Naringin

Naringin: A Comprehensive Reference

1. Identity, Chemistry, and Natural Sources

Chemical Identity

Naringin is a flavanone-7-O-glycoside between the flavanone naringenin and the disaccharide neohesperidose. Its molecular formula is C₂₇H₃₂O₁₄ with a molecular weight of 580.4 g/mol; it is a flavanone-7-O-glycoside containing the flavanone naringenin at the 7-carbon position and two sugar (rhamnose) units attached to its aglycone portion, appearing as a white to light yellow crystalline powder. Naringin belongs to the flavanone family of flavonoids and is considered the principal flavonoid constituent of the citrus family, including tomatoes, grapefruits, and oranges.

Naringin belongs to the flavonoid family, which is characterized by the presence of 15 carbon atoms in three rings: two benzene rings connected by a three-carbon chain. Naringin contains the basic flavonoid structure along with one rhamnose and one glucose unit attached to the phenol naringenin; the steric hindrance provided by the two sugar units makes naringin less potent as an antioxidant than its aglycone.

A key distinction in nomenclature: naringin (the glycoside) should not be confused with naringenin, its aglycone metabolite. Naringin occurs naturally in an inactive form and is converted into its active form, naringenin, by bacteria belonging to the gut microbiome. In humans, naringin is metabolized to the aglycone naringenin (which is not bitter) by naringinase present in the gut. More specifically, naringin is hydrolyzed into rhamnose and prunin by naringinase, which also possesses l-rhamnosidase activity; D-glucosidase subsequently catalyzes the hydrolysis of prunin into glucose and naringenin.

Biosynthesis in Plants

Flavonoid biosynthesis in plants uses a phenylpropanoid metabolic pathway in which the amino acid phenylalanine is converted to 4-coumaroyl-CoA. This is combined with three units of malonyl-CoA to yield chalcones, which contain two phenyl rings. In the main pathway, the enzymes chalcone synthase and chalcone isomerase produce (S)-naringenin. Sugar units are then incorporated by transferase enzymes that use UDP-glucose (giving prunin) followed by UDP-rhamnose to yield naringin.

Natural Sources and Concentration

The flavonoid naringin occurs naturally in citrus fruits, especially in grapefruit, where it is responsible for the fruit's bitter taste. Citrus fruits provide a large number of flavonoids in the diet, and naringin is mostly found in the peel of grapefruit, lime, and their variations. The quantity of naringin in fruit is usually determined by its maturity: immature fruit has a higher concentration. Fruit maturity is an essential consideration in juice processing, particularly in grapefruit juices, which have a high level of bitterness.

The typical concentration of naringin in grapefruit juice is around 400 mg/L. Naringenin (the aglycone) is widespread in various citrus fruits including grapefruits, lemons, limes, oranges, mandarins, pomelos, and bergamots, but also in vegetables, herbs, and products of plant origin such as juices or wine. The content in plants is different and depends on the variety and part (flavedo, albedo, pith, seeds, membranes) of fruits. In plants, naringenin usually occurs in glycoside form: naringin (naringenin-7-rhamnoglucoside) and narirutin (naringenin-7-glucoside).

Naringin is a natural dihydroflavone which mainly exists in citrus fruits of the Rutaceae family, as well as traditional Chinese medicines such as trifoliate orange, fingered citron, exocarpium citri grandis, and rhizoma drynaria. Beyond citrus, the best sources of the aglycone naringenin include grapefruit, sour orange, tart cherries, tomatoes, grapes, and Greek oregano; it is also found in smaller amounts in bergamot, beans, fenugreek, milk thistle, tea, coffee, cocoa, and red wine.

Common Forms and Preparations

Naringin is commercially available in several forms for dietary supplementation and research purposes. It can be isolated directly from grapefruit and other citrus peels by solvent extraction. In commercial grapefruit juice production, the enzyme naringinase can be used to remove the bitterness (debittering) created by naringin. As a dietary supplement, naringin is typically sold as a standardized powder or capsule, often derived from grapefruit peel or immature bitter orange (Citrus aurantium). It is slightly soluble in water and completely soluble in hot water, ethanol, acetone, and dilute acetic acid. Due to its poor aqueous solubility and limited oral bioavailability, research has also explored advanced delivery forms including nanosuspensions, nanoparticles, and cyclodextrin complexes to improve absorption.

