Supplementation of licorice root and epimedium in a control or high fat diet and their effects on a preclinical metastatic breast cancer model

The natural decline in estrogen that occurs in women during menopause causes significant discomfort and decrease in quality of life for women. Botanical supplements contain multiple bioactive components, some of which have been identified to be phytoestrogenic and are used to remedy menopausal symptoms. However, due to their ability to mimic estrogen, the phytoestrogenic components contained in these botanical supplements may play a role in the progression of breast cancer. The majority of botanicals lack established data on safety and efficacy. They also present the likelihood for interactions to occur, such as with the high fat diet that is consumed in many Western countries. Two such botanicals, licorice root and epimedium, which are used to alleviate menopausal symptoms, were studied for their impact on the progression of metastatic breast cancer in an animal model. In the licorice study, mice were supplemented with licorice root powder, extract or isoliquirtigenin for 2 weeks before and 3 weeks after cell injection. The effects of supplementation with the same licorice compounds alongside a high-fat diet were also explored. Mice fed licorice root powder and isoliquiritigenin were found to have a reduction in lung metastasis compared to control. In the high fat group, no changes in lung metastasis were found in animals supplemented with licorice root compounds compared with control. Although mild hepatocellular hypertrophy was observed in the liver of mice fed licorice root compounds, no significant adverse effects were found. In the epimedium study, mice were fed epimedium powder, extract or icariin for 12 weeks before and 4 weeks after cell injection. A second cohort also received the same epimedium treatments alongside a high fat diet. Supplementation with epimedium compounds had no effect on lung metastasis in the control groups, while only epimedium powder was found to decrease lung metastasis in the high fat cohorts. No adverse effects due to epimedium supplementation were found. In this animal model, supplementation with licorice root or epimedium compounds did not have a promoting effect on breast cancer metastasis. Both licorice and epimedium possess properties that could be advantageous toward the development of novel pharmacological treatments. However, the safety of licorice root or epimedium supplement use remains uncertain due to the possibility of interaction with dietary components and should be approached with caution

Dual activation of estrogen receptor a and aryl hydrocarbon receptor by the prenylflavone, Icaritin restrict breast cancer cell growth and destabilize estrogen receptor a protein

Master'sMASTER OF SCIENC

Evaluation of Embryotoxicity of Radix scutellariae Based on Embryonic Stem Test

Purpose: To determine the potential embryotoxicity of Radix scutellariae (RS) extract using an embryonic stem cell test (EST) and to evaluate its effect on the differentiation of mouse embryonic stem (ES) cells.Methods: All the test samples were obtained by water extraction method. The embryotoxicity of RS was assessed with cytotoxicity assays, namely, embryonic stem (ES) cells (IC50ES) and 3T3 fibroblasts (IC503T3), as well as cardiac differentiation inhibition assay (ID50ES). The expression of specific genes and proteins was analyzed by quantitative reverse transcription – polymerase chain reaction (RT-PCR) and Western blot.Results: RS was weakly embryotoxic with IC50ES, IC503T3 and ID50ES of 0.1524, 0.1061, and 0.4169 mg/ml, respectively. Also RS had discordant effects on the expression of tissue-specific genes and proteins in three germ layers, promoting differentiation of the ectoderm (⋆p < 0.05; ⋆⋆p < 0.01) and endoderm (⋆p < 0.05; ⋆⋆p < 0.01; ⋆⋆⋆p < 0.001), while inhibiting mesoderm differentiation (⋆p < 0.05; ⋆⋆p < 0.01; ⋆⋆⋆p < 0.001). The effect of RS on the embryonic development of the three germ layers was concentration-dependent.Conclusion: These results indicate that RS possesses weak embryotoxicity. The variability in the effects of RS may be responsible for its weak embryotoxicity.Keywords: Embryonic stem test, Radix scutellariae, Embryotoxicity, Cardiac differentiation inhibition assay, Ectoderm, Endoderm, Mesoder

Improved sexual behavior in male rats treated with a Chinese herbal extract: hormonal and neuronal implications

