(Pseudowintera colorata) – a unique New Zealand medicinal herb
Campbell Berry-Kilgour B.Sc (Hons)
© 2002 Australian Journal of Medical Herbalism
The main biologically active chemical constituent of Pseudowintera colorata is the sesquiterpene dialdehyde polygodiali. It is known that polygodial is a component of the "hot taste" in peppery spices common in traditional Japanese cuisine, Polygodial has been shown to exhibit fungicidal activity against yeasts and filamentous fungi.
Pseudowintera colorata has recently been granted approval for therapeutic use in Australia.
Key words: Pseudowintera colorata, Horopito, polygodial, Candida albicans.
Pseudowintera colorata, (P. colorata), also known as Horopito, New Zealand Pepper Tree, Winter's Bark, and Red Horopito, is member of the Winteraceae family. It is the least specialized of all flowering plant families. It has many ancient features believed to be the same as those of the earliest evolving plants. In New Zealand, Horopito appears in the fossil record for more than sixty five million yearsiv. The main biologically active chemical constituent of P. colorata has been identified as the sesquiterpene dialdehyde polygodial, which has been shown to possess anti-fungal, and anti-bacterial properties. Whilst the Winteraceae family occurs today in most parts of the world, New Zealand has its own genus, Pseudowintera, with three species. All have the peppery, aromatic leaves and bark typical of the family. The leaves are so hot to taste that sheep, cattle and deer usually avoid them4.
Traditional Human Use
P.colorata leaves were traditionally used by Maori of New Zealand to treat fungal skin infection, venereal disease, stomach pain and diarrhoea. A decoction of leaves was used as an analgesic. Early European settlers to New Zealand also used P.colorata for medicinal purposes. For internal use leaves were either chewed or prepared as a tea. To treat skin complaints leaves were bruised and steeped in water or chewed before application 1,5,6. The leaves were chewed for toothache, and were rubbed on the breast when weaning infants. There is no historical evidence of toxicity of P.colorata leaves by either oral ingestion or topical application.
The main biologically active chemical constituent of P. colorata is the sesquiterpene dialdehyde polygodial 2,3. Fig. 1
Structure of Polygodial 9-Deoxymuxigadial (also a sesquiterpene dialdehyde) may also have pharmacological activity. Other constituents include essential oils such as pinenes, limones, humulene and eugenol, and the flavonoids quercetin, luteolin and proanthocyanidins7. Many New Zealand natives exhibit regional variations in genetic make up and consequently biological activity. In order to determine the level of any variation across P. colorata populations, the private research company Forest Herbs Research and the New Zealand government owned Industrial Research Ltd joined forces to conduct the first comprehensive study of all the major populations of Horopito. This research demonstrated a five-fold variation between the most active and the least active plant populations.
In 1982 a group from Canterbury University in New Zealand reported they had isolated a substance called polygodial in the leaves of New Zealand native Pseudowintera colorata1. The Canterbury University team grew cultures of Candida albicans and measured the zone of inhibition in these cultures produced by discs of polygodial extracted from the leaves of P. colorata. They found it was very effective at inhibiting Candida. Comparison with the drug amphotericin B (which is commonly used to treat systemic mycoses) found that polygodial gave larger zones of inhibition. Polygodial also suppressed Candida colony growth from day one, while amphotericin B required 3-4 days incubation.
Polygodial has been shown to possess strong antifungal activity, comparable to amphotericin B, against yeast-like fungi Candida albicans, Candida krusei, Candida utilis, Cryptococcus neoformans, Saccharomyces cerevisiae and also filamentous fungi Trichophyton mentagraphytes, Trichophyton ruburum and Pencillium marneffei8 .The antifungal activity of polygodial was generally not reduced by several susceptibility-testing conditions such as medium type, incubation temperature, inoculum size, and medium pH. Polygodial's antifungal activity was strongly increased in acidic conditions, however. Fungal environments in the human host, such as the mouth, vagina and skin, are often acidic and their colonisation usually creates a microenvironment with even lower pH. Under these circumstances, polygodial can be expected to act as an effective antifungal agent.
