They could upgrade the levels of ADH and ALDH in liver and decrease the concentration of alcohol in blood. The main bioactive components of Scutellaria baicalensis are baicalein, baicalin and wogonin. Baicalein at the concentrations of 40–120 μM exerted cytotoxicity to three hepatocellular carcinoma cell lines but with little cytotoxicity to a normal liver cell line in vitro 124.
Extracts from the roots of Salvia miltiorrhiza could reduce alcohol intake in sP rats. Intragastric administration of 200 mg/kg extract reduced alcohol intake by 40% and preference throughout a 4 day treatment of a 2-bottle free-choice regimen. A possible mechanism was that Salvia miltiorrhiza curbed alcohol absorption from the gastrointestinal tract 110.
6. ADH and ALDH Enzyme Activity Assay
Several drugs are available to treating the alcohol use disorder, such as disulfiram (aldehyde dehydrogenase inhibitor), naltrexone (opioid antagonist), topiramate (GABAergic anticonvulsant) and acamprosate (NMDA/glutamate receptor modulator) 97,98,99. However, compared with natural products, they have some serious side effects (such as ataxia, impaired attention and bad consciousness). Herbal remedies for alcohol use disorder have been in use in China for several centuries. Kudzu (Pueraria lobata), mentioned above, could be used for the treatment of alcohol use disorders, and puerarin isolated from kudzu could reduce the anxiogenic effects of alcohol withdrawal 47. Dihydromyricetin, a flavonoid purified from Hovenia dulcis could be another therapeutic candidate for alcohol use disorder 65.
Dehydroevodiamine, evodiamine and rutaecarpine are the dominant bioactive constituents in Fructus evodiae 50. The extract of Fructus evodiae could be used as a potential remedy for hangover symptoms induced by alcohol on mice by stimulating the expression of hepatic alcohol metabolizing and antioxidant enzymes 51. The results showed that among all groups the plasma alcohol concentrations were the lowest in Fructus evodiae treated groups. Moreover, the expressions of liver alcohol metabolizing and antioxidant enzymes were also enhanced.
Repeating administration of Jodina rhombifolia lyophilized extract markedly reduced alcohol voluntary intake in rats in self-administration model of 10 consecutive days, and the treatment was without apparent side-effects 134,135. Asian ginseng (Panax ginseng) has therapeutic potential for the treatment of alcohol toxicity and as an anti-hangover agent. Ginseng shows positive effects on alcohol metabolism and relieved hangover symptoms. In addition, it also has protective effects to alcohol-induced toxicity in major organs in animals such as reproduction and gastric. Participants were excluded if they had abnormal creatinine (two times the standard upper limit), aspartate aminotransferase (AST), or alanine transaminase (ALT) (three times the standard upper limit) levels.
5. Changes in Blood Alcohol and Acetaldehyde Levels
Hypericum perforatum and Salvia miltiorrhiza could be potential natural products to treat alcohol use disorder and will be discussed below, while Scutellaria baicalensis is important in the treatment of liver disease. Meanwhile, the roots of Pueraria lobata showed inhibitory activity against mitochondrial ALDH2, and could increase the concentration of acetaldehyde in blood. It is the only natural medication regarded by the National Institute on Alcohol Abuse and Alcoholism to treat alcohol use disorder 44.
- This extract has been demonstrated to enhance the immune system 30, thereby providing a robust defense against infections and diseases.
- Excessive alcohol consumption can lead to liver damage, typically indicated by elevated levels of liver enzymes such as alanine aminotransferase (ALT) and aspartate aminotransferase (AST) 8,9.
- The water extract of ginger could decrease the levels of both l-γ-glutamyl transpeptidase and butyryl cholinesterase 76.
- In another study, 20 men participated in a placebo-controlled, double-blind design experiment, where kudzu extract (2 g) with an active isoflavone content of 520 mg, quickly reduced alcohol intake in a binge drinking paradigm 46.
- In addition, the flowers of kudzu exerted protective effects against alcohol-induced apoptosis in human neuroblastoma cells 43.
- Therefore, ginger could be used as a candidate to the prevention and treatment of hangover and organ damages induced by overconsumption of alcohol through its antioxidant action.
The essential oil of thyme has showed free radical scavenging and antibacterial activity 74, and it could detoxify alcohol toxicity. Thymol was the major component (44.4%–58.1%), followed by p-cymene (9.1%–18.5%), γ-terpinene (6.9%–18.9%), and carvacrol (2.4%–4.2%) in the tested oil samples 75. The water extract of thyme possessed the ability of detoxifying the injuries of alcohol on liver and brain in mice. It could decrease nitric oxide and MDA level in liver and brain, and increase the total antioxidant capacity and GPx activity 76. Therefore, Thymus vulgaris was recommended to treat alcohol toxicity through its potent antioxidant properties. PL exhibits strong antioxidant activity due to its polyphenols, including puerarin 24.