Aim: To investigate the influence of an extract obtained from five Chinese medicinal plants on sexual behavior ofadult male rats. Methods: The extract was administered at doses of 30, 60 and 120 mg/kg by oral gavage, acutely (onetime, 45 min before mating test) or subchronically (daily for 10 days) in sexually potent and sexually sluggish/impotentrats. Sexual behavior, serum levels of luteinizing hormone (LH) and testosterone (T) were evaluated in treatedrats and compared with controls receiving vehicle. The effect of the extract on central dopaminergic neurotransmissionwas assessed in the nucleus accumbens using a microdialysis technique. Results: In sexually potent rats, bothacute and subchronic treatment with the extract dosed at 30 and 60 mg/kg reduced mount latency and intromissionlatency. In sluggish/impotent rats, the acutely administered extract at the dose of 60 mg/kg shortened ejaculationlatency, whereas subchronically administered at the doses of 30 and 60 mg/kg, reduced mount, intromission andejaculation latencies, increasing also the percentage of mounting and ejaculating rats. The extract dosed at 60 mg/kgsignificantly increased LH and T following acute and subchronic administration and increased 3,4-dihydroxyphenylaceticacid levels in the nucleus accumbens, 30 min after the acute administration. Conclusion: The improvement in bothappetitive and consummatory components of sexual behavior observed in male rats treated with the extract could beascribed to increased serum T level in parallel with the activation of the central dopaminergic system

Constitutional Flavonoids Derived from Epimedium Dose-Dependently Reduce Incidence of Steroid-Associated Osteonecrosis Not via Direct Action by Themselves on Potential Cellular Targets

Intravascular-thrombosis and extravascular-lipid-deposit are the two key pathogenic events considered to interrupt intraosseous blood supply during development of steroid-associated osteonecrosis (ON). However, there are no clinically employed agents capable of simultaneously targeting these two key pathogenic events. The present experimental study demonstrated that constitutional flavonoid glycosides derived from herb Epimedium (EF, composed of seven flavonoid compounds with common stem nuclear) exerted dose-dependent effect on inhibition of both thrombosis and lipid-deposition and accordingly reducing incidence of steroid-associated ON in rabbits, which was not via direct action by themselves rather by their common metabolite on potential cellular targets involved in the two pathogenic pathways. The underlying mechanism could be explained by counteracting endothelium injury and excessive adipogenesis. These findings encourage designing clinical trials to investigate potential of EF in prevention of steroid-associated ON

Icaritin Shows Potent Anti-Leukemia Activity on Chronic Myeloid Leukemia In Vitro and In Vivo by Regulating MAPK/ERK/JNK and JAK2/STAT3 /AKT Signalings

PURPOSE: To explore the effects of Icaritin on chronic myeloid leukemia (CML) cells and underlying mechanisms. METHOD: CML cells were incubated with various concentration of Icaritin for 48 hours, the cell proliferation was analyzed by MTT and the apoptosis was assessed with Annexin V and Hoechst 33258 staining. Cell hemoglobinization was determined. Western blotting was used to evaluate the expressions of MAPK/ERK/JNK signal pathway and Jak-2/Phorpho-Stat3/Phorsph-Akt network-related protein. NOD-SCID nude mice were applied to demonstrate the anti-leukemia effect of Icaritin in vivo. RESULTS: Icaritin potently inhibited proliferation of K562 cells (IC50 was 8 µM) and primary CML cells (IC50 was 13.4 µM for CML-CP and 18 µM for CML-BC), induced CML cells apoptosis and promoted the erythroid differentiation of K562 cells with time-dependent manner. Furthermore, Icaritin was able to suppress the growth of primary CD34+ leukemia cells (CML) and Imatinib-resistant cells, and to induce apoptosis. In mouse leukemia model, Icaritin could prolong lifespan of NOD-SCID nude mice inoculated with K562 cells as effective as Imatinib without suppression of bone marrow. Icaritin could up-regulate phospho-JNK or phospho-C-Jun and down-regulate phospho-ERK, phospho-P-38, Jak-2, phospho-Stat3 and phospho-Akt expression with dose- or time-dependent manner. Icaritin had no influence both on c-Abl and phospho-c-Abl protein expression and mRNA levels of Bcr/Abl. CONCLUSION: Icaritin from Chinese herb medicine may be a potential anti-CML agent with low adverse effect. The mechanism of anti-leukemia for Icaritin is involved in the regulation of Bcr/Abl downstream signaling. Icaritin may be useful for an alternative therapeutic choice of Imatinib-resistant forms of CML

