Myricitrin

Other Names

3,3′,4′,5,5′,7-Hexahydroxyflavone 3-O-rhamnoside3,3′,4′,5,5′,7-Hexahydroxyflavone, 3-rhamnoside3-((6-Deoxy-alpha-L-mannopyranosyl)oxy)-5,7-dihydroxy-2-(3,4,5-trihydroxyphenyl)-4H-benzopyran-4-one4H-1-Benzopyran-4-one, 3-((6-deoxy-alpha-L-mannopyranosyl)oxy)-5,7-dihydroxy-2-(3,4,5-trihydroxyphenyl)-5,7-dihydroxy-3-((2S,3R,4R,5R,6S)-3,4,5-trihydroxy-6-methyl-tetrahydro-pyran-2-yloxy)-2-(3,4,5-trihydroxy-phenyl)-1-benzopyran-4-one5,7-dihydroxy-3-[(2S,3R,4R,5R,6S)-3,4,5-trihydroxy-6-methyl-tetrahydropyran-2-yl]oxy-2-(3,4,5-trihydroxyphenyl)chromen-4-one5,7-dihydroxy-3-[(2S,3R,4R,5R,6S)-3,4,5-trihydroxy-6-methyloxan-2-yl]oxy-2-(3,4,5-trihydroxyphenyl)chromen-4-one5,7-Dihydroxy-4-oxo-2-(3,4,5-trihydroxyphenyl)-4H-chromen-3-yl 6-deoxy-α-L-mannopyranosideEINECS 241-856-7FEMA No. 4491Flavone, 3,3′,4′,5,5′,7-hexahydroxy-, 3-rhamnosideMyricetin 3-O-alpha-L-rhamnopyranosideMyricetin 3-O-alpha-L-rhamnosideMyricetin 3-O-alpha-rhamnopyranosideMyricetin 3-O-rhamnopyranosideMyricetin 3-O-rhamnosideMyricetin 3-O-α-L-rhamnopyranosideMyricetin 3-rhamnosideMyricetin-3-O-alpha-rhamnosideMyricetin-3-O-α-rhamnosideMyricetol 3-rhamnosideMyricetrinMyricitrin [INCI]MyricitrineMyricitrosideNSC 19803

Synopsis

Myricitrin: A Comprehensive Reference

1. Identity and Chemical Characterization

Chemical Names and Classification

Myricitrin is a plant compound, the 3-O-α-L-rhamnopyranoside of myricetin. It is therefore formally classified as a flavonol glycoside — specifically, the rhamnoside of the aglycone myricetin. Myricitrin (the 3-O-rhamnoside of myricetin) is a member of the flavonol class of flavonoids commonly derived from vegetables, fruits, nuts, berries, tea, and red wine.

The compound is registered under CAS number 17912-87-7. Additional synonyms include myricetin 3-O-rhamnoside, myricetin 3-rhamnoside, and myricitroside. Myricitrin (myricetin-3-O-α-rhamnoside) is a member of flavonols, extracted from the fruits, leaves, and barks of numerous plants. It is a secondary metabolite of plants and synthesized from phenylalanine by the phenylpropanoid pathway, as are other phenolic compounds.

The IUPAC name of myricitrin is 5,7-dihydroxy-3-[(2S,3R,4R,5R,6S)-3,4,5-trihydroxy-6-methyloxan-2-yl]oxy-2-(3,4,5-trihydroxyphenyl)chromen-4-one. Its molecular formula is C₂₁H₂₀O₁₂, and its molecular weight is approximately 464.38 g/mol. The structure comprises a flavonol backbone bearing hydroxyl groups at positions 3, 5, 7 of the chromone ring, a 3,4,5-trihydroxyphenyl (galloyl) B-ring substituent, and an α-L-rhamnopyranosyl sugar moiety attached at the C-3 position.

Natural Sources and Botanical Occurrence

Myricitrin can be isolated from the root bark of Myrica cerifera (bayberry, a small tree native to North America), in Myrica esculenta, in Nymphaea lotus and N. odorata, in Chrysobalanus icaco, and in Polygonum aviculare. The genus Myrica (family Myricaceae) represents the primary commercial and research source. Myricetin-3-O-α-rhamnoside (myricitrin) is a botanical flavone extracted from Chinese bayberries (Myrica rubra, Myrica cerifera, Myrica esculenta, etc.).

