International Journal of Food Science and Technology 2001, 36, 229±242 229

Perspectives on the 21st century development of functional foods: bridging Chinese medicated diet and functional foods

Yue Xu

Food Technology Centre, Singapore Productivity and Standards Board, 1 Science Park Drive, Singapore 118221, Singapore (Received 10 August 1999; Accepted in revised form 12 July 2000)

Summary Functional foods, also known as nutraceuticals, medical foods or nutritional foods, are driving food markets around the world and are expected to be one of the emerging trends for the food industry in the new millennium. The concept of functional foods is rooted in a tradition, particularly in Asia, where people have always believed that a balanced diet and some herbal foods are therapeutic. However, while extensive studies in biochemistry and immunology, as well as clinical trials, have been conducted on selected functional foods or ingredients, the scienti®c features of most traditional herbals remain almost unknown. However, the fastest growing food market in the United States is that of herbal-based nutraceuticals such as ginseng, garlic and medical mushrooms. This review describes di€erent aspects of functional foods and the Chinese medicated diet on the basis of current knowledge, discusses the building blocks for the science of functional foods and proposes a possible way to fuse a Chinese medicated diet into functional foods.

Keywords Chinese medicated diets, food ingredients, functional foods, herbs, nutraceuticals.

The Yellow Emperor's Internal Classic, probably Fundamentals of Chinese medicated diet the ®rst classical Chinese medical book, was written in 745±221 BC. It recorded several medical History of the Chinese medicated diet diet prescriptions. This was followed by other Health and `healing' foods have a long history in classical TCM publications (Weng & Chen, 1996), Eastern cultures, particularly in China, where food such as `Treatise on Febrile Diseases (AD 210), and medicine are considered to be equally import- `Synopsis of Prescriptions Worth Thousand Gold' ant in preventing and curing diseases. Hence, the (AD 650) and `Compendium of Materia Medica' saying that medicine and food come from the same (AD 1578), which described extensively many more origin and perform the same functions has been medical diet recipes and prescriptions. Besides passed down to the present from the ancient these TCM works, many monographs especially legend which described a herbalist, Shennong, for medical or therapeutic foods were also docu- who had tasted a hundred types of herbs (Zhang, mented. Many up-to-date monographs and 1990). Thus, the Chinese medicated diet has been scienti®c works on the Chinese medicated diet, one of the important branches of traditional introducing modern concepts of nutritional sci- Chinese medicine (TCM) during its evolution in ence, have also been published over the past few the last 2000 years. decades (Zhang, 1990).

Principles of the Chinese medicated diet

Correspondent: Fax: +65 7740363; TCM has four major treatment approaches, e-mail: [email protected] namely acupuncture, acupressure, herbal medicine

Ó 2001 Blackwell Science Ltd 230 Chinese medicated diet and functional foods Yue Xu

and Qi gong-energy medicine (Lerner, 1994). The because they inevitably a€ect the immune function basic theories of the Chinese medicated diet of the human body. Therefore, the state of health (CMD) arose from the main theories of herbal is a function of the body's immune system. medicine in TCM such as yin±yang, visceral Accordingly, bad health indicates that the body's manifestations (pathological changes in internal immune function may be either in de®ciency or in organs), main and collateral channels (the network excess (Lu, 1991). to circulate vital energy and distribute acupunc- In TCM, several terms are used to describe the ture points), pathology, diagnostic methods, prin- symptoms of illnesses (Shen, 1999). The ®rst ciples and methods of treatment (Weng & Chen, symptom is called Yin-weakness (Yin-Xu) that 1996). Deriving from TCM theories, the principles can occur when the internal organs malfunction, of CMD comprise two main parts: (1) a balanced and the internal secretions are not optimal. It may and complete diet and (2) a tonic/therapeutic/ be owing to the organs being made to overwork medical diet. (e.g. long working hours, lack of sleep, exhaustion The imperial TCM doctors emphasized the or nervous tension). In these circumstances, the `attainment of nourishment' by selecting appropri- body is said to `lack ¯uids', which leads to the ate food in a somewhat philosophical way (Ho, organs being `dry'; therefore individuals who su€er 1993). Accordingly, `appropriate food' meant both from Yin-weakness would be deemed to have a moderate intake of food and variety in the diet. sicknesses with symptoms typical of a `®re' condi- In The Yellow Emperor's Internal Classic various tion: the tongue and throat are dry, the tongue is sources in the diet were recommended for healthy red, while the pulses are weak. The second symp- intake. According to the book, ®ve cereals (rice, tom is called as Yang-weakness (Yang-Xu) that can sesame seeds, soya beans, wheat, millet) would be obtained when internal organs malfunction in provide nourishment; ®ve fruits (dates, plum, such a way that the human body does not absorb chestnut, apricot, peach) would produce comple- the nutrients as it should. For example, Yang- mentarity; ®ve animals (beef, dog meat, pork, weakness of the stomach occurs if the stomach mutton, chicken) would give advantage; ®ve veg- does not absorb its necessary nutrients. If the etables (marrow, chive, bean spouts, shallot, Yang-weakness condition persists, that will lead to onion) were for supplementarity (Ho, 1993). Such the circulation being blocked. Therefore, individ- a concept of `a balanced and complete diet' in uals su€ering from Yang-weakness are afraid of CMD can be compared to theories of balanced the cold or have their four limbs often cold, their dietary energy and nutrients in modern nutritional tongue white and their pulse slow. In summary, science. Yin-weakness marks the ®rst stage of an illness Based on TCM theories, the human body where the organ malfunctions, while Yang-weak- should be in a perfectly balanced state in matters ness means that the organ is already damaged. of intake and out¯ow, activity and rest, sleep and By using the yin±yang principle, medicinal wakefulness, the functioning of the organs, etc. foods were classi®ed into `cold' vs. `hot', weak The balance points will, of course, vary from vs. strong, etc. Complementarity, interrelation and individual to individual. There are four major inter-transformation between two opposites are periods, i.e. period of gestation, childhood period, the basis for CMD to cure or prevent diseases. For adolescence to adulthood and adulthood to death, example (Ho, 1993), cold foods may cause diar- during which this balance is a€ected strongly by rhoea and nausea, while hot foods may lead to varying factors (Shen, 1999). constipation and gut problems such as heartburn. Ancient Chinese doctors analyzed the physical On the other hand, complementary cold foods signs and symptoms of a case by di€erentiating the will combat constipation and hot foods against appearances into two opposite categories (Ho, diarrhoea. 1993): yin vs. yang. Yin and yang are used to The concept of `neutral' and tonic foods further express the strength or weakness of the internal supports the yin±yang principle in CMD. Foods organs in TCM. All factors including psychologi- that are between cold and hot are considered cal, social and physiological are related to the `neutral', while foods that are used for strengthen- deterioration of health (the ageing process), ing and nourishment are `tonic'. Usually cold food

