Welcome to my review of Dihydromyricetin (DHM).
I recently discovered DHM and was curious to learn more about its use in alcohol abuse disorder.
After many hours of research I’ve learned that DHM has so much more potential than I originally thought.
The following review aims to synthesize and present the current knowledge on DHM, its biological activities, and its potential therapeutic applications, drawing from the latest scientific literature 1Joshua Silva et al, Modulation of Hippocampal GABAergic Neurotransmission and Gephyrin Levels by Dihydromyricetin Improves AnxietyFront. Pharmacol., 09 July 2020.
We will journey through the intricate world of DHM, exploring its chemical structure, pharmacokinetics, mechanisms of action, and potential impact on clinical practice and public health.
So if you’re ready to learn more about health-boosting effects of Dihydromyricetin, let’s jump into the article!
Overview of Dihydromyricetin
Dihydromyricetin, or DHM, is a natural compound in some plants, like the Chinese vine Ampelopsis grossedentata.
It has been used in traditional medicine and is now being studied for its potential health benefits.
Some of the positive effects of DHM include helping to fight diseases like diabetes, liver problems, and even some types of cancer.
It has also shown promise in reducing the harmful effects of alcohol on the body and brain, making it a potential treatment for alcohol-related issues.
This compound has caught scientists’ and doctors’ attention because of its many benefits. It can help protect our cells from damage, reduce inflammation, and improve our body’s energy use.
Also, DHM has positively impacted our mood and mental well-being.
Overall, dihydromyricetin is a fascinating substance with a wide range of potential benefits.
Chemical Structure and Properties of Dihydromyricetin
DHM, also known as ampelopsin, is a flavonoid belonging to the flavanonol subclass, characterized by its distinct 3-hydroxyflavan-4-one structure 2Dan Liu et al, Dihydromyricetin: A review on identification and quantification methods, biological activities, chemical stability, metabolism and approaches to enhance its bioavailabilityTrends Food Sci Technol. 2019.
It is primarily isolated from the vine Ampelopsis grossedentata, commonly known as the “treebine” or “porcelain berry” 3Jie Liu et al, Dihydromyricetin induces apoptosis and inhibits proliferation in hepatocellular carcinoma cellsOncol Lett. 2014.
Other plant sources of DHM include Hovenia dulcis, Cedrus deodara, and Ampelopsis japonica 4Ting Ting Liu et al, Dihydromyricetin ameliorates atherosclerosis in LDL receptor deficient miceAtherosclerosis. 2017 5Zhaoxiang Ren et al, Dihydromyricetin exerts a rapid antidepressant-like effect in association with enhancement of BDNF expression and inhibition of neuroinflammationPsychopharmacology (Berl). 2018.
Two major approaches for obtaining DHM are isolation from natural sources and synthetic production.
Traditional isolation methods involve the extraction, purification, and chromatographic separation 6Yi Shen et al, Dihydromyricetin as a novel anti-alcohol intoxication medicationJ Neurosci. 2012.
However, these methods are often time-consuming and yield low compound quantities.
Recent advancements in biotechnology have enabled the production of DHM through genetic engineering, offering a more efficient and sustainable alternative 7Jing Liang et al, Dihydromyricetin prevents fetal alcohol exposure-induced behavioral and physiological deficits: the roles of GABAA receptors in adolescenceNeurochem Res. 2014.
Pharmacokinetics and Metabolism of Dihydromyricetin
Understanding the pharmacokinetics of DHM is crucial for its practical therapeutic application.
Studies on absorption and distribution have shown that DHM exhibits rapid absorption and extensive tissue distribution8Liming Guo et al, Dihydromyricetin promotes autophagy and attenuates renal interstitial fibrosis by regulating miR-155-5p/PTEN signaling in diabetic nephropathyBosn J Basic Med Sci. 2020.
However, its oral bioavailability is relatively low, primarily due to its extensive metabolism in the liver 9Zhuangwei Zhang et al, Dihydromyricetin induces mitochondria-mediated apoptosis in HepG2 cells through down-regulation of the Akt/Bad pathwayNutr Res. 2017.
DHM undergoes significant biotransformation through phase I and II metabolic reactions, which include hydroxylation, methylation, glucuronidation, and sulfation 10Qinghai Li et al, Dihydromyricetin prevents monocrotaline-induced pulmonary arterial hypertension in ratsBiomed Pharmacother. 201711Hongyan Ling et al, Dihydromyricetin improves type 2 diabetes-induced cognitive impairment via suppressing oxidative stress and enhancing brain-derived neurotrophic factor-mediated neuroprotection in miceActa Biochim Biophys Sin (Shanghai). 2018 .
