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Luteolin

Luteolin

Luteolin is a fascinating flavonoid that is found in many of our daily foods. Flavonoids are a group of secondary plant substances with variable phenolic structures that occur in many plants. You can find luteolin mainly in herbs (thyme), vegetables and fruits.

It has a number of properties that make it interesting not only for nutritional science, but also for medical research. From its role as an antioxidant to its anti-inflammatory effects, luteolin has a lot to offer. Luteolin is also particularly interesting for researchers in the area of ​​aging research. It has been observed that luteolin inhibits an important enzyme (CD38), which directly influences the human aging process via NAD+ .

Where is luteolin found?

This list gives you an overview of which foods luteolin is found in. It is interesting to note that the amount of luteolin in these foods can vary significantly depending on various factors such as cultivation method and ripeness.

  • Herbs: Thyme, parsley, oregano, mint, rosemary
  • Vegetables: Beets, celery, broccoli, cauliflower, peppers, carrots, onions, cabbage, spinach
  • Fruits: Apples (especially the peel), cherries, grapes, oranges
  • Legumes: Green peas, green beans

What health properties does luteolin have?

Inhibition of CD38 and influence of luteolin on NAD metabolism

Luteolin is a substance found in many plants and has the ability to inhibit the activity of an enzyme called CD38. CD38 plays an important role in the metabolism of NAD (nicotinamide adenine dinucleotide), a substance essential for energy production and general cellular health. This interaction between luteolin, CD38 and NAD is particularly important in the context of cardiovascular diseases and aging processes.

Importance for cardiovascular system

If the heart does not receive enough blood for a short time (e.g.b: in the context of a heart attack) and then later is supplied with blood again (this is called reperfusion), an enzyme called CD38 becomes more active. CD38 subsequently reduces the amount of an important substance called NADP(H) in the heart. NADP(H) helps produce nitric oxide (NO), an important substance that keeps our blood vessels functioning properly.

When NADP(H) becomes less, the blood vessels don't function as well. Luteolinidin, a type of luteolin, can inhibit CD38, helping to retain more NADP(H). This means that the blood vessels can function better after ischemia/reperfusion.

Importance for the aging process

In the context of aging, NAD is particularly relevant as higher NAD levels are associated with improved cellular function and a potential slowing of the aging process. Especially researchers like David Sinclair and Dr. Mark Hyman are convinced of the role of NAD in longevity.

Because CD38 helps reduce NAD levels, inhibiting CD38 with substances such as luteolin could help maintain higher NAD levels, thereby delaying or preventing age-related dysfunction and disease. In addition to luteolin, quercetin and apigenin also play a role in CD38 inhibition.

Anti-inflammatory properties

Traditionally, plants with a high luteolin content were used to treat inflammation . Both isolated luteolin and extracts from luteolin-rich plants showed anti-inflammatory effects in various models.

The aim of a study was to describe the anti-inflammatory activity of luteolin based on recent research results - particularly at the molecular level. Thus, the possibilities for future research and development of luteolin as an anti-inflammatory drug should be evaluated.

The results show that luteolin and some of its derivatives, such as luteolin-7-O-glucoside, have potent anti-inflammatory properties both in vitro (in test tubes) and in vivo (in living organisms)  Effects have. The mechanisms of action of luteolin are diverse, but important target transcription factors include Src in the NF-κB signaling pathway, MAPK in the AP-1 signaling pathway, and SOCS3 in the STAT3 signaling pathway. A clinical study with a luteolin-containing formulation showed excellent therapeutic effect in inflammation-related diseases.

In summary, current scientific evidence suggests that the main mechanism of the pharmacological action of luteolin lies in its anti-inflammatory activity, which occurs through the regulation of transcription factors such as NF-κB, STAT3, and AP-1 takes place.

Antioxidant activity of luteolin

There are several mechanisms that support the antioxidant activity of luteolin:

  • Neutralization of free radicals: Luteolin acts directly as a Radical scavenger by binding free radicals. This prevents cell damage caused by oxidative processes.
  • Modulation of antioxidant enzymes: It affects the activity of enzymes that play a key role in the body's antioxidant protection, such as superoxide dismutase and glutathione peroxidase.
  • Reduction of oxidative stress: Luteolin contributes to the reduction of oxidative stress by reducing the formation of reactive oxygen species (ROS) in cells.
  • Influence on signaling pathways: It interacts with various cellular signaling pathways that are involved in the regulation of oxidative stress, thereby modulating the cellular response to oxidative challenges.
  • Protection of DNA from oxidation The molecule helps protect the DNA in cells from oxidative damage, which is important for cell health and the prevention of mutations.

At MoleQlar, luteolin is part of regeNAD – a NAD Booster – and from MoleQlar ONE – a longevity -Complex with effects on all molecular hallmarks of aging.

regeNAD is an innovatively formulated complex to increase NAD levels - with luteolin and apigenin.

Heart Health

Various studies have examined how luteolin can influence heart disease, particularly with regard to its antioxidant, anti-inflammatory and cardioprotective properties:

In one study, the molecule was found to reduce heart attack size in diabetic rats that had sustained cardiac I/R injury,  improves heart function and reduces cell death of heart muscle cells. This effect was mediated by the influence on CD38 discussed above. Luteolin also works by increasing certain proteins that protect cells from death and reducing inflammatory reactions.

In another study (also on rats) it was investigated how the secondary plant substance influences the contractility of cardiac muscle cells in heart failure. This is due to improved expression, activity and stability of numerous small signaling proteins. These changes improved heart function and reduced the formation of connective tissue instead of muscle tissue in the heart in heart failure.

