Blueberry anthocyanins improve liver fibrosis by regulating NCOA4 ubiquitination through TRIM7 to affect ferroptosis of hepatic stellate cells.

This study aims to investigate the role and molecular mechanism of anthocyanin in improving liver fibrosis through ferroptosis, providing a basis for drug development and targeted therapy. In this study, a mouse model of liver fibrosis was established using CCl4, and the anthocyanin treatment groups were administered 100 mg/kg anthocyanin daily via gavage. Furthermore, real-time fluorescent quantitative PCR (qRT-PCR), Western blotting (WB), and enzyme-linked immunosorbent assay were used to assess liver fibrosis indicators and liver injury markers. Histopathological methods were used to confirm the morphology of liver injury in different treatment groups. The effects of anthocyanins on ferroptosis markers, NCOA4 and FTH1 expression, were examined through qRT-PCR, WB, and Co-IP. Confocal microscopy was used to validate the colocalization of ferritin and lysosomes. A differential expression model of TRIM7 was constructed to verify its impact on the progression of liver fibrosis. The present study demonstrates the hepatoprotective effects of anthocyanins in liver fibrosis, highlighting their ability to enhance hepatic stellate cell (HSC) ferroptosis and regulate ferritin autophagy. Moreover, TRIM7 is identified as a key mediator of anthocyanin-induced regulation of hepatic stellate cells activation for liver fibrosis treatment through modulation of ferroautophagy. Mechanistic investigations further reveal that TRIM7 exerts its influence on the process of ferroautophagy by controlling NCOA4 ubiquitination. Our study discovered that anthocyanins could improve liver fibrosis by regulating NCOA4 ubiquitination through TRIM7, thereby affecting hepatic stellate cells' ferroptosis levels.NEW & NOTEWORTHY This was the first study to demonstrate that anthocyanins can improve the progression of liver fibrosis by promoting hepatic stellate cell (HSC) ferroptosis. Anthocyanins could affect the content of Fe2+ by promoting ferroautophagy in HSCs, thereby promoting the level of ferroptosis. This study demonstrates for the first time that anthocyanins can inhibit the expression of TRIM7 and then affect the ubiquitination of NCOA4 to regulate the level of ferritin autophagy and ferroptosis.

Cyanidin improves spatial memory and cognition in bisphenol A-induced rat model of Alzheimer's-like neuropathology by restoring canonical Wnt signaling.

INTRODUCTION: Research has unveiled the neurotoxicity of Bisphenol A (BPA) linked to neuropathological traits of Alzheimer's disease (AD) through varied mechanisms. This study aims to investigate the neuroprotective properties of cyanidin, an anthocyanin, in an in vivo model of BPA-induced Alzheimer's-like neuropathology. METHODS: Three-week-old Sprague-Dawley rats were randomly assigned to four groups: vehicle control, negative control (BPA exposure), low-dose cyanidin treatment (BPA + cyanidin 5 mg/kg), and high-dose cyanidin treatment (BPA + cyanidin 10 mg/kg). Spatial memory was assessed through behavioral tests, including the Y-maze, novel object recognition, and Morris water maze. After behavioral tests, animals were euthanized, and brain regions were examined for acetylcholinesterase inhibition, p-tau, Wnt3, GSK3ß, and ß-catenin levels, antioxidant activities, and histopathological changes. RESULTS: BPA-exposed groups displayed memory impairments, while cyanidin-treated groups showed significant memory improvement (p < 0.0001). Cyanidin down regulated p-tau and glycogen synthase kinase-3ß (GSK3ß) and restored Wnt3 and ß-catenin levels (p < 0.0001). Moreover, cyanidin exhibited antioxidant properties, elevating catalase and superoxide dismutase levels. The intervention significantly reduced the concentrations of acetylcholinesterase in the cortex and hippocampus in comparison to the groups treated with BPA (p < 0.0001). Significant gender-based disparities were not observed. CONCLUSION: Cyanidin demonstrated potent neuroprotection against BPA-induced Alzheimer's-like neuropathology by enhancing antioxidant defenses, modulating tau phosphorylation by restoring the Wnt/ß-catenin pathway, and ameliorating spatial memory deficits. This study highlights the therapeutic potential of cyanidin in countering neurotoxicity linked to BPA exposure.

Clinically Effective Molecules of Natural Origin for Obesity Prevention or Treatment.