2. Traditional and Historical Use

Traditional Chinese Medicine

Since ancient times, citrus fruits have been utilized as natural herbal treatments in traditional medicine. Citrus peel has been utilized in traditional Chinese medicine to enhance digestion, minimize gastric gas, bloating, and clear congestion. The dried, immature fruit of Citrus aurantium L., known as 'Zhiqiao' in Chinese, has been used to treat cardiovascular diseases in traditional Chinese medicine for centuries. Naringin is a naturally occurring flavonoid found in plants of the Citrus genus that has historically been used in traditional Chinese medical regimens for the treatment of osteoporosis.

Ayurvedic and Other Traditional Systems

In the context of traditional plant medicine, naringin has been identified as a marker phytochemical — specifically a flavanone glycoside derived from naringenin and neohesperidose — found in Drynaria quercifolia, a fern used in traditional medicine. Citrus species bearing naringin-rich peels have featured in multiple traditional Asian medicine systems where preparations of dried or decocted peel were used for digestive complaints, cough, and circulation.

Discovery as a Distinct Chemical Entity

As a specific compound, naringin was isolated and identified in the 20th century and does not appear in historical herbal records by that name. However, its source — grapefruit — has a more substantial history. Asahina and Inubuse found the chemical blueprints for naringin in 1928. The isolation and characterization of naringenin (its aglycone) is credited to early-20th-century phytochemical work and is distinct from the compound's ancient usage in whole-plant preparations.

3. Key Constituents, Active Compounds, and Mechanisms of Action

Primary Active Compound: Naringenin (Aglycone)

When naringin is ingested, the metabolically active form reaching systemic circulation is primarily naringenin, the aglycone. Naringenin (5,7,4′-trihydroxyflavanone) is an aglycone, a derivative of hydrogenated flavone, belonging to the group of flavonoid compounds, which are part of a huge group of polyphenols. Much of the pharmacological activity attributed to naringin in the literature is understood to be mediated via naringenin after intestinal hydrolysis.

Antioxidant Mechanisms

Naringin and naringenin are powerful antioxidants that can destroy free radicals and attenuate their formation. Naringin has been shown to neutralize reactive oxygen species (ROS), scavenge superoxide, suppress xanthine oxidase, decrease lipid peroxidation, and decrease the permeability of oxygen-stimulated potassium erythrocytes. Naringin increases antioxidant enzyme activity and glutathione content, reduces lipid peroxidation, and inhibits inflammatory cytokines. It also activates endogenous antioxidant defense enzymes: naringenin induces nuclear factor (erythroid-derived 2)-like 2 (Nrf2) / heme oxygenase (HO)-1 signaling in experimental hepatic inflammation models.

Anti-inflammatory Mechanisms

The flavanones naringin and naringenin have various anti-inflammatory properties and act via the inhibition of regulatory enzymes, changes in arachidonic acid metabolism, modulation of gene expression, and effects on transcription factors that play essential roles in controlling mediators involved in inflammation. Naringin is a natural anti-inflammatory antioxidant that actively participates in the body's immune response and maintains the integrity of the immune barrier; it can enhance autophagy flux by activating the AMPK/SIRT1 pathway, protecting cells from TNF-α-induced inflammation, oxidative stress, and loss of cellular homeostasis.

Research findings have revealed that naringin modulates many signaling cascades, such as Rho/ROCK and PPAR/STAT1, PIP3/AKT and KEAP1/Nrf2, and IκB/NF-κB and MAPK/Nrf2/HO-1, to potentially protect against sepsis-induced organ injury. Naringin has been shown to reduce the inflammatory response, oxidative stress, and endoplasmic reticulum stress by inhibiting the TLR4/NF-κB signaling pathway.

Metabolic and Lipid-Regulatory Mechanisms

Several lines of investigation suggest that naringin supplementation is beneficial for the treatment of obesity, diabetes, hypertension, and metabolic syndrome, and a number of molecular mechanisms underlying its beneficial activities have been elucidated, though their effect on obesity and metabolic disorder remains to be fully established. One proposed mechanism involves AMPK-PGC-1α pathway activation, which regulates fat metabolism and mitochondrial biogenesis. A mechanism for glucose tolerance improvement appears to involve inhibition of dipeptidyl peptidase 4 (DPP-4) by naringin, which increases glucagon-like peptide 1 (GLP-1).

