Spice-derived bioactive compounds confer colorectal cancer prevention via modulation of gut microbiota

Colorectal cancer (CRC) is the second most frequent cause of cancer-related mortality among all types of malignancies. Sedentary lifestyles, obesity, smoking, red and processed meat, low-fiber diets, inflammatory bowel disease, and gut dysbiosis are the most important risk factors associated with CRC pathogenesis. Alterations in gut microbiota are positively correlated with colorectal carcinogenesis, as these can dysregulate the immune response, alter the gut’s metabolic profile, modify the molecular processes in colonocytes, and initiate mutagenesis. Changes in the daily diet, and the addition of plant-based nutraceuticals, have the ability to modulate the composition and functionality of the gut microbiota, maintaining gut homeostasis and regulating host immune and inflammatory responses. Spices are one of the fundamental components of the human diet that are used for their bioactive properties (i.e., antimicrobial, antioxidant, and anti-inflammatory effects) and these exert beneficial effects on health, improving digestion and showing anti-inflammatory, immunomodulatory, and glucose- and cholesterol-lowering activities, as well as possessing properties that affect cognition and mood. The anti-inflammatory and immunomodulatory properties of spices could be useful in the prevention of various types of cancers that affect the digestive system. This review is designed to summarize the reciprocal interactions between dietary spices and the gut microbiota, and highlight the impact of dietary spices and their bioactive compounds on colorectal carcinogenesis by targeting the gut microbiota

NUTRACEUTICAL TO PREVENT URINARY TRACT INFECTIONS: PRECLINICAL STUDIES

In the first and second year of my PhD course the aim was to find a new non-antibiotic candidate of plant origin, which could be use in the management of the UTIs. In the first phase, I selected five different plants, which were extracted to explore their potential against uropathogenic E. coli. According to the literature the plants selected for the studies were: Camellia sinensis L. (Leaves), Punica Granatum L. (Fruit), Orthosiphon stamineus (Leaves), Morus alba L. (Leaves), H. Sabdariffa (Flowers). All the plants were extracted, and the extracts screened to select the most promising plant extract according to their polyphenol concentration, antioxidant, and antimicrobial activities. Based on these results we selected only one of the most promising extracts (H. Sabdariffa) and we performed UHPLC coupled to IT-TOF profile assessing the main compounds and understanding the possible mechanism of action of these molecules against the uropathogenic E. coli. Finally, there was the evaluation anti-invasivity activity using bladder carcinoma cells (HT-1376). In the third year of the PhD course, which took place at the Leibniz-Institut für Lebensmittel-Systembiologie an der Technischen Universität München, a non-canonical approach was followed, with the final aim to update the literature on the TAS2R expression and the in vitro bioavailability of Cucurbitacin B, which is contained in Momordica charantia L. fruits. For this reason M. charantia. fruits were divided into seeds, pulp, and skin and these parts and the whole fruit were extracted three consecutive times using water, acetonitrile/water (70/30) and ethyl acetate. The extracts were characterized with an untargeted UHPLC-Tof-MS screening. After the metabolic profile assessment and the determination of cucurbitacins in the extracts, the next step was understood if cucurbitacin B, present in each part of the fruit, was able to reach the GU tract using the transwell system. Moreover, considering the poor literature on TAS2R in CACO-2 cell line we decided also to explore their expression in this specific cell line and to treat the cells with bitter melon extract to understand if the treatment could change the expression of this receptor

Spice-Derived Bioactive Compounds Confer Colorectal Cancer Prevention via Modulation of Gut Microbiota

Colorectal cancer (CRC) is the second most frequent cause of cancer-related mortality among all types of malignancies. Sedentary lifestyles, obesity, smoking, red and processed meat, low-fiber diets, inflammatory bowel disease, and gut dysbiosis are the most important risk factors associated with CRC pathogenesis. Alterations in gut microbiota are positively correlated with colorectal carcinogenesis, as these can dysregulate the immune response, alter the gut’s metabolic profile, modify the molecular processes in colonocytes, and initiate mutagenesis. Changes in the daily diet, and the addition of plant-based nutraceuticals, have the ability to modulate the composition and functionality of the gut microbiota, maintaining gut homeostasis and regulating host immune and inflammatory responses. Spices are one of the fundamental components of the human diet that are used for their bioactive properties (i.e., antimicrobial, antioxidant, and anti-inflammatory effects) and these exert beneficial effects on health, improving digestion and showing anti-inflammatory, immunomodulatory, and glucose- and cholesterol-lowering activities, as well as possessing properties that affect cognition and mood. The anti-inflammatory and immunomodulatory properties of spices could be useful in the prevention of various types of cancers that affect the digestive system. This review is designed to summarize the reciprocal interactions between dietary spices and the gut microbiota, and highlight the impact of dietary spices and their bioactive compounds on colorectal carcinogenesis by targeting the gut microbiota

