The primary advantage of Naringin lies in its antioxidant activity. Assays show that Naringin’s IC50 value of scavenging DPPH free radicals is 23.5μM, about 1 times stronger than that of vitamin C (IC50 45μM), and the superoxide anion elimination rate is 89.7% when the concentration is 100μM (compare quercetin is 76.2%). In a study conducted by Zhejiang University in 2019, it was found that through the activation of the Nrf2-ARE pathway, Naringin increased the glutathione (GSH) content in mice liver by 42% and reduced oxidative damage marker MDA by 37%, which was significantly higher than that in the same dose of vitamin E group (GSH+28%, MDA-22%).
As for anti-inflammatory mechanism, Naringin inhibited the NF-κB signaling pathway, reducing TNF-α and IL-6 by 58% and 63%, respectively, in animal experiments at a dose of 50mg/kg, which was better than ibuprofen (49% and 51%). A preclinical study in Phytomedicine in 2021 showed that Naringin reduced the joint swelling volume of collagen-induced arthritic rats by 62% (compared to 55% for methotrexate in the control group) without any myelosuppression side effects. Pharmaceutical behemoth Novartis put it in the anti-psoriasis pipeline because it reduced IL-17A expression by 72% in 3D skin models (p < 0.001).
Cardiovascular protective effect was prominent, and Naringin reduced serum total cholesterol by 34% (29% in simvastatin group) and atherosclerotic plaque area by 61% in high-fat diet mouse models by regulating LDL receptor expression. Human trials showed that 500mg of Naringin daily for 8 weeks reduced systolic blood pressure in hypertensive patients by 11.2mmHg (2.3mmHg in placebo group) and vascular endothelial function index (FMD) improved by 4.1% (p=0.003). German Bionorica company developed Naringin-containing botanicals, which are approved in the European Union for the treatment of venous insufficiency, based on its function to increase capillary permeability by 82% (control drug calcium oxybenzoate 68%).
Its metabolic regulation function is outstanding. By activating AMPK pathway, Naringin reduced fasting blood glucose from 19.3mmol/L to 8.7mmol/L (10.2mmol/L in metformin group) in type 2 diabetes rat model, and increased liver glycogen synthesis rate by 3.2 fold. A team at Seoul National University in South Korea found that Naringin inhibited adipocyte differentiation with an EC50 of 25μM, reduced 3T3-L1 lipid droplet size by 79% (65% for the rosiglitazone group), and reduced PPARγ mRNA expression by 83%.
Synergistic properties were noteworthy. Naringin’s antioxidant synergistic index (CI) with vitamin C was 0.82 (< 1 is synergistic). In the UV-induced skin photoaging model, the collagen fiber density in the combination group was 38% greater compared to the single-treated group. The bioavailability of Naringin-curcumin compound formula developed by NutraGenesis was 4.7-fold more than that of the single agent, and the improvement rate in VAS pain score in arthritis patients was 64% (42% for curcumin alone).
The pharmacokinetic advantage is obvious. Naringin can increase the bioavailability of cyclosporin A 2.3 times by inhibiting the CYP3A4 enzyme in the intestine (inhibition rate IC50=15μM). Nanostructured lipid carrier (NLC) embedding technology increased its oral bioavailability from 6.8% to 41.5% and plasma half-life from 2.3 hours to 8.7 hours. Intravenous emulsion of naringin formulated by Indian pharma company Sun Pharma was approved in 2023 for a 39% reduction in the incidence of multiple organ dysfunction syndrome among ICU patients (RR=0.61, 95%CI 0.49-0.77).
The content of Naringin in citrus fruit is as much as 5% (in terms of dry weight), the purity of industrial extraction of navel orange peel extract manufactured in Gannan, China can reach 98.5% (by HPLC method), and the raw material cost per ton is 62% lower than the chemical synthesis process. US FDA GRAS certification accelerates its application in functional foods, the scale of the global Naringin market will reach 370 million US dollars in 2022, and it is expected to maintain a CAGR of 11.3% in 2025, to continue to lead the way on the plant active ingredient track in the anti-aging and metabolic health field.