IngredientsAmpelopsin, also known as dihydromyricetin (abbreviated DHM), is a flavanonol — a type of flavonoid. Its full IUPAC chemical name is (2R,3R)-3,5,7-trihydroxy-2-(3,4,5-trihydroxyphenyl)-2,3-dihydrochromen-4-one. It is also frequently designated by its systematic flavonoid name: 3,5,7,3′,4′,5′-hexahydroxy-2,3-dihydroflavonol.
Ampelopsin (AMP, or dihydromyricetin) is a flavanonol aglycone. Structurally, it is derived from the flavonoid myricetin by hydrogenation of the 2,3-double bond. Its PubChem Compound ID is 161557.
The compound has significant physicochemical challenges: DHM has low water solubility (only about 0.2 mg/ml at 25 °C) and poor stability in aqueous environments. Additionally, DHM is only stable at low temperatures and in a weakly acidic environment (pH 6.0).
Dihydromyricetin (DMY) or ampelopsin is a major bioactive flavonoid isolated from a traditional Chinese medicinal plant Ampelopsis grossedentata, and it is also found in various plant-based foods such as grapes and red bayberry. DMY was first isolated from Ampelopsis meliaefolia by Kotake and Kubota in 1940, and was later reported as a major bioactive component in A. grossedentata.
It is extracted from the Japanese raisin tree and found in Ampelopsis species japonica, megalophylla, and grossedentata; Cercidiphyllum japonicum; Hovenia dulcis; Rhododendron cinnabarinum; some Pinus species; and some Cedrus species, as well as in Salix sachalinensis. Other natural sources of dihydromyricetin include Myrica rubra (also called Chinese bayberry, Japanese bayberry, red bayberry, yumberry, waxberry, or Chinese strawberry).
The content of DMY is as high as 30–40% (w/w) in A. grossedentata. This remarkable concentration makes A. grossedentata (known as "vine tea" or tencha) the principal commercial source for supplement production. Commercial DHM is primarily extracted from H. dulcis due to its high content.
Long before vine tea extract was isolated and used as a supplement, these plants have been used as remedies against hangovers for centuries and consumed as teas, powder preparations, and infusions — and lately as capsules and pills.
DHM can be extracted from plant sources using solvents like alcohol/water mixtures. Purification often involves column chromatography and preparative HPLC. DHM purity and yields can vary significantly depending on technique. Currently, commercially available DHM preparations are still rare, and studies on different DHM preparations are ongoing in order to promote the clinical applications of this promising compound.
Hovenia dulcis is listed among the premier anti-hangover herbal medicines in China's first pharmacopoeia, the Tang Materia Medica (Su, 659). Hovenia dulcis has been used in traditional Japanese, Chinese, and Korean medicines to treat fever, parasitic infection, as a laxative, and as a treatment of liver diseases, and as a hangover treatment.
Ampelopsis grossedentata is a medicinal and edible plant that is widely distributed in southern China, and its tender stems and leaves have been used as medicinal tea for the prevention and treatment of common cold, sore throat, and icteric viral hepatitis for hundreds of years.
Ampelopsis grossedentata is a medicinal and edible plant widely used in China as a Traditional Chinese Medicine for the treatment of cough, fever, vomiting, hepatitis, colds, chronic nephritis, and sore throat. Tender stems and leaves of A. grossedentata are commonly consumed as vine tea in China for centuries due to its health-benefiting effects.
In traditional Chinese medicine practice, DHM is traditionally used for clearing heat and removing toxins, calming the liver and lowering blood pressure, and unblocking the veins. Hovenia dulcis is listed among the premier liver herbs and anti-hangover remedies in the Chinese pharmacopoeia, including the Tang Materia Medica.
Ampelopsin is itself the principal bioactive constituent of the plants from which it is derived. The chemical name of ampelopsin is 3,5,7,3′,4′,5′-hexahydroxyl-2,3-dihydroflavonol, initially isolated from traditional Chinese medicinal plants Ampelopsis grossedentata and Ampelopsis meliaefolia. It is a major bioactive constituent comprising approximately 30–40% (w/w) of Ampelopsis grossedentata.
Myricetin and ampelopsin (AMP, or dihydromyricetin) are flavonoid aglycones found in certain plants and dietary supplements. During the presystemic biotransformation of flavonoids, mainly sulfate and glucuronide derivatives are produced, which are the dominant metabolites in the circulation. The sulfate metabolite of ampelopsin, ampelopsin-4′-O-sulfate (A4′S), is therefore among the circulating forms following oral ingestion.
