Du Zhong
Scientific Name(s): Eucommia ulmoides Oliv.
Common Name(s): Du zhong (Chinese), Tochu (Japanese)
Medically reviewed by Drugs.com. Last updated on Oct 1, 2022.
Clinical Overview
Use
The medical literature includes numerous studies on the use of Eucommia ulmoides (du zhong) for treating diabetes, inflammation, and obesity. One clinical study exists for its use in treating hypertension.
Dosing
E. ulmoides is commercially available as a combination product or alone as a capsule, tablet, powder, or tea, primarily for treating hypertension. Tablets: 3 to 5 (100 mg) tablets 3 times per day with warm water after meals. One clinical study used a 500 mg standardized extract 3 times daily for 8 weeks.
Contraindications
Avoid use in patients who are hypersensitive to any components of E. ulmoides. The herb may be contraindicated in patients diagnosed with estrogen-dependent cancers.
Pregnancy/Lactation
Information regarding safety and efficacy in pregnancy and lactation is lacking.
Interactions
None well documented.
Adverse Reactions
One clinical study of E. ulmoides documented moderately severe headache, dizziness, edema, and onset of a cold.
Toxicology
No information in humans is available.
Scientific Family
- Eucommiaceae
Botany
E. ulmoides is native to China and is the only species of Eucommiaceae. It is a deciduous and dioecious woody species distributed throughout the valleys, hills, and mountains of central and eastern China, growing to 10 to 15 m in height. The oval-shaped leaves are 8 to 16 cm long, arranged alternately with a serrated margin. The plant’s small, green flowers are typically in bloom from March to May, and the fruits ripen between June and November.1, 2, 3
History
Use of the plant in traditional Chinese medicine began as early as 2,000 years ago.1 The plant's bark and leaves contain the lignan pinoresinol diglucoside, which has potent antihypertensive properties. In folk medicine, the dried and heated outer portion of the stem has been used for supporting muscle and lung function, lowering blood pressure, preventing miscarriages, improving the tone of the liver and kidneys, and increasing longevity.4, 5 The leaves have been used in foods. An aqueous leaf extract known as du zhong tea is popular in China and Japan for treating hypertension and improving health. In traditional Chinese medicine, the seed oil is commonly used to treat hypertension, rheumatoid arthritis, back pain in the lumbar region, and hip pain.6
The whole plant, except the transport tissue xylem, contains an isomer of natural rubber (Eucommia rubber) that is of high economic value and used as a raw material in the organic chemical industry. Commercial cultivation of E. ulmoides started in the 1980s, and utilization and overexploitation have threatened the existence of the species in the wild.1, 2, 7
Chemistry
E. ulmoides produces more than 30 active compounds in its bark and leaves.3 More than 70 components have been identified in E. ulmoides.8
The dominant fatty acid components in E. ulmoides seed oil are linolenic (57%), linolelaidic (13%), oleic (16%), palmitic (10%), and stearic (4%) acid. The percentage of polyunsaturated fatty acids in the seed oil is 70% and the fraction of monounsaturated versus saturated fatty acids is 17% and 13%, respectively.6 Approximately 27% of the seed oil is edible.2 Iridoids, phenylpropanoids, and flavonoids have been isolated from E. ulmoides and many pharmacologic activities have been attributed to the lignans and iridoids.9 Antihypertensive activity is associated with pinoresinol di-beta-D-glucopyranoside and geniposidic acid. Anti-inflammatory, antithrombotic, and anticancer activity are associated with genipin and geniposide. Antibacterial, antioxidant, and antimutagenic activity are associated with chlorogenic acid. Antioxidant, anti-inflammatory, and antiviral activity are associated with the flavonoids, which include baicalein, wogonin, and oroxylin A.
Natural rubber is classified into cis-1,4-polyisoprene and trans-1,4-polyisoprene.10, 11 Industrially, cis-1,4-polyisoprene is used in more than 40,000 products. E. ulmoides accumulates trans-1,4-polyisoprene in its leaves, bark, roots, and fruit coatings and is used for such diverse products as telegraph cables, conveyors, golf balls, chewing gums, and root canal filling materials.
