Table 1. Studies showing antiepileptic/ anticonvulsive effect of major dietary flavonoids.
| S. No. | Tested Flavonoid | Dose/ Source | Model | Species | Proposed Mechanism | Refs. | |
|---|---|---|---|---|---|---|---|
| 1. | Apigenin | 25,50 mg/kg; i.p. (Methanol extract of flower bud of Carduus crispus) |
Kainic acid induced seizures | Male ICR mice and SD rats |
Quenching of ROS and inhibition of glutathione depletion | Han et al. [118] | |
| 2. | Baicalein | 100 mg/kg; i.p. (Purified from Scutellaria baicalensis) |
Pilocarpine induced SE |
Male SD rats | Antioxidant activity and reduction in caspase-3 expression | Liu et al. [119] | |
| 3. | Gossypin | 5,10,20 mg/kg; p.o. (Sigma) |
PTZ, Strychnine and Maximal Electroshock induced seizures | Swiss albino mice | GABAergic mediation, glycine inhibition and protection from electrical kindling effect | Rasilingam et al. [120] | |
| 4. | Hesperidin/ Hesperitin | 5 to 60 µM (In vitro), 500 mg /kg; p.o (In vivo) (Sigma) | Electrical stimulation and Treatment with TEA, PTZ, 4-AP and Bicuculline | Male SD rats | Modulation of calcium dependent potassium channels | Dimpfel [121] | |
| Hesperidin | 100,200 mg/kg; p.o | PTZ induced convulsions | Male LACA mice | Modulation of GABAA-benzodiazepine receptor complex | Kumar et al. [122] | ||
| 5. | Kaempferol | 12.5, 25, 50, 75 mg/kg; p.o. (Leaf extract of Crinum jagus L.) |
PTZ induced kindling | Male Swiss albino mice | Potentiation of GABAergic neurotransmission, suppression of glutamate, elevation in glutathione and SOD | Taiwe et al. [123] | |
| 6. | Licochalcone | 15 mg/kg; i.p. | Kainic acid induced seizures |
C57BL6/J (Wild type) |
Inhibition of JNK1 | Busquets et al. [124] | |
| 7. | Luteolin | 5,10,20 mg/kg; i.p. (Methanol extract of Eclipta alba leaves) |
Acute PTZ model and PTZ-induced kindling |
Swiss albino mice | Facilitation of GABA mediated chloride channel opening and upsurge in seizure threshold | Tambe et al. [20] | |
| Luteolin | 50, 100 mg/kg; p.o. (Nanjing Zelang Biotechnology) |
PTZ induced kindling | Male SD rats | Activation of PKA/CREB/BDNF pathway | Zhen et al. [125] | ||
| 8. | Naringin | 80 mg/kg; i.p. | Kainic acid induced seizures | Male C57BL/6 mice | Suppresses KA-induced mTORC1 activation | Jang et al. [126] | |
| 9. | Naringenin | 20, 40 mg/kg; p.o. (Sigma) |
Pilocarpine induced SE | Swiss albino mice | Reduction in oxidative stress (Increase in SOD and CAT activity, Reduced MDA) | Shakeel et al. [127] | |
| Naringenin 4′,7- dimethyl ether |
100 µL; i.p. (Chemically synthetized) |
PTZ acute seizure model, psychomotor seizures (6-Hz) | Zebrafish (AB strain), Male C57Bl/6 and NMRI mice |
Action on GABAA-receptor, attenuation of IL-1β, TLR4/ NF-κB | Copmans et al. [128] | ||
| Naringenin 7-O-methyl ether | 100 µL; i.p. (Sigma) |
PTZ induced seizures | Zebrafish (AB strain) |
Modulation of GABAA dependent chloride channels, downregulation of TNF-α, IL-6, and IL-1β |
Copmans et al. [128] | ||
| 10. | Proanthocyanidin | 100, 200 mg/kg p.o | PTZ induced kindling | Male SD rats | Reduction in oxidative stress | Zhen et al. [129] | |
| S. No. | Tested Flavonoid | Dose/ Source | Model | Species | Proposed Mechanism | Refs. | |
| 11. | Quercetin | 5, 10, 20, 40 mg/kg; i.p. (Sigma) |
PTZ and PTX induced seizures | Male Wistar rats | Modulation of GABAA receptors | Sefil et al. [130] | |
| 12. | Rutin | 10, 50, 100 mg/kg; i.p. (Sigma) |
PTZ induced kindling | Male Wistar rats | ERK1-CREB, PI3K-mTOR upregulation, modulation of GABAergic and opioid receptors | Nassiri-Asl et al. [131] | |
| 13. | Vitexin | μM; 50, 100, 200 i.c.v. (Fluka) |
PTZ induced seizures | Male Wistar rats | Modulation of GABAA-benzodiazepine receptor complex | Abbasi et al. [23] | |
Abbrevations: 4AP: 4 aminopyridine; BDNF: Brain derived neurotropic growth factor; CAT: Catalase; CREB: Cyclic-AMP response element binding; ERK: Extracellular signal-regulated kinase; GABA: Gaba aminobutyric acid; GR: Glutathione reductase; ICR: Institute of Cancer Research; i.c.v.: Intracerebroventricular; IL 1 β: Interleukin 1 beta; JNK: c-Jun N-terminal kinase; KA: Kainic acid; LACA: Laboratory Animal Centre A-strain; MDA: Malondialdehyde; mTOR: Mammalian target of rapamycin; NF-Κb: Nuclear factor kappa-light-chain-enhancer of activated B cells; NMRI: Naval Medical Research Institute; PI3K: Phosphoinositide 3-kinases; PKA: Protein kinase A; PTX: Picrotoxin; PTZ: Pentylenetetrazole; ROS: Reactive oxygen species; SD: Sprague Dawley; SOD: Superoxide dismutase; SE: Status epilepticus; TEA: Tetraethylammonium; TLR4: Toll-like receptor 4; TNF: Tumor necrosis factor.