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Naringenin

Naringenin

Healing Properties

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). 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.[1:1]

  • Naringenin promotes carbohydrate metabolism.[1:2]

Antiviral

Naringenin shows a dose-dependent inhibitory effect against dengue virus .[1:3]

  • Naringenin prevents intracellular replication of chikungunya virus.[1:4]
  • Naringenin inhibits assembly and long-term production of infectious hepatitis C virus particles in a dose-dependent manner.[1:5]

Anti-inflammatory

Neuroinflammation

Naringenin-loaded nanoparticles (Nar-NPs) significantly reduced neuroinflammatory markers in brain tissue, outperforming donepezil monotherapy across multiple endpoints.[2]

  • Nar-NPs reduced nitrite levels by 48.9% compared to scopolamine-alone controls (p<0.001).[2:1]
  • Pro-inflammatory cytokines IL-6, TNF-α, and IL-1β were reduced by 41.5%, 37.6%, and 49.7%, respectively (all p<0.001).[2:2]
  • The combination of Nar-NPs with donepezil restored all neuroinflammatory markers to levels comparable to normal controls, indicating additive/complementary neuroprotection (nitrite: 161.77 vs. control 160.55; TNF-α: 10.85 vs. control 12.85; p>0.05).[2:3]
  • Anti-inflammatory action likely involves downregulation of NF-κB and iNOS signaling pathways.[2:4]

Antioxidant

Brain Antioxidant Defense

Naringenin nanoparticles potently restored brain antioxidant enzyme activity and reduced oxidative damage in a scopolamine-induced neurotoxicity model, outperforming donepezil monotherapy.[2:5]

  • Nar-NPs restored glutathione (GSH) levels by 105.6% compared to scopolamine-only controls (p<0.001).[2:6]
  • Superoxide dismutase (SOD) activity was restored by 208.0%, superior to donepezil which restored SOD by only 124.6% (p<0.01).[2:7]
  • Catalase (CAT) activity was restored by 84.5% (p<0.001).[2:8]
  • Lipid peroxidation marker malondialdehyde (MDA) was reduced by 39.8%, approaching near-complete normalization (1.90 nmol/mg tissue vs. control 2.13 nmol/mg tissue, p=0.06).[2:9]
  • Combination therapy (Nar-NPs + donepezil) restored GSH and SOD to control-equivalent levels (8.08 μmol/g tissue and 24.42 U/mg tissue, respectively).[2:10]

Brain Health

Naringenin is able to traverse the blood–brain barrier and to exert diverse neuronal effects.[2:11]

Neuroprotection

Naringenin-loaded nanoparticles (Nar-NPs) demonstrated multi-domain neuroprotective effects in a scopolamine-induced cholinergic impairment model, a well-established preclinical proxy for cholinergic dysfunction-related cognitive decline.[2:12]

  • Nar-NPs significantly reversed scopolamine-induced spatial memory deficits in the Morris Water Maze, reducing escape latency from 29.38±0.54 seconds to 18.85±0.42 seconds (p<0.001 vs. scopolamine group).[2:13]
  • Target quadrant time increased from 19.38±0.54% to 32.92±0.61%, and platform crossings were restored from 2.43±0.26 to 4.65±0.27.[2:14]
  • The combination of Nar-NPs with low-dose donepezil produced the most pronounced cognitive outcomes, nearly normalizing all parameters (escape latency: 11.85±0.27 sec; target time: 41.02±0.61%; crossings: 6.45±0.27).[2:15]
  • Nar-NPs alone (without scopolamine challenge) improved cognitive performance beyond normal controls, indicating possible nootropic effects.[2:16]

GABAergic Signaling Modulation

Naringenin modulates GABAergic neurotransmission via interaction with GABRA5α, which helps regulate neuronal excitability and guard against excitotoxicity.[2:17]

