Warning: Naturally occurring molecules can interfere with medications or adversely affect disease state. Please consult with your managing provider before adding supplements or drastically changing diet.
Flavonoid is a broad term used to describe certain plant derived metabolites. It can be used to refer to a variety of molecules, including isoflavonoids, neoflavonoids and anthoxanthins, which are categorized based on structure. A number of flavonoids have been shown experimentally to modulate mast cell behavior and function as mast cell stabilizers.
Homoisoflavonone decreases production of PGD2 and leukotrienes B4 and C4 by downregulating COX-2 and 5-LO, the enzymes that make these molecules from arachidonic acid. It also interferes directly with the manufacture of IL-6 and TNF in mast cells stimulated by IgE (the traditional allergy pathway). Homoisoflavonone can be isolated from bulbs of Cremastra appendiculata, which is commonly called Chinese tulip despite being an orchid. Chinese tulip is commonly used in Chinese medicine. Related homoisoflavonoids, extracted from the tuber of Ophiopogon japonicas, mondograss, are anti-inflammatories, possibly by interfering with COX-2 and 5-LO.
Flavonols have been noted for their anti-allergic activity for a number of years. Morin is a flavonol found in natural sources like Maclura pomifera (Osage orange) and Psidium guajava (guava). Morin prevents mast cell degranulation and manufacture of cytokines like TNF and IL-4, as well as suppressing IgE activation almost completely at higher doses (please note the study on this used mice so it’s not clear what those dose would be in humans). Other mast cell active flavonols include quercetin, myricetin, rutin, fisein and kaempferol.
Quercetin downregulates the expression of histidine decarboxylase, the enzyme that modifies histidine, an amino acid, to histamine. Quercetin also inhibits release of histamine, prostaglandins and leukotrienes. Additionally, it decreases production and release of IL-1b, IL-6, IL-8 and TNF. Quercetin was reported to be stronger and more effective at inhibiting mediator release than cromolyn when taken prophylactically, although this has not yet been judged as true by any regulatory body. Quercetin is found naturally in a number of foods, such as red onion, sweet potato, kale, and many others. It is also found in small quantities in teas made with Camellia sinensis. Rutin is a derivative of quercetin, found in citrus fruits, apples, cranberries and others.
Fisetin, kaempferol, myricetin, quercetin and rutin inhibited IgE mediated histamine release and prevented increased concentration of calcium inside mast cells, which is necessary for degranulation. Fisetin, quercetin and rutin all decreased production of IL-1b, IL-6, IL-8 and TNF. Fisetin, myricetin and rutin all decreased action of NF-kB, which controls the pathway regulating production of cytokines. Myricetin is a particularly effective mast cell stabilizer. It decreased degranulation and release of TNF and IL-6, but not IL-1b or IL-8.
Flavonols have been evaluated for other medicinal properties aside from mast cell modulation. Myricetin has been suggested as a treatment for many diseases, including diabetes, while kaempferol affects many molecular pathways, including estrogen signaling. These molecules occur naturally in a number of plants, including walnuts, onions and red grapes for myricetin; apples, onions, persimmons, strawberries and cucumbers for fisetin; and potatoes, squash, cucumbers, peaches and Aloe vera for kaempferol.
Zhang, T., et al. Mast cell stabilisers. Eur J Pharmacol (2015).
Weng Z., et al. Quercetin is more effective than cromolyn in blocking human mast cell cytokine release and inhibits contact dermatitis and photosensitivity inhumans. PLoS One. 2012; 7(3): e33805.
Park HH, et al. Flavonoids inhibit histamine release and expression of proinflammatory cytokines in mast cells. Arch Pharm Res. 2008 Oct; 31(10): 1303-11.
Lee, YS, et al. Homoisoflavonone prevents mast cell activation and allergic responses by inhibition of Syk signaling pathway. Allergy 2014; 69: 453-462.