The Pharmaceutical Journal
Vol 275 (Supplement) F32-F33
October 2005

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FIP Congress 2005

Natural product research in Egypt and the role of phytopharmaceuticals

Sigward von Laue, of the Society for Cultural Development, Egypt, in examining the scope for natural products development, asked: “Why are phytopharmaceuticals important for Egypt?” He instanced the growing importance of holistic approaches generally and the increasing popularity — and potential cost saving — of traditional, alternative and complementary medicines. There is an overwhelming reliance on these in underdeveloped countries: in Africa over 80 per cent rely on traditional medicines. He contrasted the traditional with individual allopathic drugs, which might be highly specific but also brought a variety of side effects. Such definably pure synthetic substances have great value in life-threatening situations but, he claimed, may be of limited use in many classic chronic illnesses. In the US, personalised “one patient, one care” medicines were encouraged to maximise a unique therapeutic benefit for a genetically variable population. Europe hopes to rely on nanotechnology to “keep at the forefront”. Both approaches were expensive.

Historically, in the community natural medicines treated the symptoms not the cause. Yet, despite recent advances, said Dr von Laue, relatively few data are available for the majority of remedies. He variously blamed the complex nature of plant-derived medicines, the challenges encountered in production and standardisation and control, and limited funds available. There were also problems arising from intellectual property rights. However, in the US, public funding for traditional medicines research had increased 25-fold since 1995 and, in China, $1,700m had been allocated. The World Health Organization has recommended the integration of these remedies in all national health care strategies, predicting an enormous growth potential in the market.

Synergism of complex drugs has been explored; he mentioned the various effects associated with the three main ingredients of hypericum — but their multicomponent constitution challenged inclusion in human trials. He advocated the development of novel treatments, using multicomponent drugs and complex plant extract combinations, with documented synergistic actions of their various active ingredients. Phytopharmaceuticals provide a great opportunity for countries like Egypt. These drugs must successfully compete through effective, sustainable solutions for many current medical challenges, including hepatitis and parasitic infection, and lifestyle-induced diseases such as diabetes and hypertension, and many forms of cancer.

Red Sea products

Diaa Youssef, of the Suez Canal University, Egypt, described his studies on some molecules of pharmaceutical interest derived from Red Sea marine organisms. He claimed that half of the world’s medicines were derived from traditional medicines and that 57 per cent of the 150 most-prescribed drugs in the US originated from living organisms. He recalled the major pharmaceutical discoveries that had resulted from investigation of natural products such as penicillin and many other later mould metabolites, a great diversity of alkaloids (including morphine, quinine and reserpine) and, more recently, yew extract (including taxol). Plant extracts had been employed for many millennia and had been extensively studied in the past 60 years.

Dr Youssef distinguished terrestrial from marine sources, noting that “the oceans covered some 70 per cent of the earth’s surface and account for 90 per cent of the biosphere”. Marine sources supplied many novel compounds, including some of the most powerful toxins known. Their marine hosts had grown in a radical environment of salinity, pressure, light and uniform temperature, and had generated a diverse series of molecules quite distinct from terrestrial origin, perhaps as a defence mechanism against various predators. Moreover, to counteract the enormous aqueous dilution, such molecules tended to be more potent than terrestrial products.

He described the production by marine macro-organisms, such as sponges, of highly evolved chemicals which attract food, block growth of intruding neighbours or repel predators. These marine invertebrates may be heavily colonised by prokaryotic micro-organisms which, for their part, may be rich sources of, for instance, significantly cytotoxic compounds. From Japan, Australasia, the US and the UK some 14,000 new compounds from marine organisms have been reported in the past 25 years.

Dr Youssef then illustrated the variety of Red Sea sources with pictures of parent organisms associated with the molecular structures of their principal derived substances. Among the research interests of the Suez Canal University is the discovery of novel series from Red Sea organisms and the bio-catalysis and semi-synthesis of useful derivatives. He explained how bioassays guided fractionation and separation of new substances, potentially cytotoxic, antiflammatory or antimicrobial. They especially sought targetable drugs active against a variety of cancers: six million people had died from all cancers worldwide — one third in Europe — while in Egypt mortality was higher than in the US. Another global target was tuberculosis, which affects one third of the world and results in three million deaths annually.

The SEKEM initiative

An integrative approach to the development of phytopharmaceuticals in Egypt was provided by Nebal Tambouly, of Cairo University, Egypt. She emphasised the more distant relationship of modern phytopharmaceuticals from the classic tonics and potions of traditional healers: scientific evaluation today necessitated the reliable characterisation and standardisation of plant extracts and strict quality control procedures.

Professor Tambouly described the broad economic initiative of SEKEM (an Egyptian holding company) embracing a phytopharmaceutical research academy, vocational training in six areas, ecological and agricultural adult education, and a medical centre supplying day-care for 30,000 people. Thereby they combine sustainable social, cultural and economic activities to promote comprehensive learning and development, as well as healing and helping the environment.

