Table_1_Hypouricemic Effects of Extracts From Agrocybe aegerita on Hyperuricemia Mice and Virtual Prediction of Bioactives by Molecular Docking.DOC

<p>Agrocybe aegerita has long been utilized for promoting diuresis in traditional Chinese medicine (TCM) with a close correlation to hypouricemia. Ethanol (AAE) and water (AAW) extracts of the compound led to a remarkable decrease in serum uric acid levels (SUA) in hyperuricemia mice, approaching that of the normal control. Both AAE and AAW exhibited suppression effects on hepatic xanthine oxidase (XOD) activities and elevation effects on renal OAT1 (organic anion transporter 1). However, only little negative impact was observed on the inner organ functions. The molecular docking was used to screen our in-home compound database for A. aegerita, and four compounds including 2-formyl-3,5-dihydroxybenzyl acetate, 2,4-dihydroxy-6-methylbenzaldehyde, 2-(6-hydroxy-1H-indol-3-yl)acetamide, and 6-hydroxy-1H-indole-3-carbaldehyde (HHC) were identified as potential active compounds. Their inhibitory mechanism on XOD might be attributed to their localization in the tunnel for the entrance of substrates to XOD active site, preventing the entrance of the substrates. To confirm the activity of the screened compounds experimentally, HHC was selected due to its high ranking and availability. The assaying result suggested the significant inhibitory activity of HHC on XOD. Also, these compounds were predicted to carry good ADME (absorption, distribution, metabolism, and excretion) properties, thereby necessitating further investigation. The current results provided an insight into the hypouricemic effects of macrofungi and their bioactives, which might provide the significant theoretical foundation for identifying and designing novel hypouricemia compounds.</p

Data_Sheet_2_Antitumor Activity of Extract From the Sporoderm-Breaking Spore of Ganoderma lucidum: Restoration on Exhausted Cytotoxic T Cell With Gut Microbiota Remodeling.XLSX

<p>As breast cancer is the leading cause of cancer-related deaths in women population worldwide, ongoing endeavor has been made for alternative regimens with improved efficacy but fewer adverse effects. Recently, active components from the spores of Ganoderma lucidum have attracted much attention for their versatile biological activities owing to the advance in sporoderm-breaking technology. Here, anticancer potential of an extract derived from the sporoderm-breaking spores of G. lucidum (ESG) was explored in a 4T1-breast cancer xenograft mice model. Results showed that ESG was able to suppress 4T1 tumor growth in vivo rather than in vitro. Flowcytometry analysis revealed that ESG could significantly increase both cytotoxic T cell (Tc) population and the ratio of Tc to helper T cell (Th) in peripheral blood of the tumor-bearing mouse; similar promotion on Tc was also found in tumor-infiltrating lymphocyte. Moreover, ESG evidently downregulated the two immune checkpoints, programmed cell death protein-1 (PD-1, in the spleen) and cytotoxic T lymphocyte antigen-4 (CTLA-4, in the tumor), suggesting that ESG could effectively restore the T cell paradigm by recovering the exhaustion status via suppressing the co-inhibitory checkpoints. By 16S rRNA gene sequence analysis on the fecal microbiota, it was found that ESG would remodeling the overall structure of the samples from tumor-bearing mice toward that of the normal counterparts, including 18 genera in 5 phyla, together with regulations on several genes that are responsible for signaling pathways involved in metabolism, cellular processes, and environmental information processing. Collectively, this study demonstrated that ESG would serve as a natural anticancer adjuvant via a restoration on the exhausted Tc, highlighting important clinical implications for the treatment of breast cancer.</p