Author: Anthony Russano Last Edited: April 2nd 2019, 11:52:04 PM

Naringin is a glycoside form of naringenin, which is a flavonoid belonging to flavanones subclass. It is commonly found in the pericarp of citrus fruits, bergamot, tomatoes and other fruits.

Naringenin and its glycoside (naringin) have been found in a variety of herbs and fruits, including grapefruit, bergamot, sour orange, tart cherries, tomatoes, cocoa, Greek oregano, water mint, drynaria as well as in beans. Ratios of naringenin to naringin vary among sources.

Healing Properties

  • Antioxidant: Naringin exhibits strong antioxidant potential.
  • Antibacterial:
  • Anti-inflammatory:
  • Antiadipogenic: counters adipogenesis (The formation of fatty tissue; lipogenesis).[1]
    • Weight Loss: A commercial polyphenolic extract from several Citrus fruits (Sinetrol-XPur), containing about 20% of naringenin, was tested in 95 healthy overweight volunteers (BMI ranging from 26 to 29.9 kg/m2) [100]. The main overweight-related endpoints were improved after 12-weeks randomized protocol (including waist and hip circumference, abdominal fat, body weight). Moreover, inflammatory and oxidative stress markers were all decreased.[1]
    • Naringenin promotes carbohydrate metabolism.[1]
  • Antiviral: Naringenin shows a dose-dependent inhibitory effect against dengue virus .[1]
    • Naringenin prevents intracellular replication of chikungunya virus.[1]
    • Naringenin inhibits assembly and long-term production of infectious hepatitis C virus particles in a dose-dependent manner.[1]
  • Angiogenic: Naringin exhibited pro-angiogenesis activity on the restoration of blood vessel loss.[2]
  • Brain Health: Naringenin is able to traverse the blood–brain barrier and to exert diverse neuronal effects
  • Chemopreventive:
  • DNA Repair: Naringenin has the ability to repair DNA. Cells exposed to naringenin, for a duration of 24h, had a 24% reduction in DNA damages.[1]
  • Heart Health: Cardioprotective
    • Promotes optimal mitochondrial function in the heart muscle.[3]
      • Counteracts fructose-induced cardiomyocyte (heart muscle) apoptosis (cell death).[3]
      • Naringin is able to suppress mitochondrial reactive oxygen species (ROS) production and mitochondrial dysfunction in cardiomyocytes (cardiac muscle cells) exposed to fructose.[3]
    • Antiatherogenic: prevents or inhibits atherogenesis (the formation of fatty plaques in the arteries).
    • Prevents Cardiac hypertrophy (a thickening of the walls of the heart due to high sugar diet, caused by mitochondrial dysfunction).[3]
  • Immunomodulator: modulates immune system activity.[1]
  • Lung Health: Naringin protects against acrolein-induced pulmonary injuries.[4]
  • Metabolism: A double-blinded, randomized, placebo-controlled clinical trial, involving 10 subjects per treatment group, showed that naringin is able to synergistically increase metabolic rate, without enhancing blood pressure and heart rates.[1]
  • Endothelial Health: promotes vascular endothelial growth factor.[2]
    • Naringenin's ability to improve endothelial function has been well-established.[1]
    • Postprandial endothelial dysfunction was reduced, probably through a specific flavanone’s metabolites action on nitric oxide.[1]
    • In a very interesting trial, the long-term effect of 340 mL of grapefruit juice/day, containing about 480 μM naringenin glycoside, was investigated on endothelial function. From the 48 healthy menopausal women recruited, arterial stiffness beneficial effects were found 6 months after treatment (carotid-femoral pulse wave velocity was significantly reduced).[1]

