Table 2.
Preclinical research based on ethnopharmacological applications targeting alcohol abuse.
| Species | Common name | Plant extract or compound | Test model | Results | Reference |
|---|---|---|---|---|---|
| Aesculus hippocastanum L. | Horse Chestnut | Escins Ia, Ib, IIa, IIb, and IIIa | Male Wistar rats | Escins Ia, Ib, IIa, and IIb inhibit ethanol absorption. | (Yoshikawa et al., 1996b) |
| Aralia elata (Miq.) Seem. | Chinese angelica-tree, Japanese angelica-tree, and Korean angelica-tree | Oleanolic acid, 28-O-bisdesmosides, and oleanolic acid 3-O-monodesmosides | Male Wistar rats | Inhibitory effect on ethanol absorption. | (Yoshikawa et al., 1996a) |
| Chinese angelica-tree, Japanese angelica-tree, and Korean angelica-tree | 3-O-monodesmosides | Male Wistar rats | Elatoside A showed potent inhibitory activity on ethanol absorption. | (Yoshikawa et al., 1993) | |
| Buzui | Buzui | Fruit of Schisandra chinensis (Turcz.) Baill., Terminalia chebula Retz., Dark plum fruit and Crataegus pinnatifda Bunge, Chicken's gizzard membrane and Silkworm excrement | Male pathogen-free (SPF) Kunming mice | Induces wakefulness and prevents acute alcohol intoxication, accelerates alcohol metabolism and thereby reduces oxidative damage. | (Chen et al., 2016) |
| Camellia japonica L. | Common camellia, Japanese camellia, Rose of Winter | Camellia saponins A1, A2, B1, B2, C1, and C2 | Male Wistar rats | Camellia saponins B1, B2, C1, and C2 exhibit inhibitory ethanol absorption activity. | (Yoshikawa et al., 1996) |
| Galanthus nivalis L. and Peganum harmala L. | Snowdrop and Syrian rue | Galanthamine | Female Alko alcohol (AA) rats | Desoxypeganine–HCl reduces ethanol preference and intake while systemically increasing the dose concentration (10 and 30 mg/kg of the body weight). Desoxypeganine–HCl when applied in subcutaneous and intraperitoneal regions of the body leads to prominent reduction in ethanol preference and intake. |
(Doetkotte et al., 2005) |
| Ginkgo biloba L., Mentha arvensis L. var. piperascens, Citrus deliciosa Ten. (syn. Citrus unshiu) Blanco, and Pueraria montana var. lobata (Willd.) Maesen & S.M.Almeida ex Sanjappa & Predeep | - | Combined aqueous extracts (BHR) | Male Sprague-Dawley rats | BHR extract significantly reduces BALs and reduces area under curve (AUC) and Cmax values in BHR treated rats at a dose concentration of 1 and 3 g/kg. | (Soo Shin et al., 2005) |
| Glycine max (L.) Merr. | Soybean | Milk | Male Sprague-Dawley rats | Demonstrates that soymilk products inhibit ethanol absorption and enhance ethanol metabolism in rats. | (Kano et al., 2002; Kano and Kubota, 2013) |
| Hovenia dulcis Thunb. | Korean raisin tree | Fruit extract | Mice | Reduces blood alcohol concentration by increasing the efficiency of ADH and glutathione-S-transferase (GST) activity and thus increases detoxification. | (An et al., 1999) |
| Seed extract from China and Korea | Rats | Both extracts (crude and partitioned) accelerate the reducing rate of blood alcohol concentrations down to 1–2 h, compared to that of control. | (Kim et al., 2000) | ||
| Ethanol and aqueous fruit extract | Rats | Reduces blood alcohol concentration by increasing the activity of ADH, ALDH, and GST activity and thus increases detoxification. | (Cha et al., 2004) | ||
| Fruit water extract | Rats | Shows significant alcohol decrease in blood and hepatoprotective activity against CCl4-toxicity. | (Kim et al., 2006) | ||
| Fruit water extract | Rats | The fruit extract (methanol and hot water extract) reduces acute alcohol toxicity and shows potent hepatoprotective activity against chemically, i.e., CCl4, induced liver injury model. | (Kim et al., 2008) | ||
| Dihydromyricetin (DHM) | Sprague-Dawley rats | Determines anti-alcoholic effects of DHM on animal models and put forward a major molecular target and cellular mechanism of DHM against alcohol dependence and intoxication. | (Shen et al., 2012) | ||
| Hypericum perforatum L. | St John's wort (SJW) | Hypericum perforatum extract (HPE) | cAA rats |
Hypericum extract Ze 117 (Remotiv®) reduces EtOH intake in a selective manner thus revealing that the extract may be an interesting adjunct for the treatment of alcoholism. |
(De Vry et al., 1999) |
| Hypericum perforatum extract (HPE) | Marchigian Sardinian alcohol-preferring (msP) rats | Antidepressant-like effect of HPE extract in the force swimming test (FST) may be mediated by interaction of sigma receptors and to some extent by increased serotonergic neurotransmission. | (Panocka et al., 2000) | ||
| Hypericum perforatum extracts (HPE) | Marchigian Sardinian alcohol-preferring (msP) rats | HPE noticeably reduces ethanol intake in msP rats, without affecting food intake. | (Perfumi et al., 1999) | ||
| Methanolic extract (with 0.3% hypericin and 3.8% hyperforin) (HPE1) and CO2 extract (HPE2) with 24.33% hyperforin and very less hyperricin. | Marchigian Sardinian alcohol-preferring (msP) rats | HPE2 hinders ethanol intake more effectively than HPE1; higher HPE2 potency parallels the content of hyperforin, taking the role of hyperforin in reducing ethanol intake. | (Perfumi et al., 2001) | ||
| Hypericum perforatum extracts (HPE) | Marchigian Sardinian alcohol-prefering (msP) rats | HPE inhibitory effects on ethanol intake are not mediated by GABA agonist actions. | (Perfumi et al., 2002) | ||
| Hypericum perforatum CO2 Extract | Marchigian Sardinian alcohol-prefering (msP) rats | CO2 extract of H. perforatum and opiate receptor antagonists synergistically act to induce selective reduction of voluntary consumption of ethanol in alcohol-preferring rats. |
(Perfumi et al., 2003) | ||
| Hypericum perforatum extracts (HPE) | Fawn-hooded (FH) and high-alcohol drinking (HAD) rats | Demonstrates that acute or repeated oral administration of HPE produce dose-dependent reduction in alcohol intake in rats. | (Rezvani et al., 1999) | ||
| Hypericum perforatum extracts (HPE) | Adult male C57BL/6J mice | Hyperforin contributes to observed reduction in alcohol intake. | (Wright et al., 2003) | ||
| Jodina rhombifolia (Hook. & Arn.) Reissek | Sombra de toro | Lyophilized aqueous extract (JRLE) | Male Wistar rats | Repeated administration of JRLE extract, noticeably reduce voluntary ethanol intake in male Wistar rats. This reduction in terms of consumption was of notable magnitude and remained stable during the 10-days of treatment. | (Teves et al., 2015) |
| NPI-028 | NPI-028 | Chinese herbal mixture: Pueraria montana var. lobata (Willd.) Maesen & S.M.Almeida ex Sanjappa & Predeep (syn. Pueraria lobata) (roots and leaves) and Citrus × aurantium L. (syn. Citrus reticulata) (fruit peel), Panax ginseng C.A.Mey. (leaves), Glycyrrhiza uralensis Fisch. ex DC. (roots), Hovenia dulcis Thunb. (seeds), Silybum marianum (L.) Gaertn. (seeds), and Stevia rebaudiana (Bertoni) Bertoni (leaves) |
Rats and monkeys | Significantly reduces alcohol intake in alcohol-preferring (P) rats deprived of alcohol, suggesting that it might reduce desire for alcohol intake. However, NPI-028 did not produce a taste aversion to a novel saccharin solution, so it does not have a similar mechanism of action as that of naltrexone, the opiate antagonist. NPI-028 also selectively and chronically reduced alcohol intake in high alcohol drinking (HAD) rats, which are resistant to the effects of many other drugs. Finally, it was shown that NPI-028 dose-dependently reduced alcohol intake in a group of alcohol-preferring African green monkeys after intramuscular or oral administration. | (Overstreet et al., 1997) |
| Alcohol-preferring P and Fawn-Hooded (FH) rats |
NPI-028 was also effective in counteracting the increase in alcohol intake normally seen after a period of alcohol deprivation, both following the IP and following oral routes of administration. | (Overstreet et al., 1996) | |||
| Panax ginseng C.A.Mey. | Red ginseng | Red ginseng extract | Male Fischer rats | Rats plasma levels of ethanol are lowered when ethanol is administered orally along with ginseng than when administered singly, but the previous one has no effect on plasma levels of ethanol administered intraperitneally. |
(Lee et al., 1993) |
| Male Fischer rats | Rats ethanol plasma levels are lowered by (20%) when alcohol and red ginseng extract were orally administered than when only alcohol was administered. | (Kwak and Joo, 1980) | |||
| Rats | Increased the rate of oxidation of ethanol in alcohol-fed rats. | (Joo et al., 1982) | |||
| Panax guingnefolium L. | Ginseng | Total saponin from steam and leaves | Rats | Inhibition of gastro-intestinal tract absorption of ethanol. | (Ma et al., 1992) |
| Passiflora edulis Sims | Passion flower | Benzoflavone moiety extract | Swiss albino mice | In Chronic and acute administrations the benzoflavone moiety significantly prevented the alcohol withdrawal expression and decreased ethanol induced anxiety behavior in mice. | (Dhawan et al., 2002) |
| Piper caldense C. DC. | Pimenta-darda | Hydroalcoholic extract of leaves | Male Wistar rats | Showed a significant effect, reducing alcohol consumption compared to the control group. | (Pereira et al., 2015) |
| Pueraria montana var. lobata (Willd.) Maesen & S.M.Almeida ex Sanjappa & Predeep (syn. Pueraria lobata (Willd.) Ohwi) | Radix puerariae (kudzu) | Daidzin and diazein | Syrian Golden hamsters | Daidzin and daidzein, at doses of 150 and 230 mg/kg suppressed ethanol intake by >50%. However, the above treatment did not significantly affect the body weight and water or food intake. | (Keung and Vallee, 1993a) |
| Daidzin | Syrian golden hamsters | Daidzin treatment at a dose of 150 mg/kg per day (i.p. for 6 days) significantly suppresses voluntary ethanol intake by ≈70% in golden hamster but when its ability to inhibit acetaldehyde metabolism in vivo was tested, plasma acetaldehyde metabolism was not affected at all. Also Daidzin, effectively suppressed golden hamster liver mitochondria-catalyzed acetaldehyde oxidation with an IC50 value of 0.4 µM, which is substantially lower than the daidzin concentration (70 μM) found in the liver mitochondria of daidzin-treated hamsters. | (Keung et al., 1995) | ||
| Daidzin | Male Wistar rats | Daidzin decreased sweetened ethanol consumption more than it did starch consumption. Changes in consumption were dose dependent, and differences in ethanol and food consumption increased slightly (but significantly) as dose increased. | (Heyman et al., 1996) | ||
| Kudzu Root Extract (KRE) | Adult male Sprague–Dawley (SD) rats | Daidzin inhibits ALDH-2 and suppresses heavy drinking in rodents. Decreased drinking due to ALDH-2 inhibition is attributed to aversive properties of acetaldehyde accumulated during alcohol consumption. | (Arolfo et al., 2009) | ||
| Kudzu Root Extract (KRE) | Alcohol-preferring (P) rats | A daily 50 mg/kg dose of puerarin (PU) caused approximately 50% suppression in alcohol intake, but did not affect body weight and food and total fluid intake in P rats receiving “free choice” of water and 15% ethanol. PU feeding transiently suppressed alcohol intake and abolished withdrawal symptoms at a time when alcohol intake had returned to the control level. | (Benlhabib et al., 2004b) | ||
| Kudzu Root Extract (KRE) | Alcohol preferring (P) rats | A daily dose of 50 mg/kg of puerarin (PU) caused approximately 50% suppression in alcohol intake, but did not affect body weight and food and total fluid intake in P rats receiving “free choice” of water and 15% ethanol. PU feeding transiently suppressed alcohol intake and abolished withdrawal symptoms at a time when alcohol intake had returned to the control level. | (Benlhabib et al., 2004a) | ||
| Ethanol extract | Male Wistar rats | Daidzin delayed and decreased peak blood alcohol concentration (BAC) level after ethanol intake. When ethanol (40% solution, 3 g/kg of body weight) was given to fasted rats intragastrically, BAC peaked at 30 min after alcohol ingestion and reached 1.77 ± 0.14 mg/mL. But when daidzin (30 mg/kg) was mixed with the ethanol solution and given to animals intragastrically, BAC was found to peak at 90 min after alcohol ingestion and reached only 1.20 ± 0.30 mg/ml. | (Xie et al., 1994) | ||
| Flos puerariae lobatae water extract (FPE) | Male Sprague-Dawley rats and male BALB/C mice | FPE and its active ingredient puerarin have preventive effects on alcoholism-related disorders. Puerarin pretreatment, but not post-treatment, can reverse the changes of GABAAR subunit expression and increase ADH activity in alcoholism models. | (Zhang et al., 2010) | ||
| Puerariae Flos isoflavonoid fraction (PF-IF) | mice | blood alcohol and acetaldehyde concentrations decreased more after the treatment | (Niiho et al., 1989) | ||
| daidzin, daidzein and puerarin | Alcohol preferring (P) rats | suppressing the appetite for alcohol when taken orally | (Lin et al., 1996) | ||
|
Pyrus pyrifolia (Burm.f.) Nakai (syn. Pyrus pyrifolia cv. Shingo) |
Korean Pear | Korean Pear extract | ALDH2 normal (C57BL/6) and deficient (ALDH2 -/-) male mice | Pear extract stimulated both ADH and ALDH activities by 2∼3 in vivo and 1.3 fold in in vitro studies. The pharmacokinetic data (i.e., AUCα and Cmax) showed that the pear extract decreased the alcohol level in blood regardless of ALDH2 genotype and increased the acetaldehyde level in blood in Aldh2 deficient mice but not in ALDH2 normal mice. | (Lee et al., 2012) |
| Sedum rosea (L.) Scop. (syn. Rhodiola rosea L.) | Rhodiola (golden root) | Salidroside | Male Wistar rats | Indicates that salidroside at a dose of 45 mg/kg inhibited the development of tolerance to the hypothermic effect of ethanol. Observed inhibition of tolerance to the sedative effect of ethanol seems to be associated with salidroside influence on the CNS. | (Szulc et al., 2018) |
| Salvia miltiorrhiza Bunge | “Danshen” or “Tanshen” | Methanol extract | Sardinian alcohol-preferring (sP) rats | Effect due to its ability to alter ethanol absorption from the gastrointestinal tract. It reduced voluntary alcohol intake, and decreased BALs by approximately 60%. |
(Colombo et al., 1999) |
| S. miltiorrhiza extracts, differing in miltirone content (0, 2, 3, and 7%) | Sandinian alcohol-preferring (sP) rats | Alcohol intake was positively and significantly correlated with miltirone content of the extracts. S. miltiorrhiza extracts, miltirone markedly reduced BALs when alcohol was administered i.g. but not i.p., suggesting that miltirone hampered alcohol absorption from the gastrointestinal system. | (Colombo et al., 2006) | ||
| Standardized extract (IDN 5082) | Sardinian alcohol-preferring (sP) rats | Dose-dependently delayed acquisition of alcohol-drinking behavior. | (Brunetti et al., 2003) | ||
| Standardized extract (IDN 5082) | Sardinian alcohol-preferring (sP) rats | Prevents the development of the alcohol deprivationeffect (ADE). The acute, intragastric administration of 25, 50, and 100 mg/kg resulted in the complete suppression of the extra amount of alcohol consumed during the first hour of re-access to alcohol after 7 days of deprivation. The results indicated that IDN 5082 might possess antirelapse properties. | (Serra et al., 2003) | ||
