Antioxidant evaluation study of black rice anthocyanins nano-composite as prospective against infertility induced by AlCl3 in rats.

Anthocyanins are known as an antioxidant, and their water-soluble purple-colored pigments are very nutritive. Therefore, the present study investigated the antioxidant activity of black rice anthocyanins nano-composite against infertility induced by AlCl3 in rats. Anthocyanin silver nanoparticles (An-AgNPs) were prepared by reducing black rice anthocyanin with the metallic ions. Antioxidant activity (DPPH %) of anthocyanin was determined. Also, the morphology of (An-AgNPs) was examined by scanning electron microscopy (SEM). Albino rats were divided into five groups (negative control (NC): fed on basel diet, positive control (PC): treated with AlCl3 (34 mg/kg bw) for seventy days, and three other groups treated with AlCl3 (34 mg/kg bw) + An-AgNPs at 10, 15, and 20 mg/kg, b.w/ day, respectively for seventy days. Serum testosterone, LH, FSH, and estradiol were measured. Additionally, Sperm motility, Sperm count (Testicular and Epididymal), fructose in semen, and semen quality were determined. The values of the anthocyanin component and DPPH radical scavenging activity obtained were 3603.82±6.11 mg CCE/g and 84.62±1.98, respectively. An-AgNPs shows tend to agglomerate, particles are uniform in size and shape, and the diameter of the particles ranges between 70nm to 130nm. LH, estradiol and testosterone levels increased significantly in rats treated with An-AgNPs 10, 15, 20 mg/kg b.w+ AlCl3 (34 mg/kg bw) also exhibited significantly higher sperm motility, sperm count, and daily sperm production, and decreased sperm transit rate than G2. In comparison to G2, animals treated with AlCl3 (34 mg/kg bw) + An-AgNPs 10, 15, 20 mg/kg b.w(G3 to G5) had significantly higher semen and semen quality (P 0.05). We can conclude that the An-AgNPs showed a strong effect against infertility induced by AlCl3; this represents a suitable natural supply of biological substances for medicine and anthocyanins could be considered the ideal ingredients against oxidative stress-induced infertility.

Health-Promoting Effects, Phytochemical Constituents and Molecular Genetic Profile of the Purple Carrot 'Purple Sun' (Daucus carota L.).

The purple carrot cultivar 'Purple Sun' (Daucus carota L.) is characterized by a relevant content of phenolic compounds and anthocyanins, which may play an important role in reducing the risk of chronic diseases and in the treatment of metabolic syndrome. In the present study, the genetic diversity, phytochemical composition, and bioactivities of this outstanding variety were studied for the first time. Genetic analysis by molecular markers estimated the level of genetic purity of this carrot cultivar, whose purple-pigmented roots were used for obtaining the purple carrot ethanol extract (PCE). With the aim to identify specialized metabolites potentially responsible for the bioactivities, the analysis of the metabolite profile of PCE by LC-ESI/LTQ Orbitrap/MS/MS was carried out. LC-ESI/HRMS analysis allowed the assignment of twenty-eight compounds, putatively identified as isocitric acid (1), phenolic acid derivatives (2 and 6), hydroxycinnamic acid derivatives (9, 10, 12-14, 16, 17, 19, 22, and 23), anthocyanins (3-5, 7, 8, 11, and 18), flavanonols (15 and 21), flavonols (20 and 24), oxylipins (25, 26, and 28), and the sesquiterpene 11-acetyloxytorilolone (27); compound 26, corresponding to the primary metabolite trihydroxyoctanoic acid (TriHOME), was the most abundant compound in the LC-ESI/HRMS analysis of the PCE, and hydroxycinnamic acid derivatives followed by anthocyanins were the two most represented groups. The antioxidant activity of PCE, expressed in terms of reactive oxygen species (ROS) level and antioxidant enzymes activity, and its pro-metabolic effect were evaluated. Moreover, the antibacterial activity on Gram (-) and (+) bacterial strains was investigated. An increase in the activity of antioxidant enzymes (SOD, CAT, and GPx), reaching a maximum at 0.5 mg/mL of PCE with a plateau at higher PCE concentrations (1.25, 2.5, and 5.0 mg/mL), was observed. PCE induced an initial decrease in ROS levels at 0.1 and 0.25 mg/mL concentrations, reaching the ROS levels of control at 0.5 mg/mL of PCE with a plateau at higher PCE concentrations (1.25, 2.5, and 5.0 mg/mL). Moreover, significant antioxidant and pro-metabolic effects of PCE on myoblasts were shown by a reduction in ROS content and an increase in ATP production linked to the promotion of mitochondrial respiration. Finally, the bacteriostatic activity of PCE was shown on the different bacterial strains tested, while the bactericidal action of PCE was exclusively observed against the Gram (+) Staphylococcus aureus. The bioactivities of PCE were also investigated from cellular and molecular points of view in colon and hematological cancer cells. The results showed that PCE induces proliferative arrest and modulates the expression of important cell-cycle regulators. For all these health-promoting effects, also supported by initial computational predictions, 'Purple Sun' is a promising functional food and an optimal candidate for pharmaceutical and/or nutraceutical preparations.