Osteogenic Mechanisms

Emerging studies indicate that naringin may promote osteogenic differentiation, inhibit osteoclast formation, and exhibit protective effects against osteoporosis; many signaling pathways, such as BMP-2, Wnt/β-catenin, and VEGF/VEGFR, participate in the biological actions of naringin in mediating the pathological development of osteoporosis. Specifically, naringin has been shown to induce osteoblastic differentiation of bone marrow stromal cells by activating the BMP2/Runx2/Osterix signaling pathway and by promoting regulation of estrogen receptor pathway protein expression.

Neuroprotective Mechanisms

Naringin can exert neuroprotective effects through a variety of mechanisms, including the BDNF/CREB/TrkB signaling pathway, TLR4/NF-κB signaling pathway, renin-angiotensin system, amyloid-β metabolism, tau protein hyperphosphorylation, acetylcholinergic system, oxidative stress, and apoptosis. The intracellular mechanisms responsible for anti-apoptotic activity and neuroprotective effects are connected with the inhibition of caspase-3, activation of PI3K/AKT, and modulation of GSK-3β signaling pathways.

Cardiovascular Mechanisms

Naringin consistently exhibits antioxidant, anti-inflammatory, and vasoprotective effects; mechanistic studies have highlighted modulation of key signaling pathways including PI3K/Akt, NF-κB, Nrf2, the renin-angiotensin system (RAS), and enhancement of KATP channel expression, as well as its ability to inhibit apoptosis, autophagy, and ferroptosis.

4. Scientific Evidence by Health Area

4.1 Cardiovascular Health and Lipid Metabolism

Naringin has garnered significant attention over the past two decades for its potential cardiovascular benefits. A systematic review (2025) evaluated the effects of naringin on endothelial function and myocardial performance, with particular emphasis on ischemia-reperfusion (I/R) injury, based on literature published from January 2000 to June 2025. A comprehensive search of PubMed, Scopus, EMBASE, and Web of Science databases was performed, and a total of 62 studies were included and categorized into three domains: cellular models, animal studies, and human trials.

In animal models, naringin improved endothelium-dependent vasorelaxation, reduced infarct size, and preserved myocardial function. Although limited, human trials reported beneficial effects on lipid profiles, arterial stiffness, and adiponectin levels. Naringin demonstrates strong potential as a dietary adjunct for cardiovascular protection, especially in the context of ischemic injury and vascular dysfunction; however, further well-designed clinical trials are needed to define optimal dosing strategies and improve its bioavailability in humans.

In human clinical research specifically: dyslipidemic patients treated with a commercial bergamot-derived extract containing naringin showed plasmatic lipid reduction and an improved lipoprotein profile after 6 months. The same glycoside was also able to decrease total plasma cholesterol levels and to enhance antioxidant defenses in hypercholesterolemic subjects. Jung and colleagues prescribed 400 mg naringin per capsule per day, and after 8 weeks reported a decrease in LDL-cholesterol levels and an increase in antioxidant enzyme activity, specifically superoxide dismutase and catalase.

One grapefruit daily for 30 days has been used in a clinical trial to improve lipid profiles. Fresh grapefruit, grapefruit juice, and grapefruit capsules for 6 or 12 weeks, with naringin doses of the formulations ranging from 81 to 142 mg/day, have been used in randomized controlled trials evaluating effects on cardiovascular risk factors in obese adults. In a trial of healthy postmenopausal women, 340 mL/day of grapefruit juice (providing 201 mg/day of naringenin) was administered for 6 months to evaluate effects on arterial stiffness.

Evidence strength: Most of the data reported has 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. Clinical studies were largely done in compromised patients (i.e., hypercholesterolemic and overweight), with a dosage ranging between 600 and 800 μM/day, while the effect on healthy volunteers remains debatable. The totality of evidence is preliminary; large, well-controlled RCTs specifically using isolated naringin are lacking.

4.2 Metabolic Syndrome, Diabetes, and Obesity

Naringin and its aglycone naringenin have been found to display strong anti-inflammatory and antioxidant activities, and several lines of investigation suggest naringin supplementation is beneficial for the treatment of obesity, diabetes, hypertension, and metabolic syndrome. A systematic review of naringin's preventive effects on metabolic syndrome identified beneficial findings in animal studies of hypertension, diabetes, dyslipidemia, and obesity.

Specific preclinical dosage findings from animal studies provide context: rats treated with 10 mg/kg of naringin for 46 days showed decreased MDA levels and increased levels of SOD and catalase in diabetic models. Naringin-treated diabetic rats at a dosage of 50 mg/kg for 42 days significantly ameliorated serum and hepatic oxidative stress markers.

