Beneficial Effects of Organosulfur Compounds from Allium cepa on Gut Health: A Systematic Review

Dietary changes affect the composition and structure of gut microbiota (GM) in animals and humans. One of the beneficial effects of consuming products derived from plants is the positive influence on immunity and gastrointestinal health. Species belonging to the genus Allium contain many organosulfur compounds (OSCs) that have been widely studied showing their biological properties and beneficial effects on intestinal health and GM. This is the first systematic review of OSCs from Allium performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, and it is based on the evidence that we found in literature about the benefits on the GM and intestinal health demonstrated by OSCs from Allium, and specifically from onion. OSCs from Allium cepa have shown a significant antibacterial activity against a broad spectrum of antibiotic-resistant Gram-positive and Gram-negative bacteria. In addition, the intake of OSCs from onion was able to modulate the composition of GM, increasing the beneficial bacterial populations in animal models. Moreover, the beneficial effects observed in murine models of colitis suggest that these compounds could be suitable candidates for the treatment of inflammatory bowel disease (IBD) or reverse the dysbiosis caused by a high-fat diet (HFD). Despite the evidence found both in vitro and in vivo, we have not found any article that tested OSCs different from allicin in clinical trials or dietary intervention studies in humans. In this sense, it would be interesting to conduct new research that tests the benefits of these compounds in human GM

In Vitro Antiparasitic Activity of Propyl-Propane-Thiosulfinate (PTS) and Propyl-Propane-Thiosulfonate (PTSO) from Allium cepa against Eimeria acervulina Sporozoites

Among the alternatives to control avian coccidiosis, alliaceous extracts stand out due to their functional properties. Despite this, most of the references are focused just on garlic. In this study, we analyze the in vitro effects of propyl-propane thiosulfinate (PTS) and propyl-propane thiosulfonate (PTSO), two organosulfur compounds from onion, on MDBK cells infected with sporozoites of Eimeria acervulina. To this aim, two different experiments were performed. In the first experiment, sporozoites were previously incubated for 1 h at 1, 5 and 10 mu g/mL of PTS or PTSO and added to MDBK cells. In the second experiment, MDBK cells were first incubated for 24 h at different concentrations of PTS or PTSO and then infected with E. acervulina sporozoites. Then, 24 h after inoculation, the presence of E. acervulina was quantified by qPCR. MDBK viability was measured at 72 h post-infection. Sporozoites incubated at 10 mu g/mL of PTS and PTSO inhibited the capability to penetrate the cells up to 75.2% +/- 6.44 and 71.7% +/- 6.03, respectively. The incubation of MDBK with each compound resulted in a preventive effect against sporozoite invasion at 1 mu g/mL of PTS and 1 and 10 mu g/mL of PTSO. Cells incubated with PTSO obtained similar viability percentages to uninfected cells. These results suggest that the use of PTS and PTSO is a promising alternative to coccidiosis treatment, although further in vivo studies need to be performed.Centre for the Development of Industrial Technology in Spain (CDTI) IDI-2022025

Antioxidant Intake and Antitumor Therapy: Toward Nutritional Recommendations for Optimal Results

This study was supported by the Regional Government of Andalusia (Project P11-CTS-7651 and assistance to the CTS-107 group).The role of the induction of oxidative stress as the mechanism of action of many antitumor drugs is acquiring an increasing interest. In such cases, the antitumor therapy success may be conditioned by the antioxidants present in our own body, which can be synthesized de novo (endogenous) or incorporated through the diet and nutritional supplements (exogenous). In this paper, we have reviewed different aspects of antioxidants, including their classification, natural sources, importance in diet, consumption of nutritional supplements, and the impact of antioxidants on health. Moreover, we have focused especially on the study of the interaction between antioxidants and antitumor therapy, considering both radiotherapy and chemotherapy. In this regard, we found that the convenience of administration of antioxidants during cancer treatment still remains a very controversial issue. In general terms, antioxidants could promote or suppress the effectiveness of antitumor treatment and even protect healthy tissues against damage induced by oxidative stress. The effects may depend on many factors discussed in the paper. These factors should be taken into consideration in order to achieve precise nutritional recommendations for patients. The evidence at the moment suggests that the supplementation or restriction of exogenous antioxidants during cancer treatment, as appropriate, could contribute to improving its efficiency.Junta de Andalucia P11-CTS-765