Persimmon Fiber-Rich Ingredients Promote Anti-Inflammatory Responses and the Growth of Beneficial Anti-Inflammatory Firmicutes Species from the Human Colon.

Persimmon fruit processing-derived waste and by-products, such as peels and pomace, are important sources of dietary fiber and phytochemicals. Revalorizing these by-products could help promote circular nutrition and agricultural sustainability while tackling dietary deficiencies and chronic diseases. In this study, fiber-rich fractions were prepared from the by-products of Sharoni and Brilliant Red persimmon varieties. These fractions were quantified for their phenolic composition and assessed for their ability to promote the growth of beneficial human colonic Firmicutes species and for their in vitro anti-inflammatory potential. Gallic and protocatechuic acids, delphinidin, and cyanidin were the main phenolics identified. Faecalibacterium prausnitzii strains showed significantly higher growth rates in the presence of the Brilliant Red fraction, generating more than double butyrate as a proportion of the total short-chain fatty acids (39.5% vs. 17.8%) when compared to glucose. The fiber-rich fractions significantly decreased the inflammatory effect of interleukin-1ß in Caco-2 cells, and the fermented fractions (both from Sharoni and Brilliant Red) significantly decreased the inflammatory effect of interleukin-6 and tumor necrosis factor-α in the RAW 264.7 cells. Therefore, fiber-rich fractions from persimmon by-products could be part of nutritional therapies as they reduce systemic inflammation, promote the growth of beneficial human gut bacteria, and increase the production of beneficial microbial metabolites such as butyrate.

Anthocyanidin-Loaded Superabsorbent Self-Pumping Dressings for Macrophage Immunomodulation and Diabetic Wound Healing.

Management of diabetic chronic wound exudate is a serious challenge in healthcare worldwide since it is related to the speed of diabetic wound healing. However, current foam dressings not only absorb fluid to generate swelling and compress the wound to hinder wound healing but also are very thick and less comfortable to use. Herein, a superabsorbent self-pumping ultrathin dressing is reported to accelerate diabetic wound healing by achieving superior exudate absorption and management in an ultrathin state. The self-pumping dressing is composed of a drainage layer loaded with anthocyanidin and a thermoplastic polyurethane absorbent layer embedded with superabsorbent particles. The dressing realizes the self-pumping process of unidirectional exudate draining to the absorption layer through the drainage layer without significant dressing swelling to compress the diabetic wound. The dressing is experimentally proven to unidirectionally drain excessive exudate with inflammatory factors and modulate the conversion of macrophages from M1 to M2 in diabetic wounds, thereby promoting the healing of diabetic skin ulcers faster than commercial foam dressings. Therefore, the dressing provides a new idea and novel method for accelerating diabetic skin ulcer healing.

Transformation of mulberry polyphenols by Lactobacillus plantarum SC-5: Increasing phenolic acids and enhancement of anti-aging effect.

