Luteolin flavonoid health benefit
November 2 2016 by
Ray Sahelian, M.D.

Luteolin is a flavonoid, and more precisely one of the citrus bioflavonoids. Just like most flavonoids, it has antioxidant, anti-inflammatory, and anti-tumor properties. It is found in high amounts in parsley, thyme, peppermint, basil herb, celery and artichoke.

Among these phytochemicals, dietary flavonoids are an important and common chemical class of bioactive products, found in several fruits and vegetables. Luteolin is an important flavone, which is found in several plant products, including broccoli, pepper, thyme, and celery. Numerous studies have shown that luteolin possesses beneficial neuroprotective effects both in vitro and in vivo.

Q. Your site give the appearance that parsley is highest in anti luteolin but in other sources it appears that celery is highest?
  A. I am not sure which is highest but it is not of great importance since both celery and parsley have many other compounds that have health benefits and focusing on just one substance does not do them justice as to their overall health benefits. One should have a wide variety of condiments and vegetables in their diet.

How it works
Luteolin exerts a variety of pharmacological activities and anti-oxidant properties associated with its capacity to scavenge oxygen and nitrogen species. It also shows potent anti-inflammatory activities by inhibiting nuclear factor kappa B (NFkB) signaling in immune cells.

Luteolin and brain inflammation
University of Illinois researchers report lutelin, found in celery and green peppers, can disrupt a component of the inflammatory response in the brain. Rodney Johnson of the University of Illinois at Urbana-Champaign and graduate student Saebyeol Jang found that luteolin inhibits a key pathway in the inflammatory response of microglia -- brain cells key to the body's immune defense. Microglial cells exposed to luteolin show a significantly diminished inflammatory response and there was reduced production of interleukin-6 -- used in cellular communication -- in the inflammatory pathway.

Cancer prevention
Chem Biol Interact. 2014. Luteolin enhances paclitaxel-induced apoptosis in human breast cancer MDA-MB-231 cells by blocking STAT3.

Oncol Rep. 2014. Protective effect of luteolin on cigarette smoke extract‑induced cellular toxicity and apoptosis in normal human bronchial epithelial cells via the Nrf2 pathway.

J Environ Pathol Toxicol Oncology. 2013. Luteolin induces growth arrest in colon cancer cells through involvement of Wnt/β-catenin/GSK-3β signaling.

Longevity, lifespan
Free Radic Res. 2013. Effect of natural exogenous antioxidants on aging and on neurodegenerative diseases. Aging and neurodegenerative diseases share oxidative stress cell damage and depletion of endogenous antioxidants as mechanisms of injury, phenomena that are occurring at different rates in each process. Nevertheless, as the central nervous system (CNS) consists largely of lipids and has a poor catalase activity, a low amount of superoxide dismutase and is rich in iron, its cellular components are damaged easily by overproduction of free radicals in any of these physiological or pathological conditions. Thus, antioxidants are needed to prevent the formation and to oppose the free radicals damage to DNA, lipids, proteins, and other biomolecules. Due to endogenous antioxidant defenses are inadequate to prevent damage completely, different efforts have been undertaken in order to increase the use of natural antioxidants and to develop antioxidants that might ameliorate neural injury by oxidative stress. In this context, natural antioxidants like flavonoids (quercetin, curcumin, luteolin and catechins), magnolol and honokiol are showing to be the efficient inhibitors of the oxidative process and seem to be a better therapeutic option than the traditional ones (vitamins C and E, and β-carotene) in various models of aging and injury in vitro and in vivo conditions. Thus, the goal of the present review is to discuss the molecular basis, mechanisms of action, functions, and targets of flavonoids, magnolol, honokiol and traditional antioxidants with the aim of obtaining better results when they are prescribed on aging and neurodegenerative diseases.

Decreased pro-inflammatory cytokine production by LPS-stimulated PBMC upon in vitro incubation with the flavonoids apigenin, luteolin or chrysin, due to selective elimination of monocytes/macrophages.
Biochem Pharmacol. 2005.
Apigenin and its structural analogues chrysin and luteolin were used to evaluate their capacity to inhibit the production of pro-inflammatory cytokines by lipopolysaccharide (LPS)-stimulated human peripheral blood mononuclear cells (PBMC). Furthermore, flowcytometric analysis was performed to compare the effects of apigenin, chrysin, luteolin, quercetin and naringenin on the different cell types present in PBMC. LPS-stimulated PBMC were cultured in the presence of the flavonoids and TNFalpha, IL-1beta and IL-6 were measured in the supernatants. In parallel, metabolic activity of the PBMC was determined by measuring succinate dehydrogenase activity. Apigenin, chrysin and luteolin dose-dependently inhibited both pro-inflammatory cytokine production and metabolic activity of LPS-stimulated PBMC. With increasing concentration of apigenin, chrysin or luteolin the monocytes/macrophages disappeared as measured by flowcytometry. This also appeared to occur in the non-LPS-stimulated PBMC. At the same time there was an increase in dead cells. T- and B-lymphocytes were not affected. Quercetin and naringenin had virtually no effects on cytokines, metabolic activity or on the number of cells in the studied cell populations. In conclusion, monocytes were specifically eliminated in PBMC by apigenin, chrysin or luteolin treatment in vitro at low concentrations (around 8 microM), in which apigenin appeared to be the most potent.