Further botanical sources of myricitrin are well documented. The metabolite myricitrin, 3-O-rhamnoside of myricetin, is found in plants such as the bark of Myrica esculenta (Myricaceae) and in the leaves of Myrica gale and in Chrysobalanus icaco. Myricitrin has also been isolated and identified from Daebong persimmon peel. Myricitrin has been isolated from a plant of northeast India named the Indian olive (Elaeocarpus floribundus; family Elaeocarpaceae), where four flavonoids — myricitrin, mearnsitrin, myricetin, and mearnsetin — are found in leaf extract. Additionally, flavonoids including myricitrin have been identified in the leaves, stems, and bark of Acacia species.

Common Forms and Preparations

Myricitrin is typically obtained commercially via solvent extraction and chromatographic purification of plant materials, particularly the bark and fruit of Myrica rubra and related species. Myricitrin extracted from Chinese bayberry (Myrica rubra Siebold) has been used in Japan since 1992 as a flavour modifier in snack foods, dairy products, and beverages. In research and supplement contexts it is available as a purified powder (purity grades commonly ≥95–98%). Myricitrin has been isolated with high purity (≥98%) from bayberry leaves by preparative liquid chromatography. Researchers have also investigated novel delivery formats: myricitrin is a plant-derived antioxidant whose solid lipid nanoparticle (SLN) form may be more potent, and SLN preparations have been evaluated for their effects on type 2 diabetes mellitus models. Myricitrin's clinical application is limited by poor solubility and low oral bioavailability; accordingly, myricitrin-loaded proliposomes have been prepared using thin-film dispersion combined with freeze-drying.

2. Traditional and Historical Use

East Asian Traditions

The primary traditional context for myricitrin-containing plants centers on the genus Myrica/Morella and the Chinese bayberry (Myrica rubra). Myrica and Morella (Myricaceae) are taxonomically close genera that include species of trees or shrubs with edible fruits that exhibit relevant uses in traditional medicine. In Chinese or Japanese folk medicine, they are used to treat diarrhea, digestive problems, headache, burns, and skin diseases.

South Asian (Ayurvedic and Folk) Traditions

Myrica esculenta, from the Myricaceae family, is widely recognized in traditional medicine for its use against anemia, jaundice, fever, inflammation, and infectious conditions. Myrica esculenta Buch.-Ham. ex D. Don, commonly known as Kaiphal, is a nutritionally rich tree species of the Indian Himalayan region that holds significant ethnomedicinal and nutraceutical importance. Ethnobotanical reports indicate that the fruits and bark are the most widely used parts, traditionally employed for managing cardiac debility, respiratory ailments, gastrointestinal disorders, and wound healing. Although these ethnobotanical uses encompass the whole plant, key phytochemicals including myricitrin (myricetin 3-O-rhamnoside) have been identified and validated as constituents of Myrica esculenta by chromatographic methods.

North African and Mediterranean Traditions

Tetraclinis articulata (Cupressaceae), a traditional Moroccan herbal drug, is used in oriental Morocco to treat diabetes and arterial hypertension. Phytochemical analysis of the extracts has revealed the presence of polyphenolic compounds known for their vasorelaxant effect, including myricitrin and quercitrin. Their presence may explain the traditional use of T. articulata twigs in the treatment of hypertension in oriental Morocco.

North American Context

Myricitrin is a plant flavonoid found in numerous herbs such as witch hazel (Hamamelidaceae hamamelis virginia), bayberry (Myrica cerifera), Corylus avellana L., and Myrtaceae. Bayberry bark (Myrica cerifera) has long been used in North American herbal traditions. Preparations in all these traditions consisted primarily of decoctions, infusions, and poultices of bark, leaf, or fruit — though historical use was directed at the whole plant rather than the isolated compound.