Fermentation can transform bioactive compounds in food and improve their biological activity. This study aims to explore the transformation of polyphenols in mulberry juice and the improvement of its anti-aging effect. The results demonstrated that Lactobacillus plantarum SC-5 transformed anthocyanin in mulberry juice into more phenolic acids, especially improved 2-hydroxy-3-(4-hydroxyphenyl) propanoic acid from 4.16 ± 0.06 to 10.07 ± 0.03. In the D-gal-induced mouse model, fermented mulberry juice significantly raised the abundance of Bifidobacteriaceae (303.7 %) and Lactobacillaceae (237.2 %) and Short-chain fatty acids (SCFAs) in intestine, further reducing the level of oxidative stress (12.3 %). Meanwhile, the expression of Sirtuin 1 (SIRT1) and Brain-derived neurotrophic factor (BDNF) increased, which protected the integrity of hippocampal tissue. Morris water maze results approved that fermented mulberry juice improved cognitive ability in aging mice (30.3 %). This study provides theoretical support for the view that fermentation is an effective means of developing functional foods.

Transcriptomic and multi-cytokines profile analysis revealed new insights into the integrating mechanisms of cyanidin-3-O-glucoside on male reproductive damage amelioration.

Ulcerative colitis is a public health issue with a rising worldwide incidence. It has been found that current medications for treating UC may cause varying degrees of damage to male fertility. Our previous study demonstrated that cyanidin-3-O-glucoside (C3G) treatment could effectively restore reproductive damage in a mouse model of DSS induced colitis. However, the underlying mechanism of C3G alleviates UC induced male reproductive disorders remain scarce. The aim of this study is to discover the molecular mechanisms of C3G on the amelioration of UC stimulated reproductive disorders. The targeted genes toward UC-induced reproductive injury upon C3G treatments were explored by transcriptomic analysis. Hematological analysis, histopathological examination, and real time transcription-polymerase chain reaction (RT-PCR) analysis were applied for conjoined identification. Results showed that C3G may effectively target for reducing pro-inflammatory cytokine IL-6 in testis through cytokine-cytokine receptor interaction pathway. Transcriptome sequencing found that a series of genetic pathways involved in the protective effects of C3G on male reproduction were identified by gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Further results presented that C3G could effectively restore mRNA expression levels of Ly6a and Col1a1, closely linked with UC induced male reproductive damage pathways. Sufficient results implied that Ly6a and Col1a1 may be treated as the promising therapeutic targets for the mechanism of C3G in treating UC induced reproductive impairment. C3G administration might be an effective dietary supplementation strategy for male reproduction improvement.

Preparation of thermochromic ink from anthocyanidin-encapsulated alginate nanoparticles for anticounterfeiting applications.

In order to make commercial products less vulnerable to counterfeiting, thermochromic inks have proven to be a viable authentication strategy. Herein, we developed a thermochromic ink for authentication by combining an anthocyanidin (ACYD) extract with alginate (ALG). To increase the anthocyanidin/alginate ink stability, a mordant (ferrous sulfate) was employed to tie up the anthocyanidin biomolecules with alginate. ACYD was extracted from red-cabbage and then immobilized into alginate to serve as an environmentally friendly spectroscopic probe. Thermochromic composite inks (ACYD@ALG) were made by adjusting the content of anthocyanidin. A homogenous blue film (608 nm) was printed on a paper surface and investigated by the CIE Lab coordinate system. The blue color transformed into reddish (477 nm) when heated from 35°C to 65°C. Nanoparticles (NPs) of anthocyanidin/mordant (ACYD/M) were examined for their size and morphology to indicate diameters of 80-90 nm, whereas the ACYD/M-encapsulated alginate nanoparticles showed diameters of 120-150 nm. Multiple analytical techniques were utilized to examine the printed papers. The mechanical and rheological performance of both stamped sheets and ink fluid were explored. The cytotoxicity and antimicrobial efficacy of ink (ACYD@ALG) were investigated.

Effects of Anthocyanins on Cognition and Vascular Function: A Systematic Review.

SCOPE: Good vascular function is crucial for cerebral blood flow and cognitive performance. Diets high in anthocyanins have been shown to improve vascular function and are associated with improvements in cognition. This systematic review investigates randomized controlled trials examining the impact of anthocyanin intake on both cognition and vascular function. METHODS AND RESULTS: Of the 1486 studies identified through searching Ovid Medline and AMED, PsychInfo, Web of Science, and Scopus, 20 studies are selected which measured cognitive and vascular function. Overall, positive effects on verbal and working memory are observed, which are supported by studies using functional magnetic resonance imaging to demonstrate increased blood flow in brain regions related to these cognitive domains. However, effects of anthocyanins on blood pressure and markers of endothelial function are inconsistent. CONCLUSION: This systematic review provides evidence for a positive effect of anthocyanins on cognition and insight into the relevance of endothelial function. Anthocyanins are widely available and can be easily consumed in a range of different fruits, vegetables, and other products. Further studies should establish the optimal daily intake of anthocyanins for cardiovascular and cognitive health.

