Corrigendum to "Optimization of a tannase-assisted process for obtaining teas rich in theaflavins from Camellia sinensis leaves" [Food Chemistry: X 13 (2022) 100203].

[This corrects the article DOI: 10.1016/j.fochx.2022.100203.].

Effectiveness of anthocyanin-containing foods and nutraceuticals in mitigating oxidative stress, inflammation, and cardiovascular health-related biomarkers: a systematic review of animal and human interventions.

Cardiovascular diseases (CVDs) are a group of chronic health disorders prevalent worldwide that claim millions of lives yearly. Inflammation and oxidative stress are intricately associated with myocardial tissue damage, endothelial dysfunction, and increased odds of heart failure. Thus, dietary strategies aimed at decreasing the odds of CVDs are paramount. In this regard, the consumption of anthocyanins, natural pigments found in edible flowers, fruits, and vegetables, has attracted attention due to their potential to promote cardiovascular health. The main mechanisms of action linked with their protective effects on antioxidant and anti-inflammatory activities, serum lipid profile modulation, and other cardiovascular health parameters are explained and exemplified. However, little is known about the dose-dependency nature of the effects, which anthocyanin has better efficiency, and whether anthocyanin-containing foods display better in vivo efficacy than nutraceuticals (i.e., concentrated extracts containing higher levels of anthocyanins than foods). Thus, this systematic review focused on determining the effects of anthocyanin-containing foods and nutraceuticals on biomarkers associated with CVDs using animal studies and human interventions supported by in vitro mechanistic insights. Overall, the results showed that the regular consumption of anthocyanin-containing foods and nutraceuticals improved vascular function, lipid profile, and antioxidant and anti-inflammatory effects. The daily dosage, the participants' health status, and the duration of the intervention also significantly influenced the results.

Blackcurrant press cake by-product: Increased chemical bioaccessibility and reduced antioxidant protection after in vitro simulation of gastrointestinal digestion.

This study describes the bioaccessibility in terms of total phenolic content (TPC) and antioxidant capacity before and after in vitro digestion from blackcurrant press cake extracts (BPC) and the bioactivity in cell culture, human erythrocytes as well as the in silico analysis. Chemical analysis of BPC presented an increase in TPC (270%) and anthocyanins (136%) after in vitro digestion, resulting in an improvement of antioxidant activity (DPPH 112%; FRAP: 153%). This behavior may be related to the highest activity of cyanidin-3-rutinoside, as confirmed by in silico analysis. The digested BPC did not exert cytotoxicity in cells and showed less antioxidant activity against the oxidative damage induced in endothelial cells and human erythrocytes compared to the non-digested extract. The results raise a question about the reliability we should place on results obtained only from crude samples, especially those that will be used to produce foods or nutraceuticals.

Characterization of Azorean Plant Leaves for Sustainable Valorization and Future Advanced Applications in the Food, Cosmetic, and Pharmaceutical Industries.

The historical use of plants as sources of natural compounds has persisted over time. Increasing the intake of bioactive substances shows significant potential for promoting overall well-being and health. This study delves into the pigments, phenolic composition, and profile, along with antioxidant properties, of leaf extracts rich in bioactives from plants in the Azores region, contributing to sustainable primary food production. Analyses encompassed chlorophylls, carotenoids, total phenols, ortho-diphenols, and flavonoids, as well as antioxidant capacity assessment, polyphenolic profiling, and quantification. Psidium guajava L. and Smallanthus sonchifolius (Poepp.) H.Rob. exhibited elevated chlorophyll content, while Colocasia esculenta (L.) Schott displayed the highest carotenoid levels. Annona cherimola Mill., Eriobotrya japonica (Thunb.) Lindl, and Psidium guajava L. demonstrated pronounced total phenols, ortho-diphenols, and flavonoids. These findings align with heightened antioxidant capacity. HPLC-DAD (high-performance liquid chromatography with diode-array detection) characterization unveiled elevated hydroxycinnamic acids in E. japonica and Ipomea batatas (L.) Lam. compared to A. cherimola Mill., while C. esculenta exhibited increased flavone content. Among the quantified compounds, flavonols were the ones that predominantly demonstrated contribution to the antioxidant capacity of these leaves. This research highlights Azorean leaf plants' antioxidant potential, fostering natural product development for better health.

