Blockade of Atopic Dermatitis-Like Skin Lesions by DA-9102, a Natural Medicine Isolated from Actinidia arguta, in the Mg-Deficiency Induced Dermatitis Model of Hairless Rats

Abstract

DA-9102 isolated from Actinidia arguta is a candidate of natural medicine currently under Phase II clinical trial for atopic dermatitis in Korea. In this study, spontaneous dermatitis was induced by magnesium deficiency in hairless rats and this system was applied to assess the suppressive effects of DA-9102 on atopic dermatitis-like skin disease. Oral administration of DA-9102 at a dose of 100 mg/kg for 16 days substantially suppressed the occurrence of spontaneous dermatitis. Eczematous skin lesions, water loss and scratching behavior were significantly decreased by DA-9102 in a dose-dependent manner. Infiltration of inflammatory cells into the skin and pathologic remodeling of the epidermis and dermis were much less than the Mg-def. group. Results from flow cytometry analysis of peripheral blood mononuclear cells indicated that DA-9102 suppressed activation of leukocytes. The decrease in the number of CD45RA+ cells was accompanied by a lower level of IgE in DA-9102 treated rats, and the reduction in the number of CD11b+ cells by DA-9102 in both periphery and skin was significant. Further, DA-9102 not only suppressed the mRNA expression of T(H)2 cytokines including IL-4 and IL-10 in the lymph node but it also decreased the levels of inflammatory mediators such as nitric oxide and leukotriene B(4) (LTB(4)) in the serum. Taken together, these results suggest that DA-9102 is an orally applicable potent immune modulator capable of controlling the occurrence of atopic dermatitis-like skin disease.

Transient Receptor Potential Channels as Drug Targets: From the Science of Basic Research to the Art of Medicine

“…Importantly, TRPV3 appears to be under the negative control of Mg 2+ and it was postulated that dietary Mg 2+ deficiency may liberate TRPV3 from this tonic inhibitory control, leading to a constitutively active TRPV3 channel . Indeed, a Mg 2+ -deficient diet causes dermatitis and scratching behavior in rats (Choi et al, 2008). Taken together, these findings imply a therapeutic potential for topically applied TRPV3 antagonists in the management of pruritus secondary to (atopic) dermatitis.…”

Complementary and alternative medicine: Herbs, phytochemicals and vitamins and their immunologic effects

“…84 In an animal model, Actinidia arguta improved dermatitis skin lesions in magnesium-deficient hairless rats by decreasing infiltration of the skin by inflammatory cells and preventing histopathological remodeling of the dermis and epidermis while preventing transepidermal water loss. 85 Saururus chinensis, described by the same group, 86 demonstrated similar anti-inflammatory effects to A arguta, resulting in decreased hypertrophy and hyperkeratosis of the dermis and epidermis and decreased itching behavior in the atopic subjects. In addition, they demonstrated a shift toward the T H 1 cell pathway with no effect demonstrated on T H 2.…”

Inhibition of hardy kiwifruit (Actinidia aruguta) ripening by 1-methylcyclopropene during cold storage and anticancer properties of the fruit extract

“…The reports have shown that the natural immune modulator system derived from the fruit extract has a therapeutic effect on atopic dermatitis Kim, Lee, Son, & Kim, 2009;Park et al, 2005Park et al, , 2007. The extract obtained from dried A. aruguta, named DA-9102, was a natural medicine candidate to control atopic dermatitis in Korea (Choi et al, 2008).…”