naringenin

Overview

Naringenin (Wikidata: Q418374) is a naturally occurring flavanone — a subclass of flavonoids — found abundantly in citrus fruits, tomatoes, and a variety of medicinal herbs. Chemically, it is the aglycone form of naringin and bears the systematic name (2S)-5,7-dihydroxy-2-(4-hydroxyphenyl)-2,3-dihydrochromen-4-one. As a polyphenolic secondary metabolite, naringenin occupies a central position in the plant flavonoid biosynthesis pathway, serving as the direct precursor to the isoflavone genistein through the action of isoflavone synthase (IFS). In mammals, it is recognized as a bioactive compound with a broad spectrum of pharmacological properties, including antioxidant, anti-inflammatory, hepatoprotective, and metabolic-regulatory activities. Its capacity to modulate multiple molecular targets simultaneously — spanning oxidative stress pathways, inflammatory cascades, and lipid metabolism networks — has made it a subject of intensive investigation in network pharmacology and multi-target drug discovery.

The compound exerts its biological effects through interactions with several key signaling axes. Most notably, naringenin activates the Nrf2/NQO-1 antioxidant defense pathway, suppresses proinflammatory mediators such as interleukin-6 and HMGB1, and modulates ferroptosis — a regulated, iron-dependent form of cell death increasingly implicated in inflammatory organ injury. Its favorable pharmacokinetic and safety profile, as assessed by ADMET predictions, positions naringenin as a promising lead compound for the development of therapeutics targeting metabolic, hepatic, and inflammatory diseases.

Focus of Latest Publications

Recent publications have focused on naringenin as both a bioactive natural product and an analyte of interest in analytical and formulation research. A nanobody-based indirect competitive ELISA was developed for naringenin detection in pomelo and herbal samples, using two newly isolated naringenin-specific nanobodies with superior thermal stability compared with a previously reported monoclonal antibody. The assay showed good sensitivity and reliability, and its measurements were consistent with UPLC-MS/MS results, supporting its use for accurate naringenin quantification in plant-derived materials.

Several studies examined naringenin in the context of complex natural product mixtures and pharmacology-guided network analyses. In Achillea arabica extract, naringenin was identified among the major flavonoid constituents by UHPLC-QTOF-MS2 metabolomics, alongside compounds such as apigenin and kaempferol derivatives, with in silico analyses suggesting favorable pharmacokinetic and safety properties. In Shenling Baizhu Powder, naringenin and naringenin chalcone were among the active components implicated by serum pharmacochemistry, metabolomics, and network pharmacology in the treatment of ulcerative colitis with spleen deficiency and dampness stagnation, with docking and dynamics analyses indicating strong binding to core targets including BCL2, NFKB1, TNF, IL6, Akt1, and CASP3.

Other publications investigated naringenin as a therapeutic agent or delivery cargo in disease models. In interstitial cystitis/bladder pain syndrome with metabolic syndrome, naringenin was reported to bind NFE2, downregulate its expression, activate the Nrf2/NQO-1 pathway, and reduce inflammation, fibrosis, and bladder dysfunction while inhibiting ferroptosis. In cholestatic liver injury, a nanosuspension embedded in a glycyrrhizin-based hydrogel improved naringenin solubility, oral bioavailability, and hepatic accumulation, and alleviated liver damage by suppressing oxidative stress and HMGB1-mediated inflammation. In diabetic wound repair, naringenin-loaded shellac nanoparticles incorporated into a chitosan-gelatin hydrogel provided pH-responsive release, antioxidant and antibacterial activity, hemostatic effects, and improved wound healing with enhanced angiogenesis and reduced TNF-α and IL-6.

Additional work highlighted naringenin’s role in formulation and metabolism-related research. In pomelo peel pectin-based emulsion gels, naringenin was used as an encapsulated compound, with in vitro digestion showing that about 70% of the encapsulated naringenin was available for intestinal release. In Anoectochilus roxburghii, naringenin was identified as one of the key ingredients associated with modulation of lipid metabolism, complementing broader findings that the plant extract may improve glucose and lipid metabolism disorders.

Key Publications

NEWJul Nanobody-based enzyme immunoassay for naringenin in pummelos and herbal samples. (Analytical methods : advancing methods and applications, 2026, PMID 42300510): "In this study, two naringenin-specific nanobodies, Nb-C9 and Nb-C13, were successfully isolated."
May Integrated UHPLC-QTOF-MS2 metabolomics, biological assays and in silico analysis reveal multi-target potential of Achillea arabica Kotschy. (Journal of computer-aided molecular design, 2026, PMID 42126671): "Key compounds included chlorogenic acid, isorhamnetin, kaempferide, Kaempferol-3-O-glucoside, cyanidin-3-O-glucoside, delphinidin-3-O-β-glucopyranoside, naringenin and apigenin."
Jun Integrated Serum Pharmacochemistry, Metabolomics, and Network Pharmacology Uncover Potential Active Components and Mechanisms of Shenling Baizhu Powder in Treating Ulcerative Colitis With Spleen Deficiency and Dampness Stagnation. (Biomedical chromatography : BMC, 2026, PMID 42089391): "...nine active components (butein, calycosin-7-o-β-d-glucoside, glabridin, isochlorogenic acid B, naringenin chalcone, naringenin, neoliquiritin, oroxyloside, and vanillic acid) were identified from SLBZP for treating UC-SDDS..."
Apr Dielectric barrier discharge plasma-assisted extraction of Rhamnogalacturonan-I pectin from pomelo peel: Structural characterization and application in an emulsion gel delivery system. (Food chemistry, 2026, PMID 42056777): "After simulated in vitro digestion, 70% of the encapsulated naringenin available for release in intestine."
Mar Shellac nanoparticle based intelligent drug-delivery composite sponge for hemostasis and healing of diabetic wounds. (Biomaterials advances, 2026, PMID 41887025): "we developed an intelligent composite sponge (NSCG) by incorporating naringenin (NGN) loaded shellac nanoparticles (N-SNPs) into a chitosan-gelatin (CG) hydrogel via freeze drying."
May Naringenin inhibits Ferroptosis and ameliorates interstitial cystitis with metabolic syndrome by activating the Nrf2/NQO-1 pathway. (International immunopharmacology, 2026, PMID 41806694): "We further demonstrated that the natural flavonoid naringenin (NAG) specifically binds to NFE2, downregulates its expression, and activates the Nrf2/NQO-1 pathway, resulting in improved bladder function, reduced inflammation, and attenuated fibrosis in animal models."
May Naringenin nanosuspensions embedded glycyrrhizin-based hydrogel ameliorates cholestatic liver injury in mice by inhibiting oxidative stress and HMGB1-mediated inflammation. (Colloids and surfaces. B, Biointerfaces, 2026, PMID 41576734): "Naringenin (NAR) possesses remarkable hepatoprotective potential."
May Exploring the therapeutic potential of Anoectochilus roxburghii in glucose and lipid metabolism disorder: From phenotypic effects to molecular mechanisms and network pharmacology. (Journal of pharmaceutical and biomedical analysis, 2026, PMID 41538970): "Key ingredients such as morin and kaempferol participated in glucose metabolism, while kinsenoside and naringenin modulating lipid metabolism."