Optimization of an onion oil microemulsion by response surface methodology for enhanced physicochemical stability and biological activity

Onion oil (OO) containing propyl-propane thiosulfinate (PTS) and propyl-propane thiosulfonate (PTSO) is known for various therapeutic properties. However, its industrial use in hydrophilic matrices is challenging due to the lack of physicochemical stability. Applying Box-Behnken design (BBD), we developed an optimal OO microemulsion (OOME) with a minimum droplet size and maximum chemical stability. The OOME comprised 2 % w/w oily phase (high oleic acid sunflower oil), 120 mg/L of OO containing PTS+PTSO, 1.47 % w/w emulsifier (Diacetyl tartaric acid ester of mono-diglycerides, DATEM), 0.25 % stabilizer (xanthan gum) and 573 mM phosphate buffer. Turbidimetry as well as laser and dynamic light scattering over 30 days was used to characterize physical stability of the OOME, assessing chemical stability by HPLC. Cytotoxicity and quantification of cytokines (IL-4 and IL-8) were evaluated in colorectal cancer cells (HT-29, T-84 and SW-837) culture supernatants. After 30 days of storage, OOME remained stable, with no flocculation or coalescence phenomena. It achieved a PTS+PTSO amount of 98 mg/L, a droplet size of 329 nm, a particle size dispersal coefficient of 0.89, and Z-potential was −40.17 mV. The OOME improved the antitumor effect of OO in lines HT-29 and SW-837, as well as its influence on the inflammatory response.Grupo de Investigación TEP025 Tecnología de Procesos Químicos y Bioquímico

Antioxidant Intake and Antitumor Therapy: Toward Nutritional Recommendations for Optimal Results

The role of the induction of oxidative stress as the mechanism of action of many antitumor drugs is acquiring an increasing interest. In such cases, the antitumor therapy success may be conditioned by the antioxidants present in our own body, which can be synthesized de novo (endogenous) or incorporated through the diet and nutritional supplements (exogenous). In this paper, we have reviewed different aspects of antioxidants, including their classification, natural sources, importance in diet, consumption of nutritional supplements, and the impact of antioxidants on health. Moreover, we have focused especially on the study of the interaction between antioxidants and antitumor therapy, considering both radiotherapy and chemotherapy. In this regard, we found that the convenience of administration of antioxidants during cancer treatment still remains a very controversial issue. In general terms, antioxidants could promote or suppress the effectiveness of antitumor treatment and even protect healthy tissues against damage induced by oxidative stress. The effects may depend on many factors discussed in the paper. These factors should be taken into consideration in order to achieve precise nutritional recommendations for patients. The evidence at the moment suggests that the supplementation or restriction of exogenous antioxidants during cancer treatment, as appropriate, could contribute to improving its efficiency

Phytochemicals Determination, and Antioxidant, Antimicrobial, Anti-Inflammatory and Anticancer Activities of Blackberry Fruits