Bridging the gap in antioxidant activity of flavonoids: Correlating the oxidation of human plasma with chemical and cellular assays.

Traditional antioxidant screening relies on chemical assays to assess compounds' potential in combating oxidative processes. However, translating chemical antioxidant activity to complex biological systems poses challenges. In this study, the antioxidant potential of fruit-derived phenolic compounds, hyperoside (HP), epicatechin (EC), and phlorizin (PZ), and their combinations in a specific ratio were investigated using a simplex-centroid design of experiments. The research included in vitro antioxidant assays, plasma protection against oxidation tests, and cytotoxicity assessments in human cell lines. The results revealed the complex relationship between chemical antioxidant activity and its relevance to cellular oxidative and antioxidative processes. HP and EC exhibited significant antioxidant activity, with HP outperforming EC in multiple assessments. Cytotoxicity assay confirmed that these compounds did not induce cell death or hinder proliferation, even at higher concentrations (>100 µmol/mL). In the cell antioxidant activity (CAA) test, HP and EC exhibited higher CAA, while PZ displayed lower antioxidant activity. In conclusion, a synergistic effect emerged when HP, EC, and PZ were combined, particularly in plasma protection, suggesting protective effects and potential health benefits. This research emphasized the need for a nuanced understanding of the interplay between chemical assays and cellular behavior in comprehending the relationship between chemical-based, human plasma oxidation, and CAA.

Anthocyanin-rich extract from purple tea: Chemical stability, cellular antioxidant activity, and protection of human erythrocytes and plasma.

This study aimed to obtain an anthocyanin extract from the purple leaves of Camellia sinensis cv. Zijuan using a sustainable, non-toxic, and low-cost solid-liquid extraction, employing an aqueous citric acid solution (0.2 mol/L) as the extracting solvent, and to evaluate its chemical stability at different pH values, as well as its in vitro antioxidant properties in chemical and biological terms. The phenolic composition, in vitro antioxidant activity, and the stability of anthocyanins against pH, temperature, and light of the crude extract (CE) were evaluated, as well as the phenolic composition and bioactivity in the crude lyophilised extract (CLE). In the direct/reverse spectrophotometric titration, anthocyanins showed structural changes between pH 2 and 10, and reversibility of 80%. The antioxidant activity against the DPPH radical showed inhibition percentages of 73% (pH 4.5) to 39% (pH 10). Thermal stability was observed at 60 °C, and prolonged exposure of the extract to light caused photodegradation of the anthocyanins. Thirty-three phenolic compounds, including anthocyanins and catechins, were quantified in the CLE by UPLC-ESI-MS and HPLC, totalling 40.18 mg/g. CLE reduced cell viability (IC50 from 18.1 to 52.5 µg GAE/mL), exerted antiproliferative (GI50 from 0.0006 to 17.0 µg GAE/mL) and cytotoxic (LC50 from 33.2 to 89.9 µg GAE/mL) effects against A549 (human lung adenocarcinoma epithelial cells), HepG2 (hepatocellular carcinoma), HCT8 (ileocecal colorectal adenocarcinoma), and Eahy926 (somatic cell hybrid cells); and showed protection against oxidation of human plasma (635 ± 30 mg AAE/g). The results showed the diversity of compounds in the extracts and their potential for technological applications; however, temperature, pH, and light must be considered to avoid diminishing their bioactivity.

The effects of tea plant age on the color, taste, and chemical characteristics of Yunnan Congou black tea by multi-spectral omics insight.