The prevalence and incidence of obesity and the comorbidities linked to it are increasing worldwide. Current therapies for obesity and associated pathologies have proven to cause a broad number of adverse effects, and often, they are overpriced or not affordable for all patients. Among the alternatives currently available, natural bioactive compounds stand out. These are frequently contained in pharmaceutical presentations, nutraceutical products, supplements, or functional foods. The clinical evidence for these molecules is increasingly solid, among which epigallocatechin-3-gallate, ellagic acid, resveratrol, berberine, anthocyanins, probiotics, carotenoids, curcumin, silymarin, hydroxy citric acid, and α-lipoic acid stand out. The molecular mechanisms and signaling pathways of these molecules have been shown to interact with the endocrine, nervous, and gastroenteric systems. They can regulate the expression of multiple genes and proteins involved in starvation-satiety processes, activate the brown adipose tissue, decrease lipogenesis and inflammation, increase lipolysis, and improve insulin sensitivity. This review provides a comprehensive view of nature-based therapeutic options to address the increasing prevalence of obesity. It offers a valuable perspective for future research and subsequent clinical practice, addressing everything from the molecular, genetic, and physiological bases to the clinical study of bioactive compounds.

Anthocyanins: Potential phytochemical candidates for the amelioration of non-alcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) is described by too much hepatic fat deposition causing steatosis, which further develops into nonalcoholic steatohepatitis (NASH), defined by necroinflammation and fibrosis, progressing further to hepatic cirrhosis, hepatocellular carcinoma, and liver failure. NAFLD is linked to different aspects of the metabolic syndrome like obesity, insulin resistance, hypertension, and dyslipidemia, and its pathogenesis involves several elements including diet, obesity, disruption of lipid homeostasis, and a high buildup of triglycerides and other lipids in liver cells. It is therefore linked to an increase in the susceptibility to developing diabetes mellitus and cardiovascular diseases. Several interventions exist regarding its management, but the availability of natural sources through diet will be a benefit in dealing with the disorder due to the immensely growing dependence of the population worldwide on natural sources owing to their ability to treat the root cause of the disease. Anthocyanins (ACNs) are naturally occurring polyphenolic pigments that exist in the form of glycosides, which are the glucosides of anthocyanidins and are produced from flavonoids via the phenyl propanoid pathway. To understand their mode of action in NAFLD and their therapeutic potential, the literature on in vitro, in vivo, and clinical trials on naturally occurring ACN-rich sources was exhaustively reviewed. It was concluded that ACNs show their potential in the treatment of NAFLD through their antioxidant properties and their efficacy to control lipid metabolism, glucose homeostasis, transcription factors, and inflammation. This led to the conclusion that ACNs possess efficacy in the amelioration of NAFLD and the various features associated with it. However, additional clinical trials are required to justify the potential of ACNs in NAFLD.

Chemopreventive effects of anthocyanins on colorectal and breast cancer: A review.

The present review has analyzed the scientific literature, available in the PubMed and Scopus databases, in order to summarize the current state of diet anthocyanin research in breast cancer (BC) and colorectal cancer (CRC) animal models but also for up-to-date human studies. For CRC, 28 preclinical and 9 clinical studies were selected in line with our search query in science databases. In relation to BC, 14 preclinical and 5 clinical studies were selected. Remarkably, all the preclinical studies, to a greater or lesser degree, suggested a chemoprevention effect of anthocyanin in BC/CRC rodent models. These encouraging results from animal models are not extrapolated to the same degree to human studies where, from the similar theoretical daily doses of anthocyanins in these studies, the opposite results were reported. Nevertheless, it is worth mentioning that the anthocyanin doses in the human studies carried out recently are low if we consider the estimated exposure to anthocyanins issued by the European Food Safety Agency (EFSA) or extremely low if we consider with caution the human equivalent dose based on body surface area from the preclinical dosage regimes used. Therefore, although some clinical data has demonstrated an inverse relation between anthocyanin consumption and BC/CRC, this could, in fact, be more relevant if we increase the daily human anthocyanin dose (as observed in animal model dose-effect studies) while new toxicological data for this flavonoid subtype are brought to light.

Cyanidin-3-O-glucoside protects the brain and improves cognitive function in APPswe/PS1ΔE9 transgenic mice model.