In vitro studies by the Cawthron Institute, Nelson, New Zealand, show that dried P.colorata was twice as powerful at killing Candida albicans (i.e. can kill at half the concentration) as sodium caprylate (an alternative natural antifungal), (Table 1) Table 1. Cawthron Institute Report 1999, Ref. M26050/2.
Polygodial is not mutagenic, as determined by three variants of the Ames salmonella test 9 and further confirmed by the mammal-based V79/HGPRT method10. This is unique in that many other sesquiterpene dialdehydes possessing strong biological activity are mutagenic. In comparison with members of this group, polygodial exhibits the least cytotoxicity for compounds, which have antifungal activity9, 11. Polygodial and closely related epipolygodial, controlled fungi (Mucor miehei, Paecilomyces variotii, Pencillium notatum, Nematospora corylii and Saccharomyces cerevisiae) at comparatively low concentrations. At higher concentrations they inhibited bacteria and algae. At about the same concentrations required to control gram-positive organisms (5-20 mcg/ml), they showed antitumour activity against Ehrlich ascites tumour cells and lyphocytic leukemia mouse cells. No mutagenic activity was observed with polygodial or epipolygodial.
Anke & Sterner found that polygodial exhibited antifungal, antibacterial and cytotoxic activity9. No mutagenicity was observed. Huntingdon Life Sciences Ltd., UK, established that the highest non-lethal dose to rats of capsules containing 50% powdered P.colorata, 50% powdered Pimpinella anisum (Anise seed) is greater than 2g/kg body weight. At 2g/kg
dosing the rats maintained satisfactory body weight gains and macroscopic examination of the abdominal and thoracic cavities revealed no abnormalities12.
Mechanism of Action
Polygodial exhibits fungicidal activity against yeast-like fungi. This is in comparison to the actions of some of the fungistatic triazoles, such as fluconazole. It has been reported in literature that the antifungal activity of polygodial is the result of structural disruption of cell membranes, leading to cell leakage and ultimately cell death. Radioactive monomer incorporation studies have shown no selective inhibition of uptake in polymers of DNA, RNA, protein or polysaccharide, as all uptake tapered off after sixty minutes13 . Polygodial produces amounts of potassium leakage from
yeast cells similar to those produced by Amphotericin B and miconazole14.
Polygodial's synergy with Anise seed
The seeds of Pimpinella anisum (aniseed) are used as a spice throughout the world and also as folk medicine in South America6. Anethole, identified as an active principle in aniseed, has previously been demonstrated to have moderate antifungal activity. Though not potent enough to be considered for practical use by itself, Anise seed has been considered worthy of further investigation by virtue of being a natural product isolated from a food spice. Polygodial has been found to synergise the antifungal activity of antibiotics such as actinoycin and rifampicin. Anethole has been shown to exhibit a significant synergistic effect on the antifungal activity of polygodial against Candida albicans and Saccharomyces cerevisiae. Activity increased sixty four times against S. cerevisiae and thirty two times against C. albicans. The authors of this work have concluded 'since the control of opportunistic yeast pathogens is becoming increasingly important, the current study to enhance the total biological activity by combining two or more substances may provided a new approach to solve this problem. In particular, two phytochemicals isolated from common food spices, anethole and polygodial, may be considered for practical application.'
In 1992 an open study conducted by New Zealand naturopaths for Forest Herbs Research Limited examined the therapeutic effect of capsules containing milled P.colorata and milled Anise seed, (Kolorex â), in patients diagnosed with chronic intestinal candidiasis. This study demonstrated a symptom improvement rate in 76% of cases16.
In 1997 the Pavlodar City Centre for Clinical Immunology and Reproduction compared twenty two patients taking capsules containing milled P. colorata and milled Anise seed, (Kolorex â), with ten patients administered fluconazole (Diflucan, Pfizer).