International Journal of Food Science and Technology 2001, 36, 229±242 Ó 2001 Blackwell Science Ltd Chinese medicated diet and functional foods Yue Xu 231 is cooked or consumed together with some hot Current status of the Chinese foods for the purpose of neutralization. Weng & medicated diet Chen (1996) reported on some foods that have cold, hot and neutral properties in CMD, whereas Categories ginseng, mushrooms and other herbs are regarded as tonic. It is not easy to classify CMD scienti®cally Shen (1999) has described the principle of because the boundary between traditional Chinese indirect causes and the treatment of disease. medicine and diet has always been blurred. Zhang Chinese medical theories emphasize illnesses that (1990) divided the Chinese medicated diet into two a€ect one another, such that a damaged organ `A' types, i.e. dietetic Chinese drugs (DCDs) and can a€ect organ `B', resulting in an illness. For medicated diet for dietetic therapy (MDDT). example, bad intestines or stomach or gall bladder may lead to a liver disease; nervous tension may Dietetic Chinese drugs (DCDs) lead to high blood pressure; weak lungs can cause frequent occurrences of the common cold; weak Dietetic Chinese drugs are also known as `edible kidneys can cause nervous tension; these are all Chinese drugs', `dietetic materia medica' or interrelated diseases. In terms of treatment, an `medicinal food', although the word `drug' could individual with weak lungs needs nourishment be misinterpreted in the West. DCDs actually refer to strengthen his lungs; an individual with weak to materials that can be used either for the preven- kidneys needs to have his Qi nourished to streng- tion and cure of diseases or for health care and then his kidneys; an individual with a weak heart recovery. DCDs are composed of two types of needs an ample supply of blood to strengthen his material. One is the salutary foods including heart. These are the principles of indirect treat- cereals, fruits, nuts, vegetables, seasonings, birds ment. and animals and aquatic products; another com- Channel tropism is another TCM concept to prises the herbs or animal/insect origin of materia supplement the principles of CMD. Channel medica in traditional Chinese medicine. tropism links the functions and sensory percep- tions of various foods to the corresponding Salutary foods in DCDs internal organs, channels or parts of the body. Weng & Chen (1996) also showed that some foods Common salutary foods in DCDs with eight could improve the functions of their correspond- categories are shown in Table 1, among which ing organs. Sensory perceptions such as bitter, some of those used less in the West are discussed in sour, sweet, pungent and salty can also a€ect detail as follows (Zhang, 1990). organs such as the heart, liver, spleen, lung and Millet and mung bean are two of the important kidney, respectively. cereals in DCDs. Millet contains about 60.27% of

Table 1 Common salutary foods

Cereals Rice, millet, wheat, buckwheat, sorghum, soybean, mung bean, black sesame Fruits Apple, banana, pear, peach, watermelon, grape, tangerin, hawthorn fruit Nuts Walnut kernel, sweet almond, chestnut, Chinese torreya, pine nut, peanut, Siberian ®lbert, sun¯ower seed, Vegetables wax gourd, cushaw, towel gourd, celery, spinach, coriander, garlic, Chinese yam, radish, carrot, lotus root, bamboo shoots, mushroom. Condiments Alcoholic drinks, table salt, vinegar, miso, peanut oil, pepper, cassia bark, honey, crystal sugar, green Chinese onion, ginger Birds and animals Pork, mutton, dog meat, black-bone chicken, quail meat, wild goose meat, sparrow meat, edible bird's nest Aquatic products Carp, crucian carp, eel, meat of soft-shelled turtle, crabs, sea cucumber, frog, kelp Miscellaneous Shepherd's purse, purslane, bean curd, quail's egg, milk, tea

Source: Zhang, 1990.

Ó 2001 Blackwell Science Ltd International Journal of Food Science and Technology 2001, 36, 229±242 232 Chinese medicated diet and functional foods Yue Xu

starch, 1.41% of fat, 2.41% of protein nitrogen, health foods in China. Edible bird's nest contains vitamin B and minerals. Millet is cool in nature and 57.07% of total nitrogen in proteins, non-protein acts on the channels of the kidney, spleen and nitrogen and free amino acids such as arginine, stomach under the theory of channel tropism. In cystine and histidine together with small amounts every 100 g of mung bean, there are 22.1 g of pro- of fat, P, S, Ca, K, hexosamine and mucinoids. It tein, 0.8 g of fat, 59 g of carbohydrate, vitamins is sweet in ¯avour, neutral in nature, and acts on and minerals. Mung bean is also cool in nature and the channels of the spleen, lung and kidney. acts on the channels of the heart and stomach. Hawthorn fruit, one of the most well-known Herbs and animal/insect origin of materia fruits in China, is the fruit of Crataegus pinnati®da medica with dual-purpose drug/food or C. cuneata. Hawthorn fruit contains tartaric Table 2 shows some of the commonly used edible acid, citric acid, crataegolic acid, malic acid, materia medica with dual-purpose drug/food. This oleanolic acid, ¯avonoid, lactone, sugars, glyco- is a group of edible Chinese drugs that can be

