Neoeriocitrina

Otros Nombres

(2S)-2-(3,4-Dihydroxyphenyl)-5-hydroxy-4-oxo-3,4-dihydro-2H-chromen-7-yl 2-O-(6-deoxy-α-L-mannopyranosyl)-β-D-glucopyranoside(2S)-7-[[2-O-(6-deoxy-α-L-mannopyranosyl)-β-D-glucopyranosyl]oxy]-2-(3,4-dihydroxyphenyl)-2,3-dihydro-5-hydroxy-4H-1-benzopyran-4-one(S)-3',4',5,7-Tetrahydroxyflavanone-7-[2-O-(α-L-rhamnopyranosyl)-β-D-glucopyranoside]3',4',5,7-Tetrahydroxyflavanone 7-neohesperidoside4H-1-Benzopyran-4-one, 7-[[2-O-(6-deoxy-α-L-mannopyranosyl)-β-D-glucopyranosyl]oxy]-2-(3,4-dihydroxyphenyl)-2,3-dihydro-5-hydroxy-, (2S)-Eriodictyol 7-neohesperidosideEriodictyol 7-O-neohesperidoside

Sinopsis

Neoeriocitrin

1. Identity and Chemical Characterization

Neoeriocitrin is a flavanone glycoside and a major flavonoid compound found in various citrus fruits, characterized by its chemical structure as eriodictyol 7-O-neohesperidoside, with the molecular formula C₂₇H₃₂O₁₅ and a molecular weight of 596.5 g/mol. More precisely, neoeriocitrin is a 7-O-glycoside of the flavanone eriodictyol and the disaccharide neohesperidose (α-L-rhamnopyranosyl-(1→2)-β-D-glucopyranose). It is classified within the flavanone subclass of flavonoids and is further categorized as a flavanone O-glycoside. Its CAS registry number is 13241-32-2.

The compound shares its aglycone backbone — eriodictyol (3′,4′,5,7-tetrahydroxyflavanone) — with the structurally related glycoside eriocitrin; the key structural distinction is the sugar moiety: neoeriocitrin carries the neohesperidose disaccharide (with an α-1→2 linkage between rhamnose and glucose), whereas eriocitrin carries rutinose (an α-1→6 linked disaccharide). The eriodictyol aglycone of neoeriocitrin possesses a 3′,4′-dihydroxy substitution pattern on its B-ring — an ortho-dihydroxy group known as a catechol moiety — which is a primary determinant of its potent antioxidant and radical-scavenging activity. The catechol structure allows for the donation of hydrogen atoms to neutralize free radicals, forming a stable ortho-quinone, which contributes significantly to its ability to counteract oxidative stress.

The neohesperidoside sugar moiety at the 7-position enhances neoeriocitrin's water solubility (approximately 30 mg/mL in DMSO, sparingly soluble in aqueous buffers) and bioavailability. The compound is light-sensitive and is therefore stored under dark conditions in chemical and analytical work.

1.1 Synonyms and Related Names

Eriodictyol 7-O-neohesperidoside
Eriodictyol-7-O-neohesperidoside-6″-O-HMG (a related acylated derivative found in bergamot)
CAS No. 13241-32-2
PubChem CID: 114627

2. Natural Sources and Distribution

Neoeriocitrin occurs naturally in species such as Citrus paradisi (grapefruit) and immature fruits of Citrus aurantium (bitter orange), where it contributes to the plant's defensive biochemistry and sensory properties. It is also a significant constituent of Citrus bergamia (bergamot). Bergamot juice (BJ) differs from the juice of other Citrus fruits due to its peculiar profile and high content of flavonoids and glycosides, including neoeriocitrin, neohesperidin, naringin, rutin, neodesmin, rhoifolin, and poncirin, which show a wide range of pharmacological activities.

The main flavanones in bergamot juice include naringin, neohesperidin, and neoeriocitrin, with respective contents measured at 167.5 ± 1.8, 123.9 ± 1.7, and 73.3 ± 1.6 mg/L. Bergamot (Citrus bergamia Risso et Poiteau) fruits are characterized by a particularly high content and a unique composition of flavonoids, such as neoeriocitrin, neohesperidin, naringin, melitidin and brutieridin. Bergamot juice and its concentrate, highly enriched in polyphenols — referred to as Bergamot Polyphenol Fraction (BPF) — has been evaluated as a food supplement.