The following supporting information can be downloaded at: https:// www.mdpi.com/article/10.3390/foods12071505/s1, Table S1: Calibration ranges, curves, regression coefficients and LOD and LOQ of the standard molecules.This study was supported by the Spanish Ministry of Science and Innovation within the project ACTIVE HONEY: Innovative formulations of main bee products using natural ingredients. 2019–2022. (EXP 00116482/INNO-20182004), funded by the Technological Center for the Industrial Development (CDTI).A comprehensive characterization of the phytochemicals present in a blackberry fruit extract by HPLC-TOF-MS has been carried out. The main compounds in the extract were ursane-type terpenoids which, along with phenolic compounds, may be responsible for the bioactivity of the extract. In vitro antioxidant capacity was assessed through Folin-Ciocalteu (31.05 +/- 4.9 mg GAE/g d.w.), FRAP (637.8 +/- 3.2 mu mol Fe2+/g d.w.), DPPH (IC50 97.1 +/- 2.4 mu g d.w./mL) and TEAC (576.6 +/- 8.3 mu mol TE/g d.w.) assays. Furthermore, the extract exerted remarkable effects on in vitro cellular antioxidant activity in HUVEC cells at a concentration of 5 mg/mL. Antimicrobial activity of the extract was also tested. Most sensible microorganisms were Gram-positive bacteria, such as E. faecalis, B. cereus and Gram-negative E. coli (MBC of 12.5 mg/mL). IC50 values against colon tumoral cells HT-29 (4.9 +/- 0.2 mg/mL), T-84 (5.9 +/- 0.3 mg/mL) and SW-837 (5.9 +/- 0.2 mg/mL) were also obtained. Furthermore, blackberry extract demonstrated anti-inflammatory activity inhibiting the secretion of pro-inflammatory IL-8 cytokines in two cellular models (HT-29 and T-84) in a concentration-dependent manner. These results support that blackberry fruits are an interesting source of bioactive compounds that may be useful in the prevention and treatment of different diseases, mainly related to oxidative stress.Spanish Ministry of Science and Innovation within the project ACTIVE HONEY: Innovative formulations of main bee products using natural ingredients. 2019-2022 - Technological Center for the Industrial Development (CDTI) EXP 00116482/INNO-2018200

Establishment of a Sonotrode Extraction Method and Evaluation of the Antioxidant, Antimicrobial and Anticancer Potential of an Optimized Vaccinium myrtillus L. Leaves Extract as Functional Ingredient

Vaccinium myrtillus L. (bilberry) leaves are an important by-product of berry production that may be used as a source of phenolic compounds which have a positive effect on human health. Therefore, an ultrasound-assisted extraction via sonotrode has been used for the first time to recover bioactive compounds from bilberry leaves. The extraction has been optimized using a Box-Behnken design. The influence of ethanol:water ratio (v/v), time of extraction (min) and amplitude (%) were evaluated considering total phenolic content (TPC) and antioxidant capacity (DPPH and FRAP assays) as dependent variables in a response surface methodology (RSM). Optimum values for the independent factors were 30:70 ethanol/water (v/v), 5 min of extraction and 55% amplitude. The empirical values of the independent variables using the optimized conditions were 217.03 +/- 4.92 mg GAE/g d.w. (TPC), 271.13 +/- 5.84 mg TE/g d.w. (DPPH) and 312.21 +/- 9.30 mg TE/g d.w. (FRAP). The validity of the experimental design was confirmed using ANOVA and the optimal extract was characterized using HPLC-MS. A total of 53 compounds were tentatively identified, of which 22 were found in bilberry leaves for the first time. Among them, chlorogenic acid was the most abundant molecule, representing 53% of the total phenolic compounds identified. Additionally, the antimicrobial and anticancer activities of the optimum extract were tested. Gram-positive bacteria demonstrated high sensitivity to bilberry leaves extract in vitro, with MBC values of 6.25 mg/mL for Listeria monocytogenes, Listeria innocua and Enterococcus faecalis, and 0.8 mg/mL for Staphylococcus aureus and Bacillus cereus. Furthermore, bilberry leaves extract exerted in vitro antiproliferative activity against HT-29, T-84 and SW-837 colon tumor cells with IC50 values of 213.2 +/- 2.5, 1140.3 +/- 5.2 and 936.5 +/- 4.6 mu g/mL, respectively. Thus, this rapid ultrasound-assisted extraction method has demonstrated to be an efficient technique to obtain bilberry leaves extract with in vitro antioxidant, antimicrobial and anticancer capacities that may be useful for the food industry as natural preservative or even for the production of functional foods or nutraceuticals

Biological Evaluation and Docking Studies of Synthetic Oleananetype Triterpenoids