The flavones luteolin and apigenin inhibit in vitro antigen-specific proliferation and interferon-gamma production by murine and human autoimmune T cells.
Biochem Pharmacol. 2004.
Plant-derived flavonoids are inhibitors of various intracellular processes, notably phosphorylation pathways, and potential inhibitors of cellular autoimmunity. In this study, the inhibiting effects of various flavonoids on antigen-specific proliferation and interferon-gamma (IFN-gamma) production by human and murine autoreactive T cells were evaluated in vitro. T-cell responses were evaluated for the human autoantigen alpha B-crystallin, a candidate autoantigen in multiple sclerosis, and for the murine encephalitogen proteolipid protein peptide PLP (139-151). The flavones apigenin and  luteolin were found to be strong inhibitors of both murine and human T-cell responses while fisitin, quercitin, morin and hesperitin, members of the subclasses of flavonoles and flavanones, were ineffective. Antigen-specific IFN-gamma production was reduced more effectively by flavones than T-cell proliferation, suggesting that the intracellular pathway for IFN-gamma production in T cells is particularly sensitive to flavone inhibition. These results indicate that flavones but not flavanoles or flavanones are effective inhibitors of the potentially pathogenic function of autoreactive T cells. The effects of flavones were the same for human and murine autoreactive T cells, stressing the usefulness of animal models of autoimmunity for further studies on the effects of flavonones on autoimmune diseases.

Determination of free radical scavenging activity of quercetin, rutin, luteolin and apigenin in H2O2-treated human ML cells K562.
Neoplasma. 2004.
We investigated protective effects of four flavonoids against H2O2- induced DNA damage in human myelogenous leukemia cells (K562) using the comet assay. The structural difference of studied flavonoids -- quercetin, rutin, luteolin and apigenin -- are characterized by the number of hydroxyl groups on the B ring. The presence of an o-dihydroxy structure on the B-ring confers a higher degree of stability to the flavonoid phenoxyl radicals by participating in electron delocalization and is, therefore, an important determinant for antioxidative potential. The results correlate with earlier published data obtained in murine leukemia cell line L1210. Hydrogen peroxide induced in human K562 cells a concentration-dependent increase of single cell DNA strand breaks. The strongest inhibition against H2O2-induced DNA damage (44%, 42%) was found in a range of luteolin and quercetin concentrations of 20-100 micromol/l. Protective effect of rutin was only marginal (8-10%). Apigenin had no protective effect on DNA single strand breaks induced by H2O2. Luteolin and quercetin are therefore effective in the protection of human single cell DNA from oxidative attack.

Flavonoids such as luteolin, fisetin and apigenin are inhibitors of interleukin-4 and interleukin-13 production by activated human basophils.
Int Arch Allergy Immunol. 2004.
We have previously shown that fisetin, a flavonol, inhibits IL-4 and IL-13 synthesis by allergen- or anti-IgE-antibody-stimulated basophils. This time, we investigated the inhibition of IL-4 and IL-13 production by basophils by other flavonoids. We additionally investigated whether flavonoids suppress leukotriene C4 synthesis by basophils and IL-4 synthesis by T cells in response to anti-CD3 antibody. Highly purified peripheral basophils were stimulated for 12 h with anti-IgE antibody alone or anti-IgE antibody plus IL-3 in the presence of various concentrations of 18 different kinds of flavones and flavonols. IL-4 and IL-13 concentrations in the supernatants were then measured. Leukotriene C4 synthesis was also measured after basophils were stimulated for 1 h in the presence of flavonoids. Regarding the inhibitory activity of flavonoids on IL-4 synthesis by T cells, peripheral blood mononuclear cells were cultured with flavonoids in anti-CD3-antibody-bound plates for 2 days. Luteolin, fisetin and apigenin were found to be the strongest inhibitors of both IL-4 and IL-13 production by basophils but did not affect leukotriene C4 synthesis. At higher concentrations, these flavonoids suppressed IL-4 production by T cells. Based on a hierarchy of inhibitory activity, the basic structure for IL-4 inhibition by basophils was determined. Due to the inhibitory activity of flavonoids on IL-4 and IL-13 synthesis, it can be expected that the intake of flavonoids, depending on the quantity and quality, may ameliorate allergic symptoms or prevent the onset of allergic diseases.

Characteristic rat tissue accumulation of nobiletin, a chemopreventive polymethoxyflavonoid, in comparison with luteolin.
Biofactors. 2002.
Nobiletin, a polymethoxyflavonoid, is an effective anti-inflammatory and chemopreventive phytochemical found in citrus fruits. We compared the absorption and metabolism characteristics of nobiletin with those of luteolin in male SD rats. Our results suggest that the metabolic properties of polymethoxyflavonoids are distinct from those of other general flavonoids, because of their wide distribution and accumulation in tissue.

Luteolin supplement questions
Q. Is it okay to take graviola or mangosteen while taking a luteolin supplement? What about 5-HTP?
     A. These supplements are probably safe to take while taking luteolin, as long as the amounts ingested are not excessive. 5-HTP is often taken in the evening, and luteolin is most often used in the morning.

Q. I want to take luteolin for my immune system. Is the NOW product, Entrox, the best way to take it? Is the amount of luteolin sufficient? Any other product that you would suggest? Could you share that with me and the proper general dosage.
   A. Each person's immune system is different and may respond differently to various herbs and supplements. There has not been enough human studies with luteolin supplements to determine the idea dosage or the long term side effects. See immune system for more information.