Eucommia

Generic name: Eucommia Ulmoides Oliv.
Brand names: Du Zhong (Chinese), Eucommia, Hardy Rubber Tree, Tochu (Japanese)

Usage of Eucommia

Numerous animal and in vitro studies evaluating effects of E. ulmoides on diabetes, inflammation, and obesity have been published. A few small clinical trials have evaluated use for treatment of hypertension.

Antifungal activity

In vitro data

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 dahliae, Gibberella zeae, Alternaria nicotianae, Fusarium moniliforme, Fusarium oxysporum, and Colletotrichum gossypii.(Huang 2002)

Anti-inflammatory activity

Animal and 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. Coagulation assays on the polysaccharide showed very limited anticoagulation activity when compared with heparin.(Zhu 2008, Zhu 2009)

In a systemic lupus erythematosus–like syndrome induced in mice, a E. ulmoides 2.2% 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.(Jiang 2011) Anti-inflammatory effects of aucubin extracted from the seeds of E. ulmoides have also been demonstrated in cardiac dysfunction mouse models.(Duan 2019, Wu 2018) In an ulcerative colitis mouse model, E. ulmoides leaf extract significantly improved symptoms (ie, bloody stool) and colonic pathology.(Murakami 2018) Inflammation in rats with induced gastric ulcers was significantly reduced by a water and ethanol extract of E. ulmoides leaves; the primary mechanism was identified as the PI3K/Akt/GSK-3beta/Nrf2 signaling pathway.(Gong 2022)

Antimicrobial activity

Experimental data

In one study, the male flower extract of E. ulmoides showed significant activity against Staphyloccus aureus, with a minimum inhibitory concentration of 40 mg/mL and a minimum bactericidal concentration of 80 mg/mL.(Xing 2022)

Antioxidant activity

Animal and in vitro data

Studies suggest du zhong tea may reduce exposure to dietary mutagens(Sasaki 1996) and carcinogens.(Nakamura 1997) Antioxidant activity includes inhibitory effects against low-density lipoprotein,(Yen 2002) oxidative modification induced by copper, and prevention of oxidative gastric injury.(Yang 2003) Geniposide and genipin from E. ulmoides bark protected rat kidney tissue from cadmium-induced oxidative stress by inhibiting nitric oxide production.(Liu 2012) Antioxidant effects of aucubin extracted from E. ulmoides seeds were observed in cardiac dysfunction mouse models.(Duan 2019, Wu 2018)

Antiviral activity

In vitro data

E. ulmoides bark extract, specifically pinoresinol-O-beta-D-glucopyranoside, demonstrated antiviral activity against 2 strains of H1N1 viruses in vitro. No activity was observed against H3N2, H9N2, or influenza B.(Li 2019)

Atherosclerosis

Animal data

In an atherosclerotic mouse model, administration of E. ulmoides leaf extract significantly reduced plaque formation in a dose-dependent manner compared with untreated controls (P=0.0023). The thickness of the intima media was also significantly reduced in the extract group (P=0.0004). No changes in serum total cholesterol levels were observed; however, decreases in inflammatory cytokine production (ie, tumor necrosis factor alpha [TNF-alpha], interleukin 1 [IL-1]) were documented.(Hashikawa-Hobara 2020)

Bone growth stimulation

In vitro data

In vitro data demonstrated that a strontium-enhanced polysaccharide complex from E. ulmoides stimulated bone growth and integration when applied to the synthetic bone implant material polyetheretherketone.(Mengdi 2022)

Cardiac dysfunction

Animal data

Improvements in cardiac dysfunction have been demonstrated in animal models administered aucubin extracted from the seeds of E. ulmoides. The mechanism was related to anti-inflammatory, antioxidant, and antifibrotic effects.(Duan 2019, Wu 2018) A 7-day regimen with aucubin significantly improved cardiac function (ie, left ventricular [LV] end diastolic dimension, LV ejection fraction, LV fractional shortening) versus vehicle (P<0.05) in a lipopolysaccharide (LPS)-induced cardiac dysfunction mouse model.(Duan 2019) Similarly, in a pressure-overload cardiac mouse model, aucubin administered for 25 days reduced hypertrophic responses compared with placebo (P<0.05).(Wu 2018)