BIOACCESSIBILITY AND BIOAVAILABILITY OF THE HYDROALCOHOLIC EXTRACT OBTAINED FROM ONION (ALLIUM CEPA L.) TUNICS

A large body of evidence suggests that high dietary consumption of polyphenol-rich fruit and vegetables protects against the development of chronic inflammatory diseases [1]. After consumption of plant-derived foods and beverages, dietary polyphenols are partially modified during gastrointestinal digestion and then absorbed in the small intestine and metabolized by the body, or reach the colon, where are subjected to catabolism by the gut microbiota followed by absorption of the resulting products. After absorption, polyphenols are submitted to metabolic detoxication processes, including glucuronidation, methylation and sulfation, and then are excreted through urine and bile. Quercetin, a flavonol present in many fruits and vegetables, especially onion (Allium cepa L.), is commonly found as glycosides, since the aglycone is highly reactive and relatively insoluble in aqueous media [2]. The pathways of quercetin absorption in the gastrointestinal tract of humans and other mammals are quite well understood. The present study aimed to provide more information regarding the in vitro bioaccessibility and bioavailability of an onion tunic hydroalcoholic extract rich in quercetin and its derivatives. In particular, to evaluate the bioaccessibility, the extract was submitted to a simulated in vitro gastro-, gastro-duodenal- and duodenal-digestion. After HPLCPDA- MS analysis, a significant increase in all quercetin derivatives was found in the extract after the in vitro digestion. The bioavailability of quercetin and its derivatives was determined using the Parallel Artificial Membrane Permeation Assay (PAMPA) model system for the evaluation of passive transcellular permeability. Through the use of PAMPA model system, the passive transport of quercetins was demonstrated. The measured rate of quercetins absorption was limited, and in line with literature data

BIOAVAILABILITY AND IN VIVO ANTIOXIDANT ACTIVITY OF M.E.D.® PROPOLIS EXTRACT

A large body of evidence highlights the biological properties of propolis, which can be ascribed to its antioxidant and anti-inflammatory activities [1]. As bioavailability is an essential measurement tool to show a systemic effect and the bioavailability of propolis is not widely known, the present research aimed to evaluate the bioavailability of a standardized polyphenol mixture obtained from brown propolis, using a patented extraction method called Multi Dynamic Extraction (M.E.D.® propolis), administered under acute and prolonged treatments. First, the content of the main polyphenols of M.E.D.® propolis was evaluate through RP-HPLC-UV-PDA-MSn analysis. The most abundant polyphenols resulted to be galangin and chrysin, which represented the 7.8% and 7.5% of the characterized polyphenols mixture, respectively. Then the bioavailability of galangin and chrysin was determined in 30 males C57BL/6 wild-type mice, 8 weeks old, following acute and prolonged oral administration of the previously characterized polyphenols mixture. In the first case, the acute setting, mice were fed with a single bolus, at the dose of 500 mg/kg body weight, containing 3.65 mg of the polyphenol mixture. While, in the second case, the prolonged setting, mice were fed with 100, 250, and 500 mg/kg bolus, for 30 days. In the acute setting, blood was taken at 30 s and 5, 10, 15, 20, 25, 30, 45, 60 and 120 min, following the administration period, and in the prolonged setting, blood samples were collected at the 10th, 20th, or 30th day of the treatment period. At the end of the both settings, the expression superoxide dismutase (SOD), catalase, and glutathione peroxidase antioxidant enzymes was evaluated in liver tissue. Following both acute and prolonged administration, neither galangin nor chrysin were detectable in the plasma of mice, whereas the glucuronide metabolite of galangin was detectable 5 min after acute administration. At the end of the prolonged treatment SOD increased significantly, unlike the other two enzymes. The obtained data suggest that oral administration of M.E.D.® propolis extract is followed by a rapid absorption and metabolization of galangin. Moreover, an adaptation of the antioxidant first line defense system was observed

OPTIMIZATION OF THE HYDROALCOHOLIC EXTRACT OF EPILOBIUM ANGUSTIFOLIUM L. AND CHEMICAL CHARACTERIZATION THROUGH UHPLCMS/ MS ANALYSIS

Epilobium angustifolium L. is a plant used in traditional medicine for the treatment of many disorders and ailments. In vitro and in vivo studies have demonstrated that the extracts obtained from the aerial parts of E. angustifolium possess a broad range of pharmacological and therapeutic effects, including antioxidant, anti-proliferative, anti-inflammatory and antimicrobial properties, mainly ascribed to flavonoids and ellagitannins (i.e oenothein B). The present study aimed to optimize the extraction method to obtain a hydroalcoholic extract rich in polyphenols through a systematic method consisting in the Design of Experiments (DoE). In addition, the second aim of this investigation was to determine the metabolic profile of the optimized E. angustifolium hydroalcoholic extract by using the latest generation of chromatography involving the use of Ultra-High-Performance Liquid Chromatography (UHPLC) coupled with a Quadrupole orbitrap Linear Trap (LTQ orbitrap), which allows for the detection of the compounds of interest at very low concentrations. This study led to the determination of the best extraction conditions with the identification of the effect of solvent, temperature, pH and duration on extraction process. The analysis of the optimized hydroalcoholic extract led to the identification of 43 compounds, including sugars, organic acids, non-flavonoids and flavonoids, both aglycones and glycosylated compounds