3. Key Constituents, Chemistry, and Established Mechanisms of Action

Structural Properties Relevant to Bioactivity

The unique biological profile of myricitrin derives from several structural features. As a flavonol glycoside, its B-ring bears three hydroxyl groups in a galloyl arrangement (3′,4′,5′-trihydroxyphenyl), providing exceptional electron-donating capacity. The C-3 position carries an α-L-rhamnose moiety, which modifies polarity and solubility relative to the free aglycone myricetin, while also influencing intestinal absorption and metabolism. The bioavailability and metabolism of flavonoids, especially flavonoid glycosides, are important properties to consider. Myricitrin is a large and highly polar compound that cannot cross membranes easily; flavonoids undergo extensive metabolism and hydrolysis by glycosidases in the cells of the liver, kidney, and gastrointestinal mucosa, and these events may reduce the biological activity of myricitrin.

Antioxidant Mechanisms

Myricitrin exerts potent antioxidant activity with robust scavenging of free radicals compared to other flavonol rhamnosides and quercetin. Myricitrin was shown to be a stronger free radical scavenger than other flavonol rhamnosides or quercetin. It inhibits ROS-induced vein endothelial cell dysfunction through reduction of MDA, H₂O₂-induced oxidative damage, and regulation of antioxidant enzyme activity. In the context of hepatoprotection, myricitrin showed higher hepatoprotective activity than silymarin and improved toxic liver damage via several mechanisms including antioxidant defense system preservation, inhibition of inflammation, suppression of profibrotic response, and enhancement of liver regeneration.

Anti-Inflammatory Mechanisms

Several overlapping signaling pathways are implicated in myricitrin's anti-inflammatory activity. Myricitrin decreased the production of pro-inflammatory factors including IL-1β, IL-6, and TNF-α, decreased the level of chemokine MCP-1, and suppressed the expressions of COX-2 and iNOS. It also suppressed HMGB1, TLR4, and MyD88 expression, and inhibited NF-κB and MAPK signaling pathways activated by LPS.

A separate investigation demonstrated that myricitrin significantly alleviated acute lung injury in mice and markedly suppressed the production of NO, TNF-α, IL-6, and MCP-1 in RAW264.7 macrophage cells. The inhibition of NO was concomitant with a decrease in protein and mRNA levels of iNOS. The phosphorylation of JAKs and STAT-1 was abrogated by myricitrin, which also inhibited the nuclear transfer and DNA binding activity of STAT1. Furthermore, myricitrin attenuated the generation of intracellular ROS by inhibiting the assembly of components of gp91^phox and p47^phox.

Myeloperoxidase activity, closely related to the progression of chronic inflammatory diseases as well as neurodegenerative and coronary disorders, was irreversibly inactivated by myricitrin.

Nitric Oxide and Protein Kinase C (PKC) Inhibition

Myricitrin is a nitric oxide and protein kinase C inhibitor and exhibits antipsychotic-like and anxiolytic-like effects in animal models of psychosis and anxiety, respectively. In vivo, myricitrin has been reported as a nitric oxide (NO) and protein kinase C inhibitor that exerts antinociceptive effects. Myricitrin produces pronounced antinociception against chemical and mechanical models of pain in rodents via preventing the protein kinase C (PKC) alpha and PKC epsilon activation by phorbol myristate acetate (PMA).

MAO Inhibition and Dopaminergic Effects

Flavonoids exhibit several biological activities including inhibition of monoamine oxidase (MAO), an enzyme that metabolizes several neurotransmitters. MAO inhibitors are well included in traditional therapeutic practices to fine-tune neuromotor behavior. Specifically for myricitrin, myricitrin's therapeutic potential was examined in a mouse brain model; in the mouse brain, myricitrin reduced MAO activity and increased dopamine (DA) levels. In a Parkinson's disease mouse model, myricitrin lessened motor incoordination and elevated DA levels in the striatum.

Biosynthetic Origin in Plants

Myricitrin is a secondary metabolite of plants, synthesized from phenylalanine by the phenylpropanoid pathway as are other phenolic compounds. In plant ecology, it is a feeding stimulant for some leaf beetles.

4. Scientific Evidence by Area of Use

Important note on evidence status: With the exception of myricitrin's established use as a flavoring agent in Japan, the entirety of the pharmacological evidence reviewed below derives from preclinical studies — that is, in vitro cell models and in vivo animal experiments. No completed randomized controlled trials in humans have been published for any therapeutic indication of isolated myricitrin as of the available literature. All findings should be interpreted accordingly.

