Eucommia ulmoides (PROSEA)

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Plant Resources of South-East Asia Introduction

List of species

Eucommia ulmoides Oliv.

Protologue: Hook., Icon. pl. 20: t. 1950 (1891), emend. Hook., Icon. pl. 24: t. 2361 (1895).

Family: Eucommiaceae

Chromosome number: 2n= 34

Vernacular names

• Hardy rubber tree, gutta-percha tree (En)
• Vietnam: dỗ trọng.

Origin and geographic distribution

E. ulmoides is probably not known in a true wild state at present. It originated from southeastern China, where it has long been cultivated as a medicinal, and recently it has also been cultivated for medicinal purposes in Korea, Japan, Taiwan and Vietnam. It is commonly encountered in Chinese pharmacies throughout South-East Asia.

Uses

E. ulmoides is well known in traditional Chinese medicine, and its recorded use dates back 2000 years. The major pharmacological effects include hypotensive, diuretic, tonic, analgesic and sedative actions. The drug is traded as "Cortex Eucommiae". In general it is used in mixtures. The bark is mainly used as a medicinal herb material for tonics and hypotensive drugs, and this use is specified in the Japanese Pharmacopoeia. In China and Vietnam it is prescribed in deficiency of liver and kidney functions, hypertension, lumbago, articular pains and rheumatism. It is further credited with strengthening the musculoskeletal system, and as a panacea during and after pregnancy. The leaves are used as a basis for beverages. The plant yields a gutta-percha, resistant to acids and alkalies. At one stage it was regarded a temperate alternative for tropical Hevea rubber. It has been used extensively in electrical insulation and as filling material in dentistry. The timber is used for furniture, construction, farming tools and as firewood.

Production and international trade

The market value in Japan of health foods and drugs containing E. ulmoides amounted to US$ 1500 million in 1991. In the United States the wholesale price of bark is US$ 20/450 g and 20 teabags (2 ounces/56.7 g) containing the leaf or bark as additive cost US$ 5.

Properties

Phytochemical investigations of bark, leaves, flowers and fruits of E. ulmoides have revealed the presence of a wide range of iridoids, lignans and related phenylpropane compounds. Several of them, as purified compounds, showed pharmacological activities in laboratory animals using in general screening assays. Examples of these are the furofuran-type lignans pinoresinol-di-O-β-D-glucoside and syringaresinol-di-O-β-D-glucoside, and the iridoid glucosides geniposide, geniposidic acid and aucubin (= aucuboside). The effects observed included hypotensive, psychogenic, hypokinesis preventive and cholagogic activities. Furthermore, eucommiol is a characteristic compound from the leaves of E. ulmoides, which is derived from the plant by reduction of C9-iridoids.

In addition, extracts of E. ulmoides also display a variety of pharmacological effects. For example, methanolic extracts strongly inhibited the growth of Clostridium perfringens in vitro, using a paper disk agar diffusion method under anaerobic conditions. An antifungal protein isolated from the bark inhibited at 0.3 mg/ml the growth of Trichoderma viride and some other crop fungal pathogens.

The methanolic extract of the bark exhibited antihyperglycaemic activity via glucose uptake and insulin induction at a dose of 100 mg/kg.

In an exercise load testing experiment with castrated 4-week-old male Wistar rats, E. ulmoides extract significantly increased the relative weight of the adrenal gland, enhanced androgen secretion from the reticular layer of the adrenal cortex, and promoted protein anabolic action. In addition, this extract appeared to increase the adaptation ability of the adrenal cortex to the stress caused by exercise.

Furthermore, in a test using spontaneous hypertensive rats, E. ulmoides leaf extract suppressed the increase in blood pressure in a dose-dependent manner.

Several experiments focused on the liver/cholesterol metabolism. In an experiment with rats, the leaf extract suppressed significantly the high-fat diet-induced increases in total serum cholesterol, serum triacylglycerol and hepatic triacylglycerol, but not the total hepatic cholesterol. The leaf extract also suppressed the high-fat diet induced increases in very-low density lipoprotein and low density lipoprotein without affecting high density lipoprotein cholesterol. These results suggest that E. ulmoides leaf extract may be beneficial for the regulation of hyperlipidemia. In addition, stroke-prone spontaneously hypertensive rats fed on a high-fat and high-cholesterol diet (HFC) were used to induce hypercholesterolaemia. The experimental group was given the HFC-diet containing 5% w/w E. ulmoides leaf powder for 2 weeks with free access to the diet and water. It was found that leaf powder prevented the elevation of serum total cholesterol. The hypocholesterolaemic effect was due mainly to a decrease in the content of cholesterol in the VLDL fraction, which was associated with decreases in the levels of apolipoprotein-B and -E. Results suggest a decrease in atherogenic and cholesterol-rich VLDL produced by the HFC diet feeding. In the liver, elevation of cholesterol content was also prevented by administration of the leaf powder, whereas no significant change in the contents of phospholipid and triglyceride was observed. Also, no significant changes were found in the activities of the microsomal enzymes cholesterol-7-α-hydroxylase and cholesterol acyltransferase.