Evidence strength: The therapeutic uses of these flavonoids are significantly limited by the lack of adequate clinical evidence. The dosage used in animal studies might not be achievable in human trials, and adequate investigation needs to be conducted to confirm naringin's effects on humans. At present, no large-scale RCTs specifically using naringin as an isolated intervention for metabolic syndrome endpoints in humans have been published.

4.3 Bone Health and Musculoskeletal Disorders

Emerging studies indicate that naringin may promote osteogenic differentiation, inhibit osteoclast formation, and exhibit protective effects against osteoporosis in vivo and in vitro. The anti-inflammatory, anti-oxidative stress, and anti-apoptosis abilities of naringin also demonstrate its beneficial effects against bone and cartilage disorders, including intervertebral disc degeneration, osteoarthritis, rheumatoid arthritis, bone and cartilage tumors, and tibial dyschondroplasia.

Naringin represents a naturally abundant, cost-efficient agent whose potential for use in novel musculoskeletal biotherapies warrants further exploration through human studies. A review of the literature examined cellular mechanisms of action on bone resident cells and the bone microenvironment, as well as in vivo evidence of naringin's osteostimulative and chondroprotective properties in the setting of osteolytic bone disease.

Evidence strength: Evidence is primarily preclinical (in vitro and animal models). Naringin represents a naturally abundant, cost-efficient agent whose potential for use in novel musculoskeletal biotherapies warrants re-visiting and further exploration through human studies. No adequately powered human clinical trials have yet demonstrated fracture risk reduction or significant bone mineral density improvement with naringin supplementation.

4.4 Neuroprotection and Neurological Disorders

Possible therapeutics for neurodegenerative disorders include naringin and naringenin polyphenols. New experimental evidence shows that these polyphenols exert a wide range of pharmacological activity with attention paid to neurodegenerative conditions. Naringin can exert neuroprotective effects through a variety of mechanisms, including the BDNF/CREB/TrkB signaling pathway, TLR4/NF-κB signaling pathway, renin-angiotensin system, amyloid-β metabolism, tau protein hyperphosphorylation, acetylcholinergic system, oxidative stress, and apoptosis.

In preclinical models of Alzheimer's disease: in an Aβ-induced mouse model of AD, oral administration of naringenin resulted in the amelioration of memory deficit; naringenin effectively rescued cells from apoptosis and inhibited lipid peroxidation by decreasing hippocampal malondialdehyde (MDA) content. For Parkinson's disease: degeneration of nerve cells in the striatum and substantia nigra pars compacta that kills dopamine-producing brain cells leading to Parkinson's disease has been an area of naringin investigation.

Evidence strength: Evidence is exclusively preclinical (animal models and cell lines). No peer-reviewed human clinical trials have been published establishing naringin as an effective treatment or preventive measure for any neurodegenerative disease. The neuroprotective research base is early-stage and exploratory.

4.5 Hepatoprotective Effects

Naringin's potential as an anti-diabetic, anti-inflammatory, and hepatoprotective substance has been extensively discussed in the pharmacological literature. In preclinical studies, naringin has been shown to reduce liver enzyme markers, decrease hepatic lipid accumulation, and attenuate oxidative stress in drug-induced liver injury models. The Nrf2/HO-1 pathway activation plays a central role in these hepatoprotective effects.

Evidence strength: Primarily in vitro and animal data. Human clinical data specifically on naringin's hepatoprotective effects is absent from the current published literature.

4.6 Renal Protection

Naringin is a flavonoid present in citrus fruits with pharmacological effects including antioxidant, anti-inflammatory, and anti-apoptotic properties, and reviews have summarized the renoprotective effects of naringin and discussed mechanisms of its action against renal injury. Naringin has been shown to improve kidney function by reducing malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), cyclooxygenase-2 (COX-2), myeloperoxidase (MPO), and enhancing glutathione (GSH) in preclinical models.

Evidence strength: Exclusively preclinical. No human clinical trial data specifically on naringin and renal protection has been identified.

4.7 Anticancer Research

Naringin and naringenin can suppress cancer development in various body parts, alleviating the conditions of cancer patients by acting as effective alternative supplementary remedies. Their anticancer activities are pleiotropic, and they can modulate different cellular signaling pathways, suppress cytokine and growth factor production, and arrest the cell cycle. Naringin has been studied in preclinical models of cervical cancer, gastric cancer, prostate cancer, breast cancer, colorectal cancer, osteosarcoma, bladder cancer, ovarian cancer, melanoma, glioma, lung cancer, esophageal cancer, thyroid cancer, liver cancer, and other malignancies.