The present study comprehensively used integrated multi-spectral omics combined with sensory evaluation analysis to investigate the quality of three types of Yunnan Congou black teas from different tree ages (decades, DB; hundreds, HB; a thousand years, TB). TB infusion presented the highest scores of sweetness and umami, higher brightness, and yellow hue. Eighty-four marker metabolites were identified, including Amadori rearrangement products, catechin oxidation products, flavonoid glycosides, and organic acids, which are simultaneously related to tea infusions' color and taste. Moreover, the content of some characteristic flavonoid glycosides and organic acids was determined. Our finding implied trans-4-O-p-coumaroylquinic acid and quercetin 3-O-rutinoside contributed to bitterness and astringency, while dehydro theanine-glucose Amadori product and xylopyranosyl-glucopyranose resulted in umami and sweetness. These results provided quantitative and qualitative information for deciphering differences among black teas with different tea plant ages, conducing to the further utilization of ancient tea plants in Southwest China.

High-throughput synchronous erythrocyte cellular antioxidant activity and protection screening of phenolic-rich extracts: Protocol validation and applications.

Oxidative/nitrosative damage takes part in chronic disease development, which generates an urgent need for intervention and better therapies to manage them. The scientific community has demanded easy-to-run, cheap, and reliable methods for cellular antioxidant activity assays. This work standardised and validated an erythrocyte cellular antioxidant activity and membrane protection/injury (HERYCA-P) protocol to study food-derive extracts. The method measures intracellular reactive oxygen species (ROS) generation, lipoperoxidation, and haemolysis induced by 2,2'-azobis(2-amidinopropane) dihydrochloride. Quercetin decreased ROS generation by 50.4% and haemolysis by 2.2%, while ascorbic acid inhibited lipid peroxidation by 40.1%. Total phenolic contents of teas were correlated with decreased ROS generation (r = -0.924), lipoperoxidation (r = -0.951), and haemolysis (r = -0.869). The erythrocyte ROS generation and lipoperoxidation were also associated with CUPRAC (r = -0.925; r = -0.951) and hydroxyl radical scavenging activity (r = -0.936; r = -0.949). The precision rates of antioxidant standards and tea samples were below 15%. HERYCA-P is feasible as a complementary antioxidant assay for food matrices.

Ameliorative effects of aqueous extract from rosemary on oxidative stress and inflammation pathways caused by a high-fat diet in C57BL/6 mice.

Rosemary is an herb exhibits biological properties, attenuates inflammation, oxidative stress, and improves lipid profile. Here, we evaluated the effects of rosemary aqueous extract (RE) on mice fed with a high-fat diet (HFD). Male C57BL/6 mice were administered a control diet or HFD for 10 weeks. The treated groups received RE in the diet at different concentrations: 25, 250, and 500 mg/100 g. After 10 weeks, serum concentrations of glucose, lipid, insulin, leptin, adiponectin, and cytokines were evaluated and the oxygen radical absorbance capacity was determined. Histological analysis was performed to determine the concentrations of triacylglycerides (TG), total cholesterol, cytokines, and antioxidant enzymes as well as the expression of genes involved in lipid metabolism, oxidative stress, and inflammation. The dietary RE ameliorated HFD-induced weight gain, adipose tissue weight, glucose intolerance, and insulin, leptin, and free fatty acid levels. Reduction in hepatic TG deposition was observed. The levels of inflammatory cytokines decreased, and the expression of genes involved in lipid metabolism increased. RE mitigated oxidative stress and reduced the production of reactive oxygen species in HepG2 and 3T3-L1 cells. Therefore, RE is a potential therapeutic agent for the prevention of inflammation and oxidative stress outcomes associated with obesity.

Comprehensive applications of metabolomics on tea science and technology: Opportunities, hurdles, and perspectives.

With the development of metabolomics analytical techniques, relevant studies have increased in recent decades. The procedures of metabolomics analysis mainly include sample preparation, data acquisition and pre-processing, multivariate statistical analysis, as well as maker compounds' identification. In the present review, we summarized the published articles of tea metabolomics regarding different analytical tools, such as mass spectrometry, nuclear magnetic resonance, ultraviolet-visible spectrometry, and Fourier transform infrared spectrometry. The metabolite variation of fresh tea leaves with different treatments, such as biotic/abiotic stress, horticultural measures, and nutritional supplies was reviewed. Furthermore, the changes of chemical composition of processed tea samples under different processing technologies were also profiled. Since the identification of critical or marker metabolites is a complicated task, we also discussed the procedure of metabolite identification to clarify the importance of omics data analysis. The present review provides a workflow diagram for tea metabolomics research and also the perspectives of related studies in the future.