Antineuroinflammatory Effects of Modified Wu-Zi-Yan-Zong Prescription in β

Modified Wu-Zi-Yan-Zong prescription (MWP), a traditional Chinese medicinal decoction, has possessed the neuroprotective and anti-inflammatory properties. The mechanisms associated with these properties, however, are not completely understood. We designed the experiments to elucidate the antineuroinflammatory property of MWP in BV2 microglia activated by β-amyloid (Aβ), which is a characteristic feature of Alzheimer’s disease (AD). The composition of MWP was studied using HPLC. BV2 microglia cells were then treated with Aβ in the presence or absence of MWP. The effects of MWP treatment on Aβ-activated neuroinflammation were determined using PCR, western blotting, and immunofluorescence staining. MWP significantly inhibited the mRNA expression of inflammatory mediators such as IL-1β, IL-6, TNF-α, and MCP-1, as well as the expression of inducible nitric oxide synthase (iNOS) in Aβ-activated BV2 microglia. MWP also inhibited the nuclear translocation and signaling pathway of nuclear factor kappa B (NF-κB) by suppressing inhibitor of nuclear factor-κB (IκB) degradation and downregulating IκB kinase β (IKKβ) phosphorylation. Moreover, MWP decreased extracellular regulated protein kinase (ERK)/p38 mitogen-activated protein kinase (MAPK) phosphorylation, which is an important signaling pathway for proinflammatory gene expression. We concluded that MWP could suppress neuroinflammatory responses in Aβ-activated BV2 microglia via the NF-κB and ERK/p38 MAPK signaling cascades and could prove an effective therapeutic agent for the prevention and treatment of neuroinflammatory diseases such as AD

Current status of prenyl flavonoids

Flavonoids are distributed across the plant kingdom and have attracted substantial attention owing to their potential benefits for human health. Several studies have demonstrated that flavonoids prenylation enhances various biological activities, suggesting an attractive tool for developing functional foods. This review provides an overview of the current knowledge on how prenylation influences the biological activity and bioavailability of flavonoids. The enhancement effect of prenylation on the biological activities of dietary flavonoids in mammals was demonstrated by comparing the effect of 8-prenyl naringenin (8PN) with that of parent naringenin in the prevention of disuse muscle atrophy in mice. This enhancement results from higher muscular accumulation of 8PN than naringenin. As to bioavailability, despite the lower absorption of 8-prenyl quercetin (8PQ) compared with quercetin, higher 8PQ accumulation was found in the liver and kidney. These data imply that prenylation interferes with the elimination of flavonoids from tissues

Bioavailability of prenyl quercetin

Prenyl flavonoids are widely distributed in plant foods and have attracted appreciable attention in relation to their potential benefits for human health. Prenylation may enhance the biological functions of flavonoids by introducing hydrophobic properties in their basic structures. Previously, we found that 8-prenyl naringenin exerted a greater preventive effect on muscle atrophy than nonprenylated naringenin in a mouse model. Here, we aimed to estimate the effect of prenylation on the bioavailability of dietary quercetin (Q). The cellular uptake of 8-prenyl quercetin (PQ) and Q in Caco-2 cells and C2C12 myotube cells was examined. Prenylation significantly enhanced the cellular uptake by increasing the lipophilicity in both cell types. In Caco-2 cells, efflux of PQ to the basolateral side was <15% of that of Q, suggesting that prenylation attenuates transport from the intestine to the circulation. After intragastric administration of PQ or Q to mice or rats, the area under the concentration-time curve for PQ in plasma and lymph was 52.5% and 37.5% lower than that of Q, respectively. PQ and its O-methylated form (MePQ) accumulated at much higher amounts than Q and O-methylated Q in the liver (Q: 3400%; MePQ: 7570%) and kidney (Q: 385%; MePQ: 736%) of mice after 18 d of feeding. These data suggest that prenylation enhances the accumulation of Q in tissues during long-term feeding, even though prenylation per se lowers its intestinal absorption from the diet