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A 30-d feeding trial was conducted to investigate effects of dietary eucommia ulmoides leaf extract (ELE) on growth performance, activities of digestive enzymes, antioxidant capacity, immunity, expression of inflammatory factors and feeding-related genes of large yellow croaker larvae. Five micro-diets were formulated with supplementation of 0 g kg−1 (the control), 5 g kg−1 (0·5 %), 10 g kg−1 (1·0 %) and 20 g kg−1 (2·0 %) of ELE, respectively. Results showed that the best growth performance was found in larvae fed the diet with 1·0 % ELE. Furthermore, ELE supplementation significantly increased the npy expression at 1·0 % dosage, while increased ghrelin in larvae at 0·5 % dosages. The activity of leucine aminopeptidase in larvae fed the diet with 1·0 % ELE was significantly higher than the control, while alkaline phosphatase was significantly upregulated in larvae fed the diet with 2·0 % ELE. A clear increase in total antioxidant capacity in larvae fed the diet with 1·0 % ELE was observed, whereas catalase activity was significantly higher in 1·0 % and 2·0 % ELE supplementation compared with the control. Larvae fed the diet with 1·0 % ELE had a significantly higher activities of lysozyme, total nitric oxide synthase and nitric oxide content than the control. Moreover, transcriptional levels of cox-2, il-1β and il-6 were remarkably downregulated by the supplementation of 0·5–1·0 % ELE. This study demonstrated that the supplementation of 1·0 % ELE in diet could increase the growth performance of large yellow croaker larvae probably by promoting expression of feeding-related genes, enhancing antioxidant capacity and immunity and inhibiting expression of inflammatory factors.

Ultraviolet (UV) irradiation is a well known photo-immunosuppressant. To determine the effect of Eucommia ulmoides leaf extract (ELE) components (chlorogenic acid, geniposidic acid, and asperuloside) on UVB induced immunosuppression, we examined mice that were contact hypersensitized. Systemic immunosuppression was induced in the C57BL/6j mice that were sensitized with 0.5% oxazolone through the skin by a single exposure to UVB. Consecutive oral administration of ELE, chlorogenic acid, or geniposidic acid significantly reduced UVB-induced suppression of the contact hypersensitivity (CHS) response. The treatment with chlorogenic acid or geniposidic acid decreased the serum interleukin-10 levels in the sensitized mice after UVB irradiation. Additionally, the level of plasma reactive oxygen species and the expression of skin mast cells decreased in the chlorogenic acid-treated mice. Contrarily, the expression of regulatory T cell in the skin decreased in the geniposidic acid-treated mice. These results suggest that chlorogenic and geniposidic acids prevent the photo-immunosuppression of the CHS response.

Asthma is characterized by chronic inflammation of the airway mucosa. As Eucommia ulmoides Oliv. leaf extract (ELE) has been known to have anti-inflammatory properties, herein, we investigated the effect of ELE on interleukin (IL-) 8 production in A549 cells, a human airway epithelial cell line. The addition of ELE 1 h before tumor necrosis factor-alpha (TNFα) stimulation inhibited IL-8 production by A549 cells in a concentration-dependent manner. The addition of geniposidic acid, the main component of ELE, also inhibited IL-8 production. To further investigate the mechanism by which ELE inhibits IL-8 production, the effect of ELE or geniposidic acid on TNFα-stimulated p38 phosphorylation was examined by Western blotting. After 30 min of TNFα stimulation, p38 phosphorylation was inhibited by the addition of ELE or geniposidic acid, suggesting that ELE inhibited IL-8 production in TNFα-stimulated A549 cells by suppressing one of the signal transducers of p38 phosphorylation. These results indicate that ELE can be used as an effective measure against asthma, particularly neutrophilic asthma.