Next-generation analytical platforms for antioxidant capacity assessment: The urge for realistic and physiologically relevant methods.

Bioactive compounds, such as carotenoids, alkaloids, and phenolics, are well known because of their alleged health benefits when consumed regularly in a balanced healthy diet. Some well-documented bioactivities are antioxidant, antihypertensive, antihyperglycemic, antilipidemic, anti-obesity, anti-inflammatory, and antimicrobial capacities. Trying to associate the chemical composition of distinct sources and their bioactivity using in vitro methods, several assays have been developed, implemented, and optimised to recapitulate human physiological conditions. However, in most cases, pitfalls are apparent, and no single test tube-based assay can predict in vivo responses. The need for a more physiologically relevant cell-based method to evaluate the antioxidant capacity of putative antioxidants is apparent. Therefore, in this Review, the current state-of-the-art in food science and nutrition is aligned with cell biology/bioengineering approaches to propose combining in vitro digestion and absorption to obtain a bioavailable fraction containing antioxidants. Overall, human plasma, 2-dimensional human cell lines, such as erythrocytes, lymphocytes, hepatocytes, enterocytes and, ultimately, 3-dimensional spheroids (organoids) could be used as biologically relevant models to assess the antioxidant activity of compounds, foods, and nutraceuticals. This versatile approach is deemed suitable, accurate, reproducible, and physiologically relevant to evaluate the protective effects of antioxidants against ROS-mediated oxidation in vitro.

Conceptual functional-by-design optimisation of the antioxidant capacity of trans-resveratrol, quercetin, and chlorogenic acid: Application in a functional tea.

Designing functional foods as delivery systemsmay become a tailored strategy to decrease the risk of noncommunicable diseases. Therefore, this work aims to optimise a combination of t-resveratrol (RES), chlorogenic acid (CHA), and quercetin (QUE) based on antioxidant assays and develop a functional tea formulation enriched with the optimal polyphenol combination (OPM). Experimental results showed that the antioxidant capacity of these compounds is assay- and compound-dependent. A mixture containing 73% RES and 27% QUE maximised the hydroxyl radical scavenging activity and FRAP. OPM upregulated the gene expressions of heme oxygenase-1, superoxide dismutase, and catalase and decreased the reactive oxygen species generation in L929 fibroblasts. Adding OPM (100 mg/L)to a chamomile tea increased FRAP:39%, DPPH:59%; total phenolic content: 57%, iron reducing capacity: 41%, human plasma protection against oxidation: 67%. However, pasteurisation (63 °C/30 min) decreased onlythe DPPH. Combining technology, engineering, and cell biology was effective for functional tea design.

Optimization of the Green Chemistry-like Extraction of Phenolic Compounds from Grape (Vitis labrusca L.) and Blackberry (Rubus fruticosus L.) Seeds with Concomitant Biological and Antioxidant Activity Assessments.

The objective of this work was to determine the phenolic composition, chemical and cellular antioxidant activity, cytotoxicity in human cells, and peroxidative inhibition of the defatted fraction of grape (Vitis labrusca) and blackberry (Rubus fruticosus) seeds. Soxhlet extraction (Sox) was used to extract the fat and obtain the degreased material. A statistical optimization study was developed to maximize the extraction of bioactive compounds and antioxidant activity from defatted grape and blackberry seeds. Simultaneous optimization was applied with a combination of 35.9 min of extraction and a solid-to-solvent ratio of 1 g of defatted grape seed to 61.28 mL of an extracting solvent (60% ethanol) and 62.1 min of extraction and a solid-to-solvent ratio of 1 g of defatted blackberry seed to 64.1 mL of an extracting solvent (60% ethanol). In the cell viability assay, HepG2 cancer cells seemed more sensitive to grape and blackberry extracts, while Ea.hy926 hybrid cells showed more resistance to their effects. In general, the extracts presented low/no cytotoxicity, exhibited a protective effect against H2O2-induced ROS production, and demonstrated antioxidant activity and a protective effect on the erythrocytes when subjected to hypotonic and isotonic conditions not presenting hemolytic behavior (5.0 to 10.0 µg GAE/mL). Thus, the results provided a broad assessment of the bioactivity of the extracts obtained using a simple and low-cost process developed by employing non-toxic solvents and with the potential to be used in technological applications.

