The Department of Science and Technology today hosted an indigenous knowledge systems bioprospecting platform as part of the South African programme at the Shanghai World Expo.
A highlight on the agenda was the presentation by Dr Gilbert Matsabisa of the Medical Research Council (MRC), who spoke on the preclinical and safety evaluation of a traditional medicinal product, PHELA, which is a potential immune modulator.
The use of traditional medicines in managing HIV and AIDS is increasing. There are several reasons for this. They include the fact that there is no cure for HIV and AIDS, and there are no simple and satisfactory programmes for managing the pandemic.
On the other hand, because most traditional medicines have been used for decades, they are often assumed to be safe and efficacious. Their concomitant use with prescription drugs has not been well studied. In addition, their efficacy has not been evaluated in controlled clinical trials.
The objectives are to develop both pre-clinical and clinical scientific methodologies for evaluating traditional medicines used in HIV and AIDS management. Researchers are doing this by using a non-human primate model to evaluate the toxicological effects of a traditional medicinal product called PHELA.
Methods used include peer-reviewed and ethical methodologies that have been developed to test the possible toxicity of traditional medicines. The methodology developed is a sub-chronic repeat dose toxicology study using PHELA on vervet monkeys (cercopithecus aethiops).
The safety evaluation of PHELA, using a parallel group, dose escalation and placebo controlled phase one clinical trials, was presented. All the studies received ethical clearance from the MRC ethics committee and the Medicines Control Council.
In vitro and in vivo studies using cytochrome P-450 metabolising enzymes have been developed to evaluate which enzymes are involved in metabolising PHELA. The in vivo models were developed to help predict how these products are metabolised and which enzymes are involved.
The research discovered that most of the products showed no toxicity at dose higher than would be consumed by humans and also that some products exhibited toxicological effects which are mild and reversible on withdrawal of the product. It was clearly shown that the toxicology was dose related. Therefore the results validated the use of this model for testing the toxicology of herbal products.
The phase one controlled clinical trial showed that the toxicity exhibited in vervet monkeys was not reproduced in healthy human participants. The prescribed doses in the latter, however, were not at the same levels. The products showed no liver toxicity and the haematology was not different between the placebo group and the treatment groups.
The herbal extract had no effect on the activity of CYP2D6, CYP3A4, CYP1A2, CYP2B6 and CYP2C9. There was no significant interaction of the herbal products with P450 isoforms CYP2D6, CYP3A4, CYP1A2, CYP2B6 and CYP2C9.
The conclusion drawn was that reliable controlled methodologies had been developed to evaluate preclinical toxicology, using a non-human primate model, and the safety of traditional medicines.
The study also showed how an in vitro system can be used to evaluate the effect of traditional medicines on P450 cytochrome enzymes and how PHELA, as a combination traditional medicine, is metabolised, giving reliable data on which enzymes are involved.
Such data can help predict possible drug-herb interactions and possible toxicities, even before the traditional medicine is given to humans.
Non-human primate toxicology studies are important for predicting the possible toxicity of traditional medicinal products before they are prescribed to humans.
Although in a phase one study of PHELA no harmful side effects could be found, a preclinical study with vervet monkeys, demonstrated toxicity where the animals showed loss of appetite and some mild diarrhoea in a dose-related response.
However, this was due to the very high doses used in vervet monkeys. Such high doses are standard in toxicity testing, and are intended to produce toxicity to explore such things as the effects of overdose and reversibility.
High doses also enable the calculation of indicators such as "No Observed Adverse Effect Level". The toxicity returned to normal when dosing with PHELA was stopped.
The results will also enable us to develop larger controlled clinical methodologies to evaluate the efficacy of traditional medicines in multipurpose centre studies. These methodologies can be the basis for developing policies for the scientific research needed to validate traditional claims for cures and health benefits from traditional medicines, not just for HIV and AIDS but also for other chronic and life threatening disease conditions.
Ms CJ Henley-Smith of the University of Pretoria also gave a presentation on South African plant extracts in combating potentially pathogenic oral micro-organisms.
Dental plaque is a complex bacterial biofilm community and, under certain circumstances, this complex microbial community can cause major dental diseases such as caries and periodontitis.
The quest for natural products, to replace the synthetic products used in the prevention of dental caries and periodontal disease, is becoming increasingly popular.
This study investigated the effects and antimicrobial activity of four plants: barleria albostellata, dichrostachys cinerea, sample three (heteropyxidaceae), and dodonaea viscosa; against actinomyces israelii, prevotella intermedia, streptococcus mutans and Candida albicans.
Four compounds were isolated and are being investigated. Synergistic effects of the selected samples with essential oils as well as a possible formulation for oral care products are currently being analysed.
The South African Department of Science and Technology will host the Seminar on Palaeontology tomorrow, 29 September 2010. Discussions will include australopithecus sediba, which are the two most complete early human ancestor skeletons yet recovered.
South Africa at the Shanghai World Expo: indigenous knowledge systems bioprospecting platform