Disease / Symptom Treatment

  • Scar Formation: (scar tissue) Naringin inhibits the development of hypertrophic scars (A hypertrophic scar is a cutaneous condition characterized by deposits of excessive amounts of collagen which gives rise to a raised scar).[5]
    • Naringin inhibits the growth and motility of fibroblasts.
    • Naringin may be a new drug for the treatment of hypertrophic scars.[5]
  • Diabetes:
    • Insulin Resistance: naringenin potentiates intracellular signaling responses to low insulin doses by sensitizing hepatocytes to insulin.[1]
    • Naringin improves overall insulin sensitivity and glucose tolerance.[6]
  • Hepatitis C virus (HCV): The Naringenin flavanone has been described to reduce HCV secretion in infected cells by 80%.[1]
  • Fatty Liver: Naringenin impairs lipid accumulation in liver and thereby prevents fatty liver.[1]
  • Lung Cancer:[4]
  • Heart Disease: (Cardiovascular Disease) naringin has the potential to be developed as a therapeutic agent for diseases associated with insufficient angiogenesis, such as ischemia heart disease.[2]

Sources:

  1. Title: The Therapeutic Potential of Naringenin: A Review of Clinical Trials
    Author(s): Bahare Salehi, Patrick Valere Tsouh Fokou, Mehdi Sharifi-Rad, Paolo Zucca, Raffaele Pezzani , Natália Martins, and Javad Sharifi-Rad
    Institution(s): Student Research Committee, School of Medicine, Bam University of Medical Sciences, Bam 44340847, Iran; Antimicrobial and Biocontrol Agents Unit, Department of Biochemistry, Faculty of Science, University of Yaounde 1, Ngoa Ekelle, Annex Fac. Sci., Yaounde 812, Cameroon; Department of Medical Parasitology, Zabol University of Medical Sciences, Zabol 61663-335, Iran; Department of Biomedical Sciences, University of Cagliari, 09042 Cagliari, Italy; OU Endocrinology, Dept. Medicine (DIMED), University of Padova, via Ospedale 105, 35128 Padova, Italy; AIROB, Associazione Italiana per la Ricerca Oncologica di Base, 35128 Padova, Italy; Faculty of Medicine, University of Porto, Alameda Professor Hernâni Monteiro, 4200-319 Porto, Portugal; Institute for Research and Innovation in Health (i3S), University of Porto, 4200-135 Porto, Portugal; Zabol Medicinal Plants Research Center, Zabol University of Medical Sciences, Zabol 61615585, Iran; Department of Chemistry, Richardson College for the Environmental Science Complex, The University of Winnipeg, 599 Portage Avenue, Winnipeg, MB R3B 2G3, Canada
    Publication: Pharmaceuticals - MDPI AG, Basel, Switzerland
    Date: January 2019
    Abstract: 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. Nonetheless, most of the data reported have been obtained from in vitro or in vivo studies. Although some clinical studies have also been performed, the main focus is on naringenin bioavailability and cardioprotective action. In addition, these studies were done in compromised patients (i.e., hypercholesterolemic and overweight), with a dosage ranging between 600 and 800 μM/day, whereas the effect on healthy volunteers is still debatable. In fact, naringenin ability to improve endothelial function has been well-established. Indeed, the currently available data are very promising, but further research on pharmacokinetic and pharmacodynamic aspects is encouraged to improve both available production and delivery methods and to achieve feasible naringenin-based clinical formulations.
    Link: Source
    Citations:

  2. Title: Differential angiogenic activities of naringin and naringenin in zebrafish in vivo and human umbilical vein endothelial cells in vitro
    Author(s): Linmin Chen, Binrui Yang, Benqin Tanga, Guiy iGong, Hiotong Kam, Cheng Gao, Yan Chen, Ruibing Wang, Simon Ming Yuen Lee
    Institution(s): State Key Laboratory of Quality Research in Chinese Medicine and Institute of Chinese Medical Sciences, University of Macau, Macau, China; Department of Medical Science, Shunde Polytechnic, Foshan, China
    Publication: Journal of Functional Foods
    Date: 11 September 2018
    Abstract: Naringin, a flavanone glycoside, and naringenin, the aglycone of naringin, are commonly found in the pericarp of citrus fruits and have also been considered as potential bioactive flavanones. In the present study, treatment with naringenin showed an inhibitory effect on SIV formation in zebrafish embryos, which demonstrates its potential anti-angiogenic activity. In a chemically-induced blood vessel loss model in zebrafish, we found that naringin exhibited remarkably pro-angiogenesis activity on the restoration of blood vessel loss, and significantly reversed VRI-induced down-regulation of flt1 mRNA expression. In an in vitro study of cultured human umbilical vein endothelial cells (HUVEC), our results showed that naringin specifically promoted HUVEC migration but not proliferation. Taken together, these results suggest that naringin and naringenin have differential angiogenesis activities where naringin, as a novel angiogenic agent, has the potential to be developed as a therapeutic agent for diseases associated with insufficient angiogenesis, such as ischemia heart disease.
    Link: Source
    Citations:

  3. Title: Amelioration of High Fructose-Induced Cardiac Hypertrophy by Naringin
    Author(s): Jung Hyun Park, Hyeong Jun Ku, Jae Kyeom Kim, Jeen-Woo Park, & Jin Hyup Lee
    Institution(s): Department of Food and Biotechnology, Korea University, Sejong, Korea; School of Life Sciences and Biotechnology, BK21 Plus KNU Creative BioResearch Group, College of Natural Sciences, Kyungpook National University, Taegu, Korea; School of Human Environmental Sciences, University of Arkansas, Fayetteville, Arkansas, USA;
    Publication: Scientific Reports
    Date: June 21, 2018
    Abstract: Heart failure is a frequent unfavorable outcome of pathological cardiac hypertrophy. Recent increase in dietary fructose consumption mirrors the rise in prevalence of cardiovascular diseases such as cardiac hypertrophy leading to concerns raised by public health experts. Mitochondria, comprising 30% of cardiomyocyte volume, play a central role in modulating redox-dependent cellular processes such as metabolism and apoptosis. Furthermore, mitochondrial dysfunction is a key cause of pathogenesis of fructose-induced cardiac hypertrophy. Naringin, a major flavanone glycoside in citrus species, has displayed strong antioxidant potential in models of oxidative stress. In this study, we evaluated protective effects of naringin against fructose-induced cardiac hypertrophy and associated mechanisms of action, using in vitro and in vivo models. We found that naringin suppressed mitochondrial ROS production and mitochondrial dysfunction in cardiomyocytes exposed to fructose and consequently reduced cardiomyocyte hypertrophy by regulating AMPK-mTOR signaling axis. Furthermore, naringin counteracted fructose-induced cardiomyocyte apoptosis, and this function of naringin was linked to its ability to inhibit ROS-dependent ATM-mediated p53 signaling. This result was supported by observations in in vivo mouse model of cardiac hypertrophy. These findings indicate a novel role for naringin in protecting against fructose-induced cardiac hypertrophy and suggest unique therapeutic strategies for prevention of cardiovascular diseases.
    Link: https://doi.org/10.1038/s41598-018-27788-1
    Citations:

  4. Title: Naringin protects acrolein-induced pulmonary injuries through modulating apoptotic signaling and inflammation signaling pathways in mice
    Author(s): Jae Kyeom Kim, Jung Hyun Park, Hyeong Jun Ku, Sung Hwan Kim, Ye Jin Lim, Jeen Woo Park, Jin Hyup Lee
    Institution(s): School of Human Environmental Sciences, University of Arkansas, Fayetteville, AR 72703, USA b Department of Food and Biotechnology, Korea University, Sejong 30019, South Korea, School of Life Sciences, Kyungpook National University, Taegu, 37224, South Korea
    Publication: The Journal of Nutritional Biochemistry
    Date: 6 June 2018
    Abstract: Acrolein (2-propenal) is ubiquitous in the environment and connections exist between acrolein exposure and lung cancer risk. Here we investigated the effects of naringin on acrolein induced-lung injuries in mice. Male C57BL/6 mice were allocated into four groups: Vehicle group (no acrolein), Naringin only group (80 mg of naringin/kg bw + no acrolein), Acrolein group (ACR group; acrolein), and Naringin + Acrolein group (NAG+ACR group; 80 mg of naringin/kg bw and acrolein). The mice were subjected acute acrolein inhalation (10 ppm for 12 h) in an inhalation chamber and naringin was intraperitoneally administered to the mice one hour before acrolein exposure. The results demonstrated that, in the NAG+ACR group, pulmonary injuries (e.g., airspace enlargement, lung inflammation) were all significantly improved compared to the ACR group. Further, key markers of MAPK signaling (e.g., p-p38, p-JNK), p53 signaling markers (e.g., p-Chk2, p53), NF-κB signaling axis (e.g., IL-1 β, TNF-α), and oxidative damage markers (e.g., GSSG:GSH ratio, oxidative DNA damage) were all effectively mitigated by the naringin treatment. Naringin provided protection against the environmental toxicant, acrolein, in mice lung via modulating MAPK, p53, and NF-κB signaling pathways and our data may provide significant implications considering the prevalence of acrolein.
    Link: https://doi.org/10.1016/j.jnutbio.2018.05.012
    Citations:

  5. Title: Naringin suppresses the growth and motility of hypertrophic scar fibroblasts by inhibiting the kinase activity of Akt
    Author(s): Yingli Song, Bingyu Guo, Shudan Ma, Peng Chang, Kai Tao
    Institution(s): Reconstructive and Plastic Surgery, The General Hospital of Shenyang Military Region, Shenyang, PR China
    Publication: Biomedicine & Pharmacotherapy
    Date: September 2018
    Abstract: Hypertrophy is a very common pathologic phenomenon of scar hyperplasia after human skin injury and wound healing. In this article, we first proved that naringin could inhibit the proliferation of fibroblasts by MTT experiments. Flow cytometry indicated that naringin could block the cell cycle and promote apoptosis. Transwell experiments showed that naringin could inhibit the motility activity of fibroblasts. We also found that naringin specifically inhibits the kinase activity of Akt and the phosphorylation of Akt in hypertrophic scar fibroblasts by Kinase-Glo, western blot and real-time PCR assays. Subsequently, western blots and real-time PCR indicated that naringin can inhibit phosphorylation of Akt and downstream proteins of Akt. Our data demonstrated that naringin inhibits the development of hypertrophic scars, at least to a certain extent, by its inhibition of Aktp.
    Link: https://doi.org/10.1016/j.biopha.2018.06.103
    Citations:

  6. Title: Efficacy of bergamot: From anti‐inflammatory and anti‐oxidative mechanisms to clinical applications as preventive agent for cardiovascular morbidity, skin diseases, and mood alterations
    Author(s): Simone Perna Daniele Spadaccini Leonardo Botteri Carolina Girometta Antonella Riva Pietro Allegrini Giovanna Petrangolini Vittoria Infantino Mariangela Rondanelli
    Institution(s): Department of Earth and Environmental Sciences, Mycology and Plant Pathology Laboratory, Pavia, Italy; Department of Biology, College of Science, University of Bahrain, Zallaq, Bahrain; Research and Development Unit, Indena, Milan, Italy; Department of Public Health, Experimental and Forensic Medicine, Section of Human Nutrition, Endocrinology and Nutrition Unit, Azienda di Servizi alla Persona, University of Pavia, Pavia, Italy IRCCS Mondino Foundation, Pavia, Italy
    Publication: Food Science & Nutrition
    Date: January 2019
    Abstract: We summarize the effects of bergamot (extract, juice, essential oil, and polyphenolic fraction) on cardiovascular, bone, inflammatory, skin diseases, mood alteration, anxiety, pain, and stress. This review included a total of 31 studies (20 studies on humans with 1709 subjects and 11 in animals (rats and mice)). In humans, bergamot‐derived extract (BE) exerts positive effects on hyperlipidemia with an oral dose from 150 mg to 1000 mg/day of flavonoids administered from 30 to 180 days, demonstrating an effect on body weight and in modulating total cholesterol, triglycerides, LDL, and HDL. Studies in animals confirm promising data on glucose control (500/1000 mg/day of BE with a treatment lasting 30 days) are available in rats. In animals models, bergamot essential oil (BEO, 10 mg/kg or 20 mg/kg daily for 20 weeks) increases bone volume, decreases psoriatic plaques, increases skin collagen content, and promotes hair growth. Bergamot juice (20 mg/kg) is promising in terms of pro‐inflammatory cytokine reduction. In humans, aromatherapy (from 15 to 30 min) does not appear to be useful in order to reduce stress, anxiety, and nausea, compared to placebo. Compared to baseline, BE topical application and BEO aromatherapy reduce blood diastolic and systolic pressure and could have a significant effect on improving mental conditions.
    Link: Source
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