Glucocorticoids are widely used in the preventative treatment of asthma and other allergic diseases. Glucocorticoids bind to the glucocorticoid receptor (GR), thereby activating the GR. The activated GR then binds to a glucocorticoid responsive element and upregulates the genes for anti-inflammatory agents such as lipocortin. The induction of the anti-inflammatory protein lipocortin in turn inhibits the enzyme phospholipase A2, thereby decreasing the production of allergy mediators, such as prostaglandins and leukotrienes. Allergy and Allergic Diseases: The new Mechanism and Therapeutics, edited by J. A. Denburg, Human Press Inc., Totowa, N.J., Schleimer R P, Effects of Glucocorticosteroids on inflammatory cells relevant to their Therapeutic Application in Asthma, Am. Rev. Respir. Dis., 1990, 141, S59-S69.
One of the other main effects of activated GR is the downregulation of a wide variety of agents, including cytokines and chemokine agents such as Interleukin-4 (IL-4) and Interleukin-5 (IL-5). The ability of glucocorticoids to inhibit the production of cytokines, in particular IL-5, has proven to be a major component in their effectiveness in the treatment of allergic diseases and, especially, asthma and atopy.
Furthermore, phosphodiesterase isoenzymes (PDE's), and more particularly inhibitors of PDE 4, are receiving special interest as anti-asthmatic agents due to evidence that these enzymes can act as both anti-inflammatory agents and bronchodilators in both animals and humans. Cortijo J, Beleta J, Cardelus I, Llenas E, Morcillo E., Investigation into the role of phosphodiesterase IV in bronchorelaxation, including studies with human bronchus, Br. J. Pharmcol., 1993, 108, 562-568.
Leukotrienes are also of particular interest in the study of allergic disease, because of their marked bronchoconstrictory action. Leukotrienes have an approximate 1000-fold greater bronchoconstrictory action than histamines and prostaglandins. Leukotrienes are by-products of arachidonic acid which is located in phospholipid bi-layers in the cell membranes of mast cells. During an asthma attack, arachidonic acid is converted into five leukotrienes. This conversion is mediated by an enzyme, 5-lipoxygenase (5-LO), which converts arachidonic acid first to 5-hydroxyperoxyeicosatetraenoic acid (5-HPETE) and then into leukotriene A4 (LTA4), which is the precursor of the other four leukotrienes. Of the five leukotrienes produced during an asthma attack, the cysteinyl class of leukotrienes (LTC4, LTD4 and LTE4) are the most potent bronchoconstrictors. Werz O, Steinhilber D, Therapeutic options for 5-lipoxygenase inhibitors, Pharmacology and Therapeutics, 2006, 112, 701-718.
Within this process, leukotriene biosynthesis inhibitors have an important role to play, since they inhibit the action of 5-LO, thereby inhibiting the eventual synthesis of the bronchoconstrictory leukotrienes.
The above pathway may thus be manipulated by administering a glucocorticoid receptor (GR) binding compound, a PDE inhibitor and/or a 5-LO inhibitor to a patient in need thereof. Currently, this is accomplished in most cases by administering steroidal compounds to a patient suffering from an allergic disease or reaction, such as asthma or atopy. Due to many detrimental side-effects being associated with steroidal compounds in treating such diseases, there is a need for a non-steroidal compound exhibiting the beneficial properties associated with steroidal compounds and steroid-containing formulations.