Egypt has a range of climatic zones with a largely unexplored spread of biodiversity. SEKEM’s “systematic dynamic approach through biodynamic agriculture”, integrative education, scientific research and modern production methods, provided a basis for development and production of high quality phytopharmaceuticals. This was inspired by five millennia of traditional remedy knowledge and built on the availability of high quality herbal raw materials. In Egypt, phytopharmaceutical remedies are subject to the same controls as allopathic medicines, and are increasingly used to treat mild, or even moderately severe, chronic conditions, as well as supplying adjuvants for use with other therapy.

The SEKEM Academy has established a strong scientific basis through integration of botanical, biochemical, pharmaceutical and medical research, while encouraging biodiversity, conservation and exploration, and ecologically sustainable harvesting. Professor Tambouly referred to programmes of plant breeding and study of growth conditions, optimisation of extraction conditions, standardisation and packaging, storage and most importantly, she suggested, the verification of safety and clinical efficacy. During the past five years the SEKEM Academy has concentrated on two botanicals — one with a type-II anti-diabetic role and one for treating hypertension. Bioactivity, pharmacodynamics, oral absorption and interactions have been evaluated in vitro and in animal models and then in vivo with human subjects. Phase I clinical trials are planned.

Professor Tambouly concluded that the vision of the SEKEM Academy was to develop effective phytopharmaceuticals, free from side effects, to enable Egypt successfully “to compete internationally in this rapidly growing market”. They are in the process of establishing a formal university that will encourage analytical thinking, promote responsible business practice and focus on the economic, cultural and social empowerment of Egyptian people.

Plants from Upper Egypt

Daoud Bishay, of Assiut University, Egypt, discussed the rich variety of medicinal plants of Egypt. He drew attention to the key situation of his country, lying between Asia and Africa, and exhibiting flora indicative of each continent. Thus, the Mediterranean coast effectively continued the plants of Algeria and Tunisia, whereas the south of Egypt is similar to Red Sea hills of the northern Sudan. The Sinai Peninsula is different again, he said. Its flora are mostly related to those of Iran, while the Egyptian desert plants are typical of the great desert belt that stretches from the Sahara to India.

Professor Bishay indicated that Egyptian scientific and health-related literature has for a long time reflected interest in botanical, chemical and pharmacological properties of plants in the region. Publications have ranged from reports of parts of plants causing toxicity, to the important sources of therapeutic agents and other useful adjuvants such as essential oils and waxes. In his own university in Upper Egypt, there was a long history of plant studies, especially those from southern Egypt and the Red Sea coast.

In response to a question, Professor Bishay explained that his team investigated the chemistry and botany of plant sources but did not necessarily confirm their traditional therapeutic indication.

Value of beeswax

Mohamed Khayyal, of Cairo University, Egypt, reviewed 10 years of pharmacological studies on the anti-inflammatory and anti-bacterial properties of a 13 per cent standardised aqueous extract of propolis and its potential use as an adjuvant in bronchial asthma. (He explained that propolis is the defensive wax with which bees coat the front of their hive.) Chronic and acute models of anti-inflammatory activity had been demonstrated and the university was working with European industry to determine commercial potential of the extract.

Three areas of anti-inflammatory activity were explored. His team had shown that propolis extract significantly inhibited oedema in rats’ paws, with a dose-dependent anti-inflammatory action, and in isolated sensitised guinea pig lung the extract significantly reduced release of leukotrienes and prostaglandin E2.

Secondly, they had found that oral administration of the extract had both symptomatic and prophylactic value in alleviating the anti-inflammatory effects of ionising radiation. Either before or after exposure of rats to caesium-137 radiation, there was a dose-dependent reduction in plasma malondialdehyde and of acid phosphatase in serum.

In a third opportunity, the potent anti-oxidant properties of the extract had prompted testing against carbon tetrachloride induced hepatotoxicity in the rat both in vitro and in vivo: it was shown to guard against lipid peroxidation, increase hepatocyte viability and maintain intra-cellular levels of reduced glutathione.

Professor Khayyal recounted some clinical trials in collaboration with a Dutch company. In a limited placebo-controlled initial trial, human volunteers suffering from mild to moderate asthma responded well to propolis extract as an adjuvant to theophylline and salbutamol therapy. This outcome prompted a larger, double-blind, trial on 46 military patients taking either the extract or a placebo, in the form of a milk drink as an adjuvant to oral theophylline for two months. Tests of pulmonary function, immunological parameters and inflammatory mediator levels immediately before, and at one and two months within the treatment had revealed greatly reduced nocturnal attacks, although pulmonary function was markedly improved. There was significant reduction in indicator substances, including PGE2, with corresponding increase in interleukin-10, confirming a correlation between test parameters and clinical findings. They had concluded that propolis aqueous extract was well tolerated and an effective adjuvant in treatment of asthmatic patients.