sides, carotene, protein, tannin, vitamin C and B2, consumed as food without prescription but are calcium and iron. Hawthorn fruit is sour/sweet in claimed to have therapeutic functions based ¯avour, slightly warm in nature, and acts on the mainly on both ancient medical practices/obser- channels of the spleen, stomach and liver. It vations and modern clinical trials. enhances digestion in the stomach, strengthens blood circulation, removes blood stasis and expels Medicated diet for dietetic therapy (MDDT) worms. A nut called Chinese torreya, the seed of MDDT refers to recipes or cuisines made from Torreya grandis, contains oxalic acid, glucose, DCDs, food and condiments. Generally speaking, polysaccharides, essential oil, tannin and fatty oil. a medicated diet can be prepared, according to the Chinese torreya is sweet in ¯avour, neutral in doctor's advice, either from edible Chinese drugs nature and acts on the channels of the lung, alone or from Chinese crude drugs and foods by stomach and large intestine. It is used to treat processing and culinary skills such as stewing, abdominal pain owing to parasitization, malnu- braising, simmering, steaming, boiling, cooking in trition of children owing to impairment of the water, stir-frying, roasting, fricasseeing, deep- spleen and stomach caused by improper feeding, frying and so on. dry coughs, constipation and piles. In light of its form and process, the medicated Lotus root, the fat rhizome of Nelumbo nucifera, diet can be divided into 11 di€erent categories: is a vegetable consumed mainly in eastern and fresh juices, medicated teas, drinks, medicated southern China. It contains protein, asparagine, wines, decoctions, medicated gruels, honey vitamin C, pyrocatechol, d-gallic-catechin, neo- extracts, medicated cakes, medicated pancakes chlorogenic acid, leucocyanidin, leucodephinidin and soups (Zhang, 1990). Table 3 shows a cata- and peroxidase. Lotus root is sweet in ¯avour, cold logue of medicated diets used to treat the common in nature, and acts on the channels of the heart, diseases and syndromes, as well as for nourish- spleen and stomach. Raw lotus root can clear away ment and longevity, whereas only ®ve recipes used heat, cool the blood and dissipate blood stasis, and in medicated diets for dietetic therapy are shown thus is used to treat restlessness and thirst during in Table 4, since such recipes can be counted in the course of febrile diseases, haematemesis, nose- thousands. bleeding and stranguria of heat type. Black-bone chicken, a subspecies of the normal Healthy oral liquors/capsules (HOLC) chicken, is neutral in nature and acts on the channels of the liver and kidney. Black-bone In the past 25 years a new generation of healthy chicken can nourish the liver, kidney and yin, products, known as healthy oral liquors/capsules, and lower the fever. Edible bird's nest is produced has grown dramatically and dominated the market from saliva or saliva mixed with villus by Collo- of health foods in China. Healthy oral liquors/ calia esculenta and many other swallows of the capsules are made from ingredients such as same genus. It is one of a number of ®rst-class Chinese herbs, spices and/or animals through

International Journal of Food Science and Technology 2001, 36, 229±242 Ó 2001 Blackwell Science Ltd Chinese medicated diet and functional foods Yue Xu 233

Table 2 Selected Chinese nutraceutical ingredients in dual-purpose drug/food

Claimed therapeutic functions to treat

Animal origin Deer horn antler Fatigue, impotence, cold extremities, skeletal deformity in infant, uterine bleeding etc. Cattle gallstone bezoar Fainting, convulsions, high fever and red swellings Donkey-hide gelatin Dizziness, excessive menstrual bleeding, insomnia etc. Musk Seizures, fainting, in¯ammation and swollen glands Pearls Insomnia and vision problems Plant origin Ginkgo biloba nuts Coughing with sputum, cloudy urine and incontinence Leaf of Ginkgo biloba Hypertension, arteriosclerosis, angina pectoris Poria cocos Dark yellowish urine, epigastric pressure, dizziness, forgetfulness and insomnia Ganoderma Many forms of heart problems, allergies, pain, liver diseases, as well as to lower cholesterol, and prevent cancer development Panax ginseng Cardiovascular, digestive and liver diseases, diabetes, impotence, neurasthenia and vision problems Panax quinquefolius Chronic cough, loss of blood, de®ciency of vital energy Cordyceps sinensis Impotence, weakness, chronic cough and wheezing Ziziphus jujuba Fatigue, paleness and emotional instability Morus alba L Fever, cough, headache, and vomiting of blood Tremella fuciformis Dry cough and bloody phlegm Rhubarb Fever, red eyes, painful and irregular menstrual period, constipation, thirst and abdominal pain Lycium chinense Anaemia, sore lower back and long-term cough Notoginseng root Nosebleed, accident injuries, fractures and heart problems, slow growth in infants Gynostemma pentaphyllum Chronic bronchitis Angelica sinensis Blurred vision, menstrual problems, traumatic injury, constipation, as well as to improve blood circulation Astragalus membranaceus Fatigue, diarrhoea, prolapsed organs, severe loss of blood, oedema, chronic scores and paralysis Euphoria longan Heart palpitation, insomnia and overwork Psoralea corylifolia Impotence, painful loins and knees, frequent urination

Source: Dai & Luo (1996); Anon, 1997. modern food and pharmaceutical processing and pilled forms are also used. Some of the methods such as extraction, isolation, formula- commercial healthy oral liquors are presented in tion, bottling, pilling or capsulation and are used Table 5. for prevention and cure of diseases, or health care and recovery. Overview of functional foods One of the major distinctions between MDDT and HOLC is the raw material used. In MDDT, The term `functional foods' is used widely and recipes are formulated by using salutary foods or de®ned as foods or food components which are mixing salutary foods with edible Chinese herbal designed to help modulate the human body and or animal drugs. On the other hand, raw materials cure or prevent diseases. Many other terms, such as used for HOLC are mainly those of edible Chinese `medical foods', `nutraceuticals', `nutritional foods' herbal or animal drugs. and `designed foods' as well as their de®nitions have Another distinction is the product form. Thera- also emerged (Hasler, 1996; Silverglade, 1998). peutic cuisines are the major product form of Well-known and developed nutraceutical ingre- MDDT, either cooked at home according to the dients fall into ®ve categories, namely phytochem- doctor's advice or prepared in a hospital kitchen, icals (O'Brien, 1990; Charleux, 1996; Dreosti, 1996; whereas HOLCs are the ready-to-use products Milner, 1996; Balentine et al., 1997; Broihier, 1997; which are processed and packaged. The most Kardinaal et al., 1997; Bidlack, 1998; Pszczola, popular product form of HOLC in China is 1998), probiotics (Lee & Salminen, 1995; Rober- ampoule-bottled oral liquors, although capsulated froid, 1996; Salminen, 1996; Aso, 1997; Brassart &

Ó 2001 Blackwell Science Ltd International Journal of Food Science and Technology 2001, 36, 229±242 234 Chinese medicated diet and functional foods Yue Xu

Table 3 Catalogue of medicated diets used for the treatment of common diseases/syndromes as well as for nourishment and longevity

Medicated diets to treat diseases and syndromes of Medicated diets for

(1) Cardiovascular system: hypertension, coronary heart disease, congestive Nourishing qi, blood, yin and yan heart failure, chronic hypotension (2) espiratory system: common cold, bronchitis, pneumonia and bronchial asthma Tonifying and bene®ting the ®ve viscera, i.e. spleen, lung, heart, kidney, and liver (3) Digestive system: chronic gastritis and peptic ulcer, cirrhosis, haemorrhage of Prolonging life upper digestive tract, acute and chronic enteritis (4) Urogenital system: acute and chronic nephritis, urinary infection, prostatic hyperplasia, impotence, seminal emission, stone of urinary system (5) Blood system: anaemia, thrombopenic purpura (6) Metabolic and endocrine system: hyperlipaemia, adiposis, diabetes (7) Nervous system: cerebrovascular diseases, neurosis (8) Dermatitis: impetigo, mastitis, trauma, haemorrhoid (9) Obstetrics and gynaecology: menstrual disorder, dysmenorrhoea, leucorrhagia, sterility and vomiting during pregnancy, puerperal hypogalactia (10) Paediatrics: enuresis in children, infantile malnutrition, pertussis, infantile diarrhoea and rickets (11) Ophthalmia: acute conjunctivitis, night blindness and senile cataract. (12) ENT: tinnitus, pharyngitis, tonsillitis, voice disease (13) Infection and tumour: viral hepatitis, pulmonary tuberculosis and prevention of cancers

Source: Zhang, 1990.