From waste to the gut: Can blackcurrant press cake be a new functional ingredient? Insights on in vivo microbiota modulation, oxidative stress, and inflammation.

Blackcurrant press cake (BPC) is a source of anthocyanins, and this study evaluated the bioactivity and gut microbiota modulation of blackcurrant diets with or without 1,2 dimethylhydrazine (DMH)-induced colon carcinogenesis in rats. In colon cancer-induced rats (CRC), BPC at the highest dosages increased pro-inflammatory parameters and the expression of anti-apoptotic cytokines, accentuating colon cancer initiation by aberrant crypts and morphological changes. Fecal microbiome analysis showed that BPC altered the composition and function of the gut microbiome. This evidence suggests that high doses of BPC act as a pro-oxidant, accentuating the inflammatory environment and CRC progression.

(-)-Epigallocatechin-3-Gallate Attenuates the Adverse Reactions Triggered by Selenium Nanoparticles without Compromising Their Suppressing Effect on Peritoneal Carcinomatosis in Mice Bearing Hepatocarcinoma 22 Cells.

Increasing evidence shows that selenium and polyphenols are two types of the most reported compounds in tumor chemoprevention due to their remarkable antitumor activity and high safety profile. The cross-talk between polyphenols and selenium is a hot research topic, and the combination of polyphenols and selenium is a valuable strategy for fighting cancer. The current work investigated the combination anti-peritoneal carcinomatosis (PC) effect of selenium nanoparticles (SeNPs) and green tea (Camellia sinensis) polyphenol (-)-epigallocatechin-3-gallate (EGCG) in mice bearing murine hepatocarcinoma 22 (H22) cells. Results showed that SeNPs alone significantly inhibited cancer cell proliferation and extended the survival time of mice bearing H22 cells. Still, the potential therapeutic efficacy is accompanied by an approximately eighty percent diarrhea rate. When EGCG was combined with SeNPs, EGCG did not affect the tumor proliferation inhibition effect but eliminated diarrhea triggered by SeNPs. In addition, both the intracellular selectively accumulated EGCG without killing effect on cancer cells and the enhanced antioxidant enzyme levels in ascites after EGCG was delivered alone by intraperitoneal injection indicated that H22 cells were insensitive to EGCG. Moreover, EGCG could prevent SeNP-caused systemic oxidative damage by enhancing serum superoxide dismutase, glutathione, and glutathione peroxidase levels in healthy mice. Overall, we found that H22 cells are insensitive to EGCG, but combining EGCG with SeNPs could protect against SeNP-triggered diarrhea without compromising the suppressing efficacy of SeNPs on PC in mice bearing H22 cells and attenuate SeNP-caused systemic toxicity in healthy mice. These results suggest that EGCG could be employed as a promising candidate for preventing the adverse reactions of chemotherapy including chemotherapy-induced diarrhea and systemic toxicity in cancer individuals.

Antioxidant, antihyperglycemic, and antihyperlipidemic properties of Chimonanthus salicifolius S. Y. Hu leaves in experimental animals: modulation of thioredoxin and glutathione systems, renal water reabsorption, and gut microbiota.

