Curcumin inhibits Histamine Release from Mast Cells

Biological & Pharmaceutical Bulletin
Vol. 32 (2009) , No. 5 842

Effects of Benzylidenecyclopentanone Analogues of Curcumin on Histamine Release from Mast Cells
Agung Endro Nugroho1)2), Zullies Ikawati2) and Kazutaka Maeyama1)
1) Department of Pharmacology, Informational Biomedicine, Ehime University Graduate School of Medicine
2) Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Gadjah Mada University
3) Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Gadjah Mada University
(Received September 29, 2008)
(Accepted February 16, 2009)
Curcumin reportedly has anti-allergic effects and can inhibit the release of histamine from mast cells. In the present study, fourteen benzylidenecyclopentanone analogues of curcumin were studied for their effects on histamine release from rat basophilic leukemia (RBL-2H3) cells. After screening, four selected compounds: 2,5-bis(4-hydroxybenzylidene)cyclopentanone; 2,5-bis(4-hydroxy-3-methoxybenzylidene)cyclopentanone; 2,5-bis(4-hydroxy-3,5-dimethylbenzylidene) cyclopentanone; and 2,5-bis(4-hydroxy-3,5-diethylbenzylidene)cyclopentanone were studied for their concentration-dependent effects on histamine release and Ca2+ uptake. In RBL-2H3 cells and rat peritoneal mast cells stimulated with antigen or compound 48/80, respectively, the methoxy-hydroxy analogue was more potent than curcumin in inhibiting histamine release. In contrast, the inhibitory effects of methyl/ethyl analogues were less potent than those of curcumin. Moreover, these compounds abrogated histamine release induced by increased intracellular Ca2+ concentrations in response to stimulants such as thapsigargin and ionomycin. These compounds also showed potent inhibitory effects on 45Ca2+ uptake in RBL-2H3 cells. The mechanism of the inhibitory effects of these curcumin analogues on histamine release appeared to be related to blockade of Ca2+ signaling events. These results provide useful information to guide the development of new synthetic compounds for the treatment of allergic and inflammatory diseases related to histamine or mast cells.

To "shed" further light on the implication of mast cells, take a look at this study:
Epub 2008 Feb 20.
Dermal fibrosis in male pattern hair loss: a suggestive implication of mast cells.
Won CH, Kwon OS, Kim YK, Kang YJ, Kim BJ, Choi CW, Eun HC, Cho KH.

Department of Dermatology, Seoul National University College of Medicine, Chongno-Gu, Seoul, Republic of Korea.

A relationship has been suggested between mast cells (MCs) and male pattern hair loss (MPHL), because of histological evidence of perifollicular fibrosis and increased mast cell numbers. Two paired punch biopsies were taken from balding vertexes and non-balding occipital promontory areas of ten patients with MPHL (Ludwig-Hamilton IIIv to IV) and from five normal subjects aged from 20 to 35 years. Masson trichrome and Victoria blue staining were performed to observe collagen frameworks and elastic fiber structures. Numbers of immunoreactive MCs stained with anti-tryptase or anti-chymase antibody were counted. It was found that collagen bundles were significantly increased in balding vertexes than in non-balding occiput scalp skin. A near 4-fold increase in elastic fibers was observed in both vertex and occiput scalp skins with MPHL versus controls. Total numbers of MCs (tryptase-positive) in site-matched scalp samples were about 2-fold higher in MPHL subjects than in normal controls. Percentage elastic fiber (%) was found to be relatively well-correlated with tryptase and chymase-positive MCs. These findings suggest that accumulated MCs might be responsible for increased elastic fiber synthesis in MPHL, and indicate that future investigations are warranted.

Also by indications of this study, substance P, which is a mediator of neurogenic inflammation via mast cell degranulation.



Hypothetical scenario: human hair growth inhibition by substance P. Hypothetical scenario depicting direct and indirect pathways by which substance P may inhibit human hair growth in the context of psychoemotional stress and neurogenic inflammation. On the left an anagen VI hair bulb is depicted. Gray cells with black membrane show location of proliferating Ki-67+ cells in the hair matrix that also express weak NK1 and TrkA immunoreactivity. On the right a regressing (mid catagen) hair bulb is depicted. Light gray cells indicate rarified proliferating Ki-67+ cells that also express NGF and some of which express p75NTR and show ectopic MHC I expres​sion(gray cells with black membrane). Close by a nerve fiber in contact with degranulated mast cells and some monocytes are shown. Note that NK1, TrkA, p75NTR, and MHCII immunoreactivity outside the proliferative compartment are not schematized for easier comprehensibility. MKC, matrix keratinocyte.

http://ajp.amjpathol.org/cgi/content/full/171/6/1872

Excellent post, IH. I will share this with others at another forum.