Diabetes

Animal and in vitro data

The antioxidant and antidiabetic activities of E. ulmoides leaves are associated with 3 flavonol glycosides with glycation inhibitory activity.(Hsieh 2000, Kim 2004)

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.(Lee 2005) In a similar study of a type 2 diabetic mouse model, a 1% E. ulmoides leaf water extract reduced hyperglycemia 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.(He 2011, Park 2006) E. ulmoides leaf extract (500 and 1,000 mg/kg/day) administered orally to rats using fructose 15% solution as a drinking fluid over 4 weeks decreased plasma insulin levels, insulin resistance, and abnormal perivascular innervation.(Jin 2010) 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.(Zhang 2006)

Hepatoprotective effects

Animal data

A water E. ulmoides leaf extract decreased carbon tetrachloride–induced chronic hepatotoxicity(Hung 2006) and prevented high-fat diet−induced hepatic steatosis in rats (P<0.05).(Lee 2019) E. ulmoides polysaccharides demonstrated hepatoprotective effects in a hepatic ischemia-reperfusion injury rat model; significant improvements in ALT and AST as well as in histological injuries were observed compared with untreated controls. Mechanisms of protection included both antioxidant and anti-inflammatory (ie, TNF-alpha, IL-1beta) actions.(Gao 2020)

Hypertension

Animal and 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.(Kwan 2003) When the effects of an E. ulmoides extract on isoproterenol-stimulated lipolysis were examined in a human fat cell, beta-adrenergic activity was observed.(Greenway 2011)

An E. ulmoides 1.9% 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.(Luo 2010) 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. 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.(Li 2012) In rats administered a water extract of Eucommia orally at 200 mg/kg, up to a 20 mm Hg drop in blood pressure was observed within 2 hours.(Greenway 2011)

Clinical data

A noncontrolled Russian trial documented a 25/14 mm Hg drop in blood pressure in human subjects with hypertension treated with E. ulmoides tea.(Greenway 2011)

An aqueous bark extract of Eucommia (standardized to 8% pinoresinol di-beta-D-glucoside) was evaluated for antihypertensive activity in a controlled clinical trial. Twenty healthy participants with blood pressure between 120 to 160/80 to 100 mm Hg were randomized to receive the 500 mg standardized Eucommia extract 3 times daily for 8 weeks; no difference in blood pressure and no toxicity was observed. In a second trial, 29 healthy patients with blood pressure between 120 to 160/80 to 100 mm Hg were randomized to receive Eucommia extract 1 g 3 times daily for 2 weeks. Results showed an average reduction in blood pressure of 7.5/3.9 mm Hg (P<0.008 vs placebo), and the extract was well tolerated. The standardized extract also exhibited beta-adrenergic–blocking activity.(Greenway 2011)

Neuroprotective effects

Animal and 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.(Zhou 2009) 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.(Kwon 2012) Lignans from an Eucommia leaf extract were neuroprotective for rat pheochromocytoma cells (an in vitro Parkinson disease model), particularly via activation of the PI3K/Akt/GSK-3beta/Nrf2 pathway.(Han 2022)

An aqueous E. ulmoides extract protected mice from amyloid-beta peptide–induced learning, memory, and cognition effects by inhibiting acetylcholinesterase activity in the hippocampus and frontal cortex.(Kwon 2011) Similarly, an E. ulmoides ethanolic extract improved motor impairment and dopamine levels in a mouse model of Parkinson disease,(Fan 2020) whereas aucubin extracted from E. ulmoides has shown anticonvulsant activity in a seizure mouse model by reducing seizure intensity and prolonging latency onset (P<0.05); mortality rate also decreased to 12.5% compared with 75% in the untreated group (P<0.05).(Chen 2019) In a zebrafish model of Alzheimer disease, an extract of E. ulmoides male flowers reduced cellular apoptosis and dyskinesia and decreased deposition of amyloid-beta protein.(Sun 2022)