The antihypertensive compound (+)-pinoresinol-di-beta-D-glucopyranoside was evaluated in rats as highly lipophilic, with 95% eliminated in plasma within 24 hours.12
Uses and Pharmacology
Numerous studies have been published on the use of E. ulmoides for treating diabetes, inflammation, and obesity. One clinical study exists for its use in treating hypertension.
Diabetes
In vitro data
The antioxidant and antidiabetic activities of E. ulmoides leaves are associated with 3 flavonol glycosides with glycation inhibitory activity.13, 14
Animal data
Although the exact mechanism was not elucidated, powdered E. ulmoides leaves (1 g per 100 g diet) and its water extract (0.187 g per 100 g diet) lowered blood glucose and increased plasma insulin and C-peptide levels in streptozotocin-induced diabetic rats. The supplement also enhanced the function of pancreatic beta cells.15 In a similar study, a 1% E. ulmoides leaf water extract reduced hyperglycemia in a type 2 diabetic mouse model by increasing plasma insulin levels and lowering plasma glucagon levels; hyperlipidemia was also reduced by suppressing gluconeogenesis and the biosynthesis of fatty acid and cholesterol in the liver.16, 17 E. ulmoides leaf extract (500 and 1,000 mg/kg/day) administered orally to rats using 15% fructose as drinking water over 4 weeks decreased plasma insulin levels, insulin resistance, and abnormal perivascular innervation.18 An aqueous extract of E. ulmoides increased expression of superoxide dismutase and alpha-actin in penile tissues of rats, which may lead to an increase in nitric oxide bioavailability, improving erectile function.19
Clinical data
Limited clinical data are available.
Hypertension
In vitro data
E. ulmoides leaf and bark water extracts caused an endothelium-dependent, nitric oxide–mediated vasorelaxation in rat aorta and dog carotid arteries precontracted with 1 mcM phenylephrine. Activation of potassium channels may be involved with the mechanism of vasorelaxation.20 The effect of an E. ulmoides extract on isoproterenol-stimulated lipolysis was examined in a human fat cell with beta-adrenergic activity demonstrated by the extract.21
Animal data
A 1.9% E. ulmoides lignan bark extract reduced blood pressure in rats by increasing the release of nitric oxide, modulating the renin-angiotensin system, and directly relaxing the arterial vessel.8 In a similar study, E. ulmoides lignan bark extract reduced arterial blood pressure in spontaneously hypertensive rats and protected against both structural and functional renal injury.22 The renal protective effects may be partly due to inhibition of aldose reductase, which is involved with the pathology of hypertension and hypertensive organ injury. Rats administered a water extract of Eucommia orally at 200 mg/kg resulted in an up to 20 mm Hg drop in blood pressure within 2 hours.21
Clinical data
A noncontrolled Russian trial documented a 25/14 mm Hg drop in blood pressure in human subjects with hypertension treated with Eucommia tea.21
An aqueous bark extract of Eucommia standardized to 8% pinoresinol di-beta-D-glucoside was evaluated for antihypertensive activity in humans in a controlled clinical trial. Twenty healthy patients with blood pressure between 120 to 160/80 to 100 mm Hg were randomized to receive the 500 mg standardized extract 3 times daily for 8 weeks. No difference in blood pressure and no toxicity were found. A second trial conducted in 29 healthy patients with blood pressure between 120 to 160/80 to 100 mm Hg was randomized to administer 1 g of Eucommia extract 3 times daily for 2 weeks. Results documented an average reduction in blood pressure of 7.5/3.9 mm Hg and the extract was well tolerated. The standardized extract exhibited beta-adrenergic blocking activity.21
Inflammation
In vitro data
The mechanism of anti-inflammatory activity with a protein-bound polysaccharide isolated from the stem bark of E. ulmoides was associated with blockade of complement activation through the classical and alternative pathways.23, 24 Coagulation assays on the polysaccharide showed very limited anticoagulation activity when compared with heparin.
Animal data
A 2.2% E. ulmoides bark polysaccharide extract protected the kidneys from glomerular injury by reducing immunoglobulin deposition, lowering proteinuria, and inhibiting increased production of serum autoantibodies and total immunoglobulin G in a systemic lupus erythematosus–like syndrome induced in mice.25
Clinical data
Limited clinical data are available.
