By Campbell Berry-Kilgour, BSc (Hons.)
The Maori people of New Zealand accumulated a vast storehouse of knowledge about indigenous flora. This is evident in the myriad of spiritual and practical uses that intertwine with the medicinal use of the 200 or so plants used by the Maori for ritual or herbal purposes.
Maori believe plants and man have a common origin, both being offspring of Tane, in his capacity as controller of the forests and of fertilization. In plants, Maori saw living life forms that are senior in status to man, because Tane created plant life before mankind.1
This article provides some insight into the traditional medicinal uses of one such New Zealand plant, horopito (Pseudowintera colorata), and how such use is now corroborated by almost two decades of
Horopito also is known as New Zealand pepper tree, winter’s bark, or red horopito. Pseudowintera is so named because early taxonomists recognized the similarity between horopito and the South American Drimys winteri that provided the herbal remedy “winter’s bark.” They are both members of the Winteraceae family, which are mainly found on the land masses that once made up the great southern continent of Gondwana – South America, Australia, New Zealand and New Guinea. The reproductive parts of the Winteraceae family are primitive, reflecting their origin among the first flowering plants. In New Zealand, horopito appears in the fossil record for more than 65 million years.2
Horopito is particularly unusual in that its flowers come directly off the older stems rather than from among the leaves. It’s not surprising that New Zealand has such unique flora and fauna. Situated at the bottom of the South Pacific, plants were able to evolve in isolation from other landmasses in a climate ranging from subtropical to glacial.
Historical and Traditional Use
The Maori gave the name “horopito” to all three species of Pseudowintera they found in New Zealand, and this sometimes causes confusion. However, it’s only the very hot-tasting Pseudowintera colorata that possesses the extraordinary antifungal properties described in this article.
Maori traditionally used horopito for many complaints, several of which bear some relation to recent scientific discoveries about the plant’s properties. As far back as 1848, horopito is documented in the treatment of skin diseases such as ringworm, or for venereal diseases. “Leaves bruised and steeped in water; a remedy for the paipai, or skin complaint. The leaves and tender branches of this shrub are bruised and steeped in water, and the lotion used for ringworm; or the bruised leaves are used as a poultice for chaffing of the skin, or to heal wounds, bruises or cuts.”1 The leaves of horopito were steeped in water to extract the juice and this decoction was used in the treatment of what we now understand as oral thrush.
When compared to other natural antifungal compounds such as sodium caprylate, pau d’arco or grape seed extract, milled horopito leaf produces a far lower minimum inhibitory concentration (MIC).
Early European settlers to New Zealand also used horopito for medicinal purposes. For internal use, leaves were either chewed or prepared as a tea. “The leaves and bark are aromatic and pungent; the former are occasionally used by settlers suffering from diarrhoeic complaints.” A decoction of the leaves was taken for stomachache and was known as “Maori Painkiller” and “Bushman’s Painkiller.”1
There are accounts of the bark being used in the 19th century as a substitute for quinine: “The stimulating tonic and astringent properties of which are little inferior to winter’s bark.” A French nun, Mother Aubert, went to live among the Maori at the end of the 19th century, and the native plant remedies she later created became commercially available and widely used throughout the colony of New Zealand. Horopito was one of the two ingredients in her patent medicine, Karana.
The main biologically active chemical constituent of horopito is the sesquiterpene dialdehyde polygodial.4 It’s known that polygodial is a component of the “hot taste” in peppery spices common in traditional Japanese cuisine.5 Polygodial has been shown to exhibit fungicidal activity against yeasts and filamentous fungi.6 9-Deoxymuxigadial (also a sesquiterpene dialdehyde) also might have pharmacological activity. Other constituents include essential oils such as pinenes, limones, humulene and eugenol, and the flavonoids quercetin, luteolin and proanthocyanidins.7
In 1982, a group from Canterbury University in New Zealand reported it had isolated a substance called polygodial in horopito leaves. 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 horopito. The team found it was very effective at inhibiting Candida. Comparison with the drug amphotericin B (which commonly is used to treat systemic mycoses) found that the horopito-derived polygodial gave larger zones of inhibition. Polygodial also suppressed Candida colony growth from day one, while amphotericin B required three to four days of incubation.3
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 the filamentous fungi Trichophyton mentagraphytes, Trichophyton ruburum and Pencillium marneffe.8 The antifungal activity of polygodial generally was not reduced by several susceptibility-testing conditions such as medium type, incubation temperature, inoculum size and medium pH. However, polygodial’s antifungal activity was strongly increased in acidic conditions. Fungal environments in the human host, such as the mouth, vagina and skin, often are acidic, and their colonization usually creates a microenvironment with even lower pH. Under these circumstances, polygodial can be expected to act as an effective antifungal agent.
