The strength of Gunnera perpensa’s “evidence of traditional use”

Abstract

In South Africa, and in several countries in the world, several traditional medicines are used often, although their pharmacology is not yet clear and the extent, if any, of their benefit is not scientifically documented. The Australian’s “Therapeutic Goods Administration” guidelines for the use of traditional medicines, non-registerable medicines, and other listed medicines, is used in this paper to assess the strength of the traditional-use evidence for the utilisation of Gunnera perpensa.

Keywords:

• evidence-based medicine
• Gunnera perpensa
• Therapeutic Goods Administration
• traditional medicines

In the allopathic medicine, indications or therapeutic uses and claims are based on scientific evidence. The evidence-based medicine (EBM) or practice, as was championed by Sackett et al.^1,2 provided a model for “a judicious use of current best evidence in making decisions about the care of individual patients”. One of the objectives of EBM is to afford critical methodology for the usage of an ever-growing body of knowledge and to apply the available best evidence in answering clinical and healthcare related questions. This high volume of knowledge, the so called “information overload”, necessitated adoption of pyramidal or hierarchical levels, which placed “Systematic Reviews” (SR) or “meta analyses” of “Randomised Controlled Trials” (RCTs) at the top and observational studies and opinions of experts are at the bottom. Cook et al.³ outlined the following levels of evidence, to be used in grading evidence and in appraisal of research papers:

• Level 1: Systematic Review of Randomised

  • Controlled Trials (RCTs)

  • RCTs with Narrow Confidence Interval

• Level 2: Systematic Review Cohort Studies

• Cohort Study/Low Quality RCT

  • Outcomes Research

  • Systematic Review of Case-Controlled Studies

• Level 3: Case-Controlled Study

• Level 4: Case Series, Poor Cohort Case Controlled

• Level 5: Expert Opinion

However, due to many reasons, which are not the object of this paper, it is still difficult, especially in South Africa, to apply rigorous principles of EBM or “evidenced-based healthcare” (EBHC) to assess the claims made by those who use or sell African traditional and/or complementary medicines. As part of recognising the value of traditional medicines (TMs) and for the fact that TMs are used by many people all over the world, the Australian’s “Therapeutic Goods Administration” (TGA) has adopted guidelines to be used for traditional medicines, non-registerable medicines, and other listed medicines.⁴

The TGA defines the “evidence of traditional-use” or “use in traditional practice” as availability of “documentary evidence that a substance has been used over three or more generations of recorded use for a specific health-related or medical purpose”, and when “traditional-use has been recorded as an oral rather than written history, the evidence of such should be obtained from the appropriate practitioner or indigenous group(s), who maintain such a history”.⁴ Thus, various claims could be categorised into “two levels”.

Medium Level: Evidence required to support claims include at least TWO of the following:

• medicine is contained in the TGA approved Pharmacopoeia or

• it has TGA approved monograph;

• there are at least THREE independent written histories of use in the classical or traditional medical literature; or

• the medicine is available through any country’s government public dispensaries for the indication claimed.

General Level: Evidence required to support the claims include at least ONE of the aforementioned supporting documents/evidence.

The TGA approved Pharmacopoeia include the Australian Pharmacopoeia, the Aboriginal Pharmacopoeia, The British Pharmacopoeia (BP), the Extra Pharmacopoeia (Martindale), the United State Pharmacopoeia, the European Pharmacopoeia, as well as the World Health Organisation’s World Pharmacopoeia.⁵ These world acclaimed and TGA approved pharmacopoeias, and the African Pharmacopoeia, which was commissioned by the then Organisation of African Unity in 1984, document very few indigenous South African plants. As a result, the South African Traditional Medicines Research Group (SATMeRG) was established in 1997 to create a truly South Africa pharmacopoeia of indigenous plants – referred to as the “UWC Pharmacopoeia Monograph Project”, and the digital version of the African Traditional Medicines is under construction.⁶ Therefore, in the absence of a legal framework, in South Africa, to assist family practitioners and many other healthcare providers, whose patients regularly use traditional medicines, the TGA’s model might be helpful in assessing the strength of evidence often attributed to many preparations which contain extracts of indigenous South African plants.