Neuroprotective effects
In vitro data
Neuroprotective and antioxidant activity was demonstrated with an E. ulmoides water bark and leaf extract against amyloid-beta peptide cytotoxicity in rat pheochromocytoma PC-12 cells.26 The protective effects were associated with inhibiting excessive Ca2+ influx and reducing lactate dehydrogenase leakage. The major active constituents of the bark and leaves were geniposidic and chlorogenic acids. Several mechanisms of action were proposed in another study in which E. ulmoides bark extract protected against hydrogen peroxide–induced neuronal cell death in human neuroblastoma cells, including inhibition of cytotoxicity, reduction of reactive oxygen species, DNA condensation, mitochondria membrane potential stabilization, and regulation of key signaling proteins involved in cell death.27
Animal data
An herbal medicine composed of 6 crude herbs, including E. ulmoides, protected against peripheral nerve injury in rats by promoting nerve regeneration and improving motor function recovery by reducing oxidative stress.28 An aqueous E. ulmoides extract protected mice from amyloid-beta peptide–induced learning, memory, and cognition effects by inhibiting aceylcholinesterase activity in the hippocampus and frontal cortex.29
Clinical data
Limited clinical data are available.
Obesity
Animal data
Although the precise mechanism is unknown, E. ulmoides leaf extracts stimulated lipolysis and thermogenesis in rats by elevating epididymal white and interscapular brown adipose tissue sympathetic nerve activity. The amount of abdominal fat and body weight decreased due to suppression of appetite by inhibiting the activities of the parasympathetic nerves innervating the GI tract.30 Administration over 3 months of Eucommia leaf extract or green leaf powder stimulated several antiobesity and antimetabolic effects, including decreased adenosine-5′-triphosphate production in white adipose tissue, accelerated fatty acid beta-oxidation in the liver, and increased use of ketone bodies and glucose in skeletal muscle.31 Plasma levels of resistin, which induces insulin resistance, were decreased. Plasma levels of adipocytokines, which have an antiarteriosclerotic effect and improve insulin sensitivity, were increased. Administration over 4 weeks of a 30% methanol E. ulmoides leaf fraction identified asperuloside as the active component in reducing body weight, white adipose tissue weight, plasma triglyceride levels, and free fatty acids levels in mice.32
Clinical data
Limited clinical data are available.
Postmenopausal osteoporosis
In vitro data
A biological screening assay identified 6 estrogenic compounds from E. ulmoides capable of activating estrogen receptor–dependent transcription.33
Some compounds exerted high potency on transactivating estrogen receptor-alpha but lacked selectivity for estrogen receptor-beta signaling. Selective estrogen receptor-alpha activity may increase the risk of estrogen receptor-alpha breast cancers, uterotrophic activities, and thromboembolic disorders.
Animal data
Over a 16-week period, daily oral administration of a 10% E. ulmoides cortex extract prevented estrogen deficiency–induced bone loss and deterioration of trabecular microarchitecture, which contributes to bone strength and may reduce fracture risk in osteoporosis induced by ovariectomy in rats.34 The activity may be related to the concentration of compounds such as lignans, phenolic acid, and flavonoids.34, 35
Clinical data
Limited clinical data are available.
Wound healing
In vitro data
A formula ratio of 1:3 of ginseng to E. ulmoides leaf was effective in stimulating collagen synthesis and preventing decreased protein metabolism in rat granuloma.36 Aucubin from E. ulmoides protected against ultraviolet B–induced free radicals in a human skin fibroblast cell line by decreasing matrix metalloproteinases (MMP)–1 production and senescence-associated beta-galactosidase activity.37
Reducing MMP-1 production led to reduced degradation of the extracellular matrix by photoaging. Reducing beta-galactosidase activity led to less activity by senescent fibroblasts, producing less collagen and elastin.
Animal data
A methanol extract of E. ulmoides leaves stimulated collagen synthesis in aged model rats.38 The active ingredients of the methanol extract were identified as geniposidic acid and aucubin. A similar study in false-aged model rats administered a methanol extract of E. ulmoides leaves, with the active ingredient geniposidic acid, improved the turnover or collagen synthesis rate in the stratum corneum.39 Over 3 weeks, granuloma formation and collagen content were improved in healthy rats administered an E. ulmoides hot water leaf extract.40 Histochemical evaluation revealed new capillary vessels and a greater number of fibroblasts and monocytes.
