Luteolin
Luteolin is a polyphenolic flavone found in many herbs, fruits, and vegetables and traditionally used in Chinese medicine. It has been attributed antioxidant and anti-inflammatory properties. It can cross the blood-brain barrier and has been observed to have protective and anti-inflammatory effects in models of traumatic brain injury, spinal cord injury, and neurotoxicity.
The combination of luteolin with the plant amide palmitoylethanolamine (PEA) at a 1:10 ratio and total dose of 10 microM in isolated brain cells promoted development of oligodendrocytes. Oligodendrocytes are the myelin-producing cells of the CNS, which otherwise have limited ability to repair the damage to themselves or to other nerve cells, as seen in demyelinating diseases like MS2,3
When added to animal myelin, luteolin was observed to diminish free radical production and influence, and most importantly, the destruction of myelin by macrophages (immune cells)4.
When added to human cells, luteolin was found to be a strong inhibitor of autoimmune T-cell response5. In combination with IFN-β, Luteolin reduced, in a dose-dependent manner up to 50 microM, the generation of errant immune cells and inflammatory cytokines in cells of MS patients6.
In an animal model of MS, luteolin at a dose of 100 mg/kg substantially suppressed clinical symptoms and prevented relapse when administered either before or after disease onset. Luteolin treatment resulted in reduced inflammation and axonal damage in the CNS by preventing immune cell infiltration across the blood-brain barrier.
In another such study, the combination of luteolin with PEA at a dose of 5 mg/kg resulted in improvements in clinical score (based on weakness, poor balance, and paralysis) as well as decreases in pro-inflammatory molecules and autoimmune cells components in the brain and brainstem8.
In a study on blood vessels from pregnant rats, luteolin was associated with a lower risk factor for high blood pressure9. In pregnant women at risk for miscarriage due to bladder pain syndrome/interstitial cystitis, the anti-inflammatory influence specifically of luteolin was believed to be of benefit10. In traditional Indian medicine, luteolin has been found to be beneficial against signs of infection during pregnancy 11. On a cautionary note, a form of luteolin (luteolin 7, 3′-digalacturonide) was suspected to be a factor in the fetal toxicity of the plant Verbena officinalis, though the latter is commonly used during pregnancy12.
Luteolin is found in vegetables and fruits such as celery, parsley, broccoli, onion leaves, carrots, peppers, cabbages, and apple skins13.
References
1.Swaminathan A, Basu M, Bekri A, Drapeau P, Kundu TK. The Dietary Flavonoid, Luteolin, Negatively Affects Neuronal Differentiation. Front Mol Neurosci. 2019;12:41. doi:10.3389/fnmol.2019.00041
2.Barbierato M, Facci L, Marinelli C, et al. Co-ultramicronized Palmitoylethanolamide/Luteolin Promotes the Maturation of Oligodendrocyte Precursor Cells. Sci Rep. Nov 18 2015;5:16676. doi:10.1038/srep16676
3.Skaper SD, Barbierato M, Facci L, et al. Co-Ultramicronized Palmitoylethanolamide/Luteolin Facilitates the Development of Differentiating and Undifferentiated Rat Oligodendrocyte Progenitor Cells. Mol Neurobiol. Jan 2018;55(1):103-114. doi:10.1007/s12035-017-0722-0
4.Hendriks JJ, de Vries HE, van der Pol SM, van den Berg TK, van Tol EA, Dijkstra CD. Flavonoids inhibit myelin phagocytosis by macrophages; a structure-activity relationship study. Biochem Pharmacol. Mar 1 2003;65(5):877-85. doi:10.1016/s0006-2952(02)01609-x
5.Verbeek R, Plomp AC, van Tol EA, van Noort JM. The flavones luteolin and apigenin inhibit in vitro antigen-specific proliferation and interferon-gamma production by murine and human autoimmune T cells. Biochem Pharmacol. Aug 15 2004;68(4):621-9. doi:10.1016/j.bcp.2004.05.012
6.Sternberg Z, Chadha K, Lieberman A, et al. Immunomodulatory responses of peripheral blood mononuclear cells from multiple sclerosis patients upon in vitro incubation with the flavonoid luteolin: additive effects of IFN-beta. J Neuroinflammation. Oct 13 2009;6:28. doi:10.1186/1742-2094-6-28
7.Hendriks JJ, Alblas J, van der Pol SM, van Tol EA, Dijkstra CD, de Vries HE. Flavonoids influence monocytic GTPase activity and are protective in experimental allergic encephalitis. J Exp Med. Dec 20 2004;200(12):1667-72. doi:10.1084/jem.20040819
8.Contarini G, Franceschini D, Facci L, Barbierato M, Giusti P, Zusso M. A co-ultramicronized palmitoylethanolamide/luteolin composite mitigates clinical score and disease-relevant molecular markers in a mouse model of experimental autoimmune encephalomyelitis. J Neuroinflammation. Jun 20 2019;16(1):126. doi:10.1186/s12974-019-1514-4
9.Yang W, Li Q, Duncan JW, et al. Luteolin-induced vasorelaxation in uterine arteries from normal pregnant rats. Pregnancy Hypertens. Mar 2021;23:11-17. doi:10.1016/j.preghy.2020.10.008
10.Theoharides PC, Christodoulou S, Athanasiou A. Spontaneous miscarriages in patients with bladder pain syndrome/interstitial cystitis – effect of stress on inflammation? J Biol Regul Homeost Agents. Jan-Feb 2021;35(1):5-10. doi:10.23812/20-528-E
11.Surendran S, Prasannan P, Jeyaram Y, Palanivel V, Pandian A, Ramasubbu R. Knowledge on ethnogynaecology of Indian Tribes- a comprehensive review. J Ethnopharmacol. Mar 1 2023;303:115880. doi:10.1016/j.jep.2022.115880
12.Fateh AH, Mohamed Z, Chik Z, Alsalahi A, Md Zin SR, Alshawsh MA. Prenatal developmental toxicity evaluation of Verbena officinalis during gestation period in female Sprague-Dawley rats. Chem Biol Interact. May 1 2019;304:28-42. doi:10.1016/j.cbi.2019.02.016
13.Lin Y, Shi R, Wang X, Shen HM. Luteolin, a flavonoid with potential for cancer prevention and therapy. Curr Cancer Drug Targets. Nov 2008;8(7):634-46. doi:10.2174/156800908786241050