Apigenin Inhibits Histamine-Induced Cervical Cancer Tumor Growth by Regulating Estrogen Receptor Expression.

Apigenin is a natural flavone with anti-inflammatory and antioxidant properties and antitumor abilities against several types of cancers. Previous studies have found that the antitumor effects of apigenin may be due to its similar chemical structure to 17ß-estradiol (E2), a main kind of estrogen in women. However, the precise mechanism underlying the antitumor effects of apigenin in cervical cancer remains unknown. On the other hand, there is increasing evidence that describes a histamine role in cancer cell proliferation. In this study, we examined whether apigenin can attenuate the effects of histamine on tumors by regulating the expression level of estrogen receptors (ERs) to inhibit cervical cancer growth. Our in vitro data indicates that apigenin inhibited cell proliferation in a dose-dependent manner in human cervical cancer cells (HeLa), while histamine shows the opposite effects. After that, the xenograft model was established to explore the antitumor effects of apigenin in vivo, the results show that apigenin inhibited cervical tumor growth by reversing the abnormal ER signal in tumor tissue which was caused by histamine. We also demonstrate that apigenin inhibited cell proliferation via suppressing the PI3K/Akt/mTOR signaling pathway. Collectively, our results suggest that apigenin may inhibit tumor growth through the ER-mediated PI3K/Akt/mTOR pathway and that it can also attenuate the effects of histamine on tumors.

Silage Fermentation: A Potential Biological Approach for the Long-Term Preservation and Recycling of Polyphenols and Terpenes in Globe Artichoke (Cynara scolymus L.) By-Products.

An economic and effective method for storage is necessary to make full use of the nature of active components in artichoke by-products and ease environmental pressure. In this paper, the potential of silage fermentation for the preservation and recycling of polyphenols and terpenes in artichoke by-products is evaluated. The silage of artichoke by-products is characterized by lactic acid bacteria fermentation. Silage distinctly increases the abundance of lactic acid bacteria in artichoke by-products, such as Lactobacillus, Lactococcus, Serratia, and Weissella, and greatly increases the abundance of Firmicutes. The improvement of the microorgan structure and composition is of great significance for the quality of artichoke by-products. Polyphenols in the stems and leaves of artichokes are preserved well in silage. Among the 18 polyphenol compounds detected by high performance liquid chromatography coupled with triple quadrupole tandem mass spectrometry (HPLC-QqQ-MS/MS), the contents of 11 phenolic acids and four flavonoids increased significantly. For terpenes detected by gas chromatography-mass spectrometry (GC-MS), the contents of four pentacyclic triterpenoids increased significantly, while two sterols were kept stable in the silage process. Silage is a potential biotechnology for the long-term preservation of bioactive components, such as polyphenols and terpenes in artichoke by-products, and the results provide a scientific basis for the efficient utilization of by-products.

Cyanidin 3-O-ß-Galactoside Alleviated Cognitive Impairment in Mice by Regulating Brain Energy Metabolism During Aging.

Metabolic disorder, which commonly happens among senile people worldwide, is an important sign of aging. The early symptoms of neurodegenerative diseases include a decrease in energy metabolism and mitochondrial dysfunction. Comparably, early dietary intervention may be more effective in preventing or delaying brain aging, owing to its role in regulating metabolism. Polyphenol intake has shown its potential in preventing Alzheimer's disease. However, whether there are close connections between polyphenols and the energy metabolism of the brain during aging remains unclear. This study sought to evaluate whether cyanidin 3-O-ß-galactoside from black chokeberry (Aronia melanocarpa (Michx.) Elliott) has positive effects on energy metabolism, as well as cognitive function in aging mice. Intragastrical administration of cyanidin 3-O-ß-galactoside (25 and 50 mg/kg/day) for 8 weeks effectively alleviated the decline in brain glucose uptake (decline rate 18.29% versus 1.05%, 7.63%) of aging mice. Moreover, cyanidin 3-O-ß-galactoside also alleviated neuronal damage in the hippocampus (number of neurons 212.33 ± 16.19 versus 285.33 ± 29.53, 301.67 ± 10.07; p < 0.05) and cortex (number of neurons 82.00 ± 4.58 versus 111.67 ± 6.51, 112.00 ± 1.00; p < 0.05). Furthermore, cyanidin 3-O-ß-galactoside reduced ß-amyloid load in the brain and significantly increased the crossing-platform number (0.92 ± 1.11 versus 1.83 ± 0.68, 2.08 ± 0.58; p < 0.05) in the Morris water maze test. We further determined that protein kinase B (AKT) might be the target of cyanidin 3-O-ß-galactoside, which played a beneficial role in controlling the energy metabolism of the brain. These results suggested that early intervention of anthocyanins could promote neuroprotection under the challenge of brain energy metabolism.