The primary metabolites identified in humans are DHM-3-O-glucuronide and DHM-3′-O-glucuronide 12Zhao-xiang Ren et al, Dihydromyricetin protects neurons in an MPTP-induced model of Parkinson’s disease by suppressing glycogen synthase kinase-3 beta activityActa Pharmacol Sin. 2016.
The elimination half-life of DHM varies between species, ranging from 2.7 to 8.8 hours 13Dafeng Yang et al, Dihydromyricetin Attenuates TNF-α-Induced Endothelial Dysfunction through miR-21-Mediated DDAH1/ADMA/NO Signal PathwayBiomed Res Int. 2018.
Excretion occurs predominantly through bile and feces, with a smaller proportion excreted in urine 14Author(s), Name of studyname of publication. YEAR .
Several preclinical and clinical studies have investigated the potential therapeutic applications of DHM in the context of alcohol use disorder, neurodegenerative diseases, liver diseases, and cancer treatment.
Alcohol use disorder and hangover relief
Preclinical evidence suggests that DHM can alleviate alcohol-induced behavioral impairments and reduce the severity of hangover symptoms by accelerating alcohol metabolism and mitigating oxidative stress and inflammation 15Yingchun Zhao et al, Dihydromyricetin Reverses Thioacetamide-Induced Liver Fibrosis Through Inhibiting NF-κB-Mediated Inflammation and TGF-β1-Regulated of PI3K/Akt Signaling PathwayFront. Pharmacol. 202116Jun Xie et al, Dihydromyricetin alleviates carbon tetrachloride-induced acute liver injury via JNK-dependent mechanism in miceWorld J Gastroenterol. 2015.
By targeting specific receptors in the brain, DHM can help counteract alcohol’s impact on coordination and cognitive function and has been shown to help reduce hangover symptoms such as headache, nausea, and fatigue by promoting the body’s ability to break down alcohol and its toxic byproducts.
Clinical trials have demonstrated the potential of DHM as a hangover remedy, although larger-scale studies are needed to confirm these findings 17Aneta SKOTNICOVÁ et al, Does Dihydromyricetin Impact on Alcohol MetabolismPhysiol Res. 2020.
While preliminary studies are promising, more research is needed to establish the optimal dosage and treatment regimen for DHM to provide maximum benefit for those suffering from hangovers or alcohol use disorders.
Dihydromyricetin’s potential to alleviate anxiety has become an intriguing area of research, given its interaction with GABA receptors and influence on GABAergic neurotransmission.
Anxiety disorders, which affect millions of people worldwide, are associated with an imbalance in the brain’s excitatory and inhibitory neurotransmitters.
By modulating GABAergic neurotransmission in the hippocampus, a region crucial for emotion and memory processing, DHM may provide a promising avenue for anxiety treatment.
A recent study by Joshua Silva et al. demonstrated that DHM enhances GABAergic neurotransmission in the hippocampus and increases the levels of gephyrin, a protein responsible for clustering and stabilizing GABA receptors at the synapses.18Joshua Silva et al, Modulation of Hippocampal GABAergic Neurotransmission and Gephyrin Levels by Dihydromyricetin Improves AnxietyFront. Pharmacol. 2020
This increase in gephyrin levels leads to more GABA receptor sites, which results in heightened sensitivity to GABA, the primary inhibitory neurotransmitter in the brain.
Consequently, DHM’s ability to modulate GABAergic neurotransmission and its impact on gephyrin levels contribute to its anxiolytic (anxiety-reducing) effects.
While more research is needed to understand the mechanisms and optimal treatment regimens fully, dihydromyricetin shows great promise as a potential therapeutic agent for anxiety and other neurological disorders linked to GABAergic neurotransmission.
Blood Sugar/Insulin Resistance/Glucose Metabolism
DHM may have the ability to help stabilize blood glucose metabolism, thus lowering instances of insulin resistance and eventual metabolic syndrome.
In one double-blind, randomized controlled clinical trial, sixty adult nonalcoholic fatty liver disease patients were randomly assigned to receive either two dihydromyricetin or two placebo capsules (150 mg)twice daily for three months 19Joshua Silva et al, Modulation of Hippocampal GABAergic Neurotransmission and Gephyrin Levels by Dihydromyricetin Improves AnxietyFront. Pharmacol., 09 July 2020.