Cyanidin-3-O-glucoside (C3G) is a natural anthocyanin with antioxidant, anti-inflammatory, and antitumor properties. However, as the effects of C3G on the amyloidogenic pathway, autophagy, tau phosphorylation, neuronal cell death, and synaptic plasticity in Alzheimer's disease models have not been reported, we attempted to investigate the same in the brains of APPswe/PS1ΔE9 mice were analyzed. After oral administration of C3G (30 mg/kg/day) for 16 weeks, the cortical and hippocampal regions in the brains of APPswe/PS1ΔE9 mice were analyzed. C3G treatment reduced the levels of soluble and insoluble Aß (Aß40 and Aß42) peptides and reduced the protein expression of the amyloid precursor protein, presenilin-1, and ß-secretase in the cortical and hippocampal regions. And C3G treatment upregulated the expression of autophagy-related markers, LC3B-II, LAMP-1, TFEB, and PPAR-α and downregulated that of SQSTM1/p62, improving the autophagy of Aß plaques and neurofibrillary tangles. In addition, C3G increased the protein expression of phosphorylated-AMPK/AMPK and Sirtuin 1 and decreased that of mitogen-activated protein kinases, such as phosphorylated-Akt/Akt and phosphorylated-ERK/ERK, thus demonstrating its neuroprotective effects. Furthermore, C3G regulated the PI3K/Akt/GSK3ß signaling by upregulating phosphorylated-Akt/Akt and phosphorylated-GSK3ß/GSK3ß expression. C3G administration mitigated tau phosphorylation and improved synaptic function and plasticity by upregulating the expression of synapse-associated proteins synaptophysin and postsynaptic density protein-95. Although the potential of C3G in the APPswe/PS1ΔE9 mouse models has not yet been reported, oral administration of the C3G is shown to protect the brain and improve cognitive behavior.

Pelargonidin ameliorates inflammatory response and cartilage degeneration in osteoarthritis via suppressing the NF-κB pathway.

Pelargonidin (PG), a derivative of anthocyanins, has anti-oxidant and anti-inflammatory properties. Herein, the protective effect and the mechanism of PG in counteract the osteoarthritis (OA) progression were needed to further evaluate. In the current study, C57BL/6 mice was induced by destabilization of medial meniscus (DMM) surgery to establish the OA model. Primary chondrocytes were acquired from the knee cartilage of newborn mice. Then, PG was administrated to OA mice and IL-1ß-stimulated chondrocytes to evaluate its protective effects, respectively. Results uncovered that no conspicuous cytotoxic effects were observed when chondrocytes were treated with PG at a concentration lower than 40 µM for 24-72 h. Thus, 10 µM, 20 µM, and 40 µM PG were chosen for subsequent experiments in vitro. Then, we observed that 10, 20, and 40 µM PG reduced the levels of IL-6, TNF-α, COX-2 and iNOS in chondrocytes. In line, PG inhibited the IL-1ß-induced ECM catabolism in chondrocytes, as evidenced by deepening toluidine blue staining, increased expression of Collagen II, and decreased expressions of ADAMTS5 and MMP13. Moreover, PG also reduced the IL-1ß-stimulated p-p65 overexpression and nuclear translocation of p65 in chondrocytes. In vivo, Safranin O/Fast green and HE staining showed that articular cartilage surface morphology was basically smooth and complete after PG treatment for 8 weeks. Similarly, OARSI scores and MMP13 expression were apparently decreased, whereas Aggrecan expression was elevated in PG-treated mice 8 weeks after DMM surgery. In conclusion, PG can effectively ameliorate inflammatory reactions and cartilage degeneration via suppressing the NF-κB pathway, thereby restraining the OA progression.

Cyanidin-3-O-glucoside and its phenolic metabolites ameliorate intestinal diseases via modulating intestinal mucosal immune system: potential mechanisms and therapeutic strategies.

The incidence of the intestinal disease is globally increasing, and the intestinal mucosa immune system is an important defense line. A potential environmental cause to regulate gut health is diet. Cyanidin-3-O-glucoside is a natural plant bioactive substance that has shown rising evidence of improving intestinal disease and keeping gut homeostasis. This review summarized the intestinal protective effect of Cyanidin-3-O-glucoside in vivo and in vitro and discussed the potential mechanisms by regulating the intestinal mucosal immune system. Cyanidin-3-O-glucoside and phenolic metabolites inhibited the presence and progression of intestinal diseases and explained from the aspects of repairing the intestinal wall, inhibiting inflammatory reaction, and regulating the gut microbiota. Although the animal and clinical studies are inadequate, based on the accumulated evidence, we propose that the interaction of Cyanidin-3-O-glucoside with the intestinal mucosal immune system is at the core of most mechanisms by which affect host gut diseases. This review puts forward the potential mechanism of action and targeted treatment strategies.

