Eriocitrin Encyclopedia — Scientific Background

What Is Eriocitrin?

Eriocitrin (CAS 13463-28-0), also known as eriodictyol-7-O-rutinoside, eriodictioside, or eriodictyol glycoside, is a flavanone glycoside with the molecular formula C₂₇H₃₂O₁₅ and a molecular weight of 596.53 g/mol. It is a disaccharide derivative that consists of eriodictyol substituted by a 6-O-(α-L-rhamnopyranosyl)-β-D-glucopyranosyl moiety at position 7 via a glycosidic linkage. Eriocitrin is a member of the flavonoid class of polyphenols and is characterized as an antioxidant—a substance that opposes oxidation or inhibits reactions brought about by dioxygen or peroxides.

Botanical Source

Eriocitrin is predominantly found in citrus fruits, especially lemons (Citrus limon). The amount of eriocitrin in lemon is over 300-fold higher than that in other citrus fruits. It is found mainly in the peel (1,540 ppm in lemons and 1,280 ppm in limes), comprising the albedo and flavedo, and in juice vesicles (216 ppm in lemons and 197 ppm in limes), being more than 7 times more abundant in lemon peel than in the juice, whereas its concentration in the juice represents half of the ascorbic acid. Lemon fruit contained abundant amounts of eriocitrin and hesperidin and also contained narirutin, diosmin, and DGD, but GD, neoeriocitrin, naringin, and neohesperidin were present only in trace amounts. The content of DGD, GD, and eriocitrin was especially abundant in lemons and limes; however, they were scarcely found in other citrus fruits.

Metabolism and Bioavailability

Eriocitrin metabolism, similar to hesperidin, is resistant to pancreatic enzymes and is mostly deglycosylated by intestinal bacteria (Bacteroides distasonis or Bacteroides uniformis) to eriodictyol before absorption. A minimal amount can be absorbed as glycosylated in the upper intestine. Eriodictyol, the aglycon of eriocitrin, can be metabolized by intestinal bacteria (with 3,4-dihydroxycinnamic acid formation) to homoeriodictyol and hesperetin through methoxylation. In the liver, eriodictyol is metabolized into glucuronides and conjugated sulfates of eriodictyol, homoeriodictyol, and hesperitin, through sulfation, glucuronidation and methylation, and later released into the circulation to exert biological activity. The half-lives of the metabolites in plasma were between 3 and 3.2 hours, and the total bioavailability of eriocitrin was less than 1%. Nine metabolites of eriocitrin were identified in rat urine, and seven in various tissues (eriodictyol, homoeriodictyol, hesperetin, and glucuronidated metabolites), with homoeriodictyol and homoeriodictyol-7-O-glucuronide being the major metabolites.

Mechanisms of Action

Metabolic Regulation — GLP-1 and Inflammatory Pathways

A double-blind, randomized, placebo-controlled, crossover study demonstrated that 200 mg/day of eriocitrin for 12 weeks significantly decreased blood glucose (−5%), HOMA-IR (−11%), glucagon (−13%), IL-6 (−14%), TNF-α (−20%), and alkaline phosphatase (−13%), while increasing GLP-1 by 17% (P ≤ .05). Treatment with Eriomin benefited the glycemic control of prediabetic and diabetic patients by increasing GLP-1 and decreasing systemic inflammation.

Joint Health — Nrf2/HO-1/NF-κB Pathways

Eriocitrin mitigates osteoarthritis development by suppressing chondrocyte inflammation and extracellular matrix degradation via the Nrf2/HO-1/NF-κB pathways. Network pharmacology identified 52 potential targets of Eri in OA, and molecular docking analysis revealed strong binding affinity between Eri and two critical regulators: Nrf2 and p65. Eri activated the Nrf2 and HO-1 pathway to enhance antioxidant defenses, while simultaneously inhibiting the NF-κB pathway to reduce inflammation. In vivo, Eri significantly slowed cartilage degeneration and mitigated chondrocyte inflammation and ECM breakdown in OA mice.