Beyond citrus species, neoeriocitrin has been identified in a second, taxonomically unrelated plant family: neoeriocitrin occurs botanically in Citrus sp. and Drynaria sp. Specifically, neoeriocitrin is a compound isolated from Drynaria Rhizome. Naringin is considered the main effective compound of Drynaria Rhizome, which is used commonly in the treatment of osteoporosis in traditional Chinese medicine. The identification of neoeriocitrin as a constituent of Drynaria fortunei (Gusuibu) rhizome substantially broadened its phytochemical and therapeutic significance. In bergamot fruit, structural characterization work has also revealed a new flavonoid named peripolin, whose peculiarity lies in the presence of the HMG chemical group linked to the sugar portion of neoeriocitrin.

3. Traditional and Historical Use

Neoeriocitrin as an isolated compound is a product of modern phytochemistry, and no historical tradition explicitly identified or used the isolated molecule. However, the plant sources from which it is derived carry documented histories of medicinal use across cultures, and their preparations would have delivered neoeriocitrin as part of a complex phytochemical mixture.

3.1 Drynaria fortunei (Gusuibu) in Traditional Chinese Medicine

Naringin is considered the main effective compound of Drynaria Rhizome, which is used commonly in the treatment of osteoporosis in traditional Chinese medicine. The rhizome of Drynaria fortunei, a fern in the family Polypodiaceae, has been officially recorded in the Chinese Pharmacopoeia and has historically been employed in classical Chinese herbal medicine as a tonic for bone and kidney, used to strengthen sinew and bone, alleviate pain from fracture, and promote healing. Traditional preparations typically involved decoctions of the dried rhizome. Neoeriocitrin, along with naringin, is among the flavonoid constituents responsible for the osteogenic activity attributed to this herb in the traditional context.

3.2 Citrus Species in Mediterranean and Asian Traditions

Citrus fruits and their preparations have been central to both Mediterranean and Asian medicinal traditions for centuries. Bitter orange (Citrus aurantium), containing neoeriocitrin, was used in traditional Ayurvedic and Chinese medicine as a digestive tonic, and in European folk medicine for conditions including indigestion and nervous disorders. Bergamot (Citrus bergamia), native to Calabria in southern Italy, has a history of use in folk medicine for fever, infections, and digestive complaints. The tree Citrus bergamia belonging to the Rutaceae family is found in the Calabria region specifically due to its unique climate that is suitable for its growth. Essential oils of the bergamot peel are well characterized and used extensively in products ranging from the food industry, pharmaceutical industry, and the cosmetic industry. The juice and polyphenol-rich fractions of bergamot have more recently transitioned from traditional use to nutraceutical applications in the context of cardiovascular health.

4. Active Constituents and Structural Pharmacology

The pharmacological profile of neoeriocitrin is determined by the specific arrangement of its constituent parts: the flavanone core (eriodictyol) and the attached neohesperidoside sugar moiety. Several structural features are considered critical for its biological activities, particularly its antioxidant and anti-inflammatory effects.

The catechol B-ring (3′,4′-dihydroxy configuration) is the primary antioxidant pharmacophore. Beyond this, the carbonyl group at C-4, the hydroxyl at C-5, and the double bond between C-2 and C-3 (absent in neoeriocitrin's saturated flavanone core but present in certain metabolites) collectively define its electron donation capacity and metal-chelating ability. The glycosylation at the C-7 position modulates water solubility and absorption profile compared with the free aglycone eriodictyol.

4.1 Relationship to Eriodictyol (Aglycone)

Eriodictyol, the aglycone produced upon hydrolysis of neoeriocitrin's sugar moiety, is itself biologically active and is believed to be the primary circulating form after oral ingestion. For neoeriocitrin, preclinical studies, primarily in rat models, have begun to elucidate its pharmacokinetic properties. Following oral administration, the compound is absorbed from the gastrointestinal tract. However, like many flavonoid glycosides, its direct absorption in its original form is thought to be limited. Instead, it is likely hydrolyzed by intestinal enzymes and gut microbiota into its aglycone form, eriodictyol, which is then more readily absorbed.

5. Mechanisms of Action

5.1 Antioxidant Activity

Neoeriocitrin demonstrates significant antioxidant activity, scavenging DPPH radicals by approximately 17% and superoxide radicals by 48% in cell-free assays, while also reducing low-density lipoprotein (LDL) oxidation in ex vivo models. Studies using naringin, neoeriocitrin, and rutin reported them to have antioxidant activity in in vitro antioxidant models by beta-carotene–linoleic acid, DPPH, superoxide, and hamster low-density lipoprotein (LDL) assays.