Table 4 Recipes of medicated diet for dietetic therapy

Claimed therapeutic Recipes Ingredients Preparation bene®ts to treat

(1) Soup of Tremella Tremella (Tremella), 9±12 g Jew's ear Wash mushrooms in warm water; Hypertension and Jew's ear (Auricularia), 9±12 g Crystal sugar add sugar to mushrooms, then steam them for an hour (2) Gruel of galangal Galangal rhizome, 9 g Cyperus tuber, Decoct the ®rst two ingredients in Chronic gastritis hizome and 9 g Polished short-grained rice, water, sift the decoction from the and peptic cyperus tuber 100 g dregs; then add the rice and water to ulcer the decoction to cook them into gruel (3) Decoction of Herba taraxaci (dandelion herb), 30 g Add a certain amount of water and Mastitis dandelion herb and Caulis lonicerae (honeysuckle), 30 g rice wine to the mixture of two honeysuckle stem ingredients and decoct them until a thick extract (4) Gruel of Succus H. leonuri juice, 10 mL Make gruel with rice ®rst, add Menstrual motherwort juice Succus R. rehmanniae juice, other ingredients to gruel, and keep disorder 40 mL Lotus root juice, cooking until thin gruel is obtained 40 mL Ginger juice, 2 mL Honey, 10 mL Polished short-grained rice, 100 g (5) Loach and tofu Tofu, 100 g Living loach, 250 g Put loach together with corn stigma, Viral hepatitis Corn stigma, 30 g tofu and water in earthenware pot to decoct

Source: Zhang, 1990.

International Journal of Food Science and Technology 2001, 36, 229±242 Ó 2001 Blackwell Science Ltd Chinese medicated diet and functional foods Yue Xu 235

Table 5 Some of the healthy oral liquors marketed in China

Product types Ingredients Claimed health bene®ts

(1) Ginseng and royal Panax ginseng or Panax quinquefolius,30% Anti-ageing Stimulation of jelly liquors Fresh royal jelly, 30%; Honey and water 40%. immune activity (2) Mushroom tonic liquors Lentinus edode (Shiitake) Poria cocos Anticarcinogenicity Anti-virus Gannoderma (Lingzhi) Lowering blood lipids (3) Bee pollen liquors, Treated bee pollen Anti-ageing essence, wines, teas, etc. (4) Ant liquors, wines, Extracts of ants Anti-ageing Improvement and beverages of cardiovascular function (5) Chinese caterpillar fungus Extracts of Cordyceps, Anti-ageing Improvement (Cordyceps sinensis) 80% Extracts of Ziziphus jujuba,5% of cardiovascular Extracts of Gannoderma, 5% function Extracts of Joponica lindl, 5% Lowering blood lipids and Extracts of Radix glycyrrhizae, 5% pressure Strengthening kidney

Source: Dai & Luo 1996, Wu (1996).

Schi€rin, 1997), prebiotics (Tomomatsu, 1994; of nutrition vs. immunology, as one of the most Crittenden & Playne, 1996; Roberfroid, 1996; important recent developments in the scienti®c Brassart & Schi€rin, 1997), polyunsaturated fatty food community, is being emphasized and is acids (Linko & Hayakawa, 1996; Uauy-Dagach & progressing rapidly (Sherman & Hallquist, 1990). Valenzuela, 1996) and bioactive proteins/peptides Thus, the reasons for human nutrition are: (1) the (Anon, 1991; Kitts & Yuan, 1992; Sharpe et al., primary purpose is to take foods for promoting 1994). growth and maintaining a healthy life: that is, The science of nutraceuticals or functional food nutrition; (2) a secondary reason for eating foods is far from being established systematically is for pleasure: that is, food ¯avour; (3) a tertiary as an independent discipline. It will probably be purpose is to modulate the biodefence system developed through absorbance and interdisciplin- which may lead to cure or prevention of diseases: ary penetration of elements from food nutrition, that is, functional foods or nutraceuticals. immunology, biochemistry and molecular biology With regard to regulation of functional foods, (Fig. 1). Although in its early stages, the study putting health claims on labels is an ongoing battle between regulators and manufacturers. The cur- rent status of legislation of functional foods in the United States, Japan, China, the European com- munity, Australia and Singapore has been reviewed by Jordan (1996), Kan (1996) and DNS (1998). Among the countries listed, only the United States, Japan and China allow health claims on the label and only under speci®c categories.

Bridging Chinese medicated diets and functional food Western medical and biological science is based on `anatomy or dissection', where a complicated object is fragmented into many single components that are then studied extensively in vitro. This is Figure 1 Building blocks of nutraceutical/functional food the so-called `reductionism' approach. When the science. complete nature or function of fragments are

Ó 2001 Blackwell Science Ltd International Journal of Food Science and Technology 2001, 36, 229±242 236 Chinese medicated diet and functional foods Yue Xu