| Ethanol extract | Sardinian alcohol-preferring (sP) rats | A significant and specific reduction in alcohol intake was recorded only in rats treated with the combination of Polysorbate 80 plus the S. miltiorrhiza extract. | (Vacca et al., 2003) | ||
| Salvia przewalskii Maxim. | Red sage | Hairy roots and callus cultures extract | Male Warsaw High Preferring Wistar rats (WHP) | Significantly reduced alcohol intake in alcohol-dependent animals. This activity was correlated with the content of tanshinones (cryptotanshinone) in callus extract, but not with phenolic acids. | (Gryszczynska et al., 2015) |
| SKV | Asuuam | Fermentation of cane sugar, raisins, and water and 12 herbal ingredients: Piper nigrum L. seeds, Piper longum L. seeds, Santalum album L. heartwood, Pterocurpus santalinus L.f. heartwood, Nardostachys
jatamansi (D.Don) DC. roots, Symplocos racemosa Roxb. bark, Chrysopogon zizanioides (L.) Roberty (syn. Andropogen muricatus) roots, Elettaria cardamomum (L.) Maton seeds, Berberis aristata DC. root/bark/- stem, Plumbago zeylanica L. roots and Cyprus rotundus L. tubers, Woodfordia fruticosa (L.) Kurz (syn. Woodfordia floribunda) flowers. |
Adult albino male rats | Brought down voluntary alcohol ingestion and increased food intake. | (Shanmugasundaram and Shanmugasundaram, 1986) |
| Adult albino male rats | Rats on SKV therapy with free access to 15% ethanol showed a marked reduction in voluntary ethanol intake. | (Shanmugasundaram et al., 1986) | |||
| Strychnos nux-vomica L. | Nux vomica | Mother tincture (MT), Nux 30c, and its principal alkaloid, strychnine | Albino rats of the Charles Foster strain |
Nux MT and Nux 30c could reduce ethanol intake in rats. The altered solution structure of Nux 30c is thought to mimic Nux MT and produce ethanol aversion in rats. | (Sukul et al., 2001) |
| Tabernathe iboga Baill. | Iboga | Ibogaine | Sprague-Dawley rats | Reduces volitional alcohol consumption in alcohol-preferring rats. Exerted its anti-craving effects on voluntary alcohol intake by interacting with the brain parts involved in stimulating dopaminergic and serotonergic systems. | (Glick et al., 1991) |
| Fawn-Hooded rats | Ibogaine when injected into different regions of the body, i.e., intraperitoneal or intragastric but not subcutaneous, can significantly reduce alcohol intake without an effect on blood alcohol concentrations or food intake. | (Rezvani et al., 1995b) | |||
| Noribogaine | P and Fawn-Hooded rats | Significantly suppressed alcohol intake in alcohol preferring rats. | (Rezvani et al., 1995a) | ||
| 18-Methoxycoronaridine (18-MC) | Adult male alcohol-preferring rats | Significantly and dose-dependently attenuated alcohol consumption and preference and commensurately increased water intake. | (Rezvani et al., 1997) | ||
| Thymus vulgaris L. | Thyme | Water extract | Male Albino mice | Detoxifying and antioxidant effects. | (Shati and Elsaid, 2009) |
| Withania somnifera (L.) Dunal | Indian ginseng | Roots extract (WSE) | Adult male Wistar rats | WSE reduced the acquisition, maintenance breakpoint of ethanol self-administration and reinstatement of ethanol-seeking behaviors. The GABAB receptor antagonist, phaclofen, counteracted the ability of WSE to impair the maintenance of ethanol self-administration. | (Peana et al., 2014) |
| Zingiber officinale Roscoe | Ginger | Water extract | Male Albino mice | Significant increase in NO and malondialdehyde level in liver and brain and a decrease in the total antioxidant capacity and GPx activity in alcoholic group. The extract has potent detoxifying and antioxidant effects. |
(Shati and Elsaid, 2009) |