Naringenin is a flavonoid belonging to flavanones subclass. It is widely distributed in several Citrus fruits, bergamot, tomatoes and other fruits, being also found in its glycosides form (mainly naringin). Several biological activities have been ascribed to this phytochemical, among them antioxidant, antitumor, antiviral, antibacterial, anti-inflammatory, antiadipogenic and cardioprotective effects. In fact, naringenin ability to improve endothelial function has been well-established.

Keywords: nutraceutics, phytochemicals, chemopreventive, cardiovascular diseases, flavonoids, citrus, flavanones, neurodegenerative diseases, naringenin, pharmacological targets, signaling pathways, molecular mechanisms, drug delivery systems, naringin, obesity, hypertension, inflammation, mitochondria, Diabetic retinopathy, Inflammation, Naringin, NF-κB pathway, Oxidative stress, Antioxidants, Flavonoids, Free radicals, Lipid peroxidation, Oxidative stress, Naringenin, liver steatosis, naringin, pluronic F68, polymeric micelles, in vitro cytotoxicity, antiulcer, antitumor ac

Summary of Abstracts:

Anxiolytic, Antidepressant-Like Proprieties and Impact on the Memory of the Hydro-Ethanolic Extract of Origanum majorana L. on Mice: Marjoram (Origanum majorana L.) infusion has been used as folk medicine against depression and anxiety. However, no studies have been carried out yet to prove those activities scientifically. In this study, the anxiolytic, antidepressant-like effects, and memory impact of the hydro-ethanolic extracts of marjoram were evaluated in mice. The phytochemical screening showed the presence of ferulic acid, naringin, hydroxytyrosol, geraniol, and quercetin. This study approves the traditional use of this plant and encourages further investigation on its bioactive compounds.

In Vitro Bioaccessibility of Citrus Pomace Compounds Possessing Health Promoting Properties with Potential to Reduce the Risk of Diabetes: Citrus (mandarin and orange) pomace is an agro-food industrial waste rich in polyphenols and dietary fiber with great potential as a functional ingredient. In this work, the chemical composition and in vitro bioaccessibility of health-promoting compounds present in raw citrus pomaces (Clemenule and Ortanique mandarins and Navel and Valencia oranges) were studied. In addition, the by-products were employed as food ingredients in cookies and the effect of the food matrix on the bioaccessibility of their bioactive compounds was evaluated. Nobiletin, hesperidin/neohesperidin, tangeretin, heptamethoxyflavone, tetramethylscutellarein, and naringin/narirutin were detected in the citrus samples by UHPLC-MS. The results obtained support the feasibility of unfractionated orange pomace as a functional ingredient for reducing the risk of diabetes. The health-promoting benefits observed in the present research might be, at least partially, associated with flavonoids.

Opposing Effect of Naringenin and Quercetin on the Junctional Compartment of MDCK II Cells to Modulate the Tight Junction: Maintaining tight junction (TJ) integrity is important for epithelial cell barriers. Previously, the enhancement of TJ integrity, induced by citrus-derived flavonoids, naringin (NRG) and hesperidin (HSD), was demonstrated, but the effects of their aglycones naringenin (NAR) and hesperetin (HST), and the mechanisms, have not been systematically investigated.

Effect of Heat Treatment and Light Exposure on the Antioxidant Activity of Flavonoids: The application of food processes can lead to a modification of both the structure and the activities of flavonoids. In this article, the effect of heat treatment and exposure to light on the antioxidant activity of 6 model flavonoid solutions (rutin, naringin, eriodictyol, mesquitol, luteolin, and luteolin 7-O-glucoside) was studied. Heated solutions of flavonoids do not exhibit toxicity on cells. The specific activities of superoxide dismutase and glutathione peroxide have been determined and have shown an increased impact on the potential anti-cancer of these solutions by enhancing their cellular antioxidant activity, as well as modulation of the oxidative stress.

Review of Evidence Available on Hesperidin-Rich Products as Potential Tools against COVID-19 and Hydrodynamic Cavitation-Based Extraction as a Method of Increasing Their Production: Based on recent computational and experimental studies, hesperidin, a bioactive flavonoid abundant in citrus peel, stands out for its high binding affinity to the main cellular receptors of SARS-CoV-2, outperforming drugs already recommended for clinical trials. Thus, it is very promising for prophylaxis and treatment of COVID-19, along with other coexistent flavonoids such as naringin, which could help restraining the proinflammatory overreaction of the immune system. Controlled hydrodynamic cavitation processes showed the highest speed, effectiveness and efficiency in the integral and green aqueous extraction of flavonoids, essential oils and pectin from citrus peel waste. This study reviews the recent evidence about hesperidin as a promising molecule, and proposes a feasible and affordable process based on hydrodynamic cavitation for the integral aqueous extraction of citrus peel waste resulting in hesperidin-rich products, either aqueous extracts or pectin tablets. The uptake of this process on a relevant scale is urged, in order to achieve large-scale production and distribution of hesperidin-rich products.