understood the object is reconstructed mainly by Ginseng using logic or deduction. Undoubtedly, western Panax ginseng, known as white or red ginseng, and philosophy in science will enable us to understand, P. quinquefolium, known as American ginseng, on one hand, the nature of the universe and on the are used commonly in TCM or CMD. The major other, the innate character of biological objects, bioactive components of ginseng are ginsenosides resulting in an unprecedented advance of science or panaxosides (Attele et al., 1999), a diverse and technology. group of steroidal saponins of which nine of their Conversely, Chinese philosophy focuses mainly chemical structures (Fig. 3) have so far been on developing universal harmony by using a identi®ed from more than 13 isolated ginsenosides. balanced approach. According to TCM, the E€orts have been made to study the mech- human body is an integrated whole; treatment is anisms of ginsenoside activity, but many still based on the concept of an integral human body remain unknown. Since ginsenosides and other and is decided through di€erentiation of symp- constituents of ginseng produce e€ects that are toms and signs. Although an over-emphasis on di€erent from one another, the overall biological harmony is probably one of the reasons why activity or pharmacology of ginseng is complex traditional Chinese medicine has regressed over (Attele et al., 1999). The in vitro antitumour past centuries, new Chinese medicine or nutrition activity of a ginseng saponin metabolite, 20-O-b- is becoming more relevant by absorbing aspects of D-glucopyranosyl-20(S)-protopanaxadiol (IH-90), western scienti®c philosophy. was examined against four human cancer cell lines, and a high inhibitory activity of this com- pound was reported (Lee et al., 1999). Kim et al. Isolation of bioactive compounds and (1999) reported a study to characterize the endo- identi®cation of their biological effects thelium-dependent relaxation elicited by ginseno- As the molecular mechanisms of Chinese herbal side Rg 1 and Rg 3 in isolated rat aorta: Rg 3 drugs and medicated diets have been ignored for a was about 100-fold more potent than Rg 1. The long time, many studies on the isolation and endothelium-dependent relaxation in response to characterization of active compounds from tradi- ginsenoside Rg 3 was associated with the forma- tional Chinese medicine have recently begun in tion of cyclic GMP. In addition to ginsenosides, Japan, China, Taiwan, Singapore and Hong Kim et al. (1998) isolated an acidic polysaccharide Kong, focused mainly on three Chinese herbal from P. ginseng, named as Ginsan, that inhibits drugs, i.e. ginseng, Ganoderma and Cordyceps the incidence of benzo[a]pyrenne-induced auto- (Fig. 2). chthonous lung tumours in mice.

Lingzhi Chinese Caterpillar Fungus Ginseng (Ganoderma lucidum) (Cordyceps sinensis) (Panax ginseng)

Figure 2 The most important ingredients in Chinese medicine.

International Journal of Food Science and Technology 2001, 36, 229±242 Ó 2001 Blackwell Science Ltd Chinese medicated diet and functional foods Yue Xu 237

organic germanium, were recognized and identi- ®ed (Zhang, 1997) in G. lucidum. Furthermore,

three active protein-bound glycans named FI0-a, FI0-b-a and FA-1-b-a were isolated from a Lingzhi polysaccharide preparation (FI) by ion-exchange chromatography, gel ®ltration and anity chromatography, and their antitumour e€ects have been identi®ed against a solid cancer,

sarcoma 180, in mice (Zhang et al., 1994). FI0-a is a glycan±protein complex containing 9.3% protein and has a tetero-glyco chain of mannose and

xylose. FI0-b-a, which is a glycan±protein complex containing 25.8% protein and has a molecular weight of 10 000 dalton, shows an inhibition ratio of 61.8% against the solid cancer sarcoma 180/ mice and a survival ratio of more than 194% of the control group. FA-1-b-a, a complex of glycan (42)±protein (58) with a molecular weight of 10 000 dalton, gives a tumour inhibition ratio of 56% and a survival ratio of more than 182%.

Chinese caterpillar fungus (Cordyceps sinensis) Chinese caterpillar fungus is composed typically of 10.85% moisture, 8.4% fat, 25.32% protein, 18.53% crude ®bre, 28.90% carbohydrate and 4.10% ash, together with hitherto identi®ed com- pounds such as cordycepic acid (Fig. 4), quinic acid, cordycepin (Fig. 4), 5-a,8-a-epidioxy-24(R)- methylcholesta-6, 22-dien-3-b-D-glucopyranoside

Figure 3 Chemical structure of ginsenoside-Ra, -Rb1, -Rb2, (EMDG), 5,6-epoxy-24(R)-methycholesta-7, -Rc, -Rd, -Re, -Rf, -Rg1, Rg2. Source: Anon, 1997. 22-dien-3-b-ol (EMDL), ergosteryl-3-O-b-D-gluco- pyranoside (EG) and 22-dihydroergosteryl-3-O-b- D-glucopyranoside (DG) (Anon, 1997; Bok et al., Lingzhi (Ganoderma) 1999). Cordycepin was reported to inhibit the Lingzhi is classi®ed into four families, namely growth of many pathogens such as Bacillus anthra- Ganoderma, Haddowia, Amauroderma and Hum- cis and B. mallei (Anon, 1997). EMDG, EMDL, phreya, with 86 species (Wang et al., 1993), while EG and DG were found to be the inhibitors of the most well-known Lingzhi is Ganoderma. proliferation of K562, Jurkat, WM-1341, HL-60 G. lucidum (red) and G. japonicum (purple) are and RPMI-8226 tumour cell lines, whereas the two common types of Ganoderma plants, although glycosylated form of ergosterol peroxide showed a the `Compendium of Materia Medica' recorded six greater e€ect than EMDL (Bok et al., 1999). types of plants coloured red, purple, green, yellow, white and black (Anon, 1997). G. japonicum was analyzed and contains ergosterol, organic acids, aminoglucose, polysaccharides, resins and mann- itol, whereas G. lucidum contains alkaloids, lac- tones and coumarin, in addition to the compounds found in G. japonicum (Anon, 1997). Four categories of active compounds, namely Figure 4 Chemical structure of compounds in Cordyceps polysaccharides, adenosine, triterpenes and sinensis. Source: Anon, 1997.

Ó 2001 Blackwell Science Ltd International Journal of Food Science and Technology 2001, 36, 229±242 238 Chinese medicated diet and functional foods Yue Xu

Biological or pharmacological functions of The question of cause and e€ect is always secon- various fractions of C. sinensis (CS), despite not dary to the overall pattern. being characterized at the molecular level, have However, since TCM/CMD was founded on attracted some investigation. Chen et al. (1997) experience, or empirical rather than in-depth isolated a polysaccharide fraction of CS and science, particularly at the molecular level, curat- studied its e€ect on the proliferation and di€eren- ive e€ects of herbal or medical dietetic remedies tiation of human leukaemic U937 cells by using an are often seen as suggestive and intriguing but in vitro culture system. The results showed that the by no means de®nitive (Lerner, 1994). Today, as conditioned medium from PSCS (10 lgmL±1)- western scienti®c standards have been accepted stimulated blood mononuclear cells (PSCS-MNC- universally, many clinical trials for TCM/CMD CM) and had an activity that could signi®cantly based on modern medical science have been inhibit the proliferation of U937 cells, resulting in a conducted extensively but have been reported growth inhibition rate of 78±83%. Xu et al. (1992) mainly in the Chinese and Japanese literature. reported a study on the e€ects of the ethanol There are a few English reports of clinical trials for extract of CS on murine and human in vitro natural TCM/CMD to treat diseases published in journals killer cell (NK) activities and on murine in vivo NK (O'Leary & Muggia, 1998; Yun & Choi, 1998) and activity. Similarly, Yang et al. (1999) isolated an on websites (Shen, 1999). Moreover, Zhu et al. unidenti®ed compound (H1-A) from CS that (1998) produced a review of CS in pre-clinical showed an immunomodulatory e€ect and was in vitro and in vivo studies, using data on open- e€ective in improving the survival of lupus mice. label and double-blinded clinical trials on the To date, initial studies have indicated that respiratory, renal, hepatic, cardiovascular, immu- many active compounds from these herbs are nological and nervous systems, and also the e€ects bioactive proteins, polysaccharides, oligosaccha- on cancer, glucose metabolism, in¯ammatory rides, sterols, alkaloids ¯avonoids and glycoside conditions and toxicological studies. derivatives. Safety or toxicity of edible Chinese drugs Clinical trials of Chinese medicated Table 6 shows the selected edible Chinese drugs diets/ingredients that are generally regarded as safe by TCM/CMD It is incorrect to claim that many of the postulated based on the centuries-long `clinics', some of health bene®ts of TCM and CMD lack the which have been also con®rmed by the modern

support of clinical trials. In fact, TCM and scienti®c methodology based on LD/LD50 of CMD has been practised `clinically' for centuries animal trials. However, concern over the safety although di€erent methodologies, directions and of known compounds contained in edible Chinese logical structures were used compared to modern drugs, particularly such as sterols, alkaloids and western medicine. ¯avonoids, is still high, and cases of poisoning As reported by Lerner (1994), western medicine by these herbs are occasionally reported. In fact, is concerned mainly with isolable disease categor- the toxicity/non-toxicity of edible Chinese drugs ies or agents of disease, which are isolated, and depends upon the content and a somewhat tricky attempts are then made to change, control or balance of potentially harmful compounds in these destroy the disease agent. The western physician herbs; these compounds are variable depending starts with a symptom, then searches for the upon planting regions, seasons, varieties and their underlying mechanism ± a precise cause for a e€ect is complicated further by the di€erences of speci®c disease. The Chinese physician, in con- allergy, immunity or genetics between human trast, directs his or her attention to the complete patients. Although some countries have raised physiological and psychological individual. All the issue of establishing a QA system or speci®- relevant information, including the symptom as cations to regulate these edible Oriental drugs, the well as the patient's other general characteristics, diculty at present is the lack of comprehensive is gathered and woven together until it forms what knowledge in relation to their composition and the Chinese medicine calls a `pattern of disharmony'. setting up of such systems.

International Journal of Food Science and Technology 2001, 36, 229±242 Ó 2001 Blackwell Science Ltd Chinese medicated diet and functional foods Yue Xu 239

Table 6 Safety and toxicity of Chinese nutraceutical ingredients in drug-food-dual-purpose

Traditional Chinese medicine

Don't or take

Toxicity carefully if Animal tests*LD50, LD or others

Animal origin Deer horn antler Non-toxic Yin in de®ciency, N/A yan in excess Cattle gallstone bezoar Non-, or little Pregnancy Mice no death in one week by 2 g kg)1 feeding toxic Donkey-hide gelatin Non-toxic De®ciency in NA spleen, stomach Plant origin Ginkgo biloba nuts Non-toxic Not clear Mice not poisoned by over-feeding Poria cocos Non-toxic Weak kidney NA )1 Ganoderma Non-toxic Not clear Mice LD50: 38.3 g kg with abdomino-injection )1 Panax ginseng Very minor Heat toxic Mice LD50: 16.5 mg kg with subcutaneous injection Panax quinquefolius Non-toxic Cold/damp stomach NA Cordyceps sinensis Very minor Not clear Mice LD: 30±50 g kg)1 with abdomino-injection toxic )1 Ziziphus jujuba Non-toxic Heat or diarrhoea Mice LD50: 14±16 g kg with abdomino-injection; Mice not poisoned by feeding stomach 150 g kg)1 Tremella fuciformis Non-toxic Cold and cough NA Rhubarb Non-toxic Cold/damp stomach NA Lycium chinense Non-toxic Not clear NA Notoginseng Non-toxic Pregnancy Mice LD for arasaponin: 460 mg kg)1 with intravenous injection Gynostemma pentaphyllum Non-toxic Not clear NA Angelica sinensis Non-toxic Diarrhoea NA

Astragalus membranaceus Non-toxic Yin in de®ciency, Mice LD50: 39±43g/kg with abdomino-injection yan in excess Euphoria longan Non-toxic Heat phlegm NA

*LD: lethal dose, LD50: median lethal dose. Source: Anon, 1997.

Submerged cultures have also been used to Biotechnological production of edible produce G. lucidum (Hiromoto, 1991; Yang & Chinese drugs Liau, 1998), C. sinensis (Taketomo et al., 1996) Plant cell suspension cultures, i.e. submerged and other mushrooms such as Lentinus edodes fermentation techniques, have been used to pro- (Hiromoto, 1991). duce ginseng saponin and polysaccharides of P. ginseng and/or P. quinquefolium (Liu & Zhong, New approaches to the product and marketing 1998; Akalezi et al., 1999; Wu & Zhong, 1999). development for functional foods Since the ®rst paper was published in 1964, the suspension culture technology for ginseng cell has The world-wide trend of `workaholics' and snac- been commercialized. Nitto Denko Corporation in king habits continues to promote the universal Japan has used 20 000-L and 25 000-L fermentors popularity of convenience foods. Food manufac- to produce ginseng cells, and achieved a dry cell turers should consider that opportunities are mass productivity of 20 g L±1 in 4 weeks; the available to increase market share through com- ginseng cells obtained showed similar chemical mercializing the thousands of recipes of the composition (e.g. saponin content) to that of ®eld- traditional Chinese medicated diet by making cultivated ginseng, and nearly identical pharma- them into convenience foods, fast foods or pre- cological e€ects on animals (Wu & Zhong, 1999). prepared meals through modern food processes