Evidence strength: All anticancer evidence is preclinical (in vitro cell lines and animal models). Accruing evidence from both in vitro and in vivo studies has unraveled numerous biological targets along with complex underlying mechanisms suggesting possible therapeutic applications in various malignant disorders. No human clinical trial data supports naringin as a cancer treatment.

4.8 Anti-inflammatory and Immune Modulation

Naringin, as an active natural product, plays a significant role in systemic diseases' anti-inflammatory and antioxidant regulation through various signaling pathways and molecular mechanisms. A review found that naringin has good therapeutic potential for inflammatory diseases, exerting anti-inflammatory, anti-apoptotic, anti-oxidative stress, anti-ulcerative, and detoxifying effects. The anti-inflammatory research spans models of colitis, arthritis, lung injury, and neuroinflammation, virtually all of which are preclinical.

5. Body Systems and Associated Health Areas

• Cardiovascular system: Lipid profile modulation, endothelial function, arterial stiffness, ischemia-reperfusion protection, anti-atherogenic activity
• Metabolic system: Blood glucose regulation, insulin sensitivity, metabolic syndrome components including hypertension and dyslipidemia
• Skeletal system: Osteoblast differentiation, osteoclastogenesis inhibition, osteoporosis prevention, cartilage protection
• Nervous system: Neuroprotection, amyloid-β clearance, tau regulation, dopaminergic neuron protection
• Hepatic system: Liver enzyme normalization, anti-steatotic effects, antioxidant defense
• Renal system: Protection against chemotherapy-induced nephrotoxicity, ischemia-reperfusion injury
• Immune and inflammatory pathways: Cytokine suppression, NF-κB inhibition, autophagy regulation
• Oncology (preclinical): Cell cycle arrest, apoptosis induction, anti-proliferative effects across multiple cancer cell lines

Clinical and epidemiologic research indicates that eating citrus fruits lowers the risk of lifestyle-related disorders like cancer, cardiovascular disease, diabetes (type-2), and osteoporosis. This population-level association, however, reflects dietary patterns and the totality of citrus phytochemicals, not naringin in isolation.

6. Pharmacokinetics and Bioavailability

Naringenin (the active metabolite of naringin) undergoes both phase I and phase II metabolism in rat liver microsomes; in human liver microsomes, it is predominantly metabolized by phase II. Glucuronidation — the addition of glucuronic acid to various functional groups — is one of the major metabolic pathways of naringenin. Metabolite structures including glucuronides, sulfates, and glucuronide sulfates have been confirmed in humans after grapefruit juice consumption.

There is saturation in maximum plasma concentration (Cmax) and exposure beyond 100 mg/kg in animal studies, and the absolute bioavailability of naringenin was found to be ≤5% at tested oral doses. This extremely low bioavailability has been a consistent finding and a major limitation of naringin/naringenin research. Poor bioavailability (estimated at 5%) limits the medicinal potential of naringenin. Novel delivery systems such as nanosuspensions have been explored to overcome this barrier: nanosuspensions can improve bioavailability of poorly soluble drugs by increasing dissolution through reduction in particle size and increased surface area, and other significant benefits include dose proportionality, reduction in fed/fasted variability, and enhanced absorption rate.

Grapefruit juice can provide much higher plasma concentrations of naringenin than orange juice. Naringenin has also been detected in breast milk following consumption of grapefruit juice, with baseline concentrations in breastfeeding mothers ranging from 420.86 to 1568.89 nmol/L in one study.

7. Dosage Forms and Dosages Reported in Studies

The following dosages are drawn directly from published studies and are reported for informational reference only. No established standardized human dosage has been approved by regulatory bodies.