The bark and the leaf of Eucommia ulmoides Oliv. content similar bioactive components, but the leaf of this medically important plant is mostly abandoned. In this study, we revealed that the aqueous extract of E. ulmoides leaf (EUL) can promote the growth of the probiotic Lactobacillus bulgaricus (LB) and inhibit the formation of osteoclast in vitro. This extract was next administrated to senescence‐accelerated mice P6 to evaluate examine its influence on the composition of gut microbiota (GM), short‐chain fatty acids (SCFAs), and osteoporosis (OP). The results showed that supplementation of the EUL aqueous extract to the mouse model: (a) increased bacterial diversity and Firmicutes/Bacteroidetes ratio in the gut, (b) increased SCFAs concentration in the feces and serum, and (c) ameliorated OP based on the results of bone mineral density (BMD), Dual‐energy X‐ray bone scan, and HE staining of distal femur., The aqueous extract of E. ulmoides leaf altered gut microbiota composition, enhanced short‐chain fatty acids production, and ameliorated osteoporosis in the osteoporotic mouse model. This study should promote the future development of EUL as a functional food to treat OP.

Eucommia ulmoides leaves (EL) are rich in phenolic acids and flavonoids, showing enhancing intestinal health effects. The intestinal microbiota-bile acid axis plays important roles in the occurrence and recovery of inflammatory bowel disease (IBD). However, whether EL extract (ELE) has regulatory effects on the intestinal microbiota, bile acid metabolism, and IBD is still unclear. To fill this gap, 2% dextran sulfate sodium (DSS)-induced mild IBD in a C57BL/6J mouse model that was treated with 200 or 400 mg/kg (intake dose/body weight) ELE was used. Oral ELE supplementation alleviated DSS-induced shortening of colon and colonic epithelial injury. Compared with the DSS group, ELE supplementation significantly decreased Toll-like receptor 4 (TLR4) and interlukin-6 (IL-6) and increased occludin and claudin-1 mRNA expression level in the colon (p < 0.05). Combined 16S rRNA gene sequencing and targeted metabolomic analyses demonstrated that ELE significantly improved the diversity and richness of the intestinal microbiota, decreased the abundance of Bacteroidaceae, and increased Akkermansiaceae and Ruminococcaceae abundance (p < 0.05) compared with DSS-induced IBD mice. Moreover, ELE significantly increased the serum contents of deoxycholic acid (DCA) and tauroursodeoxycholic acid (TUDCA), which were highly positively correlated with Akkermansia and unidentified_Ruminococccaceae relative to the DSS group. We then found that ELE increased Takeda G-protein coupled receptor 5 (TGR5), claudin-1, and occludin mRNA expression levels in the colon. In the Caco-2 cell model, we confirmed that activation of TGR5 improved the reduction in transepithelial electoral resistance (TEER) and decreased the permeability of FITC-dextran on monolayer cells induced by LPS (p < 0.05). siRNA interference assays showed that the decrease in TGR5 expression led to the decrease in TEER, an increase in FITC-dextran permeability, and a decrease in claudin-1 protein expression in Caco-2 cells. In summary, ELE alleviated IBD by influencing the intestinal microbiota structure and composition of bile acids, which in turn activated the colonic TGR5 gene expression in the colon and promoted the expression of tight junction proteins. These findings provide new insight for using ELE as a functional food with adjuvant therapeutic effects in IBD.

The recent discovery that the impairment of autophagic flux in non-alcoholic fatty liver disease (NAFLD) might be a strong determining factor in steatosis suggests the potential of therapeutic control of autophagic flux with natural agents in restoring NAFLD. We investigated the potential of Eucommia ulmoides leaf extract (EUL) to control dyslipidemia in NAFLD. EUL supplementation (200 mg/kg) promoted recovery from high fat diet (HFD)-induced lipid dysmetabolism. This hepatoprotective efficacy was accompanied by suppression of endoplasmic reticulum (ER) stress, enhancing lysosomal functions, and thereby increasing autophagic flux. We found a strong indication that inhibition of the mTOR-ER stress pathway was related to the enhanced autophagic flux. However, the direct antioxidative effect of EUL on cytoprotection cannot be ruled out as a significant contributing factor in NAFLD. Our findings will aid in further elucidating the mechanism of the anti-steatosis activity of EUL and highlight the therapeutic potential of EUL in the treatment of NAFLD.

