Many fungi, lichens, and bacteria produce xanthones (derivatives of 9H-xanthen-9-one, “xanthone” from the Greek “xanthos”, for “yellow”) as secondary metabolites. Xanthones are typically polysubstituted and occur as either fully aromatized, dihydro-, tetrahydro-, or, more rarely, hexahydro-derivatives. This family of compounds appeals to medicinal chemists because of their pronounced biological activity within a notably broad spectrum of disease states, a result of their interaction with a correspondingly diverse range of target biomolecules. This has led to the description of xanthones as “privileged structures”.(1) Historically, the total synthesis of the natural products has mostly been limited to fully aromatized targets. Syntheses of the more challenging partially saturated xanthones have less frequently been reported, although the development in recent times of novel and reliable methods for the construction of the (polysubstituted) unsaturated xanthone core holds promise for future endeavors. In particular, the fascinating structural and biological properties of xanthone dimers and heterodimers may excite the synthetic or natural product chemist.

Xanthones from fungi, lichens, and bacteria : the natural products and their synthesis

Marine natural products.

Secondary metabolites from mangrove-associated fungi: source, chemistry and bioactivities.

Secondary metabolites from mangrove-associated fungi: source, chemistry and bioactivities

This project was focused on the discovery of novel compounds that promote endogenous β-cell regeneration. Screening of extracts identified the fungus Stachybotrys chartarum as a promising candidate. After fermentation and extraction of S. chartarum, we isolated five new prenylated xanthones, namely, staprexanthones A-E (1-5), with staprexanthone A (1) being the first natural xanthone bearing a rare 4,5-dimethyl-1,3-dioxolane moiety. Compounds 1, 2, and 5 significantly increased β-cell numbers in vivo in a zebrafish model. Further analysis revealed that 2 and 5 promoted β-cell mass expansion by increasing proliferation of existing β-cells though promotion of cell-cycle progression at the G1/S transition. These findings indicate that prenylated xanthones are potential new drug leads for antidiabetes therapy by stimulating β-cell regeneration.

Staprexanthones, Xanthone-Type Stimulators of Pancreatic β-Cell Proliferation from a Mangrove Endophytic Fungus.

The glucagon receptor (GCGR) is a G-protein-coupled receptor (GPCR) that mediates the activity of glucagon. Disruption of GCGR results in many metabolic alterations, including increased glucose tolerance, decreased adiposity, hypoglycemia, and pancreatic α-cell hyperplasia. To better understand the global transcriptomic changes resulting from GCGR deficiency, we performed whole-organism RNA sequencing analysis in wild type and gcgr-deficient zebrafish. We found that the expression of 1645 genes changes more than two-fold among mutants. Most of these genes are related to metabolism of carbohydrates, lipids, and amino acids. Genes related to fatty acid β-oxidation, amino acid catabolism, and ureagenesis are often downregulated. Among gcrgr-deficient zebrafish, we experimentally confirmed increases in lipid accumulation in the liver and whole-body glucose uptake, as well as a modest decrease in total amino acid content. These results provide new information about the global metabolic network that GCGR signaling regulates in addition to a better understanding of the receptor's physiological functions.

https://www.mdpi.com/1422-0067/21/3/724/pdf

Global Transