Secondary metabolites from the Actinomadura sp. and their cytotoxic activity.

Actinomadura sp., which is usually found in muddy habitats, produces various secondary metabolites with biological activities. In this study, five new compounds named formosensin A (1), formosensin B (2), oxanthroquinone-3-O-α-d-mannose (8), oxanthromicin A (9), and oxanthromicin B (10) were isolated from the culture of Actinomadura sp. together with five known compounds (3-7). Their structures were elucidated by extensive spectroscopic methods including NMR and MS. In particular, the absolute configurations of compounds 1 and 2 were determined using computational methods. Moreover, compounds 1-2 and 8-10 were screened for cytotoxic activity using a panel of human tumor cell lines. Compound 9 induced significant cytotoxicity in five human tumor cell lines (HL-60, A-549, SMMC-7721, MCF-7, and SW480) with IC50 values of 8.7, 17.5, 15.0, 17.8, and 14.6 µM, respectively. These findings suggested that compound 9 could provide therapeutic benefits in the treatment of tumor-related diseases.

Gut microbiota and differential genes-maintained homeostasis is key to maintaining health of individuals with Yang-deficiency constitution.

OBJECTIVE: Yang-deficiency constitution (YADC) is a common unbalanced constitution that predisposes individuals to certain diseases. However, not all people with YADC manifest develop diseases. This calls for delineation of the underlying molecular mechanisms. Previous studies suggested that the gut microbiota and gene differential expression should be considered. METHODS: In the present study, we compared profiles of gut microbiota between four healthy YADC individuals and those of five healthy balanced constitution (BC) counterparts, based on 16S rRNA gene sequence analysis. Furthermore, YADC relevant genes identified by comparing 62 healthy YADC and 58 healthy BC individuals in total to perform intersection analysis, functional clustering and pathway enrichment analyses. RESULTS: The levels of harmful gut microbiota (Prevotellaceae, LDA score > 4.0, P = 0.0141) and beneficial gut microbiota (Ruminococcaceae, LDA score > 4.0, P = 0.0025, Faecalibacterium, LDA score > 4.0, P = 0.0484) were both elevated in healthy YADC individuals. Also, we found that the specific metabolic pathway with 2, 6-Dichloro-p-hydroquinone 1, 2-Dioxygenase (PcpA) as the core in gut microbiota and the glutathione transferase activity has been enriched by YADC relevant genes in healthy YADC individuals were both responsible for the detoxification of halogenated aromatic hydrocarbon substances. CONCLUSIONS: Both beneficial and harmful factors had been detected in healthy YADC individuals, functionally, they may have triggered homeostasis to maintain the health of individuals with YADC. The homeostasis may be maintained by beneficial and harmful factors from gut flora and genes. Future studies are expected to focus on halogenated aromatic hydrocarbons and their detoxification processes.