Apigenin acts as a partial agonist action at estrogen receptors in vivo.

The flavone apigenin is widely distributed in vegetables and fruits and has a variety of pharmacological effects. However, there is no definitive scientific evidence that apigenin could act as a phytoestrogen and exert exerting estrogenic or antiestrogenic efficacy in vivo. Therefore, this study was established an ovariectomy (OVX) and estrogenized mouse model to evaluate the effects of apigenin on reproductive target tissues. Our data demonstrated that apigenin could exert a double-directional adjusting estrogenic effect in vivo. Specifically, treatment with apigenin reversed the weight changes caused by abnormal estrogen levels and altered the status of vaginal epithelial cells via the estrogen receptors. In addition, we found that apigenin exhibited a significant estrogenic activity, as indicated by the reversal of uterine atrophy. Apigenin treatment could also regulate the target tissue coefficient changes and estrogen disorders caused by excessive estrogen. Importantly, the administration of apigenin could upregulated the estrogen receptor (ER) α and ER ß expression as a partial agonist. Our results demonstrate that apigenin has a double directional adjusting function in different physiological environments.

Apigenin Attenuates the Allergic Reactions by Competitively Binding to ER With Estradiol.

Apigenin (API) is a natural phytoestrogen with properties including anti-inflammatory and other abilities. This study aims to 1) systematically validate that excessive estrogen exacerbates allergic reactions; 2) explore the anti-allergic effects and mechanisms of API. We conduct a survey of college students, indicating that of the 505 effective results, 70 individuals were self-reported allergic and 74.1% of them were women, which proved the gender difference in allergic reactions. BALB/c mice are grouped into the negative control group (N-Ctrl), the OVA-sensitized group (P-Ctrl), the estrogenized OVA-sensitized group (E2), and three treatment groups administrating different dose of API (E2 + API/L/M/H). In vivo data indicated that API treatment significantly inhibited the enhancement of estradiol on clinical symptoms. Moreover, we found that high doses of API inhibited Th2 type humoral response and mast cell degranulation levels in vivo and in vitro. Additionally, medium, and high doses of API significantly reduced the potentiation of estradiol on ER expression, attenuated the transmission of estrogen/ER signaling, thereby inhibiting the phosphorylation of ERK1/2 and JNK1/2/3 in the MAPK. Besides, we found that API competitively bound to ER with estradiol, and showed a weak selectivity to ERß. Overall, we identified API can be beneficial in allergic disease.

Quail egg homogenate alleviates food allergy induced eosinophilic esophagitis like disease through modulating PAR-2 transduction pathway in peanut sensitized mice.

The present pharmacotherapy for eosinophilic esophagitis (EoE) fundamentally depend on inhaled corticosteroids. Despite the fact that oral intake of topical steroids can be successful in restricting EoE-related inflammation, there are concerns with respect to the long term utilization of steroids, especially in kids. In the current research, we assess the effect of quail egg, which is reportedly a known serine protease inhibitor, on symptomatology and immune responses in a peanut-sensitized mouse model of food allergy induced EoE. Daily oral treatment with quail egg attenuated mice symptomatology and immune response. Treatment with quail egg inhibited antigen-prompted increments in mouse tryptase and eosinophil cationic protein (ECP) in serum and eosinophil in inflamed tissues like oesophagus, lung, and digestive system. Quail egg treatment resulted in decreased antibody specific IgE and IgG1 and a variety of inflammatory genes that were abnormally expressed in EoE. Other effects included increased IL-10, decreased PAR-2 activation and NF-kB p65 in inflamed tissues. Our results suggest that quail egg treatment may have therapeutic potential in attenuating the symptoms of food allergy induced EoE like disease through regulating PAR-2 downstream pathway by blocking the activation of the transcription factor NF-kB p65 activity.