Introduction: Excessive calorie intake and physical inactivity have dramatically increased nutrient overload-associated disease, becoming a global public health issue. Chimonanthus salicifolius S. Y. Hu (CHI) is a homology plant of food and medicine in China and shows several health benefits. Methods: This work investigated the antioxidant activity, the alleviating effects, and the mechanism of action on diabetes and hyperlipidemia of CHI leaves. Results and discussion: Results showed that CHI leaves infusion displayed in vitro antioxidant activity measured by ABTS and ferric reducing antioxidant power methods. In wild-type Kunming mice, CHI leaves infusion consumption activated the hepatic antioxidant enzymes, including glutathione reductase, glutathione S-transferase, glutathione peroxidase and thioredoxin reductase as well as thioredoxin reductase 1. In alloxan-induced type 1 diabetic mice, CHI leaves infusion ameliorated diabetic symptoms, including polyuria, polydipsia, polyphagia and hyperglycemia, in a dose-dependent and time-course manners. The mechanism involved CHI leaves up-regulating renal water reabsorption associated protein - urine transporter A1-and promoting the trafficking of urine transporter A1 and aquaporin 2 to the apical plasma membrane. Despite this, in high-fat diet-induced hyperlipidemic golden hamsters, CHI leaves powder did not significantly effect on hyperlipidemia and body weight gain. This might be attributed to CHI leaves powder increasing the calorie intake. Interestingly, we found that CHI leaves extract containing a lower dose of total flavonoid than CHI leaves powder pronouncedly reduced the levels of total cholesterol, triglyceride, and low-density lipoprotein cholesterol in serum in golden hamsters fed a high-fat diet. Furthermore, CHI leaves extract elevated the diversity of gut microbiota and the abundance of Bifidobacterium and Ruminococcaceae_UCG-014. It also decreased the abundance of Lactobacillus at the genus level in golden hamsters fed a high-fat diet. Overall, CHI leaves benefit oxidative stress prevention and metabolic syndrome amelioration in vivo.

Effects of natural spring water on the sensory attributes and physicochemical properties of tea infusions.

The sensory quality of tea is influenced by water quality, with natural spring water (NSW) gaining much attention for its natural and healthy qualities. The effects of NSW on the sensory attributes, physicochemical composition, and antioxidant capacity of Chinese tea were investigated. Tea brewed with pure water was the most resistant to oxidation and darkening. NSW with low total dissolved solids (TDS) was most suitable for brewing unfermented or mildly fermented teas, improving their sensory quality. The simulated green tea infusion system was used to investigate further the dramatic darkening of tea infusions in NSW. Exposure of infusions to air promoted the degradation, epimerization, and oxidative polymerization of catechins, and further formed theabrownins which darkened the tea infusions. These findings enabled tea consumers to choose the most suitable NSW for brewing Chinese teas and illustrated the darkening mechanism of tea infusion in high pH/TDS water.

Melatonin improved glucose homeostasis is associated with the reprogrammed gut microbiota and reduced fecal levels of short-chain fatty acids in db/db mice.

Accumulated evidence shows that melatonin possesses the potential to improve lipid metabolism by modifying gut microbiota and glucose metabolism via regulating the melatonin receptor signaling pathway. However, the contribution of melatonin consumption on glucose homeostasis by affecting gut microbiota has not been investigated in diabetes. In the current work, we investigated the effect of melatonin administration on gut microbiota and glucose homeostasis in db/db mice, a type 2 diabetes model with leptin receptor deficiency. Administration of melatonin through drinking water (at 0.25% and 0.50%) for 12 weeks decreased diabetic polydipsia and polyuria, increased insulin sensitivity and impeded glycemia. The accumulated fecal levels of total short-chain fatty acids (SCFAs) and acetic acid are positively correlated with diabetes-related parameters-homeostasis model assessment of insulin resistance (HOMA-IR) index and fasting blood glucose (FBG) level. The reprogramming of gut microbiota structure and abundance and the reduction of fecal levels of SCFAs, including acetic acid, butyric acid, isovaleric acid, caproic acid, and isobutyric acid, by melatonin may be beneficial for enhancing insulin sensitivity and lowering FBG, which were verified by the results of correlation analysis between acetic acid or total SCFAs and HOMA-IR and FBG. In addition, the melatonin downregulated hepatic genes, including fructose-1,6-bisphosphatase 1, forkhead box O1 alpha, thioredoxin-interacting protein, phosphoenolpyruvate carboxy-kinase (PEPCK), PEPCK1 and a glucose-6-phosphatase catalytic subunit, that responsible for gluconeogenesis support the result that melatonin improved glucose metabolism. Overall, results showed that the melatonin supplementation reduced fecal SCFAs level via reprogramming of gut microbiota, and the reduction of fecal SCFAs level is associated with improved glucose homeostasis in db/db mice.

