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As it turns out, flavonoids seem to work mechanistically similar to anti-anxiety drugs: they are able to pass the blood-brain barrier, but without the side effects of medications.
Benzodiazepines like diazepam (Valium) are well-known drugs to help people to feel calmer through their sedating, hypnotic, anti-anxiety, muscle-relaxant effects. These effects are thought to occur, at least in part, because of the drug's ability to enhance the neurotransmitter, gamma-aminobutyric acid (GABA), at a specific receptor site in the brain. As it turns out, certain members of the class of phytochemicals called flavonoids seem to work mechanistically similar to benzodiazepines: they are able to pass the blood-brain barrier (and the blood-brain barrier is notoriously "picky" about what it lets in!) and even sit on brain receptors.
One of the first research studies published on plant flavonoids binding to these anti-anxiety receptors was from a Danish group back in 1988. They were able to identify one of the most active compounds in Karmelitergeist, an alcoholic extract of several plants, including lemon balm, nutmeg, cinnamon, and angelica root. It was a flavonoid called amentoflavon(e), and it was as potent as diazepam (Valium) in binding to certain brain receptors. Since then, the large family of flavonoids have been explored and some popular types have been identified: kaempferol, myricetin, quercetin, apigenin, luteolin, hesperetin, naringenin, catechins, epicatechins, anthocyanidins, cyanidins, to name a few. Select flavonoids from botanicals have been reported to influence brain receptors including:
- Chrysin, from the traditional medicine plant, Passiflora coerulea L. (Medina et al., 1990; Wolfman et al., 1994)
- Apigenin, from the dried flower heads of Matricaria recutita L. (Asteraceae) (Viola et al., 1995)
- Flavones from an extract of sage leaves (Salvia officinalis L.) (Kavvadias et al., 2003)
- Apigenin, from an extract of dried flowers of Matricaria chamomilla L. (Avallone et al., 2000)
- Epigallocatechin gallate, which is concentrated in green tea (Campbell et al., 2004)
- Gabrol from licorice (Glycyrrhiza glabra) (Cho et al., 2012)
- Quercetin and kaempferol in Linden flowers (Jäger AK, Saaby L., 2011)
- Quercetin in heather (Jäger AK, Saaby L., 2011)
- Flavonoid glycosides in Ginkgo biloba extract (Jäger AK, Saaby L., 2011)
- Baicalein from Scutellaria baicalensis (Jäger AK, Saaby L., 2011)
Anti-anxiety drugs like benzodiazepines have many side effects, like sedation, amnesia and ataxia, which is why some researchers are exploring safer options. In fact, one animal study suggested that, in contrast to diazepam, flavonoids like chrysin and apigenin have no amnesia-like effect on learning tasks even at higher doses relative to the levels shown to be effective for anti-anxiety effects. In fact, apigenin had a slight enhancing effect on training session performance (Salgueiro et al., 1997).
Overall, cell and animal research has shown that flavonoids found in foods and herbs may have beneficial effects for brain and nerve health. We still don't know whether these results translate to humans, but until we know the definitive answer, it might be worthwhile to get more of flavonoid-containing foods in your everyday diet. Here are some examples of the foods highest in flavonoids (milligrams of flavonoids per 100 grams of fresh weight of edible portion):
|Food||mg flavonoids/100 grams|
|Juice concentrate, elderberry||520|
|Juice concentrate, blackberry||355|
|Raspberries, black, raw||324|
|Cocoa, dry, unsweetened||261|
|Blueberries, wild, raw||133|
|Tea, green, brewed||120|
|Tea, black, brewed||119|
|Currants, red, raw||79|
|Tea, white, brewed||75|
|Grapes, Concord, raw||73|
|Mustard greens, raw||63|
|Acai berries, frozen||62|
Source: USDA Nutrient Database, 2013
For additional research on the health benefits of flavonoids view the GreenMedInfo.com database.
Avallone R, Zanoli P, Puia G, Kleinschnitz M, Schreier P, Baraldi M. Pharmacological profile of apigenin, a flavonoid isolated from Matricaria chamomilla. Biochem Pharmacol. 2000 Jun 1;59(11):1387-94.
Campbell EL, Chebib M, Johnston GA. The dietary flavonoids apigenin and (-)-epigallocatechin gallate enhance the positive modulation by diazepam of the activation by GABA of recombinant GABA(A) receptors. Biochem Pharmacol. 2004 Oct 15;68(8):1631-8.
Cho S, Park JH, Pae AN, Han D, Kim D, Cho NC, No KT, Yang H, Yoon M, Lee C, Shimizu M, Baek NI. Hypnotic effects and GABAergic mechanism of licorice (Glycyrrhiza glabra) ethanol extract and its major flavonoid constituent glabrol. Bioorg Med Chem. 2012 Jun 1;20(11):3493-501. doi: 10.1016/j.bmc.2012.04.011. Epub 2012 Apr 11.
Jäger AK, Saaby L. Flavonoids and the CNS. Molecules. 2011 Feb 10;16(2):1471-85. doi: 10.3390/molecules16021471.
Kavvadias D, Monschein V, Sand P, Riederer P, Schreier P. Constituents of sage (Salvia officinalis) with in vitro affinity to human brain benzodiazepine receptor. Planta Med. 2003 Feb;69(2):113-7.
Nielsen M, Frøkjaer S, Braestrup C. High affinity of the naturally-occurring biflavonoid, amentoflavon, to brain benzodiazepine receptors in vitro. Biochem Pharmacol. 1988 Sep 1;37(17):3285-7.
Medina JH, Paladini AC, Wolfman C, Levi de Stein M, Calvo D, Diaz LE, Peña C. Chrysin (5,7-di-OH-flavone), a naturally-occurring ligand for benzodiazepine receptors, with anticonvulsant properties. Biochem Pharmacol. 1990 Nov 15;40(10):2227-31.
Salgueiro JB, Ardenghi P, Dias M, Ferreira MB, Izquierdo I, Medina JH. Anxiolytic natural and synthetic flavonoid ligands of the central benzodiazepine receptor have no effect on memory tasks in rats. Pharmacol Biochem Behav. 1997 Dec;58(4):887-91.
Viola H, Wasowski C, Levi de Stein M, Wolfman C, Silveira R, Dajas F, Medina JH, Paladini AC. Apigenin, a component of Matricaria recutita flowers, is a central benzodiazepine receptors-ligand with anxiolytic effects. Planta Med. 1995 Jun;61(3):213-6.
Wolfman C, Viola H, Paladini A, Dajas F, Medina JH. Possible anxiolytic effects of chrysin, a central benzodiazepine receptor ligand isolated from Passiflora coerulea. Pharmacol Biochem Behav. 1994 Jan;47(1):1-4.