Effects of Calaguala and an Active Principle, Adenosine, on Platelet Activating Factor

Abstract

Calaguala, an extract from the fern Polypodium decumanum, has been used to treat psoriasis and related immunological disorders. In an effort to explain Calaguala's medicinal effects the inhibitory activity of the extract in two platelet activating factor (PAF) related models has been investigated. In the first model, PAF was used to induce release of the proteolytic enzyme elastase in human neutrophils. Calaguala inhibited this effect with an IC50 of 0.1 mg/ml. The known PAF antagonist ginkgolide BN 52021 was used as a positive control and had an IC50 of 0.034 mg/ml. In the second model the inhibition of biosynthesis of PAF in neutrophils using lyso-PAF and labeled acetyl-CoA was studied. Also in this assay Calaguala showed a dose-dependent activity, the IC50 being 0.2 mg/ml. Since recent findings have indicated that PAF might be involved in the pathogenesis of psoriasis, it is possible that the activity shown by Calaguala in these PAF assays may contribute to the clinical efficacy of the extract. The PAF induced exocytosis assay was further used to guide the fractionation of the crude extract. From the acetone supernatant the nucleoside adenosine was isolated as an active principle. Pure adenosine dose-dependently inhibited the exocytosis induced by PAF (IC50 = 0.024 micrograms/ml) but was inactive in the biosynthesis assay. Adenosine is most probably one of the bioactive compounds of Calaguala responsible for its therapeutic properties.

Platelet-Activating Factor Is Crucial in Psoralen and Ultraviolet A-Induced Immune Suppression, Inflammation, and Apoptosis

“…9 For instance, phospholipase-A2, a key enzyme in PAF production, can be induced by UVB exposure 8 and possibly also by PUVA. 21,22 The possibility that reactive oxygen species-associated effects are responsible for PUVA-induced effects such as immune suppression is supported by the observation that the antioxidative polypodium leucotomos extract has been shown to inhibit PAF production 23 and several types of UV and/or PUVA-induced immunological alterations, such as depletion of antigenpresenting Langerhans cells in human skin. 24 Moreover, the isoflavone genistein, a specific inhibitor of tyrosine kinase, has been shown to inhibit chemical carcinogeninduced reactive oxygen species and PUVA-induced photodamage, including inflammatory skin changes such as dermal neutrophilic and lymphocytic infiltration.…”

Inhibition of ultraviolet‐induced formation of reactive oxygen species, lipid peroxidation, erythema and skin photosensitization by Polypodium leucotomos

“…leucotornos extract is a hydroalcoholic extract containing a saponin formed by a ketosteroid and deoxyhexose with little published information on its composition and structure of active ingredient(s) (19). The extract has been shown to exhibit immunomodulating activities in vitro and in vivo, exemplified by an increase in number of lymphocytes CD8+ (20), a prolongation of the survival of skin allografts in mice (21), suppression of effector and memory T-cells and increase of NK activity, modulation of brain levels of some cytokines in rats (22), suppression of proliferative response to exogenous r-IL-2 and antiCD3 mononuclear antibodies (23), and inhibition of both the release of elastase in human neutrophils induced by platelet activating factor (PAF), and the biosynthesis of PAF (24). In recent years, Z?…”

A Sulphonoglycolipid from the Fern Polypodium decumanum and its Effect on the Platelet Activating-factor Receptor in Human Neutrophils

“…We have previously studied calaguala in connection with mediators that are considered significant in inflammatory disorders, including PAF. One of the pharmacological models used is the PAFinduced release of the proteolytic enzyme elastase in human neutrophils, on which calaguala had dose-related inhibitory activity (Tuominen et al 1992). The present fractionation of calaguala with the aim of identifying components of the plant responsible for the activity resulted in the isolation of the sulphoquinovosy 1 diacylglycerol 1,2-di-O-palmitoyl-3-0-( 6sulpho-a-D-quinovopyranosy1)-glycerol.…”