Ó 2001 Blackwell Science Ltd International Journal of Food Science and Technology 2001, 36, 229±242 240 Chinese medicated diet and functional foods Yue Xu

such as chilling, freezing, instantizing, snack It is worthwhile for leading carbohydrate ingre- processing, canning and bottling. dients producers to study the application of Recipes for traditional Chinese medicated diets oligosaccharides or dietary ®bre such as resistant are available to enable cooked meals to be starch to Asian breakfast meals rice gruels/ prepared in several forms such as drinks, gruels, porridges, noodles and even curry gravy. These soups, cakes and syrups. These recipes are com- studies should include the contribution and e€ect- posed mainly of food materials and food-type iveness of healthy oligosaccharide ingredients to herbs such as mushrooms and ginseng that are the texture and ¯avour of Asian meals, as well as generally recognized as safe. Well-processed prod- marketing. Fusion of physiologically functional ucts are delicious and can be served either as dairy ingredients with healthy soy or rice foods is dishes or beverages with staple foods or as snacks another interesting area. for eating to promote health or aid medical In the new millennium, we are experiencing two treatments. The latest product releases such as important trends in the food industry. First, there `lotus root chrysanthemum tea' and `ginseng is a wide acceptance of diversity. While ethnic chrysanthemum' by a leading beverage company food is now becoming popular in the western in Singapore are good examples of the develop- world, US and European foods have also become ment of new uses for the traditional Chinese widely accepted in the eastern world, resulting in a medicated diet. great development of mixed or fused cuisines and Combined therapy using Chinese and western ¯avourings around the world (Sloan, 1996). Sec- medicine has been practised widely in China, ondly, there is a new global awareness of the western scienti®c standards have penetrated into concept of functional foods beyond simple nutri- TCM so that related theories can be described by tion, as people in the developed western and newly using physiology, immunology, pathology and developed Asian countries are ageing and becom- biology. Isolation and identi®cation of physiolog- ing more health-conscious. So, the melting-pot ically active compounds are expected to attract boils and health foods will dominate the food more attention from the scienti®c community. industry and consumer trends in the 21st century Chinese edible drugs, after they are understood in (Sloan, 1998). regard to their composition, chemical structure and biochemical properties of bioactive com- Acknowledgments pounds, animal LD tests and human trials, can thus be used as functional food ingredients in an Dr Steve Lai, Dr Loh Wah Sing and Dr Chong e€ective and safe way. Hooi Long in PSB are gratefully acknowledged In all modern societies, snacking is becoming a for their invaluable comments and supports in the way of life. Even snacks can be healthy, and in preparation of this article. Europe and Australia a large area of development is in the fruit snacks sector. Many recipes of the References traditional Chinese medicated diet, e.g. water chestnut and hawthorn jelly, with physiological Akalezi, C.O., Liu, S., Li, Q.S. et al. (1999). Combined functions of invigorating the spleen, regulating the e€ects of initial sucrose concentration and inoculum size stomach, clearing sputum and arresting coughs on cell growth and ginseng saponin production by suspension cultures of Panax ginseng. Process Biochem- (Zhang, 1990), are candidates ready to be trans- istry, 34, 639±642. formed to western-type health snacks. Attele, A.S., Wu, J.A. & Yuan, C.S. (1999). Ginseng The culinary art based on the skills of stewing, pharmacology: multiple constituents and multiple braising, simmering, steaming, boiling, cooking in actions. Biochemical Pharmacology, 58, 1685±1693. water, stir-frying, roasting, fricasseeing, deep- Anonymous (1991). Immune milk. Nutrition Update, 7, 1170±7526 (New Zealand Dairy Board). frying and so on is at the core of Asian foods. Anonymous (1997). Great Pharmacopoeia of Traditional Are the re®ned western ingredients suitable to be 1 Chinese Medicine [in Chinese]. Pp. 3, 11. Shanghai, China: used in such culinary processes for health promo- Shanghai Publishing House of Science & Technology. tion? The answer is positive if food scientists and Aso, Y. (1997). Lactic Acid Bacteria and Cancer Prevention. technologists are ready to work on it. Pp. 65±165. Tokyo: Shufunotomo Co., Ltd.

International Journal of Food Science and Technology 2001, 36, 229±242 Ó 2001 Blackwell Science Ltd Chinese medicated diet and functional foods Yue Xu 241