  • Scopolamine reduced GABRA5α expression by 50%; Nar-NPs treatment achieved an 80% restoration, compared to only 40% restoration with donepezil (p<0.001).[2:18]
  • Molecular docking reveals naringenin binds GABRA5α with a binding affinity of ΔG = -6.59 kcal/mol, forming hydrogen bonds with residues TYR157 and THR160, π-π stacking with PHE200, and van der Waals interactions with LEU204.[2:19]
  • The IC₅₀ for GABRA5α inhibition by Nar-NPs was 20.3 ± 1.2 μM (95% CI: 18.9–21.7 μM).[2:20]

GSK-3β Inhibition

Naringenin inhibits glycogen synthase kinase-3β (GSK-3β), a kinase centrally involved in tau phosphorylation and neuroinflammation in neurodegenerative disorders.[2:21]

  • Scopolamine increased GSK-3β expression by 150%; Nar-NPs reduced this excess by 52%, compared to 30% reduction with donepezil (p<0.001).[2:22]
  • Molecular docking shows naringenin binds the ATP-binding pocket of GSK-3β (ΔG = -6.90 kcal/mol), forming hydrogen bonds with VAL135, electrostatic interactions with ASP133, π-π stacking with TYR134, and a salt bridge with LYS85.[2:23]
  • The IC₅₀ for GSK-3β inhibition was 15.1 ± 0.8 μM (95% CI: 14.2–16.0 μM).[2:24]

Hippocampal Preservation

Histological examination confirmed structural neuroprotection by Nar-NPs in hippocampal tissue.[2:25]

  • Scopolamine-treated animals showed marked neuropil vacuolation, neuronal degeneration, microgliosis, necrosis, and architectural disruption (histological score 3.2 ± 0.3).[2:26]
  • Nar-NPs treatment reduced histological pathology score to approximately 0.8 ± 0.2, representing ~85% structural recovery in the hippocampus (p<0.001).[2:27]
  • Combined therapy (Nar-NPs + donepezil) produced nearly normal hippocampal architecture with minimal vacuolation and absent microgliosis or necrosis.[2:28]

pERK Pathway Restoration

Naringenin nanoparticles restore pERK expression, a key mediator of memory storage and pro-survival synaptic plasticity.[2:29]

  • Scopolamine decreased pERK levels by 40%; Nar-NPs restored pERK by 42%, compared to only 30% restoration with donepezil (p<0.001).[2:30]
  • Full normalization of pERK expression was achieved with combination therapy.[2:31]

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.[1:6]

Hypolipidemic

Naringenin nanoparticles (Nar-NPs) significantly corrected lipid dysregulation induced by scopolamine-associated neurotoxicity, demonstrating broader metabolic neuroprotective effects.[2:32]

  • Scopolamine induced substantial lipid dysregulation: total cholesterol increased by 39.8%, triglycerides by 68.2%, and HDL-C decreased by 51.0% (all p<0.001 vs. normal controls).[2:33]
  • Nar-NPs decreased total cholesterol by 23.2% (p<0.001) and triglycerides by 37.7% (p<0.001) compared to the scopolamine-only group.[2:34]
  • Nar-NPs increased HDL-C by 69.0% (p<0.001), outperforming donepezil which increased HDL-C by only 25.1% (p<0.01).[2:35]
  • Combination therapy (Nar-NPs + donepezil) reduced triglycerides by 45.2% and increased HDL-C by 88.2%, approaching normal levels (35.2 mg/dL vs. control 38.2 mg/dL, p=0.06).[2:36]

Endothelial Health

Promotes vascular endothelial growth factor.[3]

  • Naringenin’s ability to improve endothelial function has been well-established.[1:7]
  • Postprandial endothelial dysfunction was reduced, probably through a specific flavanone’s metabolites action on nitric oxide.[1:8]
  • 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).[1:9]

Disease / Symptom Treatment

Diabetes

Insulin Resistance

Naringenin potentiates intracellular signaling responses to low insulin doses by sensitizing hepatocytes to insulin.[1:10]

  • Naringin improves overall insulin sensitivity and glucose tolerance.[4]

Hepatitis C virus (HCV)