Antioxidant Defense

Eriocitrin's antioxidative activity was examined using a linoleic acid autoxidation system, and its activity was found to be stronger than that of neoeriocitrin, narirutin, naringin, hesperidin, and neohesperidin. The free-radical scavenging effects of flavonoids help prevent the formation of advanced glycated end products (AGE) and other diabetic complications associated with high oxidative stress conditions. Eriocitrin increased blood serum antioxidant capacity and had protective effects against inflammation in high-fat diet-fed mice.

Anti-Inflammatory Activity — MAPK and Glycolysis Pathways

Eriocitrin attenuates sepsis-induced acute lung injury in mice by regulating the MKP1/MAPK pathway-mediated glycolysis. Eri increased the resistance of LPS-treated cells to excessive inflammation and oxidative stress by inhibiting the enhancement of glycolysis. Eriocitrin also suppresses cell proliferation and induces apoptosis through modulation of JAK2/STAT3 and JNK/p38 MAPKs signaling pathways.

Clinical Evidence

Hyperglycemia and Prediabetes — Randomized Controlled Trial

A double-blind, randomized, placebo/controlled, crossover study evaluated the efficacy of Eriomin® (70% eriocitrin) in reducing hyperglycemia and improving diabetes-related biomarkers in individuals with hyperglycemia above 110 mg/dL (mean 123 ± 18 mg/dL). Subjects (n = 30) received a dose of 200 mg/d of the designated supplement for 12 weeks. Treatment with 200 mg/d of Eriomin significantly decreased blood glucose (−5%), HOMA-IR (−11%), glucagon (−13%), IL-6 (−14%), and TNF-α (−20%), but increased GLP-1 by 17% (P ≤ .05). The study concluded that intervention with Eriomin benefited the glycemic control of prediabetic and diabetic patients by increasing GLP-1 and decreasing systemic inflammation.

Ongoing Clinical Trial — Eriomin + Metformin

A clinical trial (NCT06005142) is evaluating Eriomin at a dose of 250 mg/d in combination with metformin (1,000 mg/d) in adults diagnosed with pre-diabetes. This clinical trial was designed as a placebo-control, double-blind, two-arm, crossover design to assess clinical characteristics, body composition, food consumption, metabolic and inflammatory biomarkers, and microbiota before, during, and at the end of the 12-week period.

Oral Cavity Protection — liposomal Vesicle Study

The nanoincorporation of the extract of Citrus limon into liposomes was aimed at improving its antioxidant and antibacterial effects. The extract phytochemical fingerprint was obtained by HPLC and mass spectrometry, and it was determined that gallic acid, neohesperidin, eriocitrin, and neoeriocitrin were the most abundant components. The freeze-dried extract was loaded in liposomes, glycerosomes, and penetration-enhancer-containing vesicles prepared with propylene glycol (PG-PEVs). Results showed that the vesicles, especially glycerosomes and PG-PEVs, prevented oxidative damage and cell death, and inhibited bacterial proliferation against Streptococcus mutans, Lactobacillus acidophilus, and Streptococcus sanguinis.

Safety and Regulatory

Eriocitrin has demonstrated concentration-dependent hemolysis and eryptosis in human erythrocytes at concentrations of 20–100 μM, characterized by phosphatidylserine externalization, Ca²⁺ accumulation, membrane blebbing, loss of cellular volume, and oxidative stress. These toxic effects were mediated through casein kinase 1α and Rac1 GTPase and were significantly ameliorated in the presence of urea, sucrose, and polyethylene glycol 8000 (PEG).

Regulatory status varies by region:

• United States — Eriocitrin is regulated as a dietary supplement ingredient. The UNII code AS293HR5XQ has been assigned, and Eriocitrin is listed in the FDA Global Substance Registration System.

• European Union — Eriocitrin is authorized for use in food supplements. Eriomin® is a lemon flavonoid extract composed mainly of eriocitrin (70%) and other flavonoids (30%).

• Global Standards — Eriocitrin is available as a research chemical with purity ≥98% (HPLC) from major suppliers. It is characterized by its Beilstein number 1304401 and KEGG compound C09732.

Testing protocols must adhere to international standards including USP, European Pharmacopoeia, and FAO/WHO Codex Alimentarius. Formulators should verify local regulatory requirements prior to market entry.

This product is intended for research, nutraceutical, and functional food applications. Not intended to diagnose, treat, cure, or prevent any disease.

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