Saponins are potential wide-spectrum antitumor drugs, and copper(I) catalyzed azide−alkyne 1,3-dipolar cycloaddition is a suitable approach to synthesizing saponinlike compounds by regioselective glycosylation of the C2/C3 hydroxyl and C28 carboxylic groups of triterpene aglycones maslinic acid (MA) and oleanolic acid (OA). Biological studies on the T-84 human colon carcinoma cell line support the role of the hydroxyl groups at C2/C3, the influence of the aglycone, and the bulky nature of the substituents in C28. OA bearing a α-D-mannose moiety at C28 (compound 18) focused our interest because the estimated inhibitory concentration 50 was similar to that reported for ginsenoside Rh2 against colon cancer cells and it inhibits the G1−S phase transition affecting the cell viability and apoptosis. Considering that triterpenoids from natural sources have been identified as inhibitors of nuclear factor kappa-light-chain-enhancer of activated B cell (NF-κB) signaling, docking studies were conducted to evaluate whether NF-κB may be a potential target. Results are consistent with the biological study and predict a similar binding mode of MA and compound 18 to the p52 subunit from NF- κB but not for OA. The fact that the binding site is shared by the NF-κB inhibitor 6,6-dimethyl-2-(phenylimino)-6,7- dihydrobenzo[d][1,3]oxathiol-4(5H)-one supports the result and points to NF-κB as a potential target of both MA and compound 18.This work was supported by a grant from Ramón Areces Foundation (Madrid, Spain) and by grant CTQ2014-55474- C2-1-R from the Spanish Ministerio de Economia y Competitividad (MINECO) co-financed by FEDER funds

Functionalized immunostimulating complexes with protein A via lipid vinyl sulfones to deliver cancer drugs to trastuzumab-resistant HER2-overexpressing breast cancer cells.

Around 20%-30% of breast cancers overexpress the proto-oncogene human epidermal growth receptor 2 (HER2), and they are characterized by being very invasive. Therefore, many current studies are focused on testing new therapies against tumors that overexpress this receptor. In particular, there exists major interest in new strategies to fight breast cancer resistant to trastuzumab (Tmab), a humanized antibody that binds specifically to HER2 interfering with its mitogenic signaling. Our team has previously developed immunostimulating complexes (ISCOMs) as nanocapsules functionalized with lipid vinyl sulfones, which can incorporate protein A and bind to G immunoglobulins that makes them very flexible nanocarriers. The aim of this in vitro study was to synthesize and evaluate a drug delivery system based on protein A-functionalized ISCOMs to target HER2-overexpressing cells. We describe the preparation of ISCOMs, the loading with the drugs doxorubicin and paclitaxel, the binding of ISCOMs to alkyl vinyl sulfone-protein A, the coupling of Tmab, and the evaluation in both HER2-overexpressing breast cancer cells (HCC1954) and non-overexpressing cells (MCF-7) by flow cytometry and fluorescence microscopy. Results show that the uptake is dependent on the level of overexpression of HER2, and the analysis of the cell viability reveals that targeted drugs are selective toward HCC1954, whereas MCF-7 cells remain unaffected. Protein A-functionalized ISCOMs are versatile carriers that can be coupled to antibodies that act as targeting agents to deliver drugs. When coupling to Tmab and loading with paclitaxel or doxorubicin, they become efficient vehicles for the selective delivery of the drug to Tmab-resistant HER2-overexpressing breast cancer cells. These nanoparticles may pave the way for the development of novel therapies for poor prognosis resistant patients

Antioxidant Intake and Antitumor Therapy: Toward Nutritional Recommendations for Optimal Results

The role of the induction of oxidative stress as the mechanism of action of many antitumor drugs is acquiring an increasing interest. In such cases, the antitumor therapy success may be conditioned by the antioxidants present in our own body, which can be synthesized de novo (endogenous) or incorporated through the diet and nutritional supplements (exogenous). In this paper, we have reviewed different aspects of antioxidants, including their classification, natural sources, importance in diet, consumption of nutritional supplements, and the impact of antioxidants on health. Moreover, we have focused especially on the study of the interaction between antioxidants and antitumor therapy, considering both radiotherapy and chemotherapy. In this regard, we found that the convenience of administration of antioxidants during cancer treatment still remains a very controversial issue. In general terms, antioxidants could promote or suppress the effectiveness of antitumor treatment and even protect healthy tissues against damage induced by oxidative stress. The effects may depend on many factors discussed in the paper. These factors should be taken into consideration in order to achieve precise nutritional recommendations for patients. The evidence at the moment suggests that the supplementation or restriction of exogenous antioxidants during cancer treatment, as appropriate, could contribute to improving its efficiency