Pigmented corn as a gluten-free source of polyphenols with anti-inflammatory and antioxidant properties in CaCo-2 cells.

A high number of varieties from corn (Zea mays L.) have been consumed for long time all over the world, however pigmented varieties are recently gaining renewed attention due to their beneficial effects and polyphenolic content. The natural lack of gluten makes corn suitable for consumption by celiac population, who need to control their inflammatory state through an appropriate gluten-free diet. The biological effects of polyphenols from pigmented corn are poorly investigated in the context of celiac disease. In this work, we analyzed through HPLC-DAD the phenolic composition of two Italian purple and red varieties ("Scagliolo Rosso" and "Rostrato di Rovetta", respectively) comparing their effects in human intestinal epithelial cells (CaCo-2 cells). The possible impact of gastro-intestinal digestion following oral consumption was assessed as well. The phenolic profile showed the presence of phenolic acids in both varieties, while anthocyanins were identified in Scagliolo Rosso only. After simulated digestion, the level of polyphenols did not significantly change and paralleled with an increased scavenging activity. In CaCo-2 cells, stimulated by a proinflammatory cocktail containing gliadin-derived peptides (IL-1ß, IFN-γ, digested gliadin), pigmented corn extracts inhibited the release of CXCL-10 and sICAM-1, with mechanisms partially ascribed to NF-κB impairment. At the same concentration (200 µg/mL), ROS production and catalase depletion were reverted through Nrf-2-independent mechanisms. Our data suggest that polyphenols from pigmented corns might help in controlling the inflammatory and oxidative state of people with celiac disease at intestinal level, at concentrations potentially achievable through a gluten-free diet.

[Anthocyanins as an element of nutritional support for athletes: effects and molecular mechanisms of action].

Antioxidants are among the common components of sports nutrition designed to counteract oxidative stress that develops during intense physical activity. One of the promising antioxidants are anthocyanins which belong to polyphenolic compounds of plant origin (class of flavonoids). The purpose of the research was to analyze the results of prospective controlled studies on the effect of anthocyanins on physical performance, and to consider the possible molecular mechanisms of their action. Material and methods. Sources were searched in PubMed, Google Scholar, and CyberLeninka databases of peer-reviewed scientific literature without restrictions on the year of publication using the following keywords: anthocyanins, physical performance, recovery, sport and exercise nutrition, oxidative stress, inflammation. Results. The main data set on the effects of anthocyanins in athletes was obtained using extracts of blackcurrant and Montmorency tart cherry. Volunteers received anthocyanins at a dose of 86-547 mg per day for 1 to 10 days with subsequent evaluation of their performance in cycling, running and fitness activities. The possibility of favorable effect of anthocyanins on physical performance and acceleration of its recovery after exertion has been shown. The source, dose and duration of intake did not significantly influence the established effects of anthocyanins. Acting as exogenous regulators of metabolism, anthocyanins can activate several mechanisms of performance enhancement, including influence on antioxidant and immune status and apoptosis intensity. Anthocyanins prevent the formation of reactive oxygen species, neutralize electrophilic compounds by direct interaction or through activation of Nrf2 factor, which regulates the transcription of antioxidant enzyme genes. The basis of the anti-inflammatory action of anthocyanins is their ability to inhibit MARK and NF-κB mediated signal transduction. Inclusion of bilberry and blackcurrant extract in the diet prevented the intensification of myocyte apoptosis and suppression of cellular immunity induced by exhausting exercise. An additional mechanism of anthocyanin action on physical performance may be an increase in blood supply of organs and tissues due to vascular dilation caused by activation of endothelial nitric oxide synthase. Conclusion. The intake of plant extracts with a high anthocyanin content can increase physical performance and improve recovery after physical exertion, which may be due to the antioxidant and anti-inflammatory effects of anthocyanins, their ability to regulate apoptosis processes and improve blood supply to organs and tissues.