In vitro polyphenol effects on apoptosis: An update of literature data

Polyphenols are secondary plant metabolites which have been studied extensively for their health-promoting properties, and which could also exert pharmacological activities ranging from anti-inflammatory effects, to cytotoxic activity against cancer cells. The main mechanism for programmed cell death is represented by apoptosis, and its dysregulation is involved in the etiopathology of cancer. As such, substances able to induce apoptosis in cancer cells could be used as new anticancer agents. The aim of this paper is to review literature data on the apoptotic effects of polyphenols and the molecular mechanisms through which they induce these effects in cancer cells. In addition, a brief summary of the new delivery forms used to increase the bioavailability, and clinical impact of polyphenols is provided. The studies reported show that many polyphenol rich plant extracts, originating from food and herbal medicine, as well as isolated polyphenols administered individually or in combination, can regulate cell apoptosis primarily through intrinsic and extrinsic mechanisms of action in in vitro conditions. Due to these promising results, the use of polyphenols in the treatment of cancer should therefore be deeply investigated. In particular, because of the low number of clinical trials, further studies are required to evaluate the anticancer activity of polyphenols in in vivo conditions

Antimicrobial Potential of Curcumin: Therapeutic Potential and Challenges to Clinical Applications

Curcumin is a bioactive compound that is extracted from Curcuma longa and that is known for its antimicrobial properties. Curcuminoids are the main constituents of curcumin that exhibit antioxidant properties. It has a broad spectrum of antibacterial actions against a wide range of bacteria, even those resistant to antibiotics. Curcumin has been shown to be effective against the microorganisms that are responsible for surgical infections and implant-related bone infections, primarily Staphylococcus aureus and Escherichia coli. The efficacy of curcumin against Helicobacter pylori and Mycobacterium tuberculosis, alone or in combination with other classic antibiotics, is one of its most promising antibacterial effects. Curcumin is known to have antifungal action against numerous fungi that are responsible for a variety of infections, including dermatophytosis. Candidemia and candidiasis caused by Candida species have also been reported to be treated using curcumin. Life-threatening diseases and infections caused by viruses can be counteracted by curcumin, recognizing its antiviral potential. In combination therapy with other phytochemicals, curcumin shows synergistic effects, and this approach appears to be suitable for the eradication of antibiotic-resistant microbes and promising for achieving co-loaded antimicrobial pro-regenerative coatings for orthopedic implant biomaterials. Poor water solubility, low bioavailability, and rapid degradation are the main disadvantages of curcumin. The use of nanotechnologies for the delivery of curcumin could increase the prospects for its clinical application, mainly in orthopedics and other surgical scenarios. Curcumin-loaded nanoparticles revealed antimicrobial properties against S. aureus in periprosthetic joint infections

Bioavailability and In Vivo Antioxidant Activity of a Standardized Polyphenol Mixture Extracted from Brown Propolis

Several lines of evidence demonstrate the antioxidant, anti-inflammatory and antimicrobial activities of propolis, mostly ascribed to its polyphenol content. However, little is known regarding the bioavailability of propolis in acute and prolonged settings of oral administration. In this study, we first determined the content of the main polyphenols in a brown propolis extract obtained using a patented extraction method (Multi Dinamic Extraction—M.E.D.) by RP-HPLC-UV-PDA-MSn analysis, followed by the bioavailability of galangin and chrysin, the most abundant polyphenols in the mixture (7.8% and 7.5% respectively), following acute (single bolus of 500 mg/kg containing about 3.65 mg of the polyphenol mixture) and prolonged (100, 250 and 500 mg/kg body for 30 days) oral administration in 30 male 8 weeks old C57BL/6 wild-type mice. In the acute setting, blood was taken at 30 s and 5, 10, 15, 20, 25, 30, 45, 60 and 120 min following the oral bolus. In the prolonged setting, blood samples were obtained after 10, 20 or 30 days of administration. At the end of treatment, expression of antioxidant enzymes (superoxyde dismutase, SOD-1; catalase, CAT; glutathione peroxidase, GSS) was evaluated in liver tissue. Following both acute and prolonged administration, neither galangin nor chrysin were detectable in the plasma of mice, whereas the glucuronide metabolite of galangine was detectable 5 min after acute administration. At the end of the prolonged treatment SOD-1 was found to have increased significantly, unlike CAT and GSS. Overall, these data suggest that oral administration of whole brown propolis extract is followed by rapid absorption and metabolization of galangin followed by adaptations of the antioxidant first line defense system