Sustainable and effective approach to recover antioxidant compounds from purple tea (Camellia sinensis var. assamica cv. Zijuan) leaves.

Camellia sinensis var. assamica cv. Zijuan (purple tea) is known for its content of anthocyanins, flavan-3-ols, and bioactivities. This study aimed to verify the influence of solvent polarity, in a solid-liquid extraction, on the content of phenolic compounds and chlorophylls, instrumental color, and antioxidant activity. Different proportions of water and ethanol (0:100, 25:75, 50:50, 75:25, and 100:0 v/v) were used for extraction. The results showed that the hydroalcoholic extract (75 % ethanol + 25 % water) had the highest contents of total flavonoids, total anthocyanins, chlorophyll A, and total carotenoids, as well as presenting the highest color intensity, proportion of yellow pigments, and antioxidant activity (total reducing capacity and scavenging of the DPPH free radical). Twenty-two compounds were identified, with chlorogenic acid, hesperidin, (-)-epicatechin, (-)-epigallocatechin gallate, and isoquercitrin being the main phenolics. This phenolic-rich extract inhibited lipoperoxidation induced in egg yolk homogenate (IC50 = 455 mg/L), showed no hemolytic behavior when human erythrocytes were subjected to osmotic stress, and exerted in vitro cytotoxic effects against cancer and hybrid cells. The extract obtained with the mixture of non-toxic solvents presented critical bioactivities, as well as a comprehensive identification of phenolic compounds in the cultivar, and has potential to be used in technological applications.

Comparison of Antioxidant Capacity and Network Pharmacology of Phloretin and Phlorizin against Neuroinflammation in Traumatic Brain Injury.

Neuroinflammation is a hallmark of traumatic brain injury (TBI)'s acute and chronic phases. Despite the medical and scientific advances in recent years, there is still no effective treatment that mitigates the oxidative and inflammatory damage that affects neurons and glial cells. Therefore, searching for compounds with a broader spectrum of action that can regulate various inflammatory signaling pathways is of clinical interest. In this study, we determined not only the in vitro antioxidant capacity of apple pomace phenolics, namely, phlorizin and its metabolite, phloretin, but we also hypothesize that the use of these bioactive molecules may have potential use in TBI. We explored the antioxidant effects of both compounds in vitro (DPPH, iron-reducing capacity (IRC), and Folin-Ciocalteu reducing capacity (FCRC)), and using network pharmacology, we investigated the proteins involved in their protective effects in TBI. Our results showed that the antioxidant properties of phloretin were superior to those of phlorizin in the DPPH (12.95 vs. 3.52 mg ascorbic acid equivalent (AAE)/L), FCRC (86.73 vs. 73.69 mg gallic acid equivalent (GAE)/L), and iron-reducing capacity (1.15 vs. 0.88 mg GAE/L) assays. Next, we examined the molecular signature of both compounds and found 11 proteins in common to be regulated by them and involved in TBI. Meta-analysis and GO functional enrichment demonstrated their implication in matrix metalloproteinases, p53 signaling, and cell secretion/transport. Using MCODE and Pearson's correlation analysis, a subcluster was generated. We identified ESR1 (estrogen receptor alpha) as a critical cellular hub being regulated by both compounds and with potential therapeutic use in TBI. In conclusion, our study suggests that because of their vast antioxidant effects, probably acting on estrogen receptors, phloretin and phlorizin may be repurposed for TBI treatment due to their ease of obtaining and low cost.