Protective effect and mechanism of Lycium ruthenicum Murray anthocyanins against retinal damage induced by blue light exposure.

Lycium ruthenicum Murray (LR) is a medicine and edible plant in Northwest China, and L. ruthenicum Murray anthocyanins (LRA) are green antioxidants with various pharmacological activities, such as antioxidant and anti-inflammatory activities. However, the protective effect and mechanism of LRA against retinal damage induced by blue light exposure are poorly understood. This study explored the protective effects and potential mechanisms of LRA on retinal damage induced by blue light exposure in vitro and in vivo. The results showed that LRA could ameliorate oxidative stress injury by activating the antioxidant stress nuclear factor-related factor 2 pathway, promoting the expression of phase II detoxification enzymes (HO-1, NQO1) and endogenous antioxidant enzymes (catalase, superoxide dismutase, glutathione peroxidase), and reducing reactive oxygen species and malondialdehyde levels. Additionally, LRA could inhibit inflammatory response by decreasing the expression of blue light exposure-induced nuclear factor-κB (NF-κB) pathway-related proteins (NF-κB and p-IκBα), as well as interleukin (IL)-6, tumor necrosis factor-α, IL-1ß pro-inflammatory factors and pro-inflammatory chemokine VEGF, and increasing the expression of anti-inflammatory factor IL-10. Furthermore, LRA could ameliorate oxidative stress-induced apoptosis by upregulating Bcl-2 and downregulating Bax and Caspase-3 protein expression. All these results indicate that LRA can be used as an antioxidant dietary supplement for the treatment or prevention of retinal diseases.

Anthocyanins as natural bioactives with anti-hypertensive and atherosclerotic potential: Health benefits and recent advances.

BACKGROUND: Hypertension is a highly prevalent chronic metabolic illness affecting individuals of all age groups. Furthermore, it is a significant risk factor for the development of atherosclerosis (AS), as a correlation between hypertension and AS has been observed. However, the effective treatments for either of these disorders appear to be uncommon. METHODS: A systematic search of articles published in PubMed, Web of Science, ScienceDirect, Scopus, and Google Scholar databases over the last decade was performed using the following keywords: hypertension, AS, anthocyanins, antioxidants, gut microbes, health benefits, and bioactivity. RESULTS: The available research indicates that anthocyanin consumption can achieve antioxidant effects by inducing the activation of intracellular nuclear factor erythroid 2-related factor (Nrf2) and the expression of antioxidant genes. Moreover, previous reports showed that anthocyanins can enhance the human body's ability to fight against inflammation and cancer through the inhibition of inflammatory factors and the regulation of related signaling pathways. They can also protect the blood vessels and nervous system by regulating the production and function of endothelial nitric oxide synthase (eNOS). Gut microorganisms play an important role in various chronic diseases. Our research has also investigated the role of anthocyanins in the metabolism of the gut microbiota, leading to significant breakthroughs. This study not only presents a unique strategy for reducing the risk of cardiovascular diseases (CVDs) without the need for medicine but also provides insights into the development and utilization of intestinal probiotic dietary supplements. CONCLUSION: In this review, different in vitro and in vivo studies have shown that anthocyanins slow down the onset and progression of hypertension and AS through different mechanisms. In addition, gut microbial metabolites also play a crucial role in diseases through the gut-liver axis.

Design and development of locust bean gum-endowed/Phyllanthus reticulatus anthocyanin- functionalized biogenic gold nanosystem for enhanced antioxidative and anticancer chemotherapy.