All patients were diagnosed as having chronic, recurring intestinal candidiasis. A significant improvement was seen in 100% (n= 10) of the fluconazole group at seven days and in 90% (n=20) of the P. colorata group at fourteen days15.
Precautions and Contraindications
Although there is no evidence of teratogenicity, as a precaution P. colorata is not recommended during pregnancy or lactation. P. colorata works rapidly against Candida albicans in the digestive tract. For this reason a Herxheimer reaction (to dead
Candida cells) is sometimes experienced in the first few days of therapy by those with Candida overgrowth. This is characterised by a headache and a nauseous feeling, both of which are usually mild and transient.
©2002 Forest Herbs Research Limited.
May not be reproduced in whole or in part without the written permission of the author.
© 2002 Australian Journal of Medical Herbalism, Vol 14, Issue 2, 2002
1McCallion, R. F., A. L. Cole, J. R. L. Walker, J. W. Blunt, and M. H. G. Munro. 1982. Antibiotic compounds from New Zealand plants, II: polygodial, an anti-Candida agent from Pseudowintera colorata. Planta Med. 44:134-138
2 Kubo, I., and I. Ganjian. 1981. Insect antifeedant terpenes, hot-tasting to humans. Experientia 37:1063-1064
3 Kubo, I., and M. Taniguchi. 1988. Polygodial, an antifungal potentiator. J. Nat. Prod. 51:22-29
4 Webb,C., Johnson, P., Sykes, B., Flowering Plants of New Zealand, Caxton Press, 1990, p 104
5 Kubo, I. & Himejima, M., Anethole, a synergist of polygodial against filamentous micro-organisms, 1991, J. Agric. Food Chem. 39, pp 2290-2292.
6 Himejima, M. & Kubo, I. Fungicidal activity of polygodial in combination with anethole and indole against Candida albicans.1993, J. Agric. Food Chem., 41, pp 1776-1779.
7, Larsen, L., A literature survey of the constituents of Pseudowintera colorata, Crop and Food Research Ltd., 2001
8 Lee, S.H., Lee, J.R., Lunde, Kubo, I., In vitro antifungal susceptibilities of Candida albicans and other fungal pathogens to polygodial, a sesquiterpene dialdehyde. , 1999, Planta Medica 65, pp 204-208
9 Anke, H., and O. Sterner, Comparison of the antimicrobial and cytotoxic activities of twenty unsaturated sesquiterpene dialdehydes from plants and mushrooms. Planta Med. 1991. 57:344-346
10 Morales, P., M. Andersson, L. Lewan, and O. Sterner. Structure-activity relationships for unsaturated dialdehydes 6. The mutagenic activity of 11 compounds in the V79/HGPRT assay. Mut. Res, 1992.. 268:315-321.
11 Forsby, A., M. Andersson, L. Lewan, and O. Sterner,1991Structure-activity relationships for unsaturated dialdehydes, 4. The cytotoxicity of 22 sesquiterpenoid unsaturated dialdehydes, as determined by the neutral red absorption assay and by protein determination. Toxicol. In Vitro,5:9-14.
12 Data on File, Forest Herbs Research Limited, Nelson, New Zealand.
13 Taniguchi, M., Y. Yano, E. Tada, K. Ikenishi, S. Oi, H. Haraguchi, K. Hashimoto, and I. Kubo. 1988. Mode of action of polygodial, an antifungal sesquiterpene dialdehyde. Agric. Biol. Chem. 52:1409-1414.
14 Yano, Y., M. Taniguchi, T. Tanaka, S. Oi, and I. Kubo. 1991. Protective effects of Ca2+ on cell membrane damage by polygodial in Saccharomyces cerevisiae. Agric. Biol. Chem. 55:603-604.
15 Pavlodar City Centre for Clinical Immunology and Reproduction. Head Physician: O. Ogorodnikova. Pavlodar. Data on File, Postgraduate Physicians' Training Faculty Assistant : M. Valivach.
16 New Zealand Naturopaths Study, 1992, Data on File, Forest Herbs Research Limited, Nelson, New Zealand.