The antimutagenic potential was furthermore investigated in vivo and vitro. The ingestion of Eucommia tea may reduce human exposure to dietary mutagens as was shown in an experiment with humans. Additionally, an anticlastogenic effect of the tea was observed in mice using the micronucleus assay. After extraction with boiling water and frozen vacuum drying, E. ulmoides leaves were tested in the Ames test in vitro. E. ulmoides (+/- S9) was found to significantly induce His⁺ revertants in Salmonella typhimurium TA98 and/or TA100. The antioxidant effect of extracts from leaves, raw cortex and roasted cortex was evaluated using various lipid peroxidation models. The antioxidant activity of extracts is correlated to their polyphenol content. Extracts of the leaves may therefore be useful in inhibiting membrane lipid peroxidation and preventing free radical-linked disease.

Other experiments with E. ulmoides investigated effects on the muscle and skeleton. For example, a diet enriched with E. ulmoides leaves results in harder muscles in cultured eel. While most characteristics of the meat remain similar, a considerable increase in muscle protein stroma fraction which mainly consists of collagen is observed. In chickens, dietary suppletion with E. ulmoides leaves resulted in improved meat quality due to the quality and quantity of collagen. The administration of geniposidic acid or aucubin as purified compounds was also found to stimulate collagen synthesis in false-aged rats. The reported pharmacological effects of E. ulmoides leaves, including healing organs and strengthening bone and muscle, seem to be closely related to collagen metabolism. Moreover, ovariectomized (OVX) or sham-operated 6-week old female rats were given a low-calcium diet (Ca 0.01%, P 0.3%) for 33 days. Subsequently, OVX rats were given a control diet or a diet containing 2% E. ulmoides bark extract. The diet for the control group and the sham group was the control diet and contained 0.3% Ca and 0.3% P. Each group was given the experimental diet for 31 days. Bone mineral density (BMD) and the breaking strength of the control group were lower than those of the sham group. However, BMD and bone strength improved in the E. ulmoides group and intestinal Ca absorption increased. Moreover, the muscle weight of the latter was higher than that of the control group.

Finally, in the carbon-clearance test in mice, used to evaluate the stimulating effect on the phagocytic activity of granulocytes, eucomman B isolated from a hot water extract, increased the phagocytic index, suggesting that it activated the reticuloendothelial system.

Adulterations and substitutes

The iridoid glucoside aucubin (= aucuboside) is also found in e.g. Aucuba japonica Thunb., Verbascum densiflorum Bertol., and Plantago lanceolata L. The closely related compound geniposide is furthermore found in e.g. Gardenia jasminoides J. Ellis.

Description

• A deciduous, dioecious tree up to 20 m tall, with ascending twiggy branches forming a broadly domed crown; branchlets hollow, pith lamellate, with articulate lactifers in phloem and cortex and scattered latex-cells elsewhere.
• Leaves spirally arranged, simple, narrowly ovate to elliptical, 7-15(-20) cm × 3-7(-9) cm, apex acuminate, margin serrulate; petiolate; stipules absent.
• Flowers solitary, shortly pedicellate in the axils of bracts racemosely arranged on the proximal section of a distally leafy shoot, sepals and petals lacking; male flowers composed of (5-)6-12 stamens, anthers red-brown; female flowers with a unilocular ovary, stigmas 2, unequal, reflexed.
• Fruit a samara, compressed ellipsoid to oblong, 3-4 cm long, winged, 1-seeded.
• Seed with large embryo embedded in copious endosperm.

Growth and development

E. ulmoides trees may flower before or simultaneously with the emergence of new foliage. Flowers are wind-pollinated.

Other botanical information

E. ulmoides is the only species of the family Eucommiaceae. The family Eucommiaceae is variously associated with Urticales, Hamamelidales (for pollen similarity) or even Magnoliales, and is morphologically nearest to the Urticales.

Ecology

E. ulmoides originated from the relative warm and humid part of south-eastern China from 300-1300 m altitude. As a medicinal raw material it has been cultivated in the same region at 500-1100 m altitude. In Vietnam it is cultivated above 1000 m altitude. The plant can tolerate frosts as low as -15°C and is grown as an occasional ornamental in temperate climates.

