was not detected. Thus, P. ecklonii aqueous extract was further studied and combined with benzophenone-4, which elevated the sun protection factor (SPF) by 19.49%. No significant cytotoxic effects were observed from the aqueous extract. The Staphylococcus epidermidis strain was used to determine a minimum inhibitory concentration (MIC) value of 10 µg.mL-1. The aqueous extract inhibited the activity of acetylcholinesterase by 59.14 ± 4.97%, and the IC50 value was 12.9 µg.mL-1. The association of the P. ecklonii extract with a UV filter substantially elevated its SPF efficacy. Following the multiple bioactivities of the extract and its active substances, a finished product could be claimed as a multifunctional cosmeceutical with broad skin valuable effects, from UV protection to antiaging action.
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PURPOSE: Little is known about the pharmacological effects of the phenolic compounds of Pennyroyal (Mentha pulegium). This Mediterranean aromatic plant, used as a gastronomic spice and as food preservative by the food industry has been studied mainly due to its essential oil antibacterial properties, composed primarily by monoterpenes. With this work, we aimed to evaluate the effects of a phenolic extract of pennyroyal in the impairment of inflammatory processes in Inflammatory Bowel Diseases (IBD) and in the potential inhibition of progression to colorectal cancer (CRC). METHODS: To that purpose, we evaluated the effect of pennyroyal extract administration in a model of TNBS-induced colitis in mice and further determined its effect on human colon carcinoma cell proliferation and invasion. RESULTS: The phenolic extract of pennyroyal exhibited antioxidant properties in in vitro assays and administration of the extract in a rat model of carrageenan-induced paw oedema led to significant anti-inflammatory effects. Further results evidenced a beneficial effect of the phenolic extract in the attenuation of experimental colitis and a potential antiproliferative effect on cultured colon cancer cells, effects not previously described, to our knowledge. A reduction in several markers of colon inflammation was observed following administration of the extract to colitis-induced mice, including functional and histological indicators. A successful inhibition of cancer cell invasion and proliferation was also observed in in vitro studies with HT-29 cells. Furthermore, the extract also led to a reduced expression of iNOS/COX-2 in the colon of colitis-induced mice, both being crucial mediators of intestinal inflammation. CONCLUSIONS: Taking into consideration the central role of inflammation in the pathophysiology of CRC and the recognised connection between inflammatory events and cancer, these results enlighten the relevance of the phenolic constituents of pennyroyal as important pharmacological sources in the investigation of new treatment options for patients with inflammatory bowel diseases.