4.1 Antioxidant Activity

In validated in vitro assays, myricitrin had the strongest antioxidant activities by ferric ion reducing antioxidant power (FRAP) and α,α-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging assays among isolated fractions from persimmon peel, suggesting that myricitrin was the major antioxidant flavonoid responsible for the strong antioxidant activities of Daebong persimmon peels. These results are consistent across multiple laboratories; the evidence for direct free radical scavenging is robust at the in vitro level, though whether these activities translate to clinically significant antioxidant effects in humans at dietary doses has not been established in clinical trials.

4.2 Anti-Inflammatory and Analgesic (Antinociceptive) Effects

In animal models of pain, myricitrin demonstrates dose-dependent antinociceptive activity. The antinociceptive effects of myricitrin in models of overt nociception were examined; nociception induced by bradykinin was stopped by prior treatment with myricitrin. The proposed mechanism involves inhibition of both the NO/L-arginine pathway and PKC activation pathways, as reviewed in preclinical studies. Myricitrin identified as a major bioactive polyphenol in bayberry leaves exhibited strong anti-inflammatory effects without cytotoxicity in Caco-2 cells by suppressing NF-κB activation and downstream inflammatory cytokines. Evidence is limited to in vitro and animal studies; no controlled human analgesic trials have been conducted.

4.3 Hepatoprotective Effects

The hepatoprotective potential of myricitrin has been evaluated in mouse models of chemically induced liver injury. The aim of one study was to determine the hepatoprotective effects of myricitrin; myricitrin at doses of 10, 30, and 100 mg/kg and silymarin at a dose of 100 mg/kg were administered to BALB/cN mice by oral gavage once daily for two consecutive days following carbon tetrachloride (CCl4)-intoxication. Myricitrin significantly ameliorated CCl4-induced increases in serum aspartate transaminase (AST) and alanine transaminase (ALT) levels and histopathological changes in the liver. Myricitrin showed higher hepatoprotective activity than silymarin in that model, improving toxic liver damage via antioxidant defense system preservation, inhibition of inflammation, suppression of profibrotic response, and enhancement of liver regeneration. All evidence is from animal models; no human clinical data exist.

4.4 Antidiabetic Effects

Multiple animal studies have evaluated myricitrin's effects on glucose metabolism. In one study using a D-galactose-induced aging mouse model, 72 female adult mice were randomly divided into six groups: control, D-galactose (D-gal) at 500 mg/kg/day, D-gal plus myricitrin at 5, 10, and 20 mg/kg/day, and D-gal plus vitamin E at 100 mg/kg/day. Aging was induced for 45 days via intraperitoneal injection, and myricitrin and vitamin E were administered orally by gavage for the last 28 days. Blood glucose, insulin level, β-cell function, insulin resistance, hepatic enzymes, lipid profile, and histology of liver and pancreas were evaluated. Myricitrin increased insulin and decreased blood glucose levels compared to the D-gal group. Myricitrin had a similar impact on insulin levels to vitamin E. Myricitrin also reduced insulin resistance and increased β-cell function. D-gal elevated cholesterol, LDL, and triglyceride levels, which were reduced by myricitrin.

In a separate study using a streptozotocin-nicotinamide-induced type 2 diabetes mouse model, myricitrin is a plant-derived antioxidant; its solid lipid nanoparticle (SLN) form was evaluated for effects on T2DM models. Myricitrin SLN improved diabetes and hyperglycemia complications in both in vivo and in vitro studies. Evidence remains preclinical; no human trials for the antidiabetic indication have been published.

4.5 Cardiovascular Effects

Anti-Atherosclerotic and Lipid-Lowering Effects

A study investigated the anti-atherosclerotic potential of myricitrin in hypercholesterolemic rats. Lipid peroxidation and reactive oxygen species (ROS) levels were reduced following myricitrin treatment. Rats supplemented with 1, 10, and 100 μM myricitrin showed significant reductions in the aortic cell wall area; this was reported as the first study of the anti-atherosclerotic and hypolipidemic effects of myricitrin in hypercholesterolemic rats. Myricitrin decreased the level of total serum cholesterol and the role of aortic atherosclerosis in hypercholesterolemic rats.