In the ORAC (oxygen radical absorbance capacity) assay, which measures peroxyl radical scavenging via hydrogen atom transfer (HAT), neoeriocitrin achieves an IC₅₀ of approximately 0.5 μM, significantly lower (indicating higher potency) than trolox (a vitamin E analog) at equivalent concentrations. Additional assays confirm its ferric-reducing antioxidant power (FRAP) and ABTS scavenging, with neoeriocitrin consistently showing the lowest IC₅₀ values among tested citrus flavonoids, highlighting its superior electron-donating ability independent of radical type.

5.2 Osteogenic Signaling

Neoeriocitrin exhibits osteogenic effects by enhancing proliferation and alkaline phosphatase activity in MC3T3-E1 osteoblast precursor cells, alongside upregulation of differentiation markers including Runx2, type I collagen, and osteocalcin. In the context of signaling pathways, neoeriocitrin upregulated key osteogenic markers (Runx2, Collagen I, and OCN) in MC3T3-E1, counteracts PD98059 (an ERK inhibitor)-mediated suppression of osteogenesis, and modulated bone remodeling by downregulating SOST and RANKL in osteocyte-like cells. In the most recently characterized mechanism, neoeriocitrin enhances osteogenesis in human dental pulp stem cells (hDPSCs) and bone regeneration by targeting Beclin1 to inhibit ubiquitination-mediated degradation, thereby stabilizing Beclin1 and increasing its protein abundance.

5.3 Neuroprotective Mechanisms: Cholinergic and MAPK Pathways

Neoeriocitrin inhibits phosphorylation of P38 mitogen-activated protein kinase, reduces acetylcholinesterase (AChE) activity, and increases choline acetyltransferase (ChAT) activity. Neoeriocitrin also reduces apoptosis and induces autophagy. These dual actions — inhibition of the enzyme that degrades acetylcholine, and suppression of the pro-inflammatory p38 MAPK pathway — place neoeriocitrin within a mechanistic framework relevant to Alzheimer's disease pathology. Amyloid beta (Aβ) toxicity, increasing RAGE expression, tau hyperphosphorylation, induction of apoptosis, and deregulated autophagy are among mechanisms partly explained by activation of MAPK signaling, with p38 MAPK being the most essential regulator of Aβ-induced toxicity from this family.

5.4 Anti-Inflammatory Mechanisms

As a citrus flavanone with a catechol-bearing aglycone, neoeriocitrin is structurally predisposed to inhibiting pro-inflammatory mediators. Citrus flavonoids are highly bioactive compounds exerting numerous health benefits including anticancer, antioxidant, antimicrobial, anti-inflammatory, mitoprotective, and neuroprotective activity. Research on their broad-scope bioactivity experienced a renaissance in the early 2000s and further accelerated after COVID-19. The compound's modulation of p38 MAPK phosphorylation, documented in cell-based studies, is a recognized mechanism for dampening cytokine-driven inflammation. No human clinical studies have yet directly investigated neoeriocitrin's anti-inflammatory efficacy as an isolated compound.

6. Scientific Evidence by Area of Use

6.1 Bone Health and Osteogenesis

Preclinical (cell-based) evidence — Strength: Moderate (cell/animal only; no human trials)

The most robustly studied pharmacological activity of neoeriocitrin is its osteogenic effect. The pivotal in vitro study was published in Phytomedicine (Li, Zeng, and Cai, 2011): neoeriocitrin, a compound isolated from Drynaria Rhizome, showed better activity than naringin on proliferation and osteogenic differentiation in MC3T3-E1. Naringin is considered the main effective compound of Drynaria Rhizome, used commonly in the treatment of osteoporosis in traditional Chinese medicine. The study found that both neoeriocitrin and naringin exhibited the best effect on proliferation and osteogenic differentiation at a concentration of 2 μg/ml. Neoeriocitrin more significantly improved proliferation and alkaline phosphatase (ALP) activity as well as up-regulated Runx2, COL I, and OCN expression by 56%, 37%, and 14% respectively compared to naringin. Furthermore, neoeriocitrin could rescue the inhibition of cell differentiation induced by PD98059 to some degree. The authors concluded that neoeriocitrin may be a new promising candidate drug for treatment of osteoporosis.