Hypoglycemic bioactivity of anthocyanins: A review on proposed targets and potential signaling pathways.

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease with complicated interrelationships responsible for initiating its pathogenesis. Novel strategies for the treatment of this devastating disease have attracted increasing attention worldwide. Anthocyanins are bioactive compounds that are widely distributed in the plant kingdom, and multiple studies have elucidated their beneficial role in preventing and managing T2DM. This review summarizes and comments on the hypoglycemic actions of anthocyanins from the perspective of molecular mechanisms and different target-related signaling pathways in vitro, in vivo, and clinical trials. Anthocyanins can ameliorate T2DM by functioning as carbohydrate digestive enzyme inhibitors, facilitating glucose transporter 4 (GLUT4) translocation, suppressing the effectiveness of dipeptidyl peptidase IV (DPP-IV), promoting glucagon-like peptide-1 (GLP-1) secretion, inhibiting protein tyrosine phosphatase 1B (PTP1B) overexpression, and interacting with sodium-glucose co-transporter (SGLT) to delay glucose absorption in various organs and tissues. In summary, anthocyanin is a promising and practical small molecule that can hyperglycemic symptoms and accompanying complications suffered by patients with diabetes. However, rational and potent doses for daily intake and clinical studies are required in the future.

Sirtuin1 (SIRT1) is involved in the anticancer effect of black raspberry anthocyanins in colorectal cancer.

PURPOSE: Abnormal acetylation modification is a common epigenetic change in tumorigenesis and is closely related to the progression of colorectal cancer (CRC). Our previous studies have suggested that black raspberry (BRB) anthocyanins have a significant chemopreventive effect against CRC. This study investigated whether protein acetylation plays an important role in BRB anthocyanins-mediated regulation of CRC progression. METHODS: We used the AOM-induced CRC mouse model and the CRC cell lines SW480 and Caco-2 to explore the potential role of acetylation of histone H4 and NF-κB signaling pathway-related proteins (non-histone proteins) in the antitumor process mediated by BRB anthocyanins. The expression of related proteins was detected by western blot. ROS level was detected by immunofluorescence. RESULTS: BRB anthocyanins affected the acetylation level by down-regulating the expression of Sirtuin1 (SIRT1) and up-regulating the expression of MOF and EP300. The acetylation level of lysine sites on histone H4 (H4K5, H4K12 and H4K16) was increased. Furthermore, following BRB anthocyanins treatment, the expression of ac-p65 was significantly up-regulated and the NF-κB signal pathway was activated, which in turn up-regulated Bax expression and inhibited Bcl-2, cyclin-D1, c-myc and NLRP3 expression to promote CRC cell cycle arrest, apoptosis and relieve inflammation. CONCLUSION: The findings suggested that protein acetylation could play a critical role in BRB anthocyanins-regulated CRC development.

Anthocyanin oligomer (grape skin extract) administration improves dry eye disease: A randomised, double-blind, placebo-controlled study.

BACKGROUND: Dry eye disease is a chronic, progressive ocular disease characterised by ocular discomfort and is one of the most common ophthalmological disorders that affects people's lives. METHODS: This study investigated the clinical efficacy of anthocyanin oligomers (grape skin extract) for the treatment of dry eye. One hundred and eight patients with dry eye were randomly divided into placebo and treatment groups, each with 54 cases. The placebo group received maltodextrin (800 mg/day) and the treatment group received anthocyanin oligomers (800 mg/day). Clinical efficacy, clinical indices, and occurrence of adverse reactions were compared between the two groups. RESULTS: Anthocyanin oligomers were safe and effective in mild-to-moderate dry eye disease, improving the tear break-up time, intraocular pressure, ocular surface disease, and patient symptomatology. CONCLUSIONS: The use of oral anthocyanin oligomers in the treatment of dry eye patients can enhance the therapeutic effect and improve the quality of life of patients while ensuring the safety of treatment, making this therapeutic option suitable for wider application.