Studies conducted by the Cawthron Institute in Nelson, New Zealand, show that dried, milled horopito leaf is effective at killing Candida albicans in an in vitro environment. When compared to other natural antifungal compounds, such as sodium caprylate, pau d’arco or grape seed extract, milled horopito leaf produces a far lower minimum inhibitory concentration (MIC).
MICs are defined as the lowest concentration of an antimicrobial that will inhibit the visible growth of a microorganism after overnight incubation. MICs are used by diagnostic laboratories mainly to confirm resistance, but most often as a research tool to determine the in vitro activity of new antimicrobials, and data from such studies have been used to determine MIC breakpoints.
Many New Zealand native plants exhibit regional variations in genetic makeup and, consequently, biological activity. In order to determine the level of any variation across horopito populations, the private research company Forest Herbs Research and the New Zealand government-owned Industrial Research Limited joined forces to conduct the first comprehensive study of all the major populations of horopito. This research demonstrated a fivefold variation between the most active and the least active plant populations. The most active horopito populations evolved in an isolated forest that, fortunately, survived burning and clearing by the early settlers to New Zealand. Seedlings from this area form the basis of the sustainable horopito plantation that supplies current commercial demand.
Polygodial is not mutagenic, as determined by three variants of the Ames salmonella test10 and further confirmed by the mammal-based V79/HGPRT method.10 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 that have antifungal activity.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 anti-tumor activity against Ehrlich ascites tumor cells and lyphocytic leukemia mouse cells. No mutagenic activity was observed with polygodial or epipolygodial fungi.
Anke and Sterner found that polygodial exhibited antifungal, antibacterial and cytotoxic activity.9 No mutagenicity was observed. Toxicology studies have established that the highest non-lethal dose to rats of capsules containing 50 percent powdered horopito and 50 percent powdered Pimpinella anisum (anise seed) is approximately 2 g/kg body weight. At 2 g/kg dosing, the rats maintained satisfactory body-weight gains, and macroscopic examination of the abdominal and thoracic cavities revealed no abnormalities.12
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 60 minutes.13 Polygodial produces amounts of potassium leakage from yeast cells, similar to those produced by amphotericin B and miconazole.14
Clinical Use and Research
A relatively unknown medicinal herb outside of its native New Zealand, horopito has been used for a number of years as a natural product for the management of issues relating to Candida (yeast) and fungal problems.
In 1992, an open study conducted by New Zealand naturopaths examined the therapeutic effect of capsules containing milled horopito leaf and milled anise seed in patients diagnosed with chronic intestinal candidiasis. This study demonstrated a symptom improvement rate in 76 percent of cases.15
In 1997, the Pavlodar City Centre for Clinical Immunology and Reproduction compared 22 patients taking capsules containing milled horopito leaf and milled anise seed with 10 patients administered fluconazole (Diflucan, Pfizer). All 32 patients were diagnosed as having chronic, recurring intestinal candidiasis. A significant improvement was seen in 100 percent (n=10) of the fluconazole group at seven days and in 90 percent (n=20) of the Kolorex group at 14 days.16
A reliable in vivo model of candidiasis recently demonstrated that an anethole/polygodial compound can indeed exert a significant protective effect against C. albicans gut colonization and dissemination.17
In addition, in vitro studies have shown that milled horopito has a very good profile of antifungal activity in terms of effectiveness and spectrum of action, while being devoid of any significant toxicity. Given the widespread environmental, nutritional and iatrogenic situations at risk of fungal infections, either de novo or as a virulent-induced gut commensal abnormality, such compound might be amenable to clinical practice application and possibly long-term regimens.18 Moreover, this natural product is also expected to be a promising compound for the development of therapeutic regimens, acting through a synergistic effect.
Although there is no evidence of teratogenicity, as a precaution, horopito is not recommended during pregnancy or lactation. Horopito works rapidly against C. 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 characterized by a headache and a nauseous feeling, both of which usually are mild and transient.
