Search

Icariin, a flavonoid glycoside isolated from Epimedium brevicornum , exerts a variety of biological activities. However, its effects on depression-induced glucocorticoid resistance in asthma and the underlying mechanisms have not been elucidated. In this study, a murine model of asthma with depression was established by exposure to ovalbumin combined with chronic unpredictable mild stress, and icariin was given orally during ovalbumin challenge and chronic unpredictable mild stress exposure. Depression-like behaviors were assessed by the open field test, forced swim test, and tail suspension test. The characteristic features of allergic asthma, including airway hyperreactivity, histopathology, inflammatory cytokine levels in bronchoalveolar lavage fluid, and immunoglobulin E and corticosterone levels in serum, were examined. Following splenocyte isolation in vitro , the inhibitory effects of corticosterone on the proliferation and cytokine secretion of splenocytes, glucocorticoid receptor DNA-binding activity, and expression of p-glucocorticoid receptor s226, glucocorticoid receptor α , and p-p38 mitogen-activated protein kinase in splenocytes were determined. We found that icariin had limited effects on depression-like behaviors, however, it markedly suppressed airway hyperresponsiveness, inflammatory infiltration in lung tissues, levels of interleukin-4, interleukin-5, and interleukin-6 in bronchoalveolar lavage fluid, and immunoglobulin E in serum. Furthermore, icariin improved the inhibitory effects of corticosterone on lipopolysaccharide-stimulated splenocytes, increased the glucocorticoid receptor expression and glucocorticoid receptor DNA-binding activity, and inhibited the phosphorylation of glucocorticoid receptors S226 and p38 mitogen-activated protein kinase. Taken together, icariin improved glucocorticoid resistance in a murine model of asthma with depression associated with enhancement of glucocorticoid receptor function and glucocorticoid receptor expression, and its effects on the glucocorticoid receptor function were related to decreased phosphorylation of glucocorticoid receptors S226 and p38 mitogen-activated protein kinase. [ABSTRACT FROM AUTHOR]

Berberine is an isoquinoline derivative alkaloid extracted from Chinese herbs. Recent studies have demonstrated the therapeutic effect of berberine on glucose metabolic disorders. However, its specific mechanism is still unclear. Our study aimed to research the glucose-lowering effect of berberine in diabetic rats and to reveal the possible role of the cholinergic anti-inflammatory pathway. Diabetic rats induced by administration of a high-calorie diet and streptozocin tail vein injection were assessed by the oral glucose tolerance test. Then, the diabetic rats were divided into two groups, those with or without the alpha7 nicotinic acetylcholine receptor gene downregulated, respectively, followed by treatment including berberine for 6 weeks. Results of this study show that the administration of berberine downregulated levels of fasting blood glucose and fasting insulin, and ameliorated insulin resistance in diabetic rats. Treatment with berberine inhibited acetylcholinesterase activity, and upregulated acetylcholine levels in the serum and alpha7 nicotinic acetylcholine receptor gene expression in the liver tissue. Meanwhile, berberine reversed elevated expression of cytokines interleukin-1 β and TNF- α in the serum and downregulated nuclear factor κ B expression. However, berberine administration showed no glucose-lowering or anti-inflammatory effect in diabetic rats in which alpha7 nicotinic acetylcholine receptor gene expression was downregulated, and acetylcholinesterase activity was also significantly inhibited. In conclusion, berberine may ameliorate glucose metabolism by activating the alpha7 nicotinic acetylcholine receptor-mediated cholinergic anti-inflammatory pathway. [ABSTRACT FROM AUTHOR]

