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From the Zulu medicine to the European phytomedicine Umckaloabo[R].

Abstract

Among the Zulus of South Africa a crude root drug of initially unknown botanical origin was used for the treatment of pulmonary diseases and tuberculosis (TB). An English TB patient called "Stevens" heard about it and travelled to South Africa where, according to his account, he was cured by taking an extract of the crude drug. It was extremely difficult to establish the imported crude herbal drug as a "new TB medicine", as neither the plant from which the drug originated was identified nor were the constituents and pharmacological effects known at that time.

It was only after a professional search and initial chemical and taxonomic investigations enabled the identity of the plant to be determined that the requirements were met for comprehensive chemical, pharmacological and clinical research into the crude drug.

The following report traces the long and difficult path of this "mystery drug" from the Zululand of South Africa to the laboratories of Europe.

[c] 2006 Elsevier GmbH. All rights reserved.

Keywords: Origin of the root botany; Taxonomy; Pelargonium sidoides; Pelargonium reniforme

Introduction

The Englishman Charles Henry Stevens discovered the crude herbal drug. After becoming ill with tuberculosis (TB) of the lungs he went to South Africa in 1897 on the advice of his doctor in order to cure the disease in the clear mountain air.

In what is today Lesotho, Stevens got to know Kagaitse, a Zulu medicine man, who gave him a boiled root preparation to drink twice a day. After 3 months of treatment, Stevens considered himself cured. Convinced of the success of the cure, he brought the crude drug to England in order to introduce it into TB therapy. At that time there was no effective medicine against TB, which was a widespread disease, particularly among the poor. The disease was also very common among the Zulus of South Africa.

In 1909, the British Medical Association published a book with the title "Secret Remedies--what they cost and what they contain". In it, Stevens' "consumption cure" was branded as quackery. As the powder rather by chance showed a microscopic similarity to the tannin drugs such as Krameria triandra (Rhatany root) and Pterocarpus marsupium (Black Kino Gum) known at the time, he was also accused of being a swindler and sentenced in a court case to pay 2000 pounds legal costs. Stevens' attempted action for libel against the British Medical Association was dismissed (Meyer, 1997).

Stevens tried to establish his "Stevens' cure" all his life without success, as neither the botanical origin of the plant source was known nor could chemical constituents or pharmacological findings be presented. Some time later, the former missionary Dr. A. Sechehaye, who was working at the University of Geneva (Switzerland), gathered information about the mysterious "wonder drug". He began to treat TB patients with Stevens' cure. During 9 years, he documented the treatment of around 800 patients. In 1930, he first published the results of treatment in a comprehensive work, together with numerous experiments and case studies (Sechehaye 1933, 1937).

Sechehaye came to the conclusion that in many TB cases, with the exception of acute, malignant or complicated cases, clear healing effects could be seen.

The mode of action was thought to be more a "neutralisation or destruction of the tuberculosis toxins" rather than a direct bactericidal effect. This mode of action, described in detail by Bojanowski (1937), may now be considered as "immune modulation". This is an indirect immunological mode of action and recent investigations suggest that the preparations acted in this way.

First phytochemical investigations

As the botanical origin of the crude drug remained unclear for a long time, our institute (1) was commissioned by the German company ISO-Arzneimittel to find information about the taxonomic family and species to which the crude drug belongs using microscopic and chemical investigations. The work carried out for a thesis (Bladt 1974) showed evidence of a high tannin content, which had been described previously, and resulted in the isolation and identification of ubiquitous sterines and 12 amino acids (e.g., histidine and glutamic acid), ethanolamine and tyramine, phenolcarboxylic acid derivatives (e.g., caffeic acid, chlorogenic acid, para-coumaric acid), an anthocyanidine, gallocatechine and a remarkably high concentration of different coumarin derivatives (seven in total), of which Umckalin, the 5, 6-dimethoxy-7-hydroxycoumarin, and its 7-O-glucoside were detected for the first time in the plant kingdom (Wagner et al. 1974; Bladt and Wagner 1975). Besides the known root pieces, the pharmacognostic and microscopic investigations of the powder showed no striking cell components, apart from a high content of large calcium oxalate crystals, which could provide evidence of a typical genus or species characteristics of a particular plant family or species.

Despite chromatographic comparisons with different South African crude drugs containing tannins and coumarins, no identity or active substance similarity could be found.

The breakthrough came after a study visit by Dr. S. Bladt to South Africa and the investigation of a root sample in Kew Botanical Gardens in England. The crude herbal drug must have originated from a Pelargonium species i.e. Pelargonium reniforme or Pelargonium sidoides, according to current nomenclature.

In addition to a further 280 known species, both species belong to the genus Pelargonium, tribe Geranieae, section Cortusina of the Geraniaceae family (Dreyer et al. 1992).

