In recent years, the prevalence of allergic diseases, including asthma, atopic dermatitis, and food allergies, has been on the rise. Food allergies, in particular, afflict millions globally, with common triggers being milk, peanuts, eggs, and shellfish. These allergies typically stem from the immune system overreacting to otherwise harmless substances in food and the environment. Amid this, flavonoids, which are naturally occurring chemicals in various fruits and vegetables, have emerged as contenders for natural allergy treatments, given their known anti-allergic properties.
Delving deeper, there’s an intriguing anti-allergic mechanism at play within our cells. In the intestines, specialized dendritic cells (DCs) produce an enzyme known as RALDH2 (retinaldehyde dehydrogenase 2). This enzyme converts retinal, derived from vitamin A, into retinoic acid. Subsequently, the retinoic acid facilitates the development of regulatory T-cells, a subset of immune cells that can temper the overzealous immune responses characteristic of allergies.
Evidently, RALDH2 holds significant sway in the fight against food allergies. But the burning question was: are there flavonoids that can boost RALDH2 levels in DCs?
A research team led by Professor Chiharu Nishiyama at the Tokyo University of Science (TUS) sought to answer this. In a letter published online in Allergy on December 11, 2024, they screened approximately 40 flavonoids to gauge their impact on RALDH2 levels in DCs. Among them, kaempferol emerged as the standout compound and was selected for further investigation. The key contributors to this study included Ms. Miki Takahashi, a 2023 graduate from TUS, Dr. Kazuki Nagata, Assistant Professor at TUS, and Ms. Yumi Watanuki, a 2019 graduate from TUS.
Kaempferol is prevalent in numerous foods like kale, beans, tea, spinach, and broccoli. It’s also one of the most extensively studied flavonoids due to its manifold benefits to the human body. The researchers discovered that treating DCs with kaempferol enhanced both the expression and functionality of RALDH2. Moreover, these kaempferol-treated DCs were found to foster the development of regulatory T-cells, highlighting its role in modulating the immune response.
To unravel the precise mechanism, they zeroed in on the aryl hydrocarbon receptor (AhR), which kaempferol targets. Experiments on DCs indicated that kaempferol acts as an antagonist, blocking AhR and thereby hastening regulatory T-cell development. Next, they turned their attention to factors influencing the Aldh1a2 gene, responsible for producing Radlh2.
“Previously, we reported that PU.1 and IRF-4 were crucial molecules regulating the Aldh1a2 gene in dendritic cells,” remarks Prof. Nishiyama. “In this study, we found that PU.1 and IRF-4 expression and function were enhanced in dendritic cells stimulated with kaempferol,” she elaborates, shedding light on the PU.1/IRF-4-dependent mechanism underpinning kaempferol’s anti-inflammatory effects.
To assess kaempferol’s impact on immune responses in living organisms, the researchers induced allergies in mice using the OVA (ovalbumin) protein from egg whites. Remarkably, they observed that administering kaempferol to these mice alleviated their allergic symptoms. “The rapid decrease in body temperature and allergic diarrhea seen after OVA administration were significantly suppressed in mice given kaempferol,” explains Prof. Nishiyama.
These findings peg kaempferol as a highly promising natural treatment for food allergies. However, the researchers caution that further studies, especially involving human cells, are essential to validate these results and translate kaempferol into an allergy medicine. While this study spotlighted kaempferol, flavonoids in general present a bright prospect as anti-allergic compounds, given their ubiquity in a wide array of foods.
The authors posit that the chemical structure of flavonoids might underpin their capacity to accelerate regulatory T-cell development. This has profound implications for allergy treatment: regular consumption of flavonoid-rich foods could potentially serve as natural remedies to ease allergic symptoms.
Reiterating the importance of incorporating flavonoids into one’s diet, Prof. Nishiyama states, “When consumed as part of a daily diet, they are expected to mitigate allergies, inflammation, and autoimmune diseases spurred or worsened by an overactive immune response.”
Indeed, these findings offer renewed hope to the countless individuals worldwide grappling with food allergies.
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