In chronic inflammatory diseases, such as asthma, rheumatoid arthritis, inflammatory bowel disease and psoriasis, several cytokines recruit activated immune and inflammatory cells to the site of lesions, thereby amplifying and perpetuating the inflammatory state. These activated cells produce many other mediators of inflammation. The vicious cycle may be suppressed by glucocorticoid or immunosuppressive therapy, but there is no curative treatment for any chronic inflammatory disease. Transcription factors play a key role in immune and inflammatory responses and one ubiquitous transcription factor of particular importance is nuclear factor-κB (NF-κB). NF-κB is a central mediator of the human immune response, regulating the transcription of various pro-inflammatory and inflammatory mediators such as the cytokines Interleukin-1 (IL-1), Interleukin-2 (IL-2), Interleukin-8 (IL-8) and TNF-α, as well as genes encoding cyclo-oxygenase II, nitic oxide synthase, immunoreceptors, cell adhesion molecules, or acute phase proteins. In clinical studies of patients with allergic asthma, plasma levels of Interleukin-8 (IL-8) were elevated in these patients. Blackwell T S, Christian J W, The role of nuclear factor-κB in cytokine gene regulation. Am. J. Respir. Cell Mol Biol 1997; 17:3-9, Hashimoto, S., Matsumoto, K., Gon, Y. et al. 2000. p 38 MAP kinase regulates TNF alpha-, IL-1 alpha-and PAF-induced RANTES and GM-CSF production by human bronchial epithelial cells. Clinical and Experimental Allergy. 30: 48-55. Herlaar, E. and Brown, Z. 1999. p 38 MAPK signaling cascades in inflammatory disease. Molecular Medicine Today. 5: 439-447. Holden, N. S., Catley, M. C., Cambridge, L. M., Barnes, P. J. and Newton, R. 2004. ICAM-1 expression is highly NF-kappaB-dependent in A549 cells. European Journal of Biochemistry. 271: 785-791. Therefore, inhibition of NF-κB resulting in the down regulation of chemokines such as IL-8 could be beneficial in the treatment of asthma and inflammatory diseases.
According to one aspect of the invention, there is provided an organic solvent extract or an essential oil of a plant of the family Zingiberaceae for use in the preventative treatment and remission of allergic diseases.
The plants of the family Zingiberaceae include the genera Siphonochilus, Kaempferia, Cienkowskia and/or Cienkowskiella. 
The organic solvent extract or essential oil may be obtained from plant material of plants selected from the species Siphonochilus aethiopicus, Siphonochilus natalensis, Kaempferia aethiopica, Kaempferia natalensis, Kaempferia ethelae, Cienkowskia aethiopica and Cienkowskiella aethiopica. 
Preferably, the said organic solvent extract or essential oil comprises as an active ingredient a compound having the structural formula 1:

The chemical name (IUPAC) of the compound of formula 1 is 4,4a,5,9-tetrahydro-3,5,8a-trimethylnaptho[2,3-b]furan-8-one.
The compound of formula 1 may be used in the form of a racemic mixture or in the form of one of its steroisomers.
Examples of the allergic diseases are asthma and atopy.
Typically, the organic solvent extract or essential oil is capable of binding to a glucocorticoid receptor (GR), inducing the production of lipocortin, and/or the inhibition of the enzyme phospholipase A2, and/or the decreasing of production of prostaglandins and/or leukotrienes.
The organic solvent extract or essential oil may have anti-bronchoconstrictory activity and further may downregulate cytokines and chemokine agents such as Interleukin-4 (IL-4) and Interleukin-5 (IL-5).
The organic solvent extract or essential oil may inhibit NF-κB a central mediator of the human immune response, down regulating the transcription of various pro-inflammatory and inflammatory mediators such as the cytokines Interleukin-8 (IL-8)
The organic solvent extract or essential oil may be obtainable by a method which includes the steps of preparing an extract from plant material of a plant of the family Zingiberaceae, and separating a fraction having activity against allergic diseases, the extracts containing the active ingredient having activity against allergic diseases.
The method may include the steps of extracting wet rhizomes or roots or ground plant samples of said plant species such as Siphonochilus aethiopicus, or drying the rhizomes and/or the roots of the plant by air drying or oven drying, followed by grinding of the rhizomes and/or roots to a powder. Extracts are prepared by extraction using organic solvents such as diethyl ether, di-isopropyl ether, t-butyl methyl ether, t-butyl ethyl ether, ethyl acetate or benzyl acetate. The active ingredient may be extracted by extraction techniques which include steam distillation, and or purification of the extracts using solvent/solvent partitioning and/or chromatographic separating techniques.
According to another aspect of the invention, there is provided a substance or composition for use in a method for the preventative treatment and remission of allergic diseases, which substance or composition includes as an active ingredient an extract as described above, and said method comprising administering to a subject an effective dosage of said substance or composition.
According to another aspect of the invention, there is provided a substance or composition for use in a method for the preventative treatment and remission of allergic diseases, which substance or composition includes as an active ingredient a compound of formula 1, and said method comprising administering to a subject an effective dosage of said substance or composition.