• 400 mg/day of naringin in capsule form (one capsule/day) for 8 weeks was used in one human study reporting reductions in LDL-cholesterol and increases in superoxide dismutase and catalase activity.
• 81 to 142 mg/day of naringin (from fresh grapefruit, grapefruit juice, or capsules) for 6 or 12 weeks was used in randomized controlled trials evaluating cardiovascular risk factors in obese adults.
• 340 mL/day of grapefruit juice providing 201 mg/day of naringenin was administered for 6 months in a trial of healthy postmenopausal women to evaluate arterial stiffness.
• A commercial bergamot-derived extract containing approximately 95 μM naringin per capsule was used in a 6-month study of dyslipidemic patients.
• In animal (rodent) studies, doses ranging from 10 mg/kg to 50 mg/kg daily have been most commonly used for metabolic and antioxidant endpoints over periods of 42–46 days.
• A dose of 100 mg/kg/day by oral gavage was used in pregnant rat studies examining effects on offspring brain redox status.
• In a registered first-in-human dose escalation safety/pharmacokinetics study (NCT03582553), the maximum recommended starting dose was estimated at approximately 135 mg, with the first dose administered being 150 mg from an orange extract standardized to 30% naringenin.

8. Safety Considerations and Drug Interactions

General Toxicology

The reported LD₅₀ of naringin in rodents is 2000 mg/kg. This high LD₅₀ in rodents suggests a relatively low acute toxicity. A notable advantage of naringin treatment identified in reviewers is that it appears safe and can even alleviate the toxic side effects associated with some other drugs. However, high-dose safety data in humans are limited.

Reproductive and Developmental Safety

The double directional adjusting function of estrogenic and anti-estrogenic activities of naringin and its aglycone naringenin has raised concern about possible risks of unwanted interference with endocrine regulation. In a regulated reproductive toxicity study, 22 male and 22 female rats per group were orally given naringin at 0, 50, 250, and 1250 mg/kg/day; male rats were administered beginning 9 weeks prior to mating while females were dosed 2 weeks before mating through gestation day 7. There were no obvious effects on physical signs, animal behavior, or survival rate, although female and male rats from the 1250 mg/kg group had lower body weight and tended to have less food consumption.

Research has shown beneficial effects of naringin supplementation to adult rodents; however, evidence has demonstrated that polyphenol supplementation can induce detrimental effects when consumed during sensitive periods of development, such as pregnancy. On postnatal day 1, maternal naringin supplementation positively modulated the pups' brain redox status, but on postnatal day 7, a pro-oxidative milieu was observed in the offspring's striatum and cerebellum in a sex-dependent manner. These animal findings raise questions about naringin supplementation during pregnancy that have not been resolved in human studies.

Cytochrome P450 Interactions and Grapefruit Juice Effect

Grapefruit juice compounds — mainly naringin, bergamottin, and 6,7-dihydroxybergamottin (DHB) — inhibit intestinal CYP3A4 enzymes, which are involved in the metabolic processes of many drugs and result in interactions between grapefruit juice and drugs that are CYP3A4 substrates when administered concomitantly. Many drugs from different classes have the potential for interaction, including calcium channel blockers such as felodipine, statins such as simvastatin, immunosuppressants, benzodiazepines such as midazolam, antihistamines such as terfenadine, and many other drugs.

The relative contribution of naringin versus other grapefruit compounds (particularly furanocoumarins) to this interaction has been debated. The compounds exerting this action are thought to be either the flavonoids such as naringin and naringenin, or the furanocoumarins such as bergamottin and its derivatives, but there is no clear consensus. Based on naringin's unique distribution in the plant kingdom, abundance in grapefruit, and ability to inhibit metabolic enzymes, naringin is likely to be one of the grapefruit components influencing drug metabolism.

Naringin inhibits some drug-metabolizing cytochrome P450 enzymes, including CYP3A4 and CYP1A2, which may result in drug-drug interactions. However, at the level of the isolated compound, naringenin at 1.0 μM and 10.0 μM did not elicit any appreciable inhibition of the 5 major CYP isoforms (CYP1A2, CYP3A4, CYP2C9, CYP2C19, and CYP2D6) in an in vitro study.

OATP Transporter Interactions

Ingestion of naringin and related flavonoids can also affect the intestinal absorption of certain drugs, leading to either an increase or decrease in circulating drug levels. To avoid interference with drug absorption and metabolism, the consumption of citrus (especially grapefruit) and other juices with medications is advised against. Specifically, OATP1A2 is inhibited by grapefruit juice, specifically its component naringin, which can reduce the intestinal uptake of drugs that are OATP1A2 substrates.

Estrogenic Activity

The double directional adjusting function of estrogenic and anti-estrogenic activities of naringin and its aglycone naringenin has raised concern about possible risks of unwanted interference with endocrine regulation. Naringenin has been characterized as a partial agonist on estrogen receptors in cell studies, which has implications for individuals on hormone-sensitive therapies, though the clinical significance of this effect at dietary or supplemental doses in humans has not been established.

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