Mangiferin is a major bioactive ingredient in Mangifera indica Linn. (Anacardiaceae) leaves. Aqueous extract of such leaves have been used as an indigenous remedy for respiratory diseases like asthma and coughing in traditional Chinese medicine. However, underlying molecular mechanisms of mangiferin on anti-asthma remain unclear. In our present study, we investigated the anti-asthmatic effect of mangiferin on Th1/Th2 cytokine profiles and explored its underlying immunoregulatory mechanism in mouse model of allergic asthma. Mangiferin significantly reduced the total inflammatory cell counts and eosinophil infiltration, decreased the production of ovalbumin-specific IgE in serum and PGD₂ in BALF. The antibody array analysis showed that mangiferin down-regulated the levels of one group of cytokines/chemokines including Th2-related IL-4, IL-5, IL-13, and others IL-3, IL-9, IL-17, RANTES, TNF-α, but simultaneously up-regulated Th1-related IFN-γ, IL-2 and IL-10 and IL-12 expression in serum. Thus it attenuates the imbalance of Th1/Th2 cells ratio by diminishing the abnormal mRNA levels of Th1 cytokines (IFN-γ and IL-12) and Th2 cytokines (IL-4, IL-5 and IL-13). Finally, mangiferin substantially inhibited the activation and expression of STAT-6 and GATA-3 in excised lung tissues. Our results suggest that mangiferin can exert anti-asthmatic effect. The underlying mechanism may attribute to the modulation of Th1/Th2 cytokine imbalance via inhibiting the STAT6 signaling pathway.

Litchi (Litchi chinensisSonnnerat, Sapindaceae), known as Chinese Cherry, is a subtropical fruit tree originating from southern China. Litchi seed extracts have diverse pharmacological effects, including anticancer. However, its anticancer effects and mechanisms on prostate cancer have not been determined. In this study, we used n-butyl alcohol extract of Litchi seed (NLS) to treat prostate cancer PC3, DU145, RM1 and C4-2B cells. NLS induced a significant decrease in cell viability and clonogenic growth in a dose-dependent manner. NLS induced cell apoptosis and cell cycle G1/S phase arrest by inactivating Akt signaling pathway, which were associated with activation of mitochondrial caspase-dependent apoptotic cascades, up-regulation of cyclin-dependent kinase (CDK) inhibitors p21 and p27, and inhibition of correlated cyclin/CDK network. In addition, NLS treatment significantly decreased cell migration and invasion via phenotypic inversion of EMT, correlated with increased expression of E-cadherin and β-catenin, and decreased expression of vimentin and snail, which is partially attributed to inhibiting Akt/GSK-3β signaling pathway. Finally, PC3 xenograft nude mice treated with NLS in vivo showed a significant decrease in tumor size without toxicity. These findings suggest that NLS has potential for development into a safe and potent alternative therapy for prostate cancer patients.

Gut microbiota dysbiosis induced by antibiotics is strongly connected with health concerns. Studying the mechanisms underlying antibiotic-induced gut microbiota dysbiosis could help to identify effective drugs and prevent many serious diseases. In this study, in rats with antibiotic-induced gut microbiota dysbiosis treated with total alkaloids of Corydalis saxicola Bunting (TACS), urinary and fecal biochemical changes and cecum microbial diversity were investigated using 16S rRNA gene sequencing analysis and untargeted metabolomics. The microbial diversity results showed that 10 genera were disturbed by the antibiotic treatment, and two of them were obviously restored by TACS. The untargeted metabolomics analysis identified 34 potential biomarkers in urine and feces that may be the metabolites that are most related to the mechanisms underlying antibiotic-induced gut microbiota dysbiosis and the therapeutic effects of TACS treatment. The biomarkers were involved in six metabolic pathways, comprising pathways related to branched-chain amino acid (BCAA), bile acid, arginine and proline, purine, aromatic amino acid, and amino sugar and nucleotide sugar metabolism. Notably, there was a strong correlation between these metabolic pathways and two gut microbiota genera (g__Blautia and g__Intestinibacter). The correlation analysis suggested that TACS might synergistically affect four of these metabolic pathways (BCAA, bile acid, arginine and proline, and purine metabolism), thereby modulating gut microbiota dysbiosis. Furthermore, we performed a molecular docking analysis involving simulating high-precision docking and using molecular pathway maps to illuminate the way that ligands (the five main alkaloid components of TACS) act on a complex molecular network, using CYP27A1 (a key enzyme in the bile acid synthesis pathway) as the target protein. This study provides a comprehensive overview of the intervening effects of TACS on the host metabolic phenotype and gut microbiome in rats with gut microbiota dysbiosis, and it presents new insights for the discovery of effective drugs and the best therapeutic approaches.

Epithelial-mesenchymal transition (EMT) plays a crucial role in breast cancer metastasis and inhibition of EMT may be an effective approach to suppress metastatic breast cancer. High LRP6 expression is usually observed in breast cancer and predicts poor prognosis. In present study, we investigated whether chlorogenic acid (CA) has an EMT inhibitory effect on breast cell lines and underlying molecular mechanism. We found that CA treatment transformed MCF-7 cell morphology from spindle shape (mesenchymal phenotype) to spherical shape (epithelial phenotype). CA clearly increased epithelial markers9 expression (E-cadherin and ZO-1) but decreased mesenchymal markers9 expression (ZEB1, N-cadherin, Vimentin, Snail and Slug). In addition, CA attenuated MMP-2 and MMP-9 activities and inhibited cell migration and invasion. CA also down-regulated LRP6 expression, knockdown LRP6 with siRNA repressed cell mobility and invasion while overexpression of LRP6 promoted EMT and antagonized the EMT inhibitory effect of CA on MCF-7 cells. In vivo study showed that CA significantly reduced tumor volume and tumor weight. Immunohistochemical analysis demonstrated that CA inhibited xenograft tumor EMT with LRP6 and Vimentin decreased and E-cadherin increased. In conclusion, CA restrained EMT and invasion of breast cancer through down-regulating LRP6 expression. CA may be developed as an EMT inhibitor for breast cancer treatment. Significance Statement chlorogenic acid (CA), one of the most common polyphenol compounds in traditional Chinese medicine, repressed EMT and weakens cellular mobility and invasion in MCF-7 cells. The mechanism studies demonstrated that CA inhibits MCF-7 cell EMT and invasion via targeting LRP6. Additionally, CA could inhibit tumor growth and xenograft tumor EMT in vivo. The EMT inhibitory property of CA warrants further studies of CA as a drug candidate for the treatment of metastatic breast cancer.