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. Abdominal fat and body weight decreased due to suppression of appetite by inhibiting the activities of the parasympathetic nerves innervating the GI tract.(Horii 2010) Administration of Eucommia leaf extract or green leaf powder over 3 months 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.(Fujikawa 2010) Plasma levels of resistin, which induces insulin resistance, were decreased. Plasma levels of adipocytokines, which have an antiatherosclerotic effect and improve insulin sensitivity, were increased. When a 30% methanol E. ulmoides leaf fraction was administered over 4 weeks in mice, asperuloside was identified as the active component in reducing body weight, white adipose tissue weight, plasma triglyceride levels, and free fatty acid levels.(Hirata 2011)

Osteoporosis

Animal and in vitro data

A biological screening assay identified 6 estrogenic compounds from E. ulmoides capable of activating estrogen receptor–dependent transcription. In the biological screening assay, some E. ulmoides estrogenic compounds exerted high potency on transactivating estrogen receptor–alpha but lacked selectivity for estrogen receptor–beta signaling.(Wang 2011) 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.(Zhang 2009) The activity may be related to the concentration of compounds such as lignans, phenolic acid, and flavonoids.(Li 2011, Zhang 2009)

Polycystic ovary syndrome

Animal data

E. ulmoides leaf extract (total flavonoids 70%) administered for 21 days in a polycystic ovary syndrome, insulin-resistant rat model significantly improved ovary pathology, body weight, and pancreatic changes compared with untreated controls (P<0.05).(Peng 2021)

Rheumatoid arthritis

Animal data

A male flower E. ulmoides extract tested in a collagen-induced rat model of arthritis reduced inflammation and bone resorption by osteoclasts and inhibited synoviocyte proliferation.(Zhang 2021)

Tobacco substitute

Animal data

No toxicity, mutagenicity, or immunotoxicity was documented for mice inhaling a tobacco substitute primarily composed of E. ulmoides leaves at levels up to 20 cigarettes per day over 4 weeks.(Kim 2003)

Uterine involution

Clinical data

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 and 6 weeks postdelivery, the anteroposterior diameter of the uterus and cavity were significantly reduced with herbal supplementation of E. ulmoides during the first postpartum month.(Ho 2011)

Wound healing

Animal and in vitro data

A ginseng to E. ulmoides leaf formula ratio of 1:3 was effective in stimulating collagen synthesis and preventing decreased protein metabolism in rat granuloma.(Metori 1997) 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. 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.(Ho 2005)

A methanol extract of E. ulmoides leaves stimulated collagen synthesis in aged model rats.(Li 1998) 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.(Li 1999) Over 3 weeks, granuloma formation and collagen content were improved in healthy rats administered an E. ulmoides hot water leaf extract.(Li 2000) Histochemical evaluation revealed new capillary vessels and a greater number of fibroblasts and monocytes.

Eucommia side effects

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.(Greenway 2011)

In a biological screening assay, some E. ulmoides estrogenic 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.(Wang 2011)

Before taking Eucommia

Avoid use. Information regarding safety and efficacy in pregnancy and lactation is lacking.

How to use Eucommia

Clinical trial data are lacking to provide dosing recommendations. E. ulmoides (du zhong) is commercially available as a combination product or alone as a capsule, tablet, powder, or tea, primarily for treating hypertension.

Warnings

No toxicology information in humans is available. One study found no acute toxic symptoms in 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.(Li 2012) No acute toxicity in rats occurred with 1,200 mg/kg of E. ulmoides bark extract (standardized to 8% pinoresinol di-beta-D-glucoside); 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.(Greenway 2011)

What other drugs will affect Eucommia

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.

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