. 2022 Mar 8;27(6):1770. doi: 10.3390/molecules27061770

Table 3.

Flavanones with relevant GABAergic effects.

Flavanone
Compound	Properties	Reference
Naringenin (5,7,4’-O-trihydroxy)	Naringenin does not produce anxiolysis by modulation of the GABA_ARs but it does decrease motor movements.	[106]
6-Prenylnaringenin	6-Prenylnaringenin acts as a positive allosteric modulator at α+ β− binding interface as well as a null modulator at the flumazenil-sensitive α+ γ₂− binding interface on GABA_ARs.	[107]
8-Prenylnaringenin	8-Prenylnaringenin potentiated GABA-induced displacement of [³H] ethynylbicycloorthobenzoate radioligand binding assay in native and recombinant α₁β₃γ₂, α₂β₃γ₂ and α₆β₃δ receptors (HEK293 cells, IC₅₀ of 7.3 µM).	[108]
Dihydromyricetin = ampelopsin (5,7,3’,4’,5’-O-tetrahydroxy)	Dihydromyricetin competitively inhibits the BZD-site [³H]-flunitrazepam binding site (IC₅₀ 4.36 μM), suggesting the interaction with the BZD sites on GABA_AR.	[109]
Dihydromyricetin = ampelopsin (5,7,3’,4’,5’-O-tetrahydroxy)	Dihydromyricetin prevents foetal alcohol exposure consequences in pregnant rats, avoiding the alterations in physiology, behaviour, and hippocampal GABA_AR function.	[110]
Hesperidin (hesperetin 7-O-rutinoside)	Hesperidin possesses anticonvulsant activity which might be mediated through the modulation of GABA-BZD receptor action.	[111]
Hesperidin (hesperetin 7-O-rutinoside)	The antihyperalgesic effect of hesperidin combined with diosmin involves central activity partially modulated by D₂, GABA_A, and opioid receptors, but not serotoninergic 5-HT_1A receptors.	[112]
Kushenol I (3β,7,2’,4’-tetrahydroxy-5-methoxy-8-lavandulyl) (–)-Kurarinone (7,2’,4’-trihydroxy-5-methoxy-8-lavandulyl) Sophoraflavanone G (5,7,2’,4’-tetrahydroxy-8-lavandulyl)	These flavanones act as GABA_AR modulators. They induced the I_GABA enhancement in Xenopus oocytes transiently expressing GABA_AR with subunit composition: α₁β₂γ_2S. EC₅₀ are 5.0, 8.1 and 15.0 μM, respectively.	[113]
Isoxanthohumol (7,4’-dihidroxy-5-methoxy-8-isoprenyl)	Isoxanthohumol potentiates GABA-induced displacement of [³H]-ethynylbicycloorthobenzoate radioligand binding assay in native and recombinant α₁β₃γ₂, α₂β₃γ₂ and α₆β₃δ receptors (HEK293 cells) in a concentration-dependent manner with an IC₅₀ of 11.6 µM.	[108]
Glycosides
Eriocitrin (eriodictyol 7-O-rutinoside) (eriodictyol is 5,7,3’,4’-tetrahydroxy flavanone)	The antinociceptive effect of eriocitrin is blocked by naltrexone (opioid receptor antagonist) and bicuculline (GABA_AR antagonist). Therefore, the antinociception in postoperative pain conditions could be mediated through opioid and GABA_ARs.	[114]