Recent insights into the hepatoprotective potential of medicinal plants and plant-derived compounds.

Liver problems are a worldwide concern, and conventional medicinal therapies are ineffective. Hence, safeguarding the healthy liver is vital for good health and well-being. Infections due to virus, immune problems, cancer, alcohol abuse, and an overdose of drugs are some of the causes of liver diseases. Antioxidants derived from medicinal plants and conventional dietary sources can protect the liver from damages caused by oxidative stress system and various chemicals. Plants and plant-derived phytochemicals are appealing hepatoprotective agents since they have less side effects and still there is a lot of interest shown in using herbal tonics for treating liver disorders. This review therefore primarily focuses on newly discovered medicinal plants and compounds produced from plants that fall under the classifications of flavonoids, alkaloids, terpenoids, polyphenolics, sterols, anthocyanins, and saponin glycosides, all of which have the potential to be hepatoprotective. Hosta plantaginea, Ligusticum chuanxiong, Daniella oliveri, Garcinia mangostana, Solanum melongena, Vaccinium myrtillus, Picrorhiza kurroa, and Citrus medica are some potential plants having hepatoprotective effects. We conclude that these phytochemicals and the plant extracts listed above are used in the future to treat a variety of liver diseases, additional research is still needed to develop safer and more potent phytochemical drugs.

Therapeutic Aspects of Prunus cerasus Extract in a Rabbit Model of Atherosclerosis-Associated Diastolic Dysfunction.

This study evaluates the potential therapeutic effects of anthocyanin-rich Prunus cerasus (sour cherry) extract (PCE) on atherosclerosis-associated cardiac dysfunction, described by the impairment of the NO-PKG (nitric oxide-protein kinase G) pathway and the antioxidant capacity. Initially, a rabbit model of atherosclerotic cardiovascular disease was established by administering a cholesterol-rich diet, enabling the examination of the impact of 9 g/kg PCE on the pre-existing compromised cardiovascular condition. After that, the animals were divided into four groups for 12 weeks: the (1) untreated control group; (2) PCE-administered healthy rabbits; (3) hypercholesterolemic (HC) group kept on an atherogenic diet; and (4) PCE-treated HC group. Dyslipidemia, impaired endothelial function, and signs of diastolic dysfunction were evident in hypercholesterolemic rabbits, accompanied by a reduced cardiac expression of eNOS (endothelial nitric oxide synthase), PKG, and SERCA2a (sarco/endoplasmic reticulum calcium ATPase 2a). Subsequent PCE treatment improved the lipid profile and the cardiac function. Additionally, PCE administration was associated with elevated myocardial levels of eNOS, PKG, and SERCA2a, while no significant changes in the vascular status were observed. Western blot analysis further revealed hypercholesterolemia-induced increase and PCE-associated reduction in heme oxygenase-1 expression. The observed effects of anthocyanins indicate their potential as a valuable addition to the treatment regimen for atherosclerosis-associated cardiac dysfunction.

Cornelian Cherry (Cornus mas L.) Iridoid and Anthocyanin-Rich Extract Reduces Various Oxidation, Inflammation, and Adhesion Markers in a Cholesterol-Rich Diet Rabbit Model.

Atherogenesis leads to the development of atherosclerosis, a progressive chronic disease characterized by subendothelial lipoprotein retention and endothelial impairment in the arterial wall. It develops mainly as a result of inflammation and also many other complex processes, which arise from, among others, oxidation and adhesion. Cornelian cherry (Cornus mas L.) fruits are abundant in iridoids and anthocyanins-compounds with potent antioxidant and anti-inflammatory activity. This study aimed to determine the effect of two different doses (10 mg and 50 mg per kg of body weight, respectively) of iridoid and anthocyanin-rich resin-purified Cornelian cherry extract on the markers that are important in the progress of inflammation, cell proliferation and adhesion, immune system cell infiltration, and atherosclerotic lesion development in a cholesterol-rich diet rabbit model. We used biobank blood and liver samples that were collected during the previous original experiment. We assessed the mRNA expression of MMP-1, MMP-9, IL-6, NOX, and VCAM-1 in the aorta, and the serum levels of VCAM-1, ICAM-1, CRP, PON-1, MCP-1, and PCT. The application of the Cornelian cherry extract at a dose of 50 mg/kg bw resulted in a significant reduction in MMP-1, IL-6, and NOX mRNA expression in the aorta and a decrease in VCAM-1, ICAM-1, PON-1, and PCT serum levels. The administration of a 10 mg/kg bw dose caused a significant decrease in serum ICAM-1, PON-1, and MCP-1. The results indicate the potential usefulness of the Cornelian cherry extract in the prevention or treatment of atherogenesis-related cardiovascular diseases, such as atherosclerosis or metabolic syndrome.