Gunnera perpensa, also known as River Pumpkin, ughobo or uklenza (isiZulu), ipuzi lomlambo (isiXhosa), and qobo (Sesotho), grows well along the river banks in many parts of South Africa.⁶ African traditional healers use it for the treatment of many maternal/foetal ailments, and other conditions such as painful joints, cancerous sores, rheumatism, and psoriasis.⁷

The benefits of traditional use of various decoctions containing G. perpensa extracts, in pregnancy, have been reported in scientific literature.⁸ However, it was Kaido et al.⁹ who confirmed that G. perpensa extracts have oxytocic-like effects on an isolated rat uterus. Khan et al.¹⁰ identified Z-venusol, a phenylpropanoid glycoside as the major constituent of G. perpensa, which caused “state of spontaneous” uterine muscle contractility. Therefore, a “traditional claim” that G. perpensa extracts are beneficial has credence and can be catogorised into TGA’s “Medium Level”. Furthermore, Brookes et al.’s¹¹ in vitro study has reported that G. perpensa extracts (up to concentrations of 500 μg/ml) were not toxic to monkey vero cells and human fibroblast cells. However, animals or in vivo studies followed by human clinical trials are needed before family practitioners and gynecologists could recommend the use of G. perpensa-containing preparations to ease childbirth and labour pains as opposed to what traditional doctors and many “health shop” keepers are currently doing.

The “traditional-use” of G. perpensa extracts as an effective anti-infective agent has been documented.⁷ However, Lall and Meyer¹² reported that the highest concentration (5.0 mg/ml) of G. perpensa extracts they used was not active against both drug-sensitive and drug-resistant strains of Mycobacterium tuberculosis. The crude extracts of G. perpensa, and 5 μg/ml concentration (which is less toxic to the peripheral blood mononuclear cells) of Z-venusol, one of many active ingredients of G. perpensa, failed to inhibit HIV-1 replication in either chronically or acutely infected cells in vitro.¹³ On the contrary, Drewes et al.¹⁴ found that a 1,4 benzoquinone (isolated from the leaves and stems of G. perpensa) inhibited the in vitro growth of the human pathogens Staphylococcus epidermidis, and Staphylococcus aureus. In the study by Koduru et al.,¹⁵ in which information was collected from herbalists, traditional healers, and rural dwellers, G. perpensa is reported as one of the medicinal plants used for treatment of cancer in the Eastern Cape Province, South Africa. Iwalewa et al.¹⁶ listed G. perpensa among other herbs used in management of joint pain and rheumatism. However, Hutchings et al.⁷ were the only original source that supported this claim. More disappointingly, there are neither in vivo nor in vitro studies that support Hutching et al.’s claim. Therefore, the evidence for traditional-use or for the claims that the extracts or pure compounds extracted from G. perpensa are beneficial in the management of joint pain, rheumatism, infections, and cancer are speculative and require more research. Thus, all these claims fall under the TGA’s “general level”.

In conclusion, one could suggest that “evidence of traditional use” is equivalent to “expert opinion” level, as used in allopathic or western medicine. In this regard, traditional doctors and individuals who have been using traditional medicines for decades provide “opinions”, or their own personal experiences or testimonies of the usefulness of these medicines. However, the disadvantage of an opinion, whether it comes from an expert or from a patient, will, especially in as far as the dominant epistemological demands set by EBM, remain guilty of bias until proven otherwise through an RCT. The landscape for research is still vast, but available evidence of traditional-use should be used as the first step for those who are willing to climb the “pyramid” to place the use of traditional medicines right at the top. It is indeed the responsibility of ALL, including Family Practitioners, who are somehow involved in traditional and complementary medicines, to put ALL claims supported by the “evidence of traditional-use” to the test; in the laboratory (in vitro), in animals (in vivo), and then in human beings (clinical trials). No medicine, traditional or western, should be parachuted to the top of the “pyramid” before rigorous scientific research is done – we ALL have to work hard and take a long walk way up, even if it seems like being in the wilderness for more than 40 years.