A more recent (2025) study published in Advanced Science extended this work to human dental pulp stem cells (hDPSCs) and moved the research into animal models: the study investigated neoeriocitrin's impact on hDPSC osteogenic differentiation and its mechanisms for bone regeneration. Neoeriocitrin effectively boosted hDPSC osteogenic differentiation in vitro and facilitated bone regeneration in rat calvarial defects in vivo. Thermal proteome profiling revealed that neoeriocitrin directly binds Beclin1, validated by cellular thermal shift assay, molecular docking, and molecular dynamics. This study also quantified the optimal concentration: 5 μM neoeriocitrin emerged as the most potent concentration for enhancing osteogenic markers, mineralization activity, and effective autophagy induction.

Summary of evidence: All osteogenesis evidence for neoeriocitrin as an isolated compound is derived from in vitro cell culture (MC3T3-E1 mouse pre-osteoblasts, human dental pulp stem cells) and one rat calvarial defect model. No human clinical trials have evaluated neoeriocitrin for bone health as an isolated ingredient. Evidence is preliminary but mechanistically consistent.

6.2 Cardiovascular Health and Dyslipidemia

Evidence: Human clinical trial data available, but for multi-flavonoid bergamot extracts standardized to contain neoeriocitrin — not for neoeriocitrin in isolation.

The benefit of bergamot on serum lipids may be attributed to the high amounts of flavonoids contained in bergamot fruit juice, including neoeriocitrin, neohesperidin, and naringin. Several constituents including naringin, neoeriocitrin, and rutin from bergamot have been reported to lower the oxidation of LDL particles. Studies using naringin, neoeriocitrin, and rutin reported antioxidant activity in in vitro antioxidant models using beta-carotene–linoleic acid, DPPH, superoxide, and hamster LDL assays.

An open-label clinical trial investigated standardized bergamot flavonoid extract: eighty subjects (42 men and 38 women, mean age: 55 ± 13 years) with moderate hypercholesterolemia (plasma LDL-cholesterol concentrations between 160 and 190 mg/dL) were included. The subjects received 150 mg of bergamot flavonoids (standardized to contain 16% neoeriocitrin, 47% neohesperidin, and 37% naringin) daily for 6 months. The bergamot group showed a decrease in total cholesterol from 255 to 224, LDL cholesterol from 159 to 132, and triglycerides from 159 to 133. An increase in HDL was observed with bergamot from 50 to 54.

Limitation: This was an open-label (non-blinded) trial using a multi-flavonoid extract. The contribution of neoeriocitrin specifically to these outcomes cannot be isolated from those of neohesperidin, naringin, or other co-occurring constituents in the bergamot extract. No clinical trials have evaluated pure neoeriocitrin alone for cardiovascular outcomes.

6.3 Neuroprotection and Alzheimer's Disease Research

Evidence: Preclinical (in vitro/cell); no human clinical trials. Strength: Weak (early stage).

Neoeriocitrin has been investigated as a dual-action neuroprotective agent targeting the cholinergic deficit and neuroinflammation associated with Alzheimer's disease. Neoeriocitrin is described as a potent acetylcholinesterase (AChE) inhibitor and shows activity on proliferation and osteogenic differentiation in MC3T3-E1. Its neuroprotective actions reported in the cell-based literature include: neoeriocitrin inhibits phosphorylation of P38 MAPK, reduces acetylcholinesterase (AChE) activity, and increases choline acetyltransferase (ChAT) activity. Neoeriocitrin reduces apoptosis and induces autophagy. Neoeriocitrin can be used for the research of osteoporosis and Alzheimer's disease.

The significance of these targets in Alzheimer's disease is established in the broader literature. Alzheimer's disease is a neurodegenerative disorder characterized by the formation of amyloid β and tau protein aggregates in the brain, neuroinflammation, impaired cholinergic neurotransmission, and oxidative stress, resulting in the gradual loss of neurons and neuronal function, which leads to cognitive and memory deficits. Inhibition of AChE is the mechanism of action of approved Alzheimer's drugs (donepezil, rivastigmine, galantamine). Amyloid beta toxicity, increasing RAGE expression, tau hyperphosphorylation, and deregulated autophagy are among other disease mechanisms that are partly explained by activation of p38 MAPK signaling; p38 MAPK is the most essential regulator of Aβ-induced toxicity from this kinase family.

Summary: Current evidence for neoeriocitrin's neuroprotective effects is confined to cell-based studies. No in vivo animal studies specifically for neoeriocitrin in neurological disease models and no human trials have been published. The mechanistic targets are scientifically credible but clinical translation remains undemonstrated.

6.4 Antimicrobial Activity

Evidence: In vitro only. Strength: Very preliminary.