Herein, the design and fabrication of an anticancer nanoplatform (LBG/PRA-NG) based on locust bean gum-stabilized nanogold and functionalized with Phyllanthus reticulatus anthocyanins was described. LBG/PRA-NG was prepared in an eco-friendly, one-pot approach at room temperature, mediated by the anthocyanins and gum as bio-reductant and stabilizer, respectively. The nanostructure was elaborately characterized by FESEM, TEM, UV-visible, DLS, Zeta potential, FTIR, XRD, TGA/DTG, and XPS analysis. Its anticancer attributes were examined based on cytotoxicity on MCF-7 and MDA-MB-231 breast cancer cell lines, as well as the generation of intracellular reactive oxygen species. The results revealed the successful formation of a homogenous and highly stable nanocomposite (LBG/PRA-NG), with quasi-spherical shape, small size (14.73 nm), Zeta potential and PDI values of -58.30 mV and 0.237, respectively. The presence of a plasmonic peak at 525 nm was indicative of AuNPs. Compared to the galactomannan and anthocyanin, LBG/PRA-NG exhibited superior antioxidative properties with IC50 values of 35.44 µg/mL against DPPH and 24.55 µg/mL against ABTS+. Notably, LBG/PRA-NG also demonstrated enhanced anticancer properties relative to LBG and anthocyanins, with IC50 values of 16.17 µg/mL and 25.06 µg/mL against MCF-7 and MDA-MB-231 cells. Meanwhile, the normal cells (HEK-293 and L929) resisted the innocuous effects of LBG/PRA-NG. Furthermore, treatment of breast cancer cells with LBG/PRA-NG drastically elevated the intracellular ROS levels. This suggested that the anticancer activity of LBG/PRA-NG may be mediated via amplification of ROS/oxidative stress-induced apoptosis. Altogether, these findings indicate the remarkable potential of LBG/PRA-NC in the development of anticancer therapy.

Recent advances on cyanidin-3-O-glucoside in preventing obesity-related metabolic disorders: A comprehensive review.

Anthocyanins, found in various pigmented plants as secondary metabolites, represent a class of dietary polyphenols known for their bioactive properties, demonstrating health-promoting effects against several chronic diseases. Among these, cyanidin-3-O-glucoside (C3G) is one of the most prevalent types of anthocyanins. Upon consumption, C3G undergoes phases I and II metabolism by oral epithelial cells, absorption in the gastric epithelium, and gut transformation (phase II & microbial metabolism), with limited amounts reaching the bloodstream. Obesity, characterized by excessive body fat accumulation, is a global health concern associated with heightened risks of disability, illness, and mortality. This comprehensive review delves into the biodegradation and absorption dynamics of C3G within the gastrointestinal tract. It meticulously examines the latest research findings, drawn from in vitro and in vivo models, presenting evidence underlining C3G's bioactivity. Notably, C3G has demonstrated significant efficacy in combating obesity, by regulating lipid metabolism, specifically decreasing lipid synthesis, increasing fatty acid oxidation, and reducing lipid accumulation. Additionally, C3G enhances energy homeostasis by boosting energy expenditure, promoting the activity of brown adipose tissue, and stimulating mitochondrial biogenesis. Furthermore, C3G shows potential in managing various prevalent obesity-related conditions. These include cardiovascular diseases (CVD) and hypertension through the suppression of reactive oxygen species (ROS) production, enhancement of endogenous antioxidant enzyme levels, and inhibition of the nuclear factor-kappa B (NF-κB) signaling pathway and by exercising its cardioprotective and vascular effects by decreasing pulmonary artery thickness and systolic pressure which enhances vascular relaxation and angiogenesis. Type 2 diabetes mellitus (T2DM) and insulin resistance (IR) are also managed by reducing gluconeogenesis via AMPK pathway activation, promoting autophagy, protecting pancreatic ß-cells from oxidative stress and enhancing glucose-stimulated insulin secretion. Additionally, C3G improves insulin sensitivity by upregulating GLUT-1 and GLUT-4 expression and regulating the PI3K/Akt pathway. C3G exhibits anti-inflammatory properties by inhibiting the NF-κB pathway, reducing pro-inflammatory cytokines, and shifting macrophage polarization from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype. C3G demonstrates antioxidative effects by enhancing the expression of antioxidant enzymes, reducing ROS production, and activating the Nrf2/AMPK signaling pathway. Moreover, these mechanisms also contribute to attenuating inflammatory bowel disease and regulating gut microbiota by decreasing Firmicutes and increasing Bacteroidetes abundance, restoring colon length, and reducing levels of inflammatory cytokines. The therapeutic potential of C3G extends beyond metabolic disorders; it has also been found effective in managing specific cancer types and neurodegenerative disorders. The findings of this research can provide an important reference for future investigations that seek to improve human health through the use of naturally occurring bioactive compounds.