Horopito has been available commercially in the United States since 1992. Currently, it is available in a number of forms as an encapsulated supplement for intestinal candidiasis; as an herbal tea for mouth and throat problems; and as a range of topical creams for Candida and fungal problems.
Despite continuing advances in antifungal and anti-Candida treatment, there is increasing demand for natural alternatives that are effective, safe and convenient. Expect to hear a lot more about products derived from horopito, the ancient herb from mountainous islands deep in the South Pacific.
- Riley M. Maori Healing and Herbal: New Zealand Ethnobotanical Sourcebook. Paraparaumu, New Zealand: Viking Sevenseas, 1994.
- Webb C, Johnson P, Sykes B. Flowering Plants of New Zealand. Christchurch, New Zealand: DSIR Botany, 1990; p. 104.
- Pomare M. Report Appendix Journal. Wellington, New Zealand: House of Representatives, 1903, H 31:73.
- McCallion RF, Cole AL, Walker JR, Blunt JW, Munro MH. Antibiotic substances from New Zealand plants, II: polygodial, an anti-Candida agent from Pseudowintera colorata. Planta Medica, 1982;44:134-38.
- Kubo I, Ganjian L. Insect antifeedant terpenes, hot-tasting to humans. Experientia, 1981;37(10):1063-4.
- Kubo I, Taniguchi M. Polygodial, an antifungal potentiator. Journal of Natural Products, 1988;51(1):22-29.
- Larsen L. “A Literature Survey of the Constituents of Pseudowintera colorata.” Dunedin, New Zealand: Crop and Food Research, Ltd., 2001.
- Lee SH, Lee JR, Lunde C, Kubo I. In vitro antifungal susceptibilities of Candida albicans and other fungal pathogens to polygodial, a sesquiterpene dialdehyde. Planta Medica, 1999;65(3):204-208.
- Anke H, Sterner O. Comparison of the antimicrobial and cytotoxic activities of twenty unsaturated sesquiterpene dialdehydes from plants and mushrooms. Planta Medica, 1991;57(4):344-346.
- Morales P, Andersson M, Lewan L, Sterner O. Structure-activity relationships for unsaturated dialdehydes. 6. The mutagenic activity of 11 compounds in the V79/HGPRT assay. Mutational Research, 1992;268(2):315-321.
- Forsby A, Andersson M, Lewan L, Sterner O. The cytotoxicity of 22 sesquiterpenoid unsaturated dialdehydes, as determined by the neutral red absorption assay and by protein determination. Toxicology In Vitro, 1991;5(1):9-14.
- Acute toxicology study. Data on file. Nelson, New Zealand: Forest Herbs Research Limited.
- Taniguchi M, Yano Y, Tada E, Ikenishi K, Oi S, Haraguchi H, et al. Mode of action of polygodial, an antifungal sesquiterpene dialdehyde. Agricultural and Biological Chemistry, 1988;52(6):1409-14.
- Yano Y, Taniguchi M, Tanaka T, Oi S, Kubo I. Protective effects of Ca2+ on cell membrane damage by polygodial in Saccharomyces cerevisiae. Agricultural and Biological Chemistry, 1991;55(2):603-4.
- New Zealand naturopath study. Data on file. Nelson New Zealand: Forest Herbs Research Limited.
- Ogorodnikova O, Valivach M. Data on file. Pavlodar City, Kazakhstan: Pavlodar City Centre for Clinical Immunology and Reproduction.
- Naito Y, Wu CC, Seal MG, et al. Protective effect of a polygodial/anethole-containing natural product against Candida albicans gastrointestinal colonization and dissemination. International Medical Journal, 2001;8(1):3-9.
- Metugriachuk Y, Kuroi O, Pavasuthipaisit K, Tsuchiya J, Minelli E, Okura R, et al. In view of an optimal gut antifungal therapeutic strategy: an in vitro susceptibility and toxicity study testing a novel phyto-compound. Chinese Journal of Digestive Diseases, 2005;6(2):98-103.
|Campbell Berry-Kilgour is a graduate of the University of Aberdeen in Scotland with a BSc (Hons.) in Pharmacology. For the past six years, he has been working with Forest Herbs Research of New Zealand, focusing on potential applications of the New Zealand native herb Pseudowintera colorata, or horopito against Candida albicans. He is a dynamic speaker who is passionate about his research into natural medicine, particularly in relation to the use of natural products and digestive well-being.