One hundred years lie between the first description of the genus Pelargonium and its sub-division into different species to today's taxonomically recognised species names. While Harvey and Sonder (1859) still considered the species P. sidoides as a natural variety of P. reniforme Curt. and described it as P. reniforme Curt. var. sidaefolium, Knuth (1912) raised this sort to the rank of an independent species with the name Pelargonium sidaefolium (Thunb). R. Knuth. In the latest revision by Wettstein (1935), this species designation was changed back to the species name P. sidoides DC, which is recognised internationally today, in favour of an earlier first author (Harvey and Sonder 1859). A current systematic revision is given in the book by van der Walt and Vorster from 1988 (van der Walt and Vorster 1988).

The morphological differences of the above-ground parts of the two plants, summarised by van der Walt and Vorster (1988) and modified in a table by Kolodziej et al. (1995) refer to the colour of the flowers, the shape of the leaves and the pollen colour as easily recognisable characteristics. P. sidoides is characterised by dark red to black flowers, heart-shaped leaves and yellow-green pollen (Fig. 1, see also cover page of this supplement). In contrast, the flowers of P. reniforme are magenta red with black markings, the leaves are more kidney-shaped than heart-shaped and the pollen whitish-green (Fig. 1).

Differentiation of the roots is more difficult. In P. sidoides the root wood is dark brown, while in P. reniforme it is markedly lighter or appears yellow (Kolodziej et al. 1995). There are also distinctive histochemical features for the trained pharmacognosist, but preference must be given to the certainty of thin-layer chromatographic fingerprint analysis.

[FIGURE 1 OMITTED]

[FIGURE 2 OMITTED]

It is interesting that the geographical range of distribution also differs. The range of the small bush extends from Lesotho via the south-western Transvaal and Orange Free State as far as the north-eastern Cape (Fig. 2). P. reniforme, in contrast, has a much wider range of distribution, which extends north-westwards well into the South African interior (Fig. 2). As Pelargonium species have been frequently crossbred during many years of hybridisation experiments, P. sidoides is now cultivated.

References

Bladt, S., 1974. Zur Chemie der Inhaltsstoffe der Pelargonium reniforme Curt.-Wurzel (Umckaloabo). Dissertation, Fakultat Chemie/Pharmazie, Maximilian Universitat Munchen, Ludwig, Juli 1974.

Bladt, S., Wagner, H., 1975. Cumarine aus sudafrikanischen Pelargonium-Arten. Phytochemistry 14, 2061-2064.

Dreyer, L.L., Albers, F., Van der Walt, J.J.A., Marschewski, D.E., 1992. Subdivision of Pelargonium sect. Cortusina (Geraniaceae). Plant Systemat. Evol. 183, 83-97.

Harvey, W.H., Sonder, O.W., 1859. Flora Capensis: Systematic Description of the Plants of Cape Colony, Caffraria and Port Natal, vol. 1. Hodges Smith and Co, Duplin, 300-301.

Knuth, R., 1912. Das Pflanzenreich. W. Engelmann Verlag, Leipzig, pp. IV 129 and 447.

Kolodziej, H., Kayer, O., Gutmann, M., 1995. Arzneilich verwendete Pelargonien aus Sudafrika, Untersuchungen an Pelargonium sidoides and P. reniforme. Dtsch. Apoth. Ztg. 135 (10), 853-864.

Meyer, E.A., 1997. Naturheilpraxis Fachforum 04, pp. 560-563.

Sechehaye, A., 1933. Die Behandlung der organischen und chirurgischen Tuberkulose durch Umckaloabo. Selbstverlag, Freiburg.

Sechehaye, A., 1937. Umcka, son role dans le traitement de la tuberculose, Cavadin, 1954. v. Bojanowski. W. Fortschr. d. Medizin 11, 1.

Van der Walt, J.J.A., Vorster, P.J., 1988. Pelargonium of Southern Africa, vol. 3. National Botanic Gardens, Kirstenbosch.

Wagner, H., Bladt, S., Abraham, D.D., Lotter, H., 1974. Neue Cumarine aus Pelargonium reniforme Curt.-Wurzel. Tetrahedron Lett. 43, 3807-3808.

Sabine Bladt, Hildebert Wagner*

Department of Pharmacy, University of Munich, Butenandtstrasse 5-13, 81377 Munich, Germany

*Corresponding author.

E-mail address: H.Wagner@cup.uni-muenchen.de (H. Wagner).

(1) At that time the Institute for Pharmaceutical Pharmacology, University of Munich.
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Title Annotation:Pelargonium
Author:Bladt, Sabine; Wagner, Hildebert
Publication:Phytomedicine: International Journal of Phytotherapy & Phytopharmacology
Geographic Code:6SOUT
Date:Feb 1, 2007
Words:1492
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