Cardioprotective Effects (Doxorubicin-Induced Cardiotoxicity)

Myricitrin, isolated from the ground bark of Myrica rubra, has been found to have a strong antioxidative effect. A study evaluated its protective effect against doxorubicin (Dox)-induced cardiotoxicity; an in vivo investigation in Sprague-Dawley rats demonstrated that myricitrin significantly reduced Dox-induced myocardial damage, as indicated by decreases in the cardiac index, amelioration of heart pathological injuries, and decreases in serum cardiac enzyme levels. Myricitrin exerted its function by counteracting oxidative stress and increasing the activities of antioxidant enzymes. Moreover, myricitrin suppressed the myocardial apoptosis induced by Dox, as evidenced by decreases in activation of caspase-3 and numbers of TUNEL-positive cells, maintenance of mitochondrial membrane potential, and increase in the Bcl-2/Bax ratio. The mechanism relied on the ERK/p53-mediated mitochondrial apoptosis pathway. This is animal model data; no human trials have been published.

Diabetic Cardiomyopathy

A study described the potential protective effects and mechanisms of myricitrin on cardiac function of streptozotocin-induced diabetic mice and on advanced glycation end products (AGEs)-induced H9c2 cardiomyocytes. In vitro experiments revealed that pretreatment with myricitrin significantly decreased AGEs-induced inflammatory cytokine expression, limited an increase in ROS levels, and reduced cell apoptosis, fibrosis, and hypertrophy. These effects were correlated with Nrf2 activation and NF-κB inhibition.

4.6 Neurological and Psychiatric Effects

Anxiolytic Effects

Flavonoid glycosides, the main class of flavonoids, have been shown to exert CNS-mediated activities, particularly as sedative-hypnotics and analgesics. One study assessed the potential anxiolytic effect of three flavonoid glycosides, including myricitrin, naringin, and gossypin, in the elevated plus maze test (EPM). Myricitrin at 1 mg/kg was effective on the EPM, showing a clear anxiolytic effect with no signs of sedation. However, higher doses showed possible sedative and myorelaxation effects. These are all rodent behavioral pharmacology data.

Antipsychotic-Like Effects

Myricitrin is a nitric oxide (NO) and protein kinase C (PKC) inhibitor that has CNS activity including anxiolytic-like action. Nitric oxide inhibitors blocked the behavioral effects of apomorphine, suggesting an antipsychotic-like effect. PKC inhibition reduced psychotic symptoms in acute mania patients and blocked amphetamine-induced hyperlocomotion, suggesting a potential antipsychotic-like effect. The study evaluated the effects of myricitrin in animal models that assess antipsychotic-like effects (apomorphine-induced stereotypy and climbing and the paw test) and extrapyramidal side effects (catalepsy test and paw test). Results supported an antipsychotic-like profile, but all evidence is from animal models.

Antidepressant-Like Effects and Neurogenesis

Myricitrin is a natural flavonoid that inhibits nitric oxide transmission and has an atypical antipsychotic-like profile in animal models. Considering that several NO inhibitors exert antidepressant-like effects, one study evaluated the antidepressant-like effect of myricitrin at doses of 3–30 mg/kg in the tail suspension test (TST). Similar to the positive control imipramine (10 mg/kg), repeated (but not acute) treatment with 10 mg/kg myricitrin reduced immobility time in the TST, indicating an antidepressant-like effect. No effect on general motor activity was observed. Myricitrin also facilitated cell proliferation in the SGZ of the hippocampal dentate gyrus and SVZ.

A subsequent study in the chronic mild stress (CMS) model — an animal model of depression — found that myricitrin at 10 mg/kg intraperitoneally for 14 days reversed depressive-like behaviors induced by CMS (increased immobility in the FST, TST, and anhedonia), as well as decreased adrenal hypertrophy and hippocampal levels of IL-6 in stressed mice. Similar results were observed with imipramine (20 mg/kg intraperitoneally for 14 days), a serotonin and norepinephrine reuptake inhibitor used as positive control. A significant correlation was observed between immobility time in the TST and hippocampal IL-6 levels. In conclusion, myricitrin exhibited an antidepressant-like profile in the CMS model, and this effect may be associated with its anti-inflammatory activity. All this evidence is preclinical; no clinical antidepressant trials exist.