Exploring the Impact of Cyanidin-3-Glucoside on Inflammatory Bowel Diseases: Investigating New Mechanisms for Emerging Interventions.

Cyanidin-3-O-glucoside (C3G), the most widely distributed anthocyanin (ACN) in edible fruits, has been proposed for several bioactivities, including anti-inflammatory, neuro-protective, antimicrobial, anti-viral, anti-thrombotic and epigenetic actions. However, habitual intake of ACNs and C3G may vary widely among populations, regions, and seasons, among individuals with different education and financial status. The main point of C3G absorption occurs in the small and large bowel. Therefore, it has been supposed that the treating properties of C3G might affect inflammatory bowel diseases (IBD), such as ulcerative colitis (UC) and Crohn's disease (CD). IBDs develop through complex inflammatory pathways and sometimes may be resistant to conventional treatment strategies. C3G presents antioxidative, anti-inflammatory, cytoprotective, and antimicrobial effects useful for IBD management. In particular, different studies have demonstrated that C3G inhibits NF-κB pathway activation. In addition, C3G activates the Nrf2 pathway. On the other hand, it modulates the expression of antioxidant enzymes and cytoprotective proteins, such as NAD(P)H, superoxide dismutase, heme-oxygenase (HO-1), thioredoxin, quinone reductase-oxide 1 (NQO1), catalase, glutathione S-transferase and glutathione peroxidase. Interferon I and II pathways are downregulated by C3G inhibiting interferon-mediating inflammatory cascades. Moreover, C3G reduces reactive species and pro-inflammatory cytokines, such as C reactive protein, interferon-γ, tumor necrosis factor-α, interleukin (IL)-5, IL-9, IL-10, IL-12p70, and IL-17A in UC and CD patients. Finally, C3G modulates gut microbiota by inducing an increase in beneficial gut bacteria and increasing microbial abundances, thus mitigating dysbiosis. Thus, C3G presents activities that may have potential therapeutic and protective actions against IBD. Still, in the future, clinical trials should be designed to investigate the bioavailability of C3G in IBD patients and the proper therapeutic doses through different sources, aiming to the standardization of the exact clinical outcome and efficacy of C3G.

Cyanidin-3-O-glucoside as a Nutrigenomic Factor in Type 2 Diabetes and Its Prominent Impact on Health.

Type 2 diabetes (T2D) accounts for a global health problem. It is a complex disease as a result of the combination of environmental as well as genetic factors. Morbidity is still increasing across the world. One of the possibilities for the prevention and mitigation of the negative consequences of type 2 diabetes is a nutritional diet rich in bioactive compounds such as polyphenols. This review is focused on cyanidin-3-O-glucosidase (C3G), which belongs to the anthocyanins subclass, and its anti-diabetic properties. There are numerous pieces of evidence that C3G exerts positive effects on diabetic parameters, including in vitro and in vivo studies. It is involved in alleviating inflammation, reducing blood glucose, controlling postprandial hyperglycemia, and gene expression related to the development of T2D. C3G is one of the beneficial polyphenolic compounds that may help to overcome the public health problems associated with T2D.

Quercetin Derivatives as Potential Therapeutic Agents: An Updated Perspective on the Treatment of Nicotine-Induced Non-Small Cell Lung Cancer.

Flavonoids are the largest group of polyphenols, represented by many compounds that exhibit high anticancer properties. Quercetin (Q) and its main derivatives (rutin, quercitrin, isoquercitrin, isorhamnetin, tamarixetin, rhamnetin, and hyperoside) in the class of flavonols have been documented to exert anticancer activity. Q has been shown to be useful in the treatment of non-small cell lung cancer (NSCLC), as demonstrated by in vitro/in vivo studies, due to its antitumor, anti-inflammatory, anti-proliferative, anti-angiogenesis, and apoptotic properties. Some flavonoids (flavone, anthocyanins, and proanthocyanidins) have been demonstrated to be effective in nicotine-induced NSCLC treatment. However, the molecular mechanisms of quercetin derivatives (QDs) in nicotine-induced NSCLC treatment remain unclear. Thus, this review aims to summarize the available literature on the therapeutic effects of QDs in nicotine-induced NSCLC.

