Naturally occurring mast cell stabilizers: Part 4

I mentioned resveratrol in the previous post under its broad classification as a phenol.  Looking more narrowly, resveratrol is a derivative of stilbene.  It is found in several foods, including grapes and berries like blueberries and raspberries.  Resveratrol can form oligomers, in which several of the same molecule are connected together.  One such oligomer is Gnetin H.  This product is isolated from Paeonia anomala and is used in Mongolian Chinese medicine.  It has been found to significantly impair mast cell degranulation and is effective at lower doses than resveratrol.  Gnetin H also decreased histamine secretion and production of TNF and IL-4, as well as COX-2 and PGE2 (not a typo, prostaglandin E2).

Polydatin is a precursor to resveratrol.  In a rat model, administration of polydatin was found to make the small intestine mucosa much less “leaky”.  It also inhibited hypersensitivity in the small intestine.  Importantly, it decreased degranulation by as much as 65% (determined by examining tissue with toluidine blue staining), and decreased histamine in both serum and intestinal mucosa.  Degranulation involves changes in calcium inside the mast cell and treatment with polydatin interfered with this process.  It also interrupted production of IgE by suppressing IL-4 secretion.  In another paper, polydatin was also found to suppress anaphylaxis in the mouse model of passive cutaneous anaphylaxis.

Hydroxytyrosol is a phenol derived from olive oil and olive leaves.  In nature, it occurs in the form of oleuropein, which can be broken down to hydroxytyrosol.  In a study that used β-hexosaminidase as a  marker for mast cell degranulation, both hydroxytyrosol and oleuropein inhibited activation in cells at high concentrations. This is promising but future research is needed.

In mouse and human mast cells, hypothemycin was found to interfere with activation of the CKIT receptor and the IgE receptor (FceRI).  This resulted in suppression of degranulation and production of cytokines, including IL-4.  This product was originally extracted from a mushroom of the Hypomyces genus.

References:

Zhang, T., et al. Mast cell stabilisers. Eur J Pharmacol (2015).

Finn, DF, Walsh, JJ. Twenty-first century mast cell stabilizers. J Pharmacol 2013 Sep; 170(1): 23-37.

Kim M, et al. Gnetin H isolated from Paeonia anomala inhibits FceRI-mediated mast cell signaling and degranulation. J Ethnopharmacol 2014 Jul 3; 154(3): 798-806.

Yang B, et al. Polydatin attenuated food allergy via store-operated calcium channels in mast cell. World J Gastroenterol 2013 Jul 7; 19(25): 3980-3989.

Yuan M, et al. Polydatin (PD) inhibits IgE-mediated passive cutaneous anaphylaxis in mice by stabilizing mast cells through modulating Ca2+ mobilization. Toxicol Appl Pharmacol 2012 Nov 1; 264(3): 462-469.

Persia FA, et al. Hydroxytyrosol and oleuropein of olive oil inhibit mast cell degranulation induced by immune and non-immune pathways.  Phytomedicine. 2014 Sept 25; 21(11): 1400-1405.