Neuroprotection in Parkinson's Disease Models

The possible mechanism of myricitrin's neuroprotection and anti-neuroinflammation in the nigrostriatum of LPS-stimulated mice was investigated. Myricitrin improved neuron injury and raised the expressions of PSD-95 protein and TH protein in the nigrostriatum of LPS-stimulated mice. It also decreased the production of pro-inflammatory factors including IL-1β, IL-6, and TNF-α, decreased the level of chemokine MCP-1, and suppressed the expressions of COX-2 and iNOS. In the mouse brain, myricitrin reduced MAO activity and increased DA levels. In a Parkinson's disease mouse model, myricitrin lessened motor incoordination and elevated DA levels in the striatum. These findings are preclinical and have not been replicated in human subjects.

4.7 Intestinal and Gut Health Effects

Oral administration of the flavonoid myricitrin was reported to prevent dextran sulfate sodium-induced experimental colitis in mice through modulation of the PI3K/Akt signaling pathway. This represents animal-level evidence only. No human clinical trial data on myricitrin for inflammatory bowel conditions have been identified.

4.8 Periodontitis and Bone Effects

A preclinical study in rats examined myricitrin as a potential adjunct therapy for periodontitis in immunosuppressed conditions. Fifty albino Wistar rats were randomly allocated to control, periodontitis, immunosuppressant, myricitrin, and alendronate groups. Ligature-associated periodontitis was induced in all groups except control. Cyclosporin A was administered subcutaneously in the immunosuppressant group. The myricitrin group received cyclosporin A and myricitrin, whereas the alendronate group received cyclosporin A and alendronate. Therapeutic efficacies of myricitrin and alendronate were compared histologically, morphometrically, and biochemically. Myricitrin reversed bone destruction in the periodontitis and immunosuppressant groups. Results demonstrated that myricitrin is effective in potentiating bone formation, with effects comparable to alendronate but with minimal side effects. Evidence is limited to this rodent study.

4.9 Anti-Hyperuricemic Effects

The uric acid-lowering activity of myricitrin-loaded proliposomes was investigated in a hyperuricemic rat model. Compared with free myricitrin, the cumulative in vitro release and in vivo oral bioavailability of the proliposomes were markedly increased. The proliposomes could significantly lower serum uric acid levels and ameliorate liver and kidney damage in hyperuricemic rats compared to the model group. This is rodent data; clinical human evidence is absent.

5. Body Systems and Health Areas Associated with Myricitrin

Nervous system: Anxiolytic, antidepressant-like, antipsychotic-like, and neuroprotective effects studied in animal models; MAO inhibition and dopamine modulation.
Cardiovascular system: Anti-atherosclerotic, hypolipidemic, cardioprotective against doxorubicin-induced injury, and protective in diabetic cardiomyopathy — all preclinical.
Hepatic system: Hepatoprotection against chemical injury (CCl4), antifibrotic activity, and liver enzyme normalization — rodent studies.
Metabolic/Endocrine system: Antidiabetic effects including reduction of blood glucose, improvement of insulin resistance, and β-cell protection — rodent studies.
Gastrointestinal system: Prevention of experimental colitis in mice, NF-κB suppression in intestinal cells.
Musculoskeletal/Periodontal system: Bone resorption inhibition and alveolar bone regeneration in periodontitis models — rodent studies.
Immune and inflammatory system: Suppression of pro-inflammatory cytokines, COX-2, iNOS, HMGB1/TLR4/MyD88, and NF-κB/MAPK/JAK-STAT pathways.
Pain pathways: Antinociceptive activity via PKC and NO inhibition — rodent studies.
Renal system: Potential urate-lowering and renoprotective effects in hyperuricemia models.
Flavoring/sensory: Use as a flavor modifier in food applications, specifically described as able to impart a fatty, slight bayberry note and help to stabilize flavor formulations.

6. Dosage Forms and Doses Reported in Studies

No established human therapeutic dose has been determined for myricitrin in any indication, as clinical trials are absent. The following doses appear exclusively in preclinical (animal) research:

Hepatoprotection (mice, oral gavage): myricitrin at doses of 10, 30, and 100 mg/kg, administered once daily for two consecutive days following CCl4-intoxication.
Antidepressant-like effect (mice, TST): 3–30 mg/kg in the tail suspension test.
Antidepressant-like effect in the CMS model (mice, intraperitoneal): 10 mg/kg intraperitoneally for 14 days.
Anxiolytic effect (mice, elevated plus maze): 1 mg/kg showed a clear anxiolytic effect with no signs of sedation; higher doses showed possible sedative and myorelaxation effects.
Antidiabetic and hepatoprotective (aged mice): myricitrin at 5, 10, and 20 mg/kg/day for 28 days (oral gavage).
Anti-atherosclerotic (hypercholesterolemic rats): supplementation with 1, 10, and 100 μM myricitrin in diet.
90-day rodent safety study: 97% pure myricitrin was fed to male and female Sprague-Dawley rats at dietary concentrations of 0.5%, 1.5%, and 5.0%.