Neoeriocitrin has been included in panels of citrus flavonoids assessed for antimicrobial activity. Among all flavonoids tested (including neohesperidin, hesperetin, neoeriocitrin, eriodictyol, naringin, and naringenin), eriodictyol showed the greatest antimicrobial activity against Gram-negative bacteria, with MICs in the range of 250–800 μg/mL. Synergism was observed between eriodictyol and hesperetin against E. coli and S. enterica, and between eriodictyol and naringenin against S. enterica and P. putida. Notably, eriodictyol (neoeriocitrin's aglycone) displayed superior antimicrobial potency compared to neoeriocitrin itself, with antimicrobial potency increasing after enzymatic deglycosylation. This indicates that neoeriocitrin may act partly as a prodrug, with its aglycone carrying the primary antimicrobial activity.

Summary: Antimicrobial data for neoeriocitrin are in vitro only, and the compound appears less potent in this regard than its aglycone eriodictyol. No animal or human data are available.

6.5 Antioxidant Effects in Context of LDL and Cardiovascular Oxidative Stress

Neoeriocitrin is a flavonoid that has been found in C. paradisi and has antioxidative and osteogenic activities. It inhibits the production of DPPH radicals by 17.2% and the formation of superoxide radicals by 48.3% in cell-free assays, as well as decreases the rate of LDL oxidation ex vivo in isolated hamster plasma. The ex vivo LDL oxidation data represent the closest preclinical approximation to a cardiovascular relevant endpoint, but do not constitute evidence from human subjects.

7. Pharmacokinetics and Metabolism

Neoeriocitrin, as a neohesperidoside-type glycoside, undergoes gut-mediated processing before systemic absorption. Preclinical studies, primarily in rat models, have begun to elucidate its pharmacokinetic properties. Following oral administration, the compound is absorbed from the gastrointestinal tract. However, like many flavonoid glycosides, its direct absorption in its original form is thought to be limited. Instead, it is likely hydrolyzed by intestinal enzymes and gut microbiota into its aglycone form, eriodictyol, which is then more readily absorbed.

Insights into the metabolism of structurally analogous eriodictyol glycosides illuminate what is likely to occur with neoeriocitrin. Evidence is accumulating that the biological activity of eriocitrin is closely related to its metabolites. Pharmacokinetic studies have shown that multiple metabolites of eriocitrin were found in the blood, feces, urine, and various organs of rats after dietary intervention of eriocitrin, and eriodictyol, hesperetin, and homoeriodictyol have been identified as the main metabolites. Eriocitrin can be metabolized into eriodictyol first, and then undergo phase II metabolism such as glucuronidation, sulfation, and methylation, thereby producing hesperetin, homoeriodictyol, eriodictyol-O-glucuronide, and other compounds.

An earlier study identified the products of eriocitrin metabolized by intestinal bacteria derived from the human gut in vitro, demonstrating that eriocitrin can be metabolized to eriodictyol by gut bacteria such as Bacteroides, Bifidobacterium, and Enterobacter. Given the structural similarity between eriocitrin and neoeriocitrin (both are eriodictyol glycosides differing only in the sugar moiety), a parallel metabolic route via intestinal cleavage of the neohesperidoside to liberate eriodictyol is the prevailing model. A sensitive UPLC-MS/MS method has been developed for simultaneous determination of neoeriocitrin and naringin in rat plasma, which was successfully applied to the pharmacokinetic study of neoeriocitrin and naringin in rats after oral administration of a Chinese compound formulation, Gushudan.

With regard to the amount of specific flavanone aglycones absorbed from bergamot juice in humans, eriodyctiol derivatives accounted for 24% of the flavanone composition. Up to 12 structurally related flavanone metabolites were identified in plasma and urine samples after bergamot juice consumption. The overall oral bioavailability of closely related glycosides (such as eriocitrin) has been measured as very low (less than 1%) in rat pharmacokinetic studies, reflecting limited gastrointestinal absorption of the intact glycoside form.

8. Dosage Forms and Reported Dosages

There are no established dosing guidelines for neoeriocitrin as an isolated supplement. Dosages described in the scientific literature refer either to isolated-compound cell-based studies or to multi-ingredient bergamot extracts standardized to a neoeriocitrin percentage. The following dosages have been reported in specific research contexts:

Cell-based osteogenic studies (in vitro): Both neoeriocitrin and naringin exhibited the best effect on proliferation and osteogenic differentiation at a concentration of 2 μg/ml in MC3T3-E1 cells.
Human dental pulp stem cell studies (in vitro): 5 μM neoeriocitrin emerged as the most potent concentration for enhancing osteogenic markers, mineralization activity, and effective autophagy induction.
Clinical trial using bergamot extract standardized to contain neoeriocitrin: Subjects received 150 mg of bergamot flavonoids (standardized to contain 16% neoeriocitrin, 47% neohesperidin, and 37% naringin) daily for 6 months.
Pharmacokinetic rat study formulation (Gushudan): Linear calibration curves of neoeriocitrin were obtained over the concentration range of 15.0–960 ng/mL in rat plasma after oral administration.