The antihypertensive effects of the Eucommia ulmoides leaf extract (ELE) and its methanol-eluted fraction (MeOH ext, Eucommia leaf (EL) glycoside) and water-eluted fraction (H2O ext), fractionated using a Diaion HP-20 column, were studied in spontaneously hypertensive rats (SHR) by intravenous (i.v.) administration. Additionally, to clarify the oral antihypertensive effect, a single oral (p.o.) administration of ELE, MeOH ext, and H2O ext as well as geniposidic acid (GA) and chlorogenic acid (CA)—the major component of the ELE and MeOH ext—were performed in SHR. The i.v. administration of the ELE and MeOH ext showed significant transient antihypertensive effects, which were attenuated with atropine pretreatment in SHR, implying that the effect was mediated via an agonistic action on the muscarinic acetylcholine receptors. In a similar manner, p.o. administration of both ELE and MeOH ext showed significant antihypertensive effects. Although both the components also showed antihypertensive effects, the effect of GA was more potent than that of CA. On the other hand, the H2O ext showed a persistent antihypertensive effect with i.v. administration, which remained unaffected on atropine pretreatment, although such an effect was not observed with p.o. administration. The findings mentioned above imply that the MeOH ext (EL glycoside) contributes to the ELE-induced antihypertensive effect, with GA contributing more to the effect than CA.

The ingestion of dietary antioxidants, including vitamin C (VC), is suggested to play an important role in the prevention of gastric cancer associated with Helicobacter pylori (HP) infection. Recently, water extracts of Tochu (Du-zhong, Eucommia ulmoidea OLIVER) leaves (WETL) have been reported to have potent antioxidant and antimutagenic effects. The present study investigated the effect(s) of VC and WETL on gastric mucosal injury induced by ammonia and a VC deficient diet. Guinea pigs fed the water containing ammonia and/or a VC-deficient diet were simultaneously treated with WETL or VC. Intramucosal levels of thiobarubiturate reactive substances (TBARS), an index of lipid peroxidation, increased significantly in animals fed ammoniated water and VC-deficient diets. This was accompanied by accelerated cell proliferation and increases in immunohistochemical staining indices for oxidative stress-induced DNA adducts and strand breaks (e.g., BrdU-uptake, 8-OhdG, ssDNA and the TUNEL reaction). The administration of either WETL or VC to the ammoniated water and VC-deficient diets ameliorated the increases in intramucosal TBARS levels and labeling indices of BrdU, 8-OHdG, ssDNA and TUNEL, i.e., the levels were similar to those measured in the normal-fed control animals. These data suggest that insufficient VC ingestion may be an important risk factor for gastric cancer development in patients with HP infections. Furthermore, our results suggest that WETL or some constituent may contribute to the prevention of oxidative gastric injury that precedes carcinogenesis.

BACKGROUND Due to its excellent adsorption capability, activated carbon(AC) has also been employed as a drug carrier. However, applications of the AC carrier in traditional Chinese medicine (TCM) have been rare. We selected the Eucommia ulmoides leaf extract as the drug of choice and AC as its carrier, to investigate the adsorption and sustained release behavior of the Eucommia ulmoides leaf extract on the AC. METHODS AC was employed in this study as the sustained release carrier and its capability for adsorption and sustained release of Eucommia ulmoides leaf extracts was systematically investigated. Acid or alkali modified AC was assessed for its ability to absorb and sustain release of Eucommia ulmoides leaf extracts according to a variety of adsorption/release rate and composition. RESULTS Results demonstrated that the adsorption rate for the differently modified AC reached above 80 %, whereas the adsorption of Eucommia ulmoides leaf extracts on the AC was selective. The composition of the sustained release liquid, which was treated by the acid modified AC, was almost similar to the original extract. The acid modified AC was therefore taken as an optimal carrier that can be used for Eucommia ulmoides leaf extracts sustained release. CONCLUSION The synchronous release and absorption of different ingredients in the active ingredient release process ensures the global and cooperative effect with sustained and less toxic advantages. The ideal synchronous release is that the absorbed component proportion is consistent with its release. The acid modified AC was therefore taken as the optimal carrier that can be used for Eucommia ulmoides leaf extracts sustained release.