Clinical data
Limited clinical data are available.
Other pharmacological uses
Antifungal activity
Two antifungal peptides from the bark of E. ulmoides inhibited 8 plant pathogenic fungi from cotton, wheat, potato, tomato, and tobacco, including Phytophthora infestans, Ascochyta lycopersici, Verticillium dahlia, Gibberella zeae, Alternaria nicotianae, Fusarium moniliforme, Fusarium oxysporum, and Colletotrichum gossypii.41
Antioxidant activity
Du zhong tea (leaf extract) is commonly used in Japan as a functional health food.14 The tea may reduce human exposure to dietary mutagens42 and carcinogens.43 Additional antioxidant activity includes inhibitory effects against low-density lipoprotein44 oxidative modification induced by copper and prevention of oxidative gastric injury.45
Tobacco substitute
No toxicity, mutagenicity, or immunotoxicity was documented for mice inhaling a tobacco substitute primarily composed of E. ulmoides leaves at levels of up to 20 cigarettes per day over 4 weeks.46
Uterine involution
Traditional Chinese postpartum care includes behavioral, dietary, and herbal therapy to help facilitate uterine recovery for women after delivery. In 1 clinical study of 127 postpartum women between 4 to 6 weeks after delivery, the anteroposterior diameter of the uterus and cavity were significantly reduced with herbal supplementation of E. ulmoides during the first postpartum month.47
Dosing
E. ulmoides (du zhong) is commercially available as a combination product or alone as a capsule, tablet, powder, or tea, primarily for treating hypertension.
Tablets
3 to 5 (100 mg) tablets 3 times per day with warm water after meals. One clinical study used a 500 mg standardized extract 3 times daily for 8 weeks.
Pregnancy / Lactation
Information regarding safety and efficacy in pregnancy and lactation is lacking.
Interactions
None well documented. Theoretically, patients self-medicating with E. ulmoides may experience additive adverse effects if taking anticoagulant, antiplatelet, low–molecular weight heparins, or thrombolytic medications. Additive adverse effects with medications for diabetes, high blood pressure, and weight reduction may also be possible.
Adverse Reactions
One clinical study documented moderately severe headache, dizziness, edema, and onset of a cold. Serum glucose levels increased by 3 ± 2 mg/dL from a baseline of 95 ± 3 mg/dL. Serum creatinine increased by 0.02 ± 0.01 mg/dL from a baseline of 0.87 ± 0.03 mg/dL.21
Toxicology
No information in humans is available. One study found no acute toxic symptoms for mice treated with 6.68 g/kg of Eucommia lignans after 14 days. The 6.68 g/kg dose is equivalent to almost 334 times the human clinical dose.22 No acute toxicity in rats was exhibited for 1,200 mg/kg. No toxicity was evident as determined by clinical appearance, histopathology, and serum chemistry for repeated dosing of 200, 600, and 1,200 mg/kg over 28 days.21
A water E. ulmoides leaf extract decreased carbon tetrachloride–induced chronic hepatotoxicity in rats.48 Geniposide and genipin from E. ulmoides bark protected rat kidney tissue from cadmium-induced oxidative stress by inhibiting nitric oxide production.49
References
Disclaimer
This information relates to an herbal, vitamin, mineral or other dietary supplement. This product has not been reviewed by the FDA to determine whether it is safe or effective and is not subject to the quality standards and safety information collection standards that are applicable to most prescription drugs. This information should not be used to decide whether or not to take this product. This information does not endorse this product as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this product. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this product. This information is not specific medical advice and does not replace information you receive from your health care provider. You should talk with your health care provider for complete information about the risks and benefits of using this product.
This product may adversely interact with certain health and medical conditions, other prescription and over-the-counter drugs, foods, or other dietary supplements. This product may be unsafe when used before surgery or other medical procedures. It is important to fully inform your doctor about the herbal, vitamins, mineral or any other supplements you are taking before any kind of surgery or medical procedure. With the exception of certain products that are generally recognized as safe in normal quantities, including use of folic acid and prenatal vitamins during pregnancy, this product has not been sufficiently studied to determine whether it is safe to use during pregnancy or nursing or by persons younger than 2 years of age.
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