The Genoprotective Role of Naringin: Since ancient times, fruits and edible plants have played a special role in the human diet for enhancing health and maintaining youthfulness. The aim of our work was to determine the interactions between naringin, a natural ingredient of grapefruits, and DNA using an electrochemical biosensor. Electrochemical methods allow analyzing the damages occurring in the structure of nucleic acids and their interactions with xenobiotics. Our study showed that the changes in the location of electrochemical signals and their intensity resulted from the structural alterations in DNA. The signal of adenine was affected at lower concentrations of naringin, but the signal of guanine was unaffected in the same condition. The dynamics of changes occurring in the peak height and surface of adenine related to naringin concentration was also significantly lower.

Effect of Citrus Flavonoids, Naringin and Naringenin, on Metabolic Syndrome and Their Mechanisms of Action: Flavonoids are important natural compounds with diverse biologic activities. Citrus flavonoids constitute an important series of flavonoids. Naringin and its aglycone naringenin belong to this series of flavonoids and were found to display strong anti-inflammatory and antioxidant activities. Several lines of investigation suggest that naringin supplementation is beneficial for the treatment of obesity, diabetes, hypertension, and metabolic syndrome. A number of molecular mechanisms underlying its beneficial activities have been elucidated.

The Therapeutic Potential of Naringenin: A Review of Clinical Trials: Naringenin is a flavonoid belonging to flavanones subclass. It is widely distributed in several Citrus fruits, bergamot, tomatoes and other fruits, being also found in its glycosides form (mainly naringin). Several biological activities have been ascribed to this phytochemical, among them antioxidant, antitumor, antiviral, antibacterial, anti-inflammatory, antiadipogenic and cardioprotective effects. In fact, naringenin ability to improve endothelial function has been well-established.

On the Neuroprotective Effects of Naringenin: Pharmacological Targets, Signaling Pathways, Molecular Mechanisms, and Clinical Perspective: As a group of progressive, chronic, and disabling disorders, neurodegenerative diseases (NDs) affect millions of people worldwide, and are on the rise. NDs are known as the gradual loss of neurons; however, their pathophysiological mechanisms have not been precisely revealed. Due to the complex pathophysiological mechanisms behind the neurodegeneration, investigating effective and multi-target treatments has remained a clinical challenge.

Naringin Improves Diet-Induced Cardiovascular Dysfunction and Obesity in High Carbohydrate, High Fat Diet-Fed Rats: Obesity, insulin resistance, hypertension and fatty liver, together termed metabolic syndrome, are key risk factors for cardiovascular disease. Chronic feeding of a diet high in saturated fats and simple sugars, such as fructose and glucose, induces these changes in rats. Naturally occurring compounds could be a cost-effective intervention to reverse these changes. Flavonoids are ubiquitous secondary plant metabolites; naringin gives the bitter taste to grapefruit. This study has evaluated the effect of naringin on diet-induced obesity and cardiovascular dysfunction in high carbohydrate, high fat-fed rats. Naringin normalised systolic blood pressure and improved vascular dysfunction and ventricular diastolic dysfunction in high carbohydrate, high fat-fed rats. These beneficial effects of naringin may be mediated by reduced inflammatory cell infiltration, reduced oxidative stress, lowered plasma lipid concentrations and improved liver mitochondrial function in rats.

Naringin attenuates diabetic retinopathy by inhibiting inflammation, oxidative stress and NF-KB activation in vivo and in vitro: Naringin, an essential flavonoid, inhibits inflammatory response and oxidative stress in diabetes. However, whether naringin has beneficial effects on diabetic retinopathy (DR) remains unknown. Naringin exhibited anti-inflammatory and antioxidative effects as confirmed by the down-regulated pro-inflammatory cytokines, tumor necrosis factor alpha (TNF-a), interleukin-1b (IL-1b) and interleukin-6 (IL-6), and the up regulated antioxidants, glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) in DR rats. Moreover, we found that naringin inhibited HG induced proliferation, abnormal inflammatory response and oxidative stress in rMC1 cells. In addition, the enhanced nuclear translocation of NF-kB p65 in diabetic rat retina and HG-induced rMC1 cells was suppressed by naringin.

Naringin Levels in Citrus Tissues: The quantitative distribution of the flavanone-7-neohesperidoside, naringin, in seeds, seedlings, young plants, branches, flowers, and fruit of Citrus paradisi Macfad., cv Duncan was analyzed by radioimmunoassay. High levels of naringin were associated with very young tissue and lower levels were found in older tissues. Seed coats of ungerminated seeds and young shoots had high naringin concentrations whereas cotyledons and roots had very low concentrations. Light grown seedlings contained nearly twice as much naringin as etiolated seedlings and, in young plants and branches, the naringin content was highest in developing leaves and stem tissue. In flowers, the ovary had the highest levels of naringin, accounting for nearly 11 percent of the fresh weight. There was a net increase in the total naringin content of fruits during growth. However, due to the large increase in fruit size, there was a concomitant decrease in the naringin concentration as the fruit matured.