Balentine, D.A., Wiseman, S.A. & Bouwens, L.C.M. (1997). Lee, S.J., Sung, J.H., Lee, S.J. et al. (1999). Antitumor The chemistry of tea ¯avonoids. Critical Reviews in Food activity of a novel ginseng saponin metalite in human Science and Nutrition, 37, 693±704. pulmonary adenocarcinoma cells resistant to cisplatin. Bidlack, W.R. (1998). Phytochemicals: a potential new Cancer Letters, 144, 39±43. health paradigm. Food Technology, 52, 168. Lerner, M. (1994). Traditional Chinese medicine ± a favored Bok, J.W., Lermer, L., Chilton, J. et al. (1999). Antitumor adjunctive therapy for American cancer patients. Chapter sterols from mycelia of Cordyceps sinensis. Phytochemis- 19. In: Choices in Healing: integrating the best of try, 51, 891±898. 3 conventional and complementary approaches to cancer. Brassart, D. & Schi€rin, E.J. (1997). The use of probiotics US: MIT Press. to reinforce mucosal defence mechanisms. Trend in Food Linko, Y.Y. & Hayakawa, K. (1996). Docosahexaenoic Science & Technology, 8, 321±325. acid: a valuable nutraceutical? Trends in Food Science & Broihier, K. (1997). Fighting cancer with phytochemicals. Technology, 7, 59±63. 2 Food Processing, November, 41±42. Liu, S. & Zhong, J.J. (1998). Phosphate e€ect on production Charleux, J.L. (1996). b-Carotene, vitamin C, and vitamin of ginseng saponin and polysaccharide by cell suspension E: the protective micronutrients. Nutrition Reviews, 54, cultures of Panax ginseng and Panax quinquefolium. S109±S114. Process Biochemistry, 33, 69±74. Chen, Y.J., Shiao, M.S., Lee, S.S. et al. (1997). E€ect of Lu, H.C. (1991). Chinese Foods for Longevity. Pp. 9±35. Cordyceps sinensis on the proliferation and di€erentiation Australia: Pelanduk Publications. of human leukemic U937 cell. Life Sciences, 59, 2349± Milner, J.A. (1996). Garlic: its anticarcinogenic and antit- 2359. umorigenic properties. Nutrition Reviews, 54, S102±S108. Crittenden, R.G. & Playne, M.J. (1996). Production, O'Brien, J. (1990). The ®rst world congress on the health properties and application of food-grade oligosaccha- signi®cance of garlic and garlic constituents. Trends in rides. Trends in Food Science & Technology, 7, 353±361. Food Science & Technology, 1, 155±157. Dai, Y. & Luo, X.Y. (1996). Functional food in China. O'Leary, J. & Muggia, F.M. (1998). Camptothecins: a Nutrition Reviews, 54, S21±S23. review of their development and schedules of administra- DNS (1998). Background paper, understanding food tion. European Journal of Cancer, 34, 1500±1508. labels. Singapore: Department of Nutrition, Ministry of Pszczola, D. (1998). The ABCs of ingredients. Food Tech- Health. nology, 52, 30±37. Dreosti, I.E. (1996). Bioactive ingredients: antioxidants and Roberfroid, M.B. (1996). Functional e€ects of food com- polyphenols in tea. Nutrition Reviews, 54, S51±S58. ponents and the gastrointestinal system: chicory fructool- Hasler, C.M. (1996). Functional foods: the Western per- igosaccharides. Nutrition Reviews, 54, S38±S42. spective. Nutrition Reviews, 54, S6±S10. Salminen, S. (1996). Functional dairy foods with Lactoba- Hiromoto, B. (1991). Method for culture of fungi including cillus strain GG. Nutrition Reviews, 54, S99±S101. shiitake (Lentinus edodes). US Patent, 5, 203. Sharpe, S.J., Gamble, G.D. & Sharpe, D.N. (1994). Cho- Ho, Z.C. (1993). Principles of diet therapy in ancient lesterol-lowering and blood pressure e€ects of immune Chinese medicine: `Huang Di Nei Jing'. Asia Paci®c milk. American Journal of Clinical Nutrition, 59, 929±934. Journal of Clinical Nutrition, 2, 91±95. Sherman, A.R. & Hallquist, N.A. (1990). Immunity. In: Jordan, S. (1996). Functional foods and related legislation. Present Knowledge in Nutrition (edited by M.L. Brown). European Food & Drink Review, Spring, 49±51. Pp. 463±476. Washington DC: International Life Science Kan, X.G. (1996). Legal aspects of functional foods: the Institute, Nutrition Foundation. situation in China. Nutrition Reviews, 54, S162±S166. Shen, J.H.F. (1999). Chinese Medicine. Website: http:// Kardinaal, A.F.M., Waalkens-Berendsen, D.H. & Arts, www.in®nite.org/shen/cmbook/index.html C.J.M. (1997). Pseudo-oestrogens in the diet: health Silverglade, B. (1998). Regulatory of health claims for foods bene®ts and safety concerns. Trends in Food Science and and dietary supplements ± the US experience. In: Nutri- Technology, 8, 327±333. 4 tional and Functional Foods Conference, Singapore Kitts, D.D. & Yuan, Y.V. (1992). Caseinophosphopeptides Sloan, A.E. (1996). America's appetite '96: the top 10 and calcium bioavailability. Trends in Food Science & trends. Food Technology, 50, 55±71. Technology, 3, 31±35. Sloan, A.E. (1998). Food industry forecast: consumer trends Kim, K.H., Lee, Y.S., Jung, I.S. et al. (1998). Acidic to 2020 and beyond. Food Technology, 52, 37±44. polysaccharide from Panax ginseng, ginsan, induces Th1 Taketomo, N., Tsunoo, A. & Itoh, H. (1996). Healthful cell and macrophage cytokines and generates LAK cells composition obtained from the hot water extract of in synergy with rIL-2. Planta Medica, 64, 110±115. Cordyceps sinensis mycelia. US Patent, 5, 404. Kim, N.D., Kang, S.Y., Park, J.H. et al. (1999). Ginseno- Tomomatsu, H. (1994). Health e€ects of oligosaccharides. side Rg3 mediates endothelium-dependent relaxation in Food Technology, 48, 61±65. response to ginsenosides in rat aorta: role of K+ Uauy-Dagach, R. & Valenzuela, V. (1996). Marine oils: the channels. European Journal of Pharmacology, 367, 41±49. health bene®ts of n-3 fatty acids. Nutrition Reviews, 54, Lee, Y.K. & Salminen, S. (1995). The coming of age of S102±S108. probiotics. Trends in Food Science & Technology, 6, Wang, G., Zhang, J., Mizuno, T. et al. (1993). Antitimor 241±245. active polysaccharides from the Chinese mushroom

Ó 2001 Blackwell Science Ltd International Journal of Food Science and Technology 2001, 36, 229±242 242 Chinese medicated diet and functional foods Yue Xu

Songshan Lingzhi, the fruiting body of Ganoderma Yang, L.Y., Chen, A., Kuo, Y.C. et al. (1999). Ecacy of a tsugae. Bioscience, Biotechnology and Biochemistry, 57, pure compound H1-A extracted from Cordyceps sinensis 894±900. on auto-immune disease of MRL 1pr/1pr mice. Journal of Weng, W.J. & Chen, J.S. (1996). The eastern perspective on Laboratory and Clinical Medicine, 134, 492±500. functional foods based on traditional Chinese medicine. Yun, T.K. & Choi, S.Y. (1998). Non-organ speci®c cancer Nutrition Reviews, 54, S11±S16. prevention of ginseng: a prospective study in Korea. Wu, D.X. (1996). Review on Healthy Liquors in China. International Journal of Epidemiology, 27, 359±364. Pp. 30±60. Shanghai: Publishing House of Shanghai Zhang, E.Q. (1990). Chinese Medicated Diet. Pp. 1±15. Science and Technology. Shangai: Publishing House of Shanghai College of Wu, J. & Zhong, J.J. (1999). Production of ginseng and its Traditional Chinese Medicine. bioactive components in plant cell culture: current tech- Zhang, J., Wang, G., Li, H. et al. (1994). Antitumor active nological and applied aspects. Journal of Biotechnology, protein-containing glycan from the Chinese mushroom 68, 89±99. songshan lingzhi, Ganoderma tsugae mycelium. Bio- Xu, R.H., Peng, X.E., Chen, G.Z. et al. (1992). E€ects of science, Biotechnology and Biochemistry, 58, 1202±1205. Cordyceps sinensis on natural killer activity and colony Zhang, L.P. (1997). Healthy Charm of Lingzhi. Pp. 30±40. formation of B16 melanoma. Chinese Medicine Journal, Taiwan: Zheng Yi Publishing House. 105, 97±101. Zhu, J.S., Halpern, G.M. & Jones, K. (1998). The scienti®c Yang, F.C. & Liau, C.B. (1998). The in¯uence of environ- rediscovery of precious ancient Chinese herbal regimen: mental conditions on polysaccharide formation by Gano- Cordyceps sinensis: part II. Journal of Alternative & derma lucidum in submerged cultures. Process Complementary Medicine, 16, 429±457. Biochemistry, 34, 547±553.

International Journal of Food Science and Technology 2001, 36, 229±242 Ó 2001 Blackwell Science Ltd