Structure-function relationships in (poly)phenol-enzyme binding: Direct inhibition of human salivary and pancreatic α-amylases.

(Poly)phenols inhibit α-amylase by directly binding to the enzyme and/or by forming starch-polyphenol complexes. Conventional methods using starch as the substrate measure inhibition from both mechanisms, whereas the use of shorter oligosaccharides as substrates exclusively measures the direct interaction of (poly)phenols with the enzyme. In this study, using a chromatography-based method and a short oligosaccharide as the substrate, we investigated the detailed structural prerequisites for the direct inhibition of human salivary and pancreatic α-amylases by over 50 (poly)phenols from the (poly)phenol groups: flavonols, flavones, flavanones, flavan-3-ols, polymethoxyflavones, isoflavones, anthocyanidins and phenolic acids. Despite being structurally very similar (97% sequence homology), human salivary and pancreatic α-amylases were inhibited to different extents by the tested (poly)phenols. The most potent human salivary α-amylase inhibitors were luteolin and pelargonidin, while the methoxylated anthocyanidins, peonidin and petunidin, significantly blocked pancreatic enzyme activity. B-ring methoxylation of anthocyanidins increased inhibition against both human α-amylases while hydroxyl groups at C3 and B3' acted antagonistically in human salivary inhibition. C4 carbonyl reduction, or the positive charge on the flavonoid structure, was the key structural feature for human pancreatic inhibition. B-ring glycosylation did not affect salivary enzyme inhibition, but increased pancreatic enzyme inhibition when compared to its corresponding aglycone. Overall, our findings indicate that the efficacy of interaction with human α-amylase is mainly influenced by the type and placement of functional groups rather than the number of hydroxyl groups and molecular weight.

Omarigliptin/rosinidin combination ameliorates cyclophosphamide-induced lung toxicity in rats: The interaction between glucagon-like peptide-1, TXNIP/NLRP3 inflammasome signaling, and PI3K/Akt/FoxO1 axis.

Cyclophosphamide is an anti-neoplastic drug that has shown competence in the management of a broad range of malignant tumors. In addition, it represents a keystone agent for management of immunological conditions. Despite these unique properties, induction of lung toxicity may limit its clinical use. Omarigliptin is one of the dipeptidyl peptidase-4 inhibitors that has proven efficacy in management of diabetes mellitus. Rosinidin is an anthocyanidin flavonoid that exhibited promising results in management of diseases characterized by oxidative stress, inflammation, and apoptosis. The present work investigated the possible effects of omarigliptin with or without rosinidin on cyclophosphamide-induced lung toxicity with an exploration of the molecular mechanisms that contribute to these effects. In a rodent model of cyclophosphamide elicited lung toxicity, the potential efficacy of omarigliptin with or without rosinidin was investigated at both the biochemical and the histopathological levels. Both omarigliptin and rosinidin exhibited a synergistic ability to augment the tissue antioxidant defenses, mitigate the inflammatory pathways, restore glucagon-like peptide-1 levels, modulate high mobility group box 1 (HMGB1)/receptors of advanced glycation end products (RAGE)/nuclear factor kappa B (NF-κB) axis, downregulate the fibrogenic mediators, and create a balance between the pathways involved in apoptosis and the autophagy signals in the pulmonary tissues. In conclusion, omarigliptin/rosinidin combination may be introduced as a novel therapeutic modality that attenuates the different forms of lung toxicities induced by cyclophosphamide.

Acylated anthocyanins from Dendrobium officinale Kimura & Migo: Structural characteristics, antioxidant and hypoglycemic activities.

Dendrobium officinale Kimura & Migo (D. officinale) has been widely used as Chinese medicine and functional food. In present study, the structural characteristics of anthocyanins in D. officinale were investigated by ultra-performance liquid chromatography with diode array detector (UPLC-DAD) and ultra-performance liquid chromatography-quadrupole-time of flight mass spectrometry (UPLC-Q-TOF-MS/MS). Totally, 14 anthocyanins were detected and identified, and 13 of them were first reported in D. officinale. Results showed that the vast majority of anthocyanins had multi-glycosylated cyanidin core, with variable acylation pattern mainly comprising phenolic acids. The composition and content of anthocyanins in D. officinale stems with different cultivation modes and years have been compared. The anthocyanins showed potent antioxidant activity in terms of radicals scavenging capacity and reducing power, as well as superior α-amylase and α-glucosidase inhibitory activity. The results provided a complete profile of anthocyanins in D. officinale and laid a foundation for further utilizing them as functional foods.

