Dihydromyricetine

Dihydromyricetin (DHM), also known as ampelopsin, is a flavanonol from the flavonoid group. Its molecular formula is: C15H12O8.

Dihydromyricetin is found as a secondary plant substance in the Japanese raisin tree (Hovenia dulcis), in plants of the genus Ampelopsis (e.g. in A. meliaefolia, A. japonica, A. megalophylla, A. cantoniensis (= A. grossedentata), in the coastal pine Pinus contoria (Rowe JW et al. 1964), in Erythrophleum africanum, in Rhododendron cinnabarinum and in the Japanese cake tree (Cercidiphyllum japonicum).

And since altered epigenomic regulation is considered a key hallmark of ageing (Falckenhayn C et al. 2024), identifying compounds that modulate epigenetic mechanisms is considered a particularly powerful approach to slowing or reversing the process. This approach identified DHM, a flavonoid with known beneficial effects such as anti-cancer, antioxidant and anti-inflammatory properties. DHM has also been discussed in the context of anti-aging therapies, as DHM has been shown to protect against cognitive impairment and ameliorate brain aging in rats by modulating apoptosis and dysfunctional autophagy of hippocampal neurons as well as astrogliosis (Falckenhayn C et al. 2024). DHM has also been proposed by others as a promising agent for the treatment of ageing in humans (Martínez-Coria et al. 2019).

Dihydromyricetin binds to GABA receptors. Animal experiments have shown that alcoholized animals that were previously administered a dose of 1 mg/kg body weight of DHM sobered up significantly faster. No toxicological effects caused by the DHM could be detected in the test animals at the quantities of active substance used. Only at 100 times the dose used in the experiments did the rats show slight orientation disorders, which are also caused by benzodiazepines, for example, which also bind to the GABAA receptor (Shen Y et al. 2012). Extracts of the Japanese raisin tree have been approved by the Korea Food & Drug Administration since 2008 for the regeneration of the liver of patients with alcohol abuse. The effect has been known for over 500 years (Mitchell D 2012).

For example, Chen et al. observed a decrease in serum TNF-α after 12 weeks of DHM intake (Chen et al. 2015)- Investigating the potential of DHM for systemic treatment of aging or age-related diseases is an interesting approach for future evaluations.

DHM is considered the active ingredient of grapevine tea, a health-promoting herbal tea. As DHM and its derivatives are estimated to make up 1/5 of dry grape leaves depending on the extraction method (Falckenhayn C et al. 2024), the amount of DHM in a prepared cup of grape leaf tea can reach concentrations in the mmol range, illustrating its excellent tolerability.

For the topical application of DHM, a safety assessment following the next generation risk assessment approaches for new cosmetic ingredients concluded that the substance has only a low potential for acute and repeated dose toxicity, allowing for a safe application of up to 0.15% on human skin (Falckenhayn C et al. 2024). This distinguishes DHM from the most commonly used DNA demethylating agents, 5-azacytidine and 2′-deoxy-5-azacytidine, which were developed as clinical anticancer drugs for abnormal DNA methylation (Jones et al. 2016). However, the broad and indirect mode of action of these hypomethylating agents is associated with noticeable toxicity. DHM reduces the DNA methylation age in cultured primary human keratinocytes (Falckenhayn C et al. 2024). This phenomenon as well as the good tolerability of DHM are characteristic features that support the use of the compound in nutraceutical and cosmetic applications.

Dihydromyricetin extracts are also used for daily skin care, whereby the methylation pattern of the skin cells (their biological age can be derived from the methylation pattern of skin cells) is changed (Falckenhayn C et al. 2024).

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1. Falckenhayn C et al. (2024) Identification of dihydromyricetin as a natural DNA methylation inhibitor with rejuvenating activity in human skin. Front Aging 4:1258184.
2. Jones PA (2012). Functions of DNA methylation: islands, start sites, gene bodies and beyond. Nat Rev Genet 13: 484-49
3. Martínez-Coria H et al. (2019) Preclinical research of dihydromyricetin for brain aging and neurodegenerative diseases. Front. Pharmacol 10: 1334.
4. Mitchell D (2012) Chinese Herbal Hangover Remedy May Fight Alcoholism. EmaxHealth. Retrieved 9.2025.
5. Shen Y et al. (2012) Dihydromyricetin as a novel anti-alcohol intoxication medication. In: The Journal of neuroscience 32: 390-401.
6. Ye J et al.(2008) Ampelopsin prevents apoptosis induced by H2O2 in MT-4 lymphocytes. In: Planta Medica 74: 252-257.
7. Zhang Y et al. (2007) Isolation and identification of metabolites from dihydromyricetin. In: Magnetic Resonance in Chemistry 45: 909-916.