A review article also looked at the cardioprotective (heart-protecting) effects. The publication examines how these mechanisms operate in cardiac diseases such as ischemia/reperfusion injury, heart failure and atherosclerosis. Overall, luteolin, a flavonoid ubiquitous in food, is an effective protection for the cardiovascular system and a promising option in the prevention of heart disease.

Protection of the nervous system

In a publication, the neuroprotective effect of luteolin on neurological trauma and neurodegenerative diseases was examined. Inflammation in the nervous system can lead to neurodegenerative disorders, cognitive defects and brain damage. During neurological trauma or traumatic brain injury, glial cells, neurons and neuroimmune cells are activated in the brain, releasing inflammatory mediators. This inflammatory response can lead to ongoing brain damage and the progression of neurodegenerative diseases.

Luteolin shows promising properties in combating these processes in various studies. It can suppress the activation of immune cells such as mast cells and the release of inflammatory mediators from these cells. It also reduces the neuroinflammatory response, activation of microglia and astrocytes, oxidative stress and the severity of neuroinflammatory diseases such as Alzheimer's, Parkinson's, multiple sclerosis.

Luteolin and skin health

In another review, the role of luteolin, was examined in the context of skin health. It appears to play an important role in protecting plants, for example against UV radiation, by partially absorbing UVA and UVB rays. This property also makes the substance interesting for human skin, as it can act as a first line of defense against harmful photobiological effects.

In addition, the already discussed antioxidant and anti-inflammatory activities of luteolin on skin cells such as keratinocytes and fibroblasts as well as on various immune cells (e.g.b macrophages, mast cells, neutrophils, dendritic cells and T cells). The molecule has been proven to be able to inhibit inflammatory factors (such asb TNF-α, COX-2, IL-1β, IL-6, IL-8, IL-17, and IL-22) suppress and various Regulate signaling pathways (such as NF-κB, JAK-STAT and TLR). In this way, the phytochemical modulates many inflammatory processes. Also those that take place in the skin.

The researchers concluded that luteolin could be a promising molecule for the development of “creamy” formulations and systemic agents against inflammatory skin diseases.

Can luteolin be supplemented?

Yes, luteolin can also be taken as a dietary supplement. These supplements often come in capsule or tablet form and may contain a concentrated amount of luteolin. They are particularly interesting for people who want to increase their intake of this flavonoid without consuming large quantities of the corresponding foods.

Literature

  1. Flavonoid Content of Vegetables – USDA. Link
  2. Miean, K H, and S Mohamed. “Flavonoid (myricetin, quercetin, kaempferol, luteolin, and apigenin) content of edible tropical plants.” Journal of agricultural and food chemistry vol. 49,6 (2001): 3106-12. Link
  3. Kellenberger, Esther et al. “Flavonoids as inhibitors of human CD38.” Bioorganic & medicinal chemistry letters vol. 21,13 (2011): 3939-42. Link
  4. Poljšak, Borut et al. “The Central Role of the NAD+ Molecule in the Development of Aging and the Prevention of Chronic Age-Related Diseases: Strategies for NAD+ Modulation.” International journal of molecular sciences vol. 24,3 2959. 3 Feb. 2023. Link
  5. Aziz, Nur et al. “Anti-inflammatory effects of luteolin: A review of in vitro, in vivo, and in silico studies.” Journal of ethnopharmacology vol. 225 (2018): 342-358. Link
  6. Lin, Yong et al. “Luteolin, a flavonoid with potential for cancer prevention and therapy.” Current cancer drug targets vol. 8,7 (2008): 634-46. Link
  7. Robak, J et al. “Screening of the influence of flavonoids on lipoxygenase and cyclooxygenase activity, as well as on nonenzymic lipid oxidation.” Polish journal of pharmacology and pharmacy vol. 40,5 (1988): 451-8. Link
  8. Lin, Yong et al. “Luteolin, a flavonoid with potential for cancer prevention and therapy.” Current cancer drug targets vol. 8,7 (2008): 634-46. Link
  9. Brown, J E, and C A Rice-Evans. “Luteolin-rich artichoke extract protects low density lipoprotein from oxidation in vitro.” Free radical research vol. 29,3 (1998): 247-55. Link
  10. Sun, Dongdong et al. “Luteolin limits infarct size and improves cardiac function after myocardial ischemia/reperfusion injury in diabetic rats.” PloS one vol. 7,3 (2012): e33491. Link
  11. Hu, Wenjing et al. “Luteolin improves cardiac dysfunction in heart failure rats by regulating sarcoplasmic reticulum Ca2+-ATPase 2a.” Scientific reports vol. 7 41017. 23 Jan. 2017. Link
  12. Luo, Yuanyuan et al. “Luteolin: A Flavonoid that Has Multiple Cardio-Protective Effects and Its Molecular Mechanisms.” Frontiers in pharmacology vol. 8 692. 6 Oct. 2017. Link
  13. Lin, Yong et al. “Luteolin, a flavonoid with potential for cancer prevention and therapy.” Current cancer drug targets vol. 8,7 (2008): 634-46. Link
  14. Kempuraj, Duraisamy et al. “Neuroprotective effects of flavone luteolin in neuroinflammation and neurotrauma.” BioFactors (Oxford, England) vol. 47,2 (2021): 190-197. Link
  15. Gendrisch, Fabian et al. “Luteolin as a modulator of skin aging and inflammation.” BioFactors (Oxford, England) vol. 47,2 (2021): 170-180. Link

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The images were acquired under license from Canva.

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