According to a further aspect of the invention, there is provided a compound of formula 1 for use in a method for the preventative treatment and remission of allergic diseases.
According to another aspect of the invention, there is provided the use of the organic solvent extract or essential oil as described above in the manufacture of a medicament having activity against allergic diseases.
Examples of the allergic diseases are asthma and atopy.
According to still a further aspect of the invention, there is provided a composition for use in the preventative treatment and remission of allergic diseases, which includes an effective quantity of one of said extract, said compound of formula 1 or said essential oil.
The extract, and compositions of the extract, may be in a form suitable for administering to mammalian subjects, particularly human subjects. The extract may be in the form of an organic solvent extract and/or an essential oil or combinations thereof.
The invention extends to the use of the organic solvent extract as described above, the essential oil or the compound of formula 1 in the downregulation of glucocorticoid receptors, the inhibition of phospholipase A2, the downregulation of allergy mediators such as prostaglandins and leukotrienes, the downregulation of cytokines such as IL-4 and IL-5, the inhibition of phosphodiesterase 4, the inhibition of 5-lipoxygenase or leukotriene biosynthesis, and the inhibition of specific activity of the NF-κB Transcription Response resulting in down regulation of IL-8.
More particularly, the invention provides the use of an extract of at least one plant selected from plants of the family Zingiberaceae in the preparation of a medicament for use in the treatment or prophylaxis of allergic diseases.
The at least one plant may be selected from the genera Siphonochilus, Kaempferia, Cienkowskia and Cienkowskiella and from the species Siphonochilus aethiopicus, Siphonochilus natalensis, Kaempferia aethiopica, Kaempferia natalensis, Kaempferia ethelae, Cienkowskia aethiopica and Cienkowskiella aethiopica. 
The extract may include, as an active ingredient, a compound selected from compounds having the structural formula 1,
stereoisomers thereof and mixtures of stereoisomers thereof.
The allergic disease may be selected from asthma and atopy.
The extract may be an essential oil obtained by steam distillation of plant material from the at least one plant. Instead, the extract may be an organic solvent extract obtained by extraction of plant material of the at least one plant with an organic solvent.
The organic solvent may be an ether selected from diethyl ether, diisopropyl ether, t-butyl methyl ether, t-amyl methyl ether and t-butyl ethyl ether. Instead, the organic solvent may be an ester selected from methyl acetate, ethyl acetate and benzyl acetate.
The plant material may be obtained from roots or rhizomes of the plant.
The invention extends to a composition for use in a method of treatment or prophylaxis of allergic diseases, the composition including an extract of at least one plant selected from plants of the family Zingiberaceae.
The at least one plant may be as hereinbefore described.
The extract may be as hereinbefore described.
The allergic disease may be selected from asthma and atopy and the plant material may be obtained from roots or rhizomes of the plant.
The invention extends to the use of an extract of at least one plant selected from plants of the family Zingiberaceae in the preparation of a medicament for use in any one or more of the downregulation of glucocorticoid receptors, the inhibition of phospholipase A2, the downregulation of allergy mediators, the downregulation of cytokines, the inhibition of phosphodiesterase 4, the inhibition of 5-lipoxygenase or leukotriene biosynthesis, and the inhibition of specific activity of the NF-κB Transcription Response.
The allergy mediators may be selected from prostaglandins and leukotrienes. The cytokines may be selected from IL-4, IL-5 and IL-8.
The at least one plant may be as hereinbefore described.
The extract may be as hereinbefore described.
The allergic disease may be selected from asthma and atopy.
The plant material may be obtained from roots or rhizomes of the plant.
The invention extends, further, to the use of a compound selected from compounds having the structural formula 1,
stereoisomers thereof and mixtures of stereoisomers thereof in the preparation of a medicament for use in the treatment or prophylaxis of allergic diseases.
The allergic disease may be selected from asthma and atopy.
The invention extends further to a method of treatment of an allergic disease, the method including administering to a person or animal in need of treatment a therapeutically effective amount of an extract, a composition or a compound selected from compounds of structural formula 1 as hereinbefore described.
The allergic disease may be as hereinbefore described.
The invention will now be described, by way of example, with reference to the accompanying diagrammatic drawings and tables.