Antioxidant Potential of Naringenin Helps to Protect Liver Tissue from Streptozotocin-Induced Damage: [ Naringenin helps to mitigate STZ-induced liver complications by promoting antioxidant defence enzyme activities and increasing glutathione levels. ] Naringenin is a bioactive flavonoid found in grapes and citrus fruits including tangelo, blood orange, lemons, and tangerines. The aims of this study were to investigate the ability of naringenin to scavenge free radicals and determine its ability to protect animals from streptozotocin (STZ) -induced liver damage. Naringenin showed potent free radical scavenging activity in vitro. Naringenin effectively neutralized (a) hydroxyl radicals, (b) superoxide, (c) hydrogen peroxide, (d) nitric oxide radical, (e) DPPH, and (f) lipid peroxidation. In animals, administration of naringenin reduced lipid peroxidation and increased antioxidant levels. Analysis of liver sections showed the restoration of normal morphology upon treatment with naringenin.

The Citrus Flavanone Naringenin Protects Myocardial Cells against Age-Associated Damage: [ These results suggested that naringenin has antiaging effects on myocardial cells. ] In recent years, the health-promoting effects of the citrus flavanone naringenin have been examined. The results have provided evidence for the modulation of some key mechanisms involved in cellular damage by this compound. In particular, naringenin has been revealed to have protective properties such as an antioxidant effect in cardiometabolic disorders. In addition, cardiac markers of aging-induced damage, including radical oxidative species levels, mitochondrial metabolic activity, mitochondrial calcium buffer capacity, and estrogenic signaling functions, were also modulated by the compound. These results suggested that naringenin has antiaging effects on myocardial cells.

Naringenin inhibits alcoholic injury by improving lipid metabolism and reducing apoptosis in zebrafish larvae: [ Naringenin inhibited alcohol-induced liver steatosis and injury in zebrafish larvae by reducing apoptosis and DNA damage and by harmonizing alcohol and lipid metabolism. ] Alcoholic liver disease (ALD) includes a spectrum of hepatic abnormalities that range from isolated alcoholic steatosis to steatohepatitis and cirrhosis. Naringenin, a predominant flavanone in grapefruit, increases resistance to oxidative stress and inflammation and protects against multiple organ injury in various animal models. The present study showed that naringenin inhibited alcohol-induced liver steatosis and injury in zebrafish larvae by reducing apoptosis and DNA damage and by harmonizing alcohol and lipid metabolism.

Naringenin Prevents Dyslipidemia, Apolipoprotein B Overproduction, and Hyperinsulinemia in LDL Receptor–Null Mice With Diet-Induced Insulin Resistance: [ Naringenin, through its correction of many of the metabolic disturbances linked to insulin resistance, represents a promising therapeutic approach for metabolic syndrome. ] The citrus-derived flavonoid, naringenin, has lipid-lowering properties and inhibits VLDL secretion from cultured hepatocytes in a manner resembling insulin. We evaluated whether naringenin regulates lipoprotein production and insulin sensitivity in the context of insulin resistance in vivo.

Antidiabetic Properties of Naringenin: A Citrus Fruit Polyphenol: Type 2 diabetes mellitus (T2DM) is a metabolic disease characterized by insulin resistance and hyperglycemia and is associated with personal health and global economic burdens. Current strategies/approaches of insulin resistance and T2DM prevention and treatment are lacking in efficacy resulting in the need for new preventative and targeted therapies. In recent years, epidemiological studies have suggested that diets rich in vegetables and fruits are associated with health benefits including protection against insulin resistance and T2DM. Naringenin, a citrus flavanone, has been reported to have antioxidant, anti-inflammatory, hepatoprotective, nephroprotective, immunomodulatory and antidiabetic properties.

Topical Formulation Containing Naringenin: Efficacy against Ultraviolet B Irradiation-Induced Skin Inflammation and Oxidative Stress in Mice: Naringenin (NGN) exhibits anti-inflammatory and antioxidant activities, but it remains undetermined its topical actions against ultraviolet B (UVB)-induced inflammation and oxidative stress in vivo. In conclusion, a formulation containing NGN may be a promising approach to protecting the skin from the deleterious effects of UVB irradiation.

Preparation and Characterization of Naringenin-Loaded Elastic Liposomes for Topical Application: Excessive production of radical oxygen species in skin is a contributor to a variety of skin pathologies. Naringenin is a potent antioxidant. The purpose of the present study was to develop elastic liposomes for naringenin topical application. It has also been demonstrated that naringenin-loaded elastic liposome was stable after three months of storage and produced less skin irritation than that of the standard irritant group. The result suggests that elastic liposome is a promising carrier for naringenin topical application.

Polymeric micelles for potentiated antiulcer and anticancer activities of naringin: Naringin is one of the most interesting phytopharmaceuticals that has been widely investigated for various biological actions. Yet, its low water solubility, limited permeability, and suboptimal bioavailability limited its use. Therefore, in this study, polymeric micelles of naringin based on pluronic F68 (PF68) were developed, fully characterized, and optimized. As well, these micelles provoked pronounced antitumor activity assessed by potentiated in vitro cytotoxicity particularly against colorectal carcinoma cells and tumor growth inhibition when compared with free naringin. In conclusion, 1:50 naringin PF68 micelles can be represented as a potential stable nanodrug delivery system with prolonged release and enhanced antiulcer as well as antitumor activities.

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