Propagation and planting

E. ulmoides is usually propagated by seed. Seed should preferably be collected from 10-20-year-old trees, and sown in spring or autumn. Natural germination is rather poor, 10%, but can be enhanced to 60% by immersing the seeds in water, and up to 80% by peeling off the seed coat. Seedlings are spaced 10 cm apart. In winter or spring 1-year-old seedlings are planted at 2.5-3 m intervals. Information on propagation by softwood cuttings is contradictory. For propagation by tissue culture, the epicotyl of the seed shortly after germination is a suitable starting material, in particular with the addition of 0.1-5 mg/l butyric acid (BA) to a B5 medium. Rooting was recorded at a rate of 60% after immersion in 100 ppm naphthalene acetic acid (NAA). When using 1-month-old seedlings as starting material, the explant is an excised shoot tip, 3-5 mm tall. Murashige and Skoog (MS) basal medium supplemented with 1 mg/l BA is employed to establish primary cultures and subsequently multiply shoots. Shoots are subculturable on the same medium and can be increased at a rate of 7.5 new shoots per 2-shoot sector every 3 weeks. Rooting is achieved in a Gelrite medium with the MS salts reduced to 1/3 strength and the BA replaced by 0.1 mg/l NAA. The method is not directly applicable to mature trees. Applicability will require explants from rejuvenated sources, possibly attainable by the method of repeated grafting of shoot apices onto juvenile rootstocks, repeated subculturing of shoots, or culturing shoot apical meristems.

In vitro production of active compounds

In vitro production of iridoids and lignans, in particular the active compounds pinoresinol di-O-β-D-glucoside (PRDG), syringaresinol di-O-glucoside (SRDG), geniposidic acid (GA) and aucubin, is inferior to the concentration present in bark or leaves of E. ulmoides.

Husbandry

Plantings for the production of bark of E. ulmoides are tended for about 15-20 years before actual production starts. Plantings for the production of leaves for beverages are pruned at 40 cm height in order to induce the growth of lateral branches in 2 years; leaves to be used are cropped from the epinasty branches after 3 years.

The application of 2000 ppm 2-diethylaminoethyl-3,4-dichlorophenyl ether (DCPTA) to greenhouse-grown E. ulmoides plants resulted in an 18% increase in the gutta content. Leaf area and plant height were also enhanced. Field studies employing 100 ppm of a proprietary regulator, FVCL2, produced a 20% increase in leaf gutta.

Diseases and pests

Regeneration of bark in E. ulmoides can be seriously affected by fungal rot after harvesting.

Harvesting

The bark of E. ulmoides is peeled in spring or early summer, from about (10-)15-20-year-old trees, at least 15 cm in diameter. Care should be taken not to girdle the tree; preferably a third should be spared.

Yield

The concentration of medicinally important compounds in the leaves of E. ulmoides is influenced by production area, harvest time and treatment after harvesting. Leaves and branches are harvested for the production of gutta-percha. 3-4-year-old plantations for gutta-percha production yield 200-250 kg gutta-percha per ha.

Handling after harvest

The pieces of bark of E. ulmoides, folded with the inner surfaces together, are tied with rice straw and left to sweat for a week. When the inside is brownish-black, the bark is untied, flattened and dried in the sun, and the coarse outer bark is scraped off. The remaining stringy inner bark, revealing silvery and extensible filaments when broken, is chopped into blocks and marketed.

Genetic resources and breeding

The high demand for E. ulmoides poses threats of genetic erosion locally as a result of over-collecting. Despite its long history of use and cultivation the genetic diversity does not seem to be fully exploited let alone properly guarded. The genetic basis for the recently established plantings outside its natural distribution is unclear.

Prospects

The extracts and compounds isolated from E. ulmoides display interesting pharmacological activities, especially in the field of hypertension, cholesterol metabolism, muscle pathology and bone-calcium metabolism. All these effects are of great interest for the treatment of major global complaints, such as heartdiseases and osteoporosis. Therefore E. ulmoides might be of interest for future developments (for example lead-compounds), and merits further research.

Literature

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• Li, Y.M., Sato, T., Metori, K., Koike, K., Che, Q.M. & Takahashi, S., 1998. The promoting effects of geniposidic acid and aucubin in Eucommia ulmoides Oliver leaves on collagen synthesis. Biological and Pharmaceutical Bulletin 21(12): 1306-1310.
• Metori, K., Ohashi, S., Takahashi, S. & Tamura, T., 1994. Effects of Du-Zhong leaf extract on serum and hepatic lipids in rats fed a high-fat diet. Biological and Pharmaceutical Bulletin 17(7): 917-920.
• Ogawa, H., Tasaka, M., Meguro, T. & Sasagawa, S., 1994. Effect of Tochu leaf powder on lipid metabolism in hypercholesterolemic SHRSP (Stroke-prone Spontaneously Hypertensive Rats). Journal of the Japanese Society of Nutrition and Food Science 47(4): 301-306.
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Authors

• Nguyen Nghia Thin