GABAA receptors (GABAARs) are major targets of acute and chronic ethanol actions on the brain. At the cellular level, DHM (1 μM) antagonized both acute ethanol-induced potentiation of GABAARs and ethanol exposure/withdrawal-induced GABAAR plasticity, including alterations in responsiveness of extrasynaptic and postsynaptic GABAARs to acute ethanol and, most importantly, increases in GABAAR α4 subunit expression in hippocampus and cultured neurons.
Dihydromyricetin is a natural bioactive flavonoid with unique GABAA receptor activity with a putative mechanism of action to reduce the intoxication effects of ethanol. More specifically, electrophysiology studies in α5β3γ2 GABAA receptors expressed in Xenopus oocytes suggest dihydromyricetin (10 µM) potentiates GABAergic activity (+43.2%), and the metabolite 4-O-methyl-dihydromyricetin (10 µM) negatively modulates GABAergic activity (−12.6%).
This flavonoid may help the body metabolize alcohol (ethanol) more efficiently by enhancing the activity of alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase (ALDH). Ethanol catabolism is mediated by ADH and ALDH: ADH converts ethanol into acetaldehyde, which is then oxidized by ALDH into the nontoxic metabolite acetyl-CoA. However, it is important to note that the precise molecular details of this mechanism remain under investigation. One study found that examining the impact of DHM on alcohol dehydrogenase (ADH) activity in vitro and enzyme induction in vivo, neither the ADH activity nor the enzyme expression were influenced by DHM. The precise liver-level mechanism therefore requires further clarification.
DHM possesses many pharmacological effects, including anti-inflammatory (NLRP-3, NF-κB, cytokines, and neuroinflammation), antioxidant, improving mitochondrial dysfunction, and regulating autophagy. In preclinical models, DHM shows a variety of beneficial anti-aging properties by reducing inflammation, oxidative stress, and lipidemia, as well as regulating energy metabolism and promoting autophagy. These effects are primarily derived from its ability to activate sirtuins.
DMY improves insulin resistance, which is related to the activation of the AMP-activated protein kinase (AMPK) signaling pathway to increase glucose uptake. In addition, this activity of DMY is also related to the reduction of glucose production via the insulin receptor substrates (IRS)/PI3K/Akt pathways.
DHM inhibited inflammatory responses, inhibited the secretion of inducible nitric oxide synthase (iNOS) and COX-2, and attenuated the activation of NF-κB and TLR4 signals in lipopolysaccharide (LPS)-induced neuroinflammation. Additionally, DHM inhibited inflammatory response via up-regulation of the AMPK/SIRT1 pathway in Alzheimer's disease mice.
DHM regulates MDM2-mediated p53 pathway to trigger apoptosis in the exogenous death receptor pathway and inhibits TGF-β-Smad3 signaling, disturbs ROS balance, and promotes apoptosis in endogenous mitochondrial and endoplasmic reticulum pathways. DHM also induces autophagy through the PDGFR/Akt/mTOR pathway, inhibiting cell proliferation. In addition, DHM inhibits miR-21/PTEN/Akt, miR-455/ZEB1/PI3K, TNF-α/P38/MMP and ERK/NF-κB/Snail pathways, thereby suppressing cancer cell metastasis and proliferation. Furthermore, DHM can activate AMPKα/GSK-3β/P21 pathway, leading to cell cycle arrest.
DHM acts via a dual regulatory mechanism: it inhibits oxidative stress and neuroinflammation, thereby reducing neuronal apoptosis, and simultaneously promotes neural repair by enhancing the expression of nerve growth factor and brain-derived neurotrophic factor (BDNF). The bidirectional nature of this mechanism highlights its therapeutic promise in neurodegenerative disorders. At the molecular level, DHM mitigates oxidative stress-induced mitochondrial dysfunction by activating the SIRT1/FOXO3a signaling pathway.
This is the area with the most extensive research and the clearest mechanistic evidence, though the bulk of high-quality data comes from preclinical models.
Preclinical (animal) evidence: A landmark 2012 study published in the Journal of Neuroscience reported that DHM (1 mg/kg, i.p. injection), a flavonoid component of herbal medicines, counteracted acute alcohol (EtOH) intoxication and also withdrawal signs in rats including tolerance, increased anxiety, and seizure susceptibility; DHM greatly reduced EtOH consumption in an intermittent voluntary EtOH intake paradigm in rats.