7. Safety, Toxicology, and Regulatory Status

Regulatory Status

Myricitrin, a flavonol rhamnoside of myricetin extracted from the Chinese bayberry plant, has been used in Japan since 1992 as a flavour modifier in snack foods, dairy products, and beverages. It is affirmed as generally recognised as safe (GRAS) by the US Flavour and Extract Manufacturers Association (FEMA) and is considered safe by the Joint FAO/WHO Expert Committee on Food Additives (JECFA) at current estimated dietary exposures.

Preclinical Toxicology

Based on the 90-day rat toxicity study, the no observed adverse effect level (NOAEL) was determined to be 2,926 mg/kg/day in males and 3,197 mg/kg/day in females. At the highest dose (5% in diet), there was increased food consumption and decreased body weight gain in males. Blood values were within laboratory reference ranges except for mean increases in basophils in low- and high-dose males and serum phosphorus in high-dose males.

A long-term study also established safety at dietary exposures: the NOAEL of 884 mg/kg body weight per day, as determined by a 52-week study in rats, is approximately 18,000 times the highest estimated human dietary exposure to myricitrin when used as a flavoring agent.

Genotoxicity

The genotoxic potential of myricitrin and myricetin was evaluated in anticipation of worldwide marketing of food products containing myricitrin. In a bacterial reverse mutation assay, myricetin tested positive for frameshift mutations under metabolic activation conditions, whereas myricitrin tested negative for mutagenic potential. Both myricitrin and myricetin induced micronuclei formation in human TK6 lymphoblastoid cells under conditions lacking metabolic activation; however, the negative response observed in the presence of metabolic activation suggests that rat liver S9 homogenate may detoxify reactive metabolites.

An important consideration regarding commercial preparations is purity: highly purified commercially available myricitrin contains a small amount of myricetin, the aglycone of myricitrin. Myricetin and structurally related flavonoids such as quercetin have shown genotoxicity and DNA damage in several studies. This distinction between the safety of myricitrin itself and its aglycone myricetin is relevant for quality control of preparations.

Intestinal Metabolism and Conversion to Myricetin

Myricitrin is converted to myricetin by intestinal microflora; myricetin also occurs ubiquitously in plants and is consumed in fruits, vegetables, and beverages. Because myricetin carries its own distinct pharmacological and toxicological profile (including the genotoxicity signal noted above in vitro), the in vivo biological effects of orally ingested myricitrin are partly mediated by this microbial conversion product.

Bioavailability Challenges and Nanoformulation Strategies

Myricitrin has many pharmacological effects, such as anti-inflammation, liver protection, and anti-oxidation; however, its clinical application is limited by poor solubility and low oral bioavailability. Researchers have explored nanoparticle-based delivery systems to address this limitation: myricitrin-loaded proliposomes were prepared using the thin-film dispersion technique combined with freeze-drying; in vitro release compared with free myricitrin was measured in different dissolution media while a pharmacokinetic study was conducted in rats. Compared with free myricitrin, the cumulative in vitro release and in vivo oral bioavailability of the proliposomes were markedly increased. Solid lipid nanoparticle formulations have similarly been explored for improving oral bioavailability and tissue targeting.

Overall Safety Assessment

Currently, myricitrin has been considered as safe. The established GRAS status for flavoring use reflects assessments at food-additive levels; pharmacological doses explored in animal research are substantially higher and their human safety profile remains uninvestigated in controlled human trials. No human drug interaction studies for myricitrin as a supplement have been identified in the peer-reviewed literature reviewed here.

References

Health Conditions

Health conditions that Myricitrin may help support.

No conditions available.

Body Systems

Body systems that Myricitrin may help support.

No body systems available.