Neoeriocitrin is available commercially as a research-grade analytical standard, typically at purities of ≥99% by HPLC, and is incorporated as a minor co-constituent in standardized bergamot polyphenol fraction (BPF) supplements. It is also a component of standardized lemon flavonoid extracts (e.g., ERIOMIN™), where it co-occurs with eriocitrin, eriodictyol, and related compounds. The neoeriocitrin component may have the structure eriodictyol-7-O-neohesperidoside and may be present in such formulations at concentrations of at least 0.1–20% wt/wt.

9. Safety Considerations

Dedicated safety or toxicology studies for neoeriocitrin as an isolated ingredient have not been identified in the published peer-reviewed literature. The following points reflect available source-supported information:

9.1 Safety of Source Plants

Citrus bergamot is generally safe to consume for most individuals. According to the Botanical Safety Handbook, citrus bergamot is in the safest category for herbs (Class 1) and has a very low potential for herb-drug interactions (Class A). This classification refers to the whole-plant/food preparation, not to isolated neoeriocitrin.

9.2 Phototoxicity Considerations (Bergamot Context)

There are possible phototoxic (sunlight sensitivity) and carcinogenic effects from furocoumarins that are present in bergamot orange. These problems can be mitigated by using furocoumarin-free bergamot oil, which is the most common variety today. This phototoxicity risk is attributed to furocoumarin compounds (e.g., bergapten), not to neoeriocitrin itself. Neoeriocitrin is a flavanone glycoside chemically unrelated to furocoumarins.

9.3 Light Sensitivity (Physical Stability)

As a compound, neoeriocitrin is light-sensitive. Analytical and research-grade material is stored in dark conditions to prevent photodegradation; this is a physical stability characteristic rather than a safety concern for human use.

9.4 Research Use Designation

Commercial suppliers of isolated neoeriocitrin note that the compound is provided for research purposes only and is not approved or labeled for human therapeutic use as an isolated pharmaceutical agent.

9.5 Drug Interactions (Inferred from Citrus Flavonoid Class)

As a citrus flavonoid, neoeriocitrin is present in fruits that, in the broader class, have been associated with interactions with cytochrome P450 3A4 (CYP3A4) drug-metabolizing enzymes. However, the most prominent CYP3A4-relevant interactions in citrus are attributed to furanocoumarins (in grapefruit) and to specific flavonoids such as naringenin, not specifically demonstrated for neoeriocitrin as an isolated compound. No direct drug interaction data for isolated neoeriocitrin were identified in the sources reviewed.

10. Body Systems and Health Areas of Association

Musculoskeletal / Bone: Osteogenic differentiation and proliferation in preclinical models; proposed utility in osteoporosis research.
Cardiovascular: LDL oxidation reduction (ex vivo); association as a constituent of bergamot extracts showing lipid-lowering effects in human trials (multi-ingredient formulations).
Neurological: Proposed AChE inhibition and p38 MAPK suppression relevant to Alzheimer's disease models; preclinical only.
Antimicrobial: In vitro activity demonstrated, primarily via its aglycone; no clinical data.
Antioxidant / Oxidative Stress: Well characterized in cell-free and ex vivo assays.

11. Evidence Quality Summary

The overall evidence base for neoeriocitrin as an isolated, clinically used compound is early-stage. The strongest mechanistic evidence relates to osteogenic activity, supported by two independent series of in vitro experiments using established osteoblast cell lines (MC3T3-E1) and, in the most recent work (2025), human dental pulp stem cells with confirmatory rat in vivo data. Human clinical trial evidence exists only for multi-ingredient bergamot extracts in which neoeriocitrin is one of several co-occurring flavanones; attributing the observed cardioprotective effects exclusively or primarily to neoeriocitrin from these trials is not scientifically justified. Neuroprotective and antimicrobial evidence is limited to cell-based studies. No randomized controlled trials, systematic reviews, or regulatory assessments focusing on neoeriocitrin as a standalone ingredient have been published.

References

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