Human/clinical evidence: Although dihydromyricetin's poor oral bioavailability limits clinical utility, the promise of this mechanism for the treatment of alcohol use disorder warrants further investigation into its specificity and druggable potential. The evidence supporting DHM's anti-intoxication effects in humans remains indirect or preliminary. One report noted that at least one human study has noted that, when taken before drinking, it can reduce circulating levels of alcohol. No large-scale phase III clinical trials in humans for alcohol use disorder had been published at the time of this writing.
Evidence strength: The animal evidence for GABAAR-mediated effects on intoxication, withdrawal, and voluntary alcohol consumption is substantial and mechanistically compelling. Human clinical evidence is preliminary and limited to small studies. The overall evidence base should be characterized as strong preclinically but insufficient at the human-trial level to support established clinical claims.
This area has the strongest human clinical evidence for ampelopsin.
Clinical Trial (NAFLD/MASLD — 2015): In a double-blind clinical trial, sixty adult nonalcoholic fatty liver disease (NAFLD) patients were randomly assigned to receive either two dihydromyricetin or two placebo capsules (150 mg) twice daily for three months. The serum levels of alanine aminotransferase, aspartate aminotransferase, γ-glutamyl transpeptidase, glucose, low-density lipoprotein-cholesterol and apolipoprotein B, and the homeostasis model assessment of insulin resistance (HOMA-IR) index were significantly decreased in the dihydromyricetin group compared with the placebo group.
Clinical Trial (MASLD — 2025): A more recent double-blind, placebo-controlled, randomized clinical trial assessed the efficacy of a DHM-containing dietary supplement in MASLD. Adult MASLD patients were randomized to receive a dietary supplement containing DHM (300 mg/day), vitamins C/E and choline (group A), or identical placebo (group B) for 12 months. Patients were assessed every ≤6 months for clinical and laboratory parameters and liver stiffness measurements. Fifty-five patients were randomized to group A (n=28) or B (n=27), but 9 patients (group A/B=2/7) were withdrawn early for personal reasons. Median liver enzymes decreased at 6 or 12 months only in group A. Group A compared to B patients achieved higher 12-month rates of combined ALT/γ-glutamyl transpeptidase (GGT) normalization (35% vs. that of the placebo group). Importantly, this trial used a combination formula (DHM + vitamins C/E + choline), which limits attribution of effects to DHM alone.
Preclinical evidence (summary): In a mouse model of alcohol-induced liver injury, oral administration of DHM was associated with less liver steatosis and triglyceride levels, which was attributed to changes in lipid metabolism and enhancement of ethanol metabolism as well as suppression of immune responses. DHM has been shown to have anti-inflammatory effects and to inhibit the activation of hepatic stellate cells, thus improving liver inflammation, steatosis and fibrosis.
A 2026 PRISMA systematic review and meta-analysis registered in PROSPERO (CRD420251119087) searched PubMed, Embase, Web of Science Core Collection, the Cochrane Library, and four major Chinese databases from inception to December 15, 2025 to quantify DHM's efficacy in diet-induced MASLD/NAFLD preclinical models, underscoring the growing volume of preclinical literature, though most is from animal or in vitro models.
Evidence strength: There are at least two small-to-moderately-sized randomized controlled trials in humans, both showing improvements in liver enzyme profiles and metabolic markers. These are encouraging findings, but sample sizes are small, one trial used a combination formula, and longer-term data are lacking. Overall, evidence is preliminary-to-moderate and warrants confirmation in larger trials.
Hypoglycemic, antioxidant, anti-thrombosis, anti-tumor, anti-inflammatory and antibacterial activities have all been observed for DHM, but no toxicity. DMY improves insulin resistance in HFD-treated rats. DMY improves insulin resistance, which is related to the activation of the AMP-activated protein kinase (AMPK) signaling pathway to increase glucose uptake. In addition, this activity is also related to the reduction of glucose production via the IRS/PI3K/Akt pathways.
The 2015 NAFLD RCT referenced above also demonstrated significant improvement in fasting glucose and HOMA-IR scores, providing limited but direct human evidence for a metabolic benefit. A review of the possible mechanism of DHM in treating nonalcoholic fatty liver disease from many in vitro and in vivo studies suggests that it has anti-inflammatory and antioxidant activities and may act via sirtuin-dependent pathways.