A fixed combination of Berberis aristata and Silybum marianum (Berberol) has been used by patients with dyslipidaemia. The aim of the present meta-analysis was to systematically evaluate the efficacy and safety of a fixed combination of B. aristata and S. marianum (Berberol) on serum lipid levels compared to placebo in a meta-analysis based on randomised, controlled trials. The meta-analysis was reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement, using the PICO (patients, intervention, comparison, outcome) format, and it was registered in the International Prospective Register of Systematic Reviews. The Cochrane Central Register of Controlled Trials, PubMed, Embase, and Web of Science databases were searched for relevant studies. Placebo-controlled clinical studies involving adult patients with a condition of dyslipidaemia and receiving a fixed combination of B. aristata and S. marianum were included. Four randomised trials, including a total of 491 patients, were pooled in statistical analysis. According to the present meta-analysis, Berberol significantly lowered the low-density lipoprotein level, total cholesterol, fasting plasma glucose levels, and the Homeostatic Model Assessment index compared to placebo; however, its effects on the high-density lipoprotein level, triglyceride level, and body mass index were not statistically significant by the end of a 3-month treatment period. Berberol appeared to be safe, and it did not increase the levels of alanine transaminase, aspartate transaminase, and creatine kinase enzymes. Berberol is an effective and presumably safe complementary therapy for the treatment of dyslipidaemia; however, the evidence supporting its use is very limited. The optimum dose and duration of treatment are unclear. A comprehensive evaluation of efficacy and safety is required in further high-quality clinical studies involving larger patient populations. [ABSTRACT FROM AUTHOR]

Endothelial dysfunction is closely associated with diabetic complications. Icariin, a flavonoid glycoside isolated from the Epimedium plant species, exhibits antidiabetic properties. However, its impact on endothelial function remains poorly understood, particularly under hyperglycemia. In this study, we investigated the potential protective effect of icariin on high glucose-induced detrimental effects on vascular endothelial cells. Human umbilical venous endothelial cells were incubated in media containing 5.5 mM glucose (normal glucose) or 25 mM glucose (high glucose) in the presence or absence of 50 µM icariin for 72 h. We found that high glucose markedly induced cell apoptosis, enhanced reactive oxygen species generation, and elevated expression levels of inflammatory factors and cell adhesion molecules, which were greatly subdued by icariin supplementation. In conclusion, icariin exerted a beneficial effect on high glucose-induced endothelial dysfunction. This new finding provides a promising strategy for future treatment of diabetic vascular complications. [ABSTRACT FROM AUTHOR]

Leaves of the Epimedium plant are traditionally consumed for bone health and other indications. The aim of this study was to establish the safety and pharmacokinetics of the metabolites of prenylflavonoids (icariin, icariside I, icariside II, icaritin, and desmethylicaritin) following single doses of a defined Epimedium prenylflavonoid extract in humans. A single oral dose of 370, 740, or 1110 mg of a standardized Epimedium prenylflavonoid extract was administered to 30 healthy male subjects in a randomized, placebo-controlled trial. Serum samples were collected over a 48-h period and analyzed by liquid chromatography-tandem mass spectrometry and non-compartmental pharmacokinetic modelling. Epimedium prenylflavonoid extracts were well tolerated and no adverse effects were observed. The principle metabolites detected in the serum were icariside II and desmethylicaritin. Icariside II had a T max of between 4.1 – 4.3 h, reaching a maximum AUC0→∞ of 23.0 (17.5, 29.9) h×ng/mL (median [IQR: interquartile range]) with the highest dose of the Epimedium prenylflavonoid. On the other hand, desmethylicaritin had a delayed T max of 24.1 – 24.4 h and reached a maximum AUC0→∞ of 126.1 (62.4, 202.9) h×ng/mL. The median maximum plasma concentration and AUC0→∞ of desmethyliciaritin showed an increase with higher doses of the Epimedium prenylflavonoid (p < 0.05). Icariin, icariside I, and icaritin levels were below detection limits. Levels of Epimedium prenylflavonoid metabolites observed in this study were consistent with levels demonstrated to have anti-osteoporotic effects in cellular and animal studies. Coupled with the favorable safety profile of the extract observed, further studies are required to explore the utility of Epimedium prenylflavonoid extracts to prevent osteoporosis in postmenopausal women. [ABSTRACT FROM AUTHOR]

