Medicinal mushrooms on the road

BioThailand 2003 shows the future

By Leo Van Griensven

The international conference and exhibition “BioThailand 2003, Technology for Life”,was held on 17 – 20 July, 2003 at Patthaya, Thailand’s internationally known beach resort, 150 kilometres south of Bangkok.

The conference was devoted to medicinal mushrooms and the related field of biodiversity and bioactive compounds, both of central interest in South East Asia. Rapidly developing Thailand with its vast resources of wild mushrooms and plants and long-standing tradition of the use of medicinal herbs, plans to become a major player in this field. Under the present government large sums of money have been reserved for investment in new universities and brain parks.

Her Royal Highness Princess Sininthon delivered the opening speech for this second Thai biotech meeting, expressing the value of the new technologies, i.e. genomics, proteomics, and nano- and information technology for the mainly agricultural country Thailand. 500 scientists and representatives of over 30 biotech companies demonstrating their materials and knowledge during the meeting also participated in the opening ceremony.

Professors Solomon Wasser of HaifaUniversity and Lene Lange of the Danish biotech company Novozyme gave opening lectures.

Wasser presented a very optimistic image of the power of medicinal mushrooms and the resulting market position that would undoubtedly be created for all the new biopharmaceuticals being developed following earlier success in the treatment of various diseases by lentinan, krestin and schizophyllan. He specifically mentioned the use of glucan preps from Agaricus brasiliensis (formerly called Agaricus blazei), Phellinus linteus, Grifola frondosa (Maitake) and especially Tremella mesenterica, the latter being a major source of glucans due to its extremely rapid growth in liquid culture. Tremella was pictured as the panacea for treatment of major diseases such as cancer and diabetes, both strongly on the increase globally.

Lene Lange described a new and as yet unpublished technique for discovering new proteins using the signals that living cells apply for generating proteins that have to function outside the cell itself. She has called this Transposon Assisted Trapping Technique (TAST). It is soon to become a new instrument for molecular biologists and gene hunters.

The remainder of the day was devoted to bio prospecting arrangements, and to setting up a biological resource information infrastructure in South East Asia. Both of which are required to prevent other parties running away with the region's natural resources.

Friday July 18 started with a plenary lecture by myself on the background of the rapid growth of the Dutch mushroom industry in the past. I explained it as mostly caused by good cooperation among growers, a helping role of the ministry of agriculture, new laws against environmental pollution requiring new techniques and a demanding market, requiring quality products.

The large scale of mushroom production in The Netherlands and its technical quality are always surprising in countries where mushrooms are grown in numerous small farms on a very small scale. 

Major medicinal mushrooms

The caterpillar fungus Cordyceps sinensis  (summer-plant, winter-worm) is a powerful  immunomodulator with multiple effects - anti-cancer, anti-oxidative and hepato-protective  being the most prominent. It is presently grown industrially in liquid culture and on solid media in Korea and China. Results are coming in rapidly now due to the better availability of the biologically active compounds, i.e. the beta glucans and the triterpinoids from Cordyceps.

This has allowed much better characterization: cordycepines are a group of hydroxy-ethyl adenosine analogs present in the extracts from different strains of Cordyceps in different types and quantities. They have been characterized, tested and the results were used by John Holliday and Dinesh Patel from the USA to obtain new highly active strains by conventional cross-breeding.

Interestingly, the Chinese scientist Zengzhi Li reported on the effects of polysaccharides from Acremonium, a fungus which he isolated from fruiting bodies of Cordyceps, the former being much more active than the latter. This is interesting because in Chinese folk-medicine mushrooms are integrally used, suggesting that the medicinal effects could be due to the presence of different fungi in the medicine.

Due to their immunomodulatory effects mushroom extracts cannot only be used to fight the spread of cancer cells in the body but they are also able to rapidly restore immune activity after radiation and/or chemotherapy. This was tested on mice using oral administration of extracts of Flammulina and Hypsizygus. Another group of scientists used powdered Hatakeshimeji ( Lyophyllum decastes)  combined with propolis from Bee honey. The implications appear important for clinical medicine. It could strongly increase the quality of life of cancer patients. In Japan 109,000 tonnes of Flammulina are currently produced annually as well as 82,000 tonnes of Hypsizygus marmoreus.

Sparassis crispa, an edible mushroom recently cultivated in Japan appears to have analogous effects. Naohito Ohno of Tokyo University of Pharmacy and Life Science reported on the positive effects of daily consumption of 300 mg Sparassis crispa  powder.

Hericium erinaceum (Monkey’s head) was reported to contain anti-dementia substances such as stimulators of Nerve Growth Factor and inhibitors of cytotoxicity of amyloid beta peptide. Both are used to treat Alzheimer’s Disease. Clinical data of Hirokazu Kawagishi of ShizuokaUniversity had shown that eating 5 grams of dried Herinaceum daily over a period of 6 months improved dementia symptoms in a group of human patients.

Ganoderma lucidum (Ling Zhi) is well known for its immunomodulatory properties. A completely new medicinal application was developed from G. tsugae. Residue material from this mushroom could be extracted for chitin. This chitin was sterilized and used to cover skin wounds. 75 % of the patients showed satisfactory healing of the wounds.

Robert Hackman of the University of California at Davis showed important curative effects of a   preparation from G. lucidum mycelial cultures containing oligosaccharides and isoflavones. This material was taken orally by patients with proven prostate cancer. Prostate specific antigen was found to be effectively stabilized allowing active surveillance instead of operation.

Noriko Kodama and collaborators of KobeUniversity showed impressive results using Grifola frondosa (Maitake) b-glucans. They had studied the interactions between transplanted tumours and immune cells after glucan application. Tumour growth was not only completely inhibited in mice but the scientists also demonstrated how this was caused.

Protection of Cordyceps in Bhutan

Cordyceps sinensis, since over 2000 years one of the basics of oriental medicine, grows upwards of 3800 metres above sea level from April to July/August in alpine meadows in the Himalayan mountains. Here, the fungus completes its life cycle in its host the lepidopterum Hepialis. The fungus infects through the cuticle of the insect and consumes the internal muscle tissue before going into a resting state which carries it through the heavy winter.

In 1993 Chinese long distance runners, breaking many world records using the wonder herbal Cordyceps, made this fungus famous. Together with its host it became widely collected from nature i.e. from Tibet, China and finally from Bhutan at prices that are up to $ 2000 a kg.

The world market at 500 kg a year is larger than the annual production. As a result Cordyceps will be extinct if collecting does not stop. Most countries have banned collecting Cordyceps sinensis. Tibetan poachers now operate in Bhutan where the local population is strictly forbidden to collect.

Nigel L. Hywel-Jones form BIOTEC undertook action against this. As a result the Bhutan government will allow limited collecting by locals. This will result in better protection of collection sites from Tibetan poachers as locals will have a vested interest in protecting their own sites.

Medicinal mushrooms: what is the future?

The medicinal effects of a number of higher fungi are now widely accepted. BioThailand 2003 allowed discussion of both in vitro and in vivo effects of application of mushrooms and their extracts i.e. polysaccharides and other bioactive compounds against a variety of diseases. 

More clinical work must be done, especially double blind assays involving human patients, before mushroom-derived compounds for treatment of disease will be accepted in western type medicine.
However, the results presented were highly challenging and form encouraging ground for further continuation of the Thai policy to become an important participant in the field. BioThailand 2005 or 2006 could be an interesting forum for further development of this fascinating specialty.