Evidence strength: Primarily preclinical (animal model and in vitro) data, with secondary support from the liver disease RCTs which measured metabolic markers as secondary endpoints. Not yet established for independent clinical indications.
The effects of DHM have been studied in different in vitro systems of oxidative damage and neuroinflammation, as well as in animal models of several neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, and Huntington's disease.
Prior work has demonstrated the anxiolytic effects of DHM in Alzheimer's disease mouse models (TG2576 and TG-SwDI) as measured in behavioral studies using the elevated plus-maze and open field.
With respect to Parkinson's disease, DHM has a positive effect on Parkinson's disease. One study developed a PD-like mouse model and demonstrated that DHM could alleviate motor dysfunction and prevent the loss of dopaminergic neurons in mice with PD.
DHM demonstrates significant neuroprotective effects by modulating TLR4/NF-κB signaling, a central pathway driving neuroinflammation in neurological disorders. The TLR4/NF-κB axis amplifies neuroinflammation through TLR4 activation and NF-κB nuclear translocation. In Alzheimer's disease, TLR4/NF-κB hyperactivation promotes amyloid-β toxicity and microglial inflammation.
In cognitive aging models, DMY alleviates the cognitive impairments in d-galactose-induced aging mice partly through regulating oxidative stress and inhibition of acetylcholinesterase.
Evidence strength: Entirely preclinical (in vitro and animal models). No human clinical trials for neurodegenerative endpoints have been published. This area is promising but speculative for human application at this time.
DHM improves anxiety through multiple pathways. Studies have revealed that DHM ameliorates anxiety behavior in a chronic social isolation mouse model by regulating mitochondrial function, reducing oxidative stress, restoring normal autophagy, and increasing brain-derived neurotrophic factor (BDNF), which plays a crucial role in neuroprotection.
In preclinical work on depression, DHM has demonstrated a protective role against cardiovascular disease, diabetes, liver disease, cancer, kidney injury and neurodegenerative disorders. In one study, researchers examined the protective effect of DHM against depression in a chronic depression mouse model induced by corticosterone.
Evidence strength: Preclinical only. No controlled human trials for anxiety or depression have been published.
DHM effectively showed anticancer activity in a variety of cancers such as breast cancer, hepatocellular carcinoma, melanoma, ovarian cancer, lung cancer, cervical carcinoma, glioma, and osteosarcoma. Among the treatments for different cancer cells, DHM has a broad dosage from 1 to 1000 µM with a duration from 6 to 72 h, presenting cell proliferation inhibition and apoptosis-inducing effects.
Several preclinical studies have revealed that DHM can inhibit the growth of a variety of cancer cells by modulating various cellular signalling pathways; for example, DHM can protect the cardiovascular system through PI3K/Akt, Nrf2/HO-1 and SIRT3 signalling pathways and can prevent or inhibit the growth of a variety of cancer cells through ERK/Akt, AMPK/MAPK/XAF1, Akt-mTOR, ROS/NF-κB and mitochondrial apoptosis signalling pathways to prevent or inhibit hepatocellular carcinoma, lung cancer, colorectal cancer, breast cancer, leukaemia and melanoma.
In leukemia cell lines specifically, ampelopsin significantly inhibited the proliferation of both HL60 and K562 leukemia cell lines at concentrations that did not affect normal cell viability. Ampelopsin induced cell cycle arrest at the sub-G1 phase in HL60 cells but the S phase in K562 cells. In addition, ampelopsin regulated the expression of cyclins, cyclin-dependent kinases (CDKs), and CDK inhibitors differently in each leukemia cell.
Evidence strength: Entirely in vitro and animal (preclinical) models. No human clinical anticancer trials have been conducted. Findings are mechanistically interesting but have not been translated to clinical evidence.
In a myocardial ischemia-reperfusion injury model, DHM improved mitochondrial integrity via SIRT3 upregulation, reduced oxidative damage, decreased infarct size, and enhanced cardiac function. DHM has demonstrated a protective role against cardiovascular disease in preclinical models, though, as with other areas, direct human trial evidence is absent.
Evidence strength: Preclinical only.
The pharmacokinetic profile of ampelopsin presents notable challenges for supplement development. The absolute bioavailability of DHM was 4.02%, which was poor. DHM has also not been associated with toxicities in preclinical rodent studies. The good safety profile of DHM may be related to its poor bioavailability of 4.02% in rats, and it is possible that new side effects may emerge with the development of more bioavailable formulations.