Epimedii Herba (EH) has been used in traditional Asian medicine to treat hemiplegia following stroke. Icariin, its major active component, is used as a quality-control marker and for its various pharmacological effects. We hypothesized that icariin would show protective effects following traumatic brain injury (TBI). The TBI mouse model was induced using a controlled cortical impact method. Body weight, brain damage, motor function, and cognitive function were evaluated. Synaptogenesis markers were analyzed to investigate potential mechanisms of action. The animals were divided into six groups: sham, control, minocycline-treated group, and icariin-treated (3, 10, and 30mg/kg, p. o.) groups. The icariin 30mg/kg-treated group regained body weight at 7 and 8 d post TBI. Icariin 30mg/kg- and 10mg/kg-treated groups showed enhanced sensory-motor function at 8 d post TBI in rotarod and balance beam tests. Icariin-treated groups showed increased recognition index in the novel object recognition test at all doses and increased spontaneous alternation in the Y-maze test at 30mg/kg. Icariin upregulated brainderived neurotrophic factor, synaptophysin and postsynaptic density protein 95 expressions. However, no protective effects against brain damage or neuronal death were observed. The current results provide a basis for using icariin following TBI and suggest that it could be a candidate for the development of therapeutic agents for functional recovery after TBI. [ABSTRACT FROM AUTHOR]

A flavonoid fraction of Herba Epimedii, including eight flavonoid glycoside compounds, epimedo-side A, ikarisoside F, baohuoside II, sagittatoside A, sagittatoside B, 7-O-rhamnosyl icariside II, 2"-O-rhamnosyl icariside II, and baohuoside I, was isolated and prepared from the leaves of Herba Epimedii. This study was conducted to assess the potential effect of the flavonoid fraction of Herba Epimedii on osteoporosis in ovariectomized rats. Rats received repeated administration of a vehicle (ovariectomized), the flavonoid fraction of Herba Epimedii (7.5, 15, 30mg/kg/d), and ipriflavone (200 mg/kg/d) once a day for 8 weeks, beginning 4 weeks after ovariectomization. Then, the bone turnover markers, bone biomechanical properties, trabecular architecture, and related protein expressions were evaluated by biochemical assay kits, mechanical testing, microcomputed tomography, immunohistochemical evaluation, and Western blot analysis. Treatment with the flavonoid fraction of Herba Epimedii (15, 30 mg/kg/d) and ipriflavone (200 mg/kg/d) significantly increased bone strength while dramatically inhibiting the serum alkaline phosphatase and tartrate-resistant acid phosphatase levels in ovariectomized rats. Furthermore, the flavonoid fraction of Herba Epimedii also increased osteoprote-gerin protein expression and reduced the receptor activator of nuclear factor-κB ligand protein expression compared with ovariectomized rats. In addition, the microcomputed tomography results showed that the flavonoid fraction of Herba Epimedii treatment significantly improved trabecular bone mineral density and restored the bone microarchitecture in ovariectomized rats. Therefore, our results indicated that the flavonoid fraction of Herba Epimedii might be beneficial for improving postmenopausal osteoporosis and should be considered as a promising candidate for treating postmenopausal osteoporosis. [ABSTRACT FROM AUTHOR]

Epimedium is popularly used in traditional Chinese medicine to treat sexual dysfunction, menstrual irregularity, and osteoporosis. The estrogenic effects of the prenylated flavonoids of Epimedium make it an attractive alternative for hormone replacement therapy. Here, we examined the therapeutic potential of the estrogenic herb extract of Epimedium brevicornum as an alternative to hormone replacement therapy in a breast cancer mouse model. To that end, athymic and ovariectomized female nude mice were subcutaneously injected into the mammary fat pads with MCF-7 breast cancer cells, randomly grouped and fed with soy-free feeds, alone or in combination with ethinyl estradiol or different doses of the estrogenic herb extract of E. brevicornum. Our findings demonstrate that unlike ethinyl estradiol, it did not promote the growth of breast cancer xenograft volume and weight, with the highest dose showing a significant reduction in growth and ERα protein content. Moreover, the extract increased uterine weight at the lowest dose, while higher doses had no effects. Put together, our data shows for the first time that despite the estrogenic activity of E. brevicornum, its action is largely tissue specific and dose-dependent. Our data on E. brevicornum presents in vivo evidence for its selective estrogen receptor modulator effect and warrants exploration of its use as an alternative to hormone replacement therapy in menopausal women. [ABSTRACT FROM AUTHOR]