Cyanidin-3-O-Glucoside Induces the Apoptosis of Human Gastric Cancer MKN-45 Cells through ROS-Mediated Signaling Pathways.

Cyanidin-3-O-glucoside (C3G), an active ingredient in anthocyanins, mainly exists in dark cereals. C3G was investigated for its effect on human gastric cancer (GC) cells, together with its molecular mechanism. The CCK-8 assay results showed that C3G had significant antiproliferative effects on GC cells, but it had little effect on normal cells. Western blot and flow cytometry results showed that C3G regulated the reduction of mitochondrial membrane potential and arrested the cell cycle in the G2/M phase through the AKT signaling pathway, causing the cells to undergo apoptosis. Additionally, in MKN-45 cells, C3G markedly raised intracellular reactive oxygen species (ROS) levels. The wound healing assay and Transwell assay results showed that MKN-45 cell migration was significantly inhibited. Western blot results showed that the expression of E-cadherin protein was upregulated and the expressions of ß-catenin, N-cadherin, and Vimentin were downregulated. Additionally, following N-acetylcysteine treatment, the expression levels of these proteins were reduced. In conclusion, C3G caused MKN-45 cells to undergo apoptosis; arrested the cell cycle in the G2/M phase; hindered cell migration; and activated the MAPK, STAT3, and NF-κB signaling pathways, by inducing an increase in ROS levels. Thus, C3G may be a promising new medication for the treatment of GC.

Anthocyanins: Potential Therapeutic Approaches towards Obesity and Diabetes Mellitus Type 2.

Overweight and obesity are present in about three-quarters of the adult population in Mexico. The inflammatory mechanisms subjacent to visceral white adipose tissue are accountable for the initiation and development of cardiometabolic alterations, including type 2 diabetes. Lifestyle changes are pillars within its therapeutics and, thus, current dietary modifications should include not only hypocaloric prescriptions with balanced macronutrient intake, preferably by increasing the amount of whole grains, fruits, vegetables, nuts and legumes, but in concomitance, bioactive substances, such as anthocyanins, have been correlated with lower incidence of this disease.

Anthocyanin improves kidney function in diabetic kidney disease by regulating amino acid metabolism.

BACKGROUND: Diabetic kidney disease (DKD) is among the most important causes for chronic kidney disease. Anthocyanins (ANT) are polyphenolic compounds present in various food and play an important role in ameliorating hyperglycemia and insulin sensitivity. However, the effects of ANT in DKD are still poorly understood. This study aimed to investigate the effect of ANT (cyanidin-3-O-glucoside [C3G]) on the renal function of DKD, and whether the anti-DKD effect of ANT is related to metabolic pathways. METHODS: To explore the role of ANT in DKD, we performed the examination of blood glucose, renal function, and histopathology. As for the mechanism, we designed the label-free quantification proteomics and nontargeted metabolomics analysis for kidney and serum. Subsequently, we revealed the anti-DKD effect of ANT through the bioinformatic analysis. RESULTS: We showed that the fasting blood glucose level (- 6.1 mmol/L, P = 0.037), perimeter of glomerular lesions (- 24.1 µm, P = 0.030), fibrosis score of glomerular (- 8.8%, P = 0.002), and kidney function (Cystatin C: - 701.4 pg/mL, P = 0.043; urine creatinine: - 701.4 mmol/L, P = 0.032) were significantly alleviated in DKD mice after ANT treatment compared to untreated in the 20th week. Further, proteins and metabolites in the kidneys of DKD mice were observed to be dramatically altered due to changes in amino acid metabolism with ANT treatment; mainly, taurine and hypotaurine metabolism pathway was upregulated (P = 0.0001, t value = 5.97). Furthermore, upregulated tryptophan metabolism (P < 0.0001, t value = 5.94) and tyrosine metabolism (P = 0.0037, t value = 2.91) pathways had effects on serum of DKD mice as responsed ANT regulating. CONCLUSIONS: Our results suggested that prevention of the progression of DKD by ANT could be related to the regulation of amino acid metabolism. The use of dietary ANT may be one of the dietary strategies to prevent and treat DKD.