Total serum exposures (AUC0→24) of dihydromyricetin (PO 50 mg/kg) via oral administration were determined to be 2.5 µM × h (male) and 0.7 µM × h (female), while intraperitoneal administration led to 23.8-fold and 7.2-fold increases in AUC0→24 in male and female mice, respectively.
Results indicate that administration route and sex significantly impact DHM bioavailability in mice, which is limited by poor absorption and rapid clearance. This correlates with the observed short duration of DHM's anti-intoxicating properties and highlights the need for further investigation.
During metabolism, mainly sulfate and glucuronide derivatives are produced, which are the dominant metabolites in the circulation.
The following dosages are drawn directly from cited research and should not be interpreted as prescriptive recommendations:
The NIH LiverTox database, maintained by the National Institute of Diabetes and Digestive and Kidney Diseases, provides an authoritative safety assessment: Dihydromyricetin preparations have not been linked to instances of serum enzyme elevations or clinically apparent liver injury with jaundice.
DHM is a flavonoid derived from natural sources with a range of confirmed biological benefits. It exhibits anti-inflammatory, antioxidant, anti-tumor, and anti-viral activities. DHM is recognized for its high biosafety, making it a promising subject for further research.
A dedicated in vitro investigation of DHM's effects on human liver cytochrome P450 enzymes is particularly relevant for drug interaction risk. The inhibitory effects of DHM on eight human liver CYP isoforms (1A2, 3A4, 2A6, 2E1, 2D6, 2C9, 2C19, and 2C8) were investigated in vitro using human liver microsomes. The results showed that DHM could inhibit the activity of CYP3A4, CYP2E1 and CYP2D6, with IC50 values of 14.75, 25.74 and 22.69 µM, respectively, but that other CYP isoforms were not affected. Enzyme kinetic studies showed that DHM was not only a non-competitive inhibitor of CYP3A4 but also a competitive inhibitor of CYP2E1 and CYP2D6, with Ki values of 6.06, 9.24 and 10.52 µM, respectively.
The in vitro studies of DHM with CYP isoforms indicate that DHM has the potential to cause pharmacokinetic drug interactions with other co-administered drugs metabolized by CYP3A4, CYP2E1 and CYP2D6. Whether these in vitro effects translate to clinically meaningful interactions in vivo — given DHM's low oral bioavailability — remains an open question not yet resolved in human studies.
In contrast, a 2024 study that tested ampelopsin and its sulfate metabolite against CYP2C9, CYP2C19, and CYP3A4 found that MYR, M3′S, AMP, and A4′S exerted no or only minor inhibitory effects on CYP2C9, CYP2C19, and CYP3A4 enzymes — findings that appear in partial conflict with the earlier microsomal data, highlighting that the net clinical drug interaction risk requires further clarification.
MYR and AMP form stable complexes with HSA (human serum albumin) occupying Site I as their high-affinity binding site. Displacement of highly protein-bound drugs from albumin binding sites is a potential interaction pathway that warrants attention, particularly for narrow therapeutic-index drugs that compete for Sudlow's Site I binding.
Myricetin and myricetin-3′-O-sulfate proved to be strong inhibitors of organic anion transporting polypeptides (OATPs) at low micromolar (OATP1B1) and at nanomolar (OATP2B1) concentrations. As the structurally closely related parent compound of myricetin, this transport inhibition at low concentrations may also be relevant to ampelopsin's pharmacokinetic interactions.
Research has documented that inhibition of xanthine oxidase-catalyzed xanthine and 6-mercaptopurine oxidation by ampelopsin and its conjugated metabolites has been observed. This raises a potential interaction between ampelopsin and 6-mercaptopurine (an immunosuppressant and chemotherapy drug) or other xanthine oxidase substrates such as allopurinol, as concurrent inhibition of this enzyme could alter the metabolism of such drugs.
DHM has low water solubility (only about 0.2 mg/ml at 25 °C) and poor stability in aqueous environments. Novel formulations are under investigation to address these limitations: phospholipid complexes, nanoscale delivery systems, and gastric floating sustained-release tablets have all been evaluated in preclinical pharmacokinetic studies. The consequences of enhanced bioavailability for the safety profile and drug interaction potential of ampelopsin are not yet fully characterized.
Health conditions that Ampelopsin may help support.
Body systems that Ampelopsin may help support.
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