Icariin is a major active component isolated from the traditional Chinese herb Epimedium brevicornum, with a wide range of pharmacological and biological activities. In this paper, we investigated the effects of icariin on hyperlipidemia, and further evaluated whether icariin could improve unfavorable hemorheological parameters, attenuate platelet activation and facilitate the balance between plasmic plasminogen activator inhibitor-1 and tissue-type plasminogen activator activities in rabbits fed a high-cholesterol diet. Icariin reduced the levels of serum total cholesterol and low-density lipoprotein cholesterol, as well as the atherosclerotic burden. In addition, this compound has been found to improve the imbalance between plasmic plasminogen activator inhibitor-1 and tissue-type plasminogen activator activities, reduce platelet adhesiveness and aggregation and modulate unfavorable hemorheological variables in hypercholesterolemia. In conclusion, icariin has lipid-lowering effects and may be used in the treatment and prevention of thrombosis in the atherosclerotic process. [ABSTRACT FROM AUTHOR]

Four new tetrahydrofuranoid lignans, (−)-tanegool-7′-methyl ether (1), (+)-7′-methoxylariciresinol (2), sinolignan C (3), and epipinoresinol-4,4′-di-O-β-D-glucopyranoside (4), were isolated from the roots and rhizomes of Sinopodophyllum emodi together with one known lignan (5). Their structures and stereochemistry were elucidated on the basis of spectroscopic and mass spectrometric evidence. The isolation of compounds 1-5 represents the first report of tetrahydrofuran lignans from the genus Sinopodophyllum. The cytotoxic activities of all isolated compounds were evaluated against HeLa and KB cell lines, and compound 1 showed the most potent cytotoxicity with IC50 values of 9.7 µM and 4.7 µM, respectively. [ABSTRACT FROM AUTHOR]

A bioassay-guided fractionation and chemical investigation of the trunk of Berberis koreana led to the isolation and identification of three new triterpenoids, 2α,3α,19α-trihydroxy-urs-12- en-24-formyl-28-oic acid (1), 2α,3β,21α-trihydroxy-urs-12-en- 28-oic acid (2), and 3β-acetyloxy-1-oxo-olean-12-en-28-oic acid (3), along with seven known triterpenoids (4-10). The structures of these new compounds were determined through spectral analysis, including extensive 2D-NMR data. The new compounds 1-3 showed significant cytotoxicity against the A549, SK-OV-3, SK-MEL-2, and HCT-15 human tumor cell lines with IC50 values ranging from 7.17 to 48.73 μM. [ABSTRACT FROM AUTHOR]

The fruit of Nandina domestica Thunberg (ND, Berberidaceae) has been used to improve cough and breathing difficulties in Japan for many years, but very little is known about the constituent of ND responsible for this effect. We have recently reported that the crude extract from ND (NDE) inhibits histamine- and serotonin-induced contraction of isolated guinea pig trachea, and the inhibitory activity was not explained by nantenine, a well-known alkaloid isolated from ND. To explore other constituent(s) of NDE with tracheal smooth muscle relaxant activity, we fractionated NDE and assessed the pharmacological effects of the fractions using isolated guinea pig tracheal ring preparations. NDE was introduced into a polyaromatic absorbent resin column and stepwise eluted to yield five fractions, among which only the 40 % methanol fraction was active in relaxing tracheal smooth muscle precontracted with histamine. Further separation of the 40 % methanol fraction with high-performance liquid chromatography yielded multiple subfractions, one of which was remarkably active in relaxing histamine-precontracted trachea. Chemical analysis with a time-of-flight mass spectrometer and nuclear magnetic resonance spectrometer identified the constituent of the most active subfraction as higenamine, a benzyltetrahydroisoquinoline alkaloid. The potency and efficacy of the active constituent from NDE in relaxing trachea were almost equivalent to synthetic higenamine. In addition, the effect of the active constituent from NDE was competitively inhibited by the selective β2-adrenoceptor antagonist ICI 118,551. These results indicate that the major constituent responsible for the effect of NDE is higenamine, which probably causes the tracheal relaxation through stimulation of β2 adrenoceptors. [ABSTRACT FROM AUTHOR]