The Naringenin flavanone has been described to reduce HCV secretion in infected cells by 80%.[1:11]

Alzheimer’s Disease / Cognitive Decline

Naringenin-loaded nanoparticles (Nar-NPs) demonstrate multi-domain neuroprotection in an acute scopolamine-induced cholinergic impairment model relevant to Alzheimer’s disease-associated cognitive dysfunction.[2:37]

  • Nar-NPs significantly reversed scopolamine-induced spatial learning and memory deficits as measured by the Morris Water Maze test (p<0.001).[2:38]
  • Nar-NPs modulate key molecular targets implicated in neurodegeneration: upregulating GABRA5α (inhibitory neurotransmission), inhibiting GSK-3β (tau hyperphosphorylation pathway), and restoring pERK (synaptic plasticity signaling).[2:39]
  • Nar-NPs exhibited superior efficacy compared to donepezil monotherapy in restoring GABRA5α (80% vs. 40% recovery) and pERK (42% vs. 30% recovery).[2:40]
  • The combination of Nar-NPs with low-dose donepezil produced additive/complementary neuroprotection, normalizing all behavioral, biochemical, and histopathological markers to near-control levels.[2:41]
  • Note: the scopolamine model reflects acute cholinergic dysfunction and its downstream oxidative/inflammatory consequences; it does not recapitulate the chronic amyloid-β and tau proteinopathy hallmarks of Alzheimer’s disease. Translational relevance to disease modification requires further validation in transgenic models (e.g., APP/PS1, 3xTg-AD).[2:42]

Fatty Liver

Naringenin impairs lipid accumulation in liver and thereby prevents fatty liver.[1:12]

  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
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  2. Title: Naringenin-Loaded Nanoparticles Ameliorate Scopolamine-Induced Neurotoxicity
    Publication: Scientific Reports
    Date: March 2026
    Study Type: Animal Study (In Vivo, In Vitro, In Silico)
    Author(s): Abdullah Alqarni, Amr A. Abd-Elghany, Mohamed A. Bedewi, Adel M. Alqarni, Helal G. Alanazi, Mohammed A. Hussein, Nawal Ibrahim El-Adl, Ahmed Salah
    Institution(s): Radiology and Medical Imaging Department, College of Applied Medical Sciences, Prince Sattam Bin Abdul-Aziz University, Al-Kharj, KSA; Department of Internal Medicine, College of Medicine, Prince Sattam Bin Abdulaziz University, Al-Kharj, KSA; Department of Medical Laboratory, College of Applied Medical Sciences, Prince Sattam Bin Abdul-Aziz University, Al-Kharj, KSA; Biochemistry Department, Faculty of Applied Medical Sciences, October 6 University, Giza, Egypt; R&D Department, Pharco B International for Chemicals (PBIC), Egypt; Department of Molecular Biology, Genetic Engineering and Biotechnology Research Institute, University of Sadat City, Egypt
    Abstract: Naringenin-loaded nanoparticles (Nar-NPs) were prepared via solvent evaporation (Span-80/Tween-80) and characterized as spherical (~95 nm), monodisperse (PDI<0.2), and negatively charged (ζ ≈ -28.5 mV) with high encapsulation efficiency (89.2 ± 3.1%) and sustained release (Korsmeyer-Peppas, n≈0.56). In vivo, Nar-NPs attenuated scopolamine-induced cognitive deficits (Morris Water Maze), normalized antioxidant defenses (GSH, SOD, CAT), reduced neuroinflammatory mediators (IL-6, TNF-α, IL-1β), corrected lipid dysregulation (TC, TG, HDL-C), and reinforced hippocampal architecture. Molecular docking indicated naringenin binding affinity for GABRA5α (ΔG = -6.59 kcal/mol) and GSK-3β (ΔG = -6.90 kcal/mol). Combination with donepezil produced additive/complementary effects greater than either monotherapy alone. LD₅₀ was 755 mg/kg, yielding an >18-fold safety margin over the therapeutic dose.
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  3. 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: ↩︎

  4. 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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