4.3. Analysis of Alcohol and Acetaldehyde in Blood
Kim et al. 70 confirmed that mango flesh and peel had ameliorating effects on plasma alcohol levels and increased the activities of ADH and ALDH in mice. A loading plot indicated that several compounds in mango fruit, such as fructose and aspartate, might enhance alcohol metabolism. As a result, mango flesh and peel could be the source of functional foods with the intention of decreasing plasma alcohol level after excessive alcohol intake. All adverse events that occurred after the ingestion of the study food were tabulated and evaluated through the calculation of an incidence rate. The proportion of human subjects with adverse events in each group was calculated and compared using the Chi-square test or Fisher’s exact test 42. The frequency and proportion of normal and abnormal urinalysis were calculated and compared using the Chi-square test or Fisher’s exact test.
Caffeic acid in water dropwort might be a contributor to the protective action from oxidative stress-induced liver damage 85,86. Therefore, water dropwort might be another potential candidate to treat hangover through accelerating alcohol metabolism. Two parts (roots and flowers) of Pueraria lobata are usually used in traditional medicine. The flowers have been used to treat the problems caused by alcohol drinking due to their ability to enhance acetaldehyde removal 40. In addition, the flowers of kudzu exerted protective effects against alcohol-induced apoptosis in human neuroblastoma cells 43. Asparagus officinalis, a popular vegetable, is consumed widely and has long been used as an herbal medicine to several diseases.
7. The Association of Hangover Score and Secondary Outcomes after Alcohol Consumption
The effective constituents might be heteropolysaccharides, which mainly consist of rhamnose, arabinose, galactose and galacturonic acid 63. In addition, administration of Hovenia dulcis extract increased ADH activity in alcohol-ingesting mice and stimulated alcohol metabolism 64. Dihydromyricetin (DHM), a flavonoid separated from Hovenia dulcis, was identified to interact with γ-aminobutyric acid receptors and block alcohol intoxication and withdrawal signs in rats such as tolerance, increased anxiety, and seizure susceptibility. DHM could remarkably reduce alcohol digestion in a voluntary alcohol intake paradigm in rats. At the cellular level, DHM treatment antagonized potentiation of GABAA receptors and plasticity. Therefore, DHM could be used as a therapeutic candidate for alcohol use disorders 44,65.
- The CO2 extract of hypericum has been also shown to mediate alcohol intake in msP rats.
- Kudzu possesses the ability of ameliorating hangover symptoms and has been used for the treatment of chronic alcoholic liver injury in traditional Chinese medicine for a long time.
- A lot of studies on the efficacy of natural materials for alcohol hangover relief have been conducted.
- Rhizoma coptidis has a long history of clinic use in traditional Chinese medicine.
- Therefore, to decompose ingested alcohol quickly or expel it from the body is essential 50,51.
The extract of water dropwort (Oenanthe javanica) is effective in alleviating alcohol intoxication by accelerating alcohol metabolism. Using New Zealand white rabbit and ICR mice as animal models, Kim et al. 84 discovered that after the treatment with hot-water extract of water dropwort in rabbit, the plasma alcohol levels were rapidly decreased, identical to treatment of standard natural products for the prevention and treatment of hangover and alcohol use disorder pmc drug, metadoxine. Specifically, the n-butanol fraction of hot-water extract was the strongest in eliminating plasma alcohol in ICR mice. Hot-water extract cleared 44% of the plasma alcohol while the n-butanol fraction eliminated around 70% in mice. Alcohol removal behaved in a dose-dependent manner in the range of 50–200 mg/kg in the n-butanol fraction.
Red ginseng extract also has protective effects from alcohol-induced male reproductive toxicity. There was a significant reduce in sperm motility and progressiveness in mice treated with alcohol for 5 weeks, while administration of red ginseng extract appeared to minimize the harmful effects of alcohol-induced toxicity on male fertility 93. Besides, Haron et al. 94 using Japanese ricefish (Oryzias latipes) as an animal model of fetal alcohol spectrum disorder, identified that Panax ginseng could attenuate alcohol toxicity in embryogenesis. Panax ginseng may provide a protection to alcohol-induced trabecular cartilage deformities in the neurocranium in 1–3 day post fertilization group embryos.
2. Salvia Miltiorrhiza
In addition, these flowers have been used to treat disorders such as alcohol abuse 19. Artemisia herbs are used as food additives and traditional medicines to treat various liver related diseases 20, for example liver cancer, and cirrhosis 21. The antioxidant capacity of herbal ingredients can be used as an effective treatment to suppress hangover symptoms and reduce alcohol absorption 22.
Natural products for the prevention and treatment of hangover and alcohol use disorder. Variations in blood alcohol and acetaldehyde concentrations by group from 0 to 15 h after drinking (PP set). Figure 2 shows the results of measuring the changes in blood alcohol and acetaldehyde concentrations from 0 to 13 h after drinking. Ibogaine, a natural alkaloid, isolated from the root bark of Tabernanthe iboga, has been reported to markedly reduce voluntary alcohol intake in alcohol-preferring rats in 2-bottle choice and operant self-administration paradigms 132.
Some natural products such as traditional herbs, fruits, and vegetables might be potential dietary supplements or medicinal products for the prevention and treatment of the problems caused by excessive alcohol consumption. The aim of this review is to provide an overview of effective natural products for the prevention and treatment of hangover and alcohol use disorder, and special emphasis is paid to the possible functional component(s) and related mechanism(s) of action. Rhizoma coptidis has a long history of clinic use in traditional Chinese medicine. It is effective in the treatment of gastrointestinal dysfunctions, including diarrhea, dysentery, and inflammation.