DHM supplementation was shown to protect liver function, improve insulin resistance, regulate glucose and lipid metabolism, and slows the progression of liver steatosis in patients with NAFLD.
While the mode of action is still under investigation, benefits may stem from improved liver health.
In preclinical models of Alzheimer’s disease, DHM has been shown to reduce amyloid-beta (Aβ) deposition and alleviate cognitive deficits 20Jing Liang et al, Dihydromyricetin ameliorates behavioral deficits and reverses neuropathology of transgenic mouse models of Alzheimer’s diseaseNeurochem Res. 2014.
Additionally, DHM exhibits neuroprotective effects in animal models of Parkinson’s disease by attenuating dopaminergic neuron loss and mitigating motor dysfunction 21Baoping Jiang et al, Dihydromyricetin ameliorates the oxidative stress response induced by methylglyoxal via the AMPK/GLUT4 signaling pathway in PC12 cellsBrain Res Bull. 2014.
Further clinical studies are warranted to validate these promising findings.
Preclinical studies have demonstrated the potential of DHM in treating NAFLD and alcoholic liver disease (ALD) by modulating lipid metabolism, oxidative stress, and inflammation 22Xianglong Zeng et al, Dihydromyricetin Ameliorates Nonalcoholic Fatty Liver Disease by Improving Mitochondrial Respiratory Capacity and Redox Homeostasis Through Modulation of SIRT3 SignalingAntioxid Redox Signal. 201923Yingchun Zhao, Dihydromyricetin Reverses Thioacetamide-Induced Liver Fibrosis Through Inhibiting NF-κB-Mediated Inflammation and TGF-β1-Regulated of PI3K/Akt Signaling PathwayFront. Pharmacol. 2021
These findings suggest that DHM could be a valuable therapeutic agent for individuals suffering from liver disorders.
Clinical trials investigating the efficacy and safety of DHM in patients with liver diseases are underway 24Joshua Silva et al, Dihydromyricetin Protects the Liver via Changes in Lipid Metabolism and Enhanced Ethanol MetabolismAlcohol Clin Exp Res. 2020.
Cancer treatment and Prevention
Although preclinical studies have demonstrated the anti-cancer potential of DHM, clinical evidence remains limited 25Qing-Yu Zhang et al, Dihydromyricetin inhibits migration and invasion of hepatoma cells through regulation of MMP-9 expressionWorld J Gastroenterol. 2014.
Challenges associated with translating preclinical findings to clinical practice include optimizing DHM formulations, determining optimal dosing regimens, and evaluating potential drug interactions 26Qin Hu et al, Dihydromyricetin inhibits NLRP3 inflammasome-dependent pyroptosis by activating the Nrf2 signaling pathway in vascular endothelial cellsBiofactors. 2018
Biological Activities and Mechanisms of Action
DHM’s diverse biological activities are primarily attributed to its potent antioxidant, anti-inflammatory, neuroprotective, hepatoprotective, and anti-cancer properties 27Zhenzhu Sun et al, Dihydromyricetin alleviates doxorubicin-induced cardiotoxicity by inhibiting NLRP3 inflammasome through activation of SIRT1Biochem Pharmacol. 2020 .
DHM’s free radical scavenging ability stems from its flavonoid structure, which allows it to donate hydrogen atoms to reactive oxygen species (ROS), neutralizing them28Hongyan Ling et al, Dihydromyricetin improves type 2 diabetes-induced cognitive impairment via suppressing oxidative stress and enhancing brain-derived neurotrophic factor-mediated neuroprotection in miceActa Biochim Biophys Sin (Shanghai). 2018.
Additionally, DHM has been shown to upregulate endogenous antioxidant defenses, such as superoxide dismutase (SOD) and glutathione peroxidase (GPx) 29XiaoJuan Wang et al, Dihydromyricetin Attenuates Colitis in Mice induced by DSS via Improving Intestinal Barrier FunctionResearch Square. 2022.
DHM modulates immune cell function and inhibits the production of pro-inflammatory mediators, such as tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) 30Linying Shi et al, Dihydromyricetin improves skeletal muscle insulin sensitivity by inducing autophagy via the AMPK-PGC-1α-Sirt3 signaling pathwayEndocrine. 2015.
This is achieved through the suppression of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways31Jun Xie et al, Dihydromyricetin alleviates carbon tetrachloride-induced acute liver injury via JNK-dependent mechanism in miceWorld J Gastroenterol. 2015
DHM attenuates neuroinflammation by inhibiting microglial activation and reducing the production of pro-inflammatory cytokines in the central nervous system 32Yongbiao Chen et al, Dihydromyricetin protects against liver ischemia/reperfusion induced apoptosis via activation of FOXO3a-mediated autophagyOncotarget. 2016.
DHM promotes neuronal survival and synaptic plasticity by modulating the expression of brain-derived neurotrophic factor (BDNF) and its downstream signaling pathways33Yongbiao Chen et al, Dihydromyricetin protects against liver ischemia/reperfusion induced apoptosis via activation of FOXO3a-mediated autophagyOncotarget. 2016.
DHM has been shown to prevent alcohol-induced liver injury by suppressing oxidative stress, inflammation, and apoptosis in hepatocytes 34Lei Chen et al, Dihydromyricetin inhibits cell proliferation, migration, invasion and promotes apoptosis via regulating miR-21 in Human Cholangiocarcinoma CellsJ Cancer. 2020.
Furthermore, DHM modulates lipid metabolism by upregulating the expression of peroxisome proliferator-activated receptor-alpha (PPAR-α) and downregulating sterol regulatory element-binding protein 1c (SREBP-1c), which can help alleviate non-alcoholic fatty liver disease (NAFLD) 35Tingjuan Ni et al, Dihydromyricetin Prevents Diabetic Cardiomyopathy via miR-34a Suppression by Activating AutophagyCardiovasc Drugs Ther. 2020
DHM induces apoptosis in various cancer cell lines by activating caspase-dependent pathways and inhibiting anti-apoptotic proteins, such as Bcl-2 and Bcl-xL 36Haili Huang et al, Dihydromyricetin suppresses the proliferation of hepatocellular carcinoma cells by inducing G2/M arrest through the Chk1/Chk2/Cdc25C pathwayOncol Rep. 2013.
Additionally, DHM has been shown to inhibit angiogenesis and metastasis by suppressing the expression of vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMPs) 37Nianshui Jing, Xinnan Li Dihydromyricetin Attenuates Inflammation through TLR4/NF-kappaB PathwayOpen Med (Wars). 2019.
Safety, Toxicity, and Drug Interactions
Preclinical safety evaluations of DHM have indicated its low toxicity and relatively high tolerability 38Joshua Silva et al, Modulation of Hippocampal GABAergic Neurotransmission and Gephyrin Levels by Dihydromyricetin Improves AnxietyFront. Pharmacol. 2020.
Clinical safety data, although limited, have not reported any significant adverse events or toxicities associated with DHM administration39Qingyu Zhang et al Dihydromyricetin promotes hepatocellular carcinoma regression via a p53 activation-dependent mechanismScientific Reports. 2014.
However, further studies are required to establish the long-term safety and potential drug interactions of DHM, particularly in combination with other therapeutic agents40Haili Huang et al, Dihydromyricetin suppresses the proliferation of hepatocellular carcinoma cells by inducing G2/M arrest through the Chk1/Chk2/Cdc25C pathwayOncol Rep. 2013.
The one human trial investigating DHM found that 150mg/day BID (300mg total) is safe and effective. 41Joshua Silva et al, Modulation of Hippocampal GABAergic Neurotransmission and Gephyrin Levels by Dihydromyricetin Improves AnxietyFront. Pharmacol., 09 July 2020.
Note that study was measuring glucose metabolism in NAFLD patients.
DHM, a unique flavonoid with diverse biological activities, holds significant promise as a therapeutic agent for various diseases.
This review has summarized the current knowledge of its chemical structure, pharmacokinetics, mechanisms of action, and potential therapeutic applications.
Although considerable progress has been made, further research is needed to overcome the challenges associated with clinical translation and optimize DHM’s potential impact on clinical practice and public health.
Future perspectives and research directions include the development of novel DHM formulations and delivery systems to improve its bioavailability, elucidating its precise molecular targets, and identifying potential synergistic effects with other therapeutic agents 42Dan Zou et al, Dihydromyricetin improves physical performance under simulated high altitudeMed Sci Sports Exerc. 2014.
Large-scale, randomized controlled trials are needed to validate the efficacy and safety of DHM in various clinical settings, providing the foundation for evidence-based recommendations 43Fei Wu et al, Preventive Effect of Dihydromyricetin against Cisplatin-Induced Nephrotoxicity In Vitro and In VivoEvid Based Complement Alternat Med. 2016.
In conclusion, DHM is a fascinating and promising compound that has the potential to contribute significantly to the prevention and treatment of a range of diseases.