Several diseases of modern world can be treated more effectively with a well-chosen herbal-pharmaceutical combination than a single drug as multi-drug concept is based on a longstanding and successful therapeutic experience and awareness. This is because the diseases always undergo a multi-causal etiology (the study of the causes of diseases) and a complex patho-physiology, according to Dr Hildebert Wagner, professor & head of Centre of Pharma Research, University of Munich, Germany.
The herbal drug combinations used by the traditional healers of India and China are the best examples of this concept. Because of the lack of high-tech analysis and methods of molecular biology in olden days this claim of a multi-target therapy from complex plant preparations could not be verified, he said.
Dr Wagner was speaking in the JSS College of Pharmacy Ootty on the subject ‘Herbal Drug Research- Present and Future Prospects’.
The doctor said multi-drug therapy is today used worldwide in the treatment of chronic and deadly diseases like Cancer, AIDS, hypertension, infectious fevers and various forms of rheumatic diseases and the efficiency and therapeutic superiority of drug combinations over single drugs are easily confirmed.
In phytotherapy, he said, the proof of the multi-target concept, based on synergy effects, is more difficult. “However today we are able to prove these synergy effects by using the pharmacological isobol method of professor Berenbaum . This method gives evidence whether the interaction of two natural products or plant extract results only in an additive or a synergistic effect. The latter can amount to a doubling or even greater multiplication of the expected effect. Synergism with over-additive or potentiated effect of two drugs 'a’ and 'b’, that are applied together as a mixture must be larger than it would be expected by the summation of the separate effects,” he said.
Wagner further said, the multi-target effects can be corroborated for various constituents of Hypericum perforatum extract by neuro-chemical in vitro studies with different CNS (central nervous system ) receptors using radioligand binding techniques. It could be shown that pre-synaptic as well as post- synaptic neurons, the hypothalamus and the pituitary gland are involved as targets and all main compounds of Hypericum show affinities to any of the targets described, he said.
In this case, the synergism of Hypericum constituents can be described as an agonistic combination of two independent mechanisms of action, a multitarget and a pharmacokinetic synergistic effect. Since many years a third possibility of synergy effects is known, which occurs when antibiotics are combined with natural products or their genuine extracts that are able to partly or completely suppress bacterial resistance mechanism.
Bacteria gain antibiotic resistance due to three reasons-- modification of active site of the target resulting in a reduction in the efficiency of binding of the drug, direct destruction or modification of the antibiotic by enzymes produced by the microorganism and blocking of a pumping system developed by several bacteria in order to inhibit agents from penetrating into the bacteria .
It is no question that all these pharmacologically evidenced synergy studies have to be verified in controlled clinical trials. In this respect, the best evidences for a synergy effect are studies which are aimed at a chosen indication in comparison with one or several standard drugs (synthetic drug) if no ethical reasons exclude it. The main criterion is a significant therapeutic equivalence and side effects equal or lesser to those of the reference drug.
Among 200 placebo-controlled randomized clinical studies carried out with standardized plant extracts in the last 10 to 15 years at least 50 per cent have been performed in comparison with several synthetic standard substances. The results have shown surprisingly that most of them showed a significant therapeutic equivalence, said Dr Wagner.