Optimized Synthesis and Antioxidant Activity of Anthocyanins Delphinidin-3-O-glucoside and Petunidin-3-O-glucoside.

The chemical synthesis of anthocyanins, especially delphinidin-3-O-glucoside and petunidin-3-O-glucoside, is preferable due to the challenges associated with their extraction and purification. However, the reported methods for the synthesis are scarce and intricate. Our research focused on exploring a one-step ester-to-ketone process and optimizing the ring formation reaction, simplifying and improving the overall synthesis strategy. Through these attempts, we were able to achieve higher production yields of delphinidin-3-O-glucoside and petunidin-3-O-glucoside. According to the results of DPPH, ABTS, and FRAP, the antioxidant activity of anthocyanins was increased with the number of B ring hydroxyl substituent. Additionally, both delphinidin-3-O-glucoside and petunidin-3-O-glucoside exhibited no cytotoxicity effects, highlighting their potential for safe application in various fields.

Comparison of the hepatoprotection of intragastric and intravenous cyanidin-3-glucoside administration: focus on the key metabolites and gut microbiota modulation.

Liver injury is a life-threatening condition, and the hepatoprotective potential of cyanidin-3-glucoside (C3G) has been previously demonstrated. However, due to the low bioavailability, it has been doubtful that relatively low concentrations of intact C3G in vivo could account for these bioactivities. In this study, the hepatoprotective effects of intragastric and intravenous administration of C3G were investigated in a CCl4 induced liver injury model. Intragastric C3G administration was more effective than intravenous C3G injection in reducing serum damage biomarkers, oxidative stress, and inflammatory responses, indicating that absorption of C3G into the bloodstream does not fully account for its observed benefits in vivo. Furthermore, intragastric C3G administration modulated the gut microbiota structure and increased the contents of five metabolites in the feces and serum with high inter-individual variation, indicating the key role of the interaction between C3G and the gut microbiota. At equivalent doses, the metabolites cyanidin and protocatechuic acid exhibited greater efficacy than C3G in reducing apoptosis and ROS production by activating the Nrf2 pathway in an AAPH-induced oxidative stress model. To achieve the desired health effects via C3G-rich food intake, more attention should be paid to microbially derived catabolites. Screening of specific metabolite-producing strains will help overcome individual differences and enhance the health-promoting effects of C3G.

Screening of Mpro Protease (SARS-CoV-2) Covalent Inhibitors from an Anthocyanin-Rich Blueberry Extract Using an HRMS-Based Analytical Platform.

BACKGROUND: The viral main protease (Mpro) of SARS-CoV-2 has been recently proposed as a key target to inhibit virus replication in the host. Therefore, molecules that can bind the catalytic site of Mpro could be considered as potential drug candidates in the treatment of SARS-CoV-2 infections. Here we proposed the application of a state-of-the-art analytical platform which combines metabolomics and protein structure analysis to fish-out potential active compounds deriving from a natural matrix, i.e., a blueberry extract. METHODS: The experiments focus on finding MS covalent inhibitors of Mpro that contain in their structure a catechol/pyrogallol moiety capable of binding to the nucleophilic amino acids of the enzyme's catalytic site. RESULTS: Among the potential candidates identified, the delphinidin-3-glucoside showed the most promising results. Its antiviral activity has been confirmed in vitro on Vero E6 cells infected with SARS-CoV-2, showing a dose-dependent inhibitory effect almost comparable to the known Mpro inhibitor baicalin. The interaction of delphinidin-3-glucoside with the Mpro pocket observed was also evaluated by computational studies. CONCLUSIONS: The HRMS analytical platform described proved to be effective in identifying compounds that covalently bind Mpro and are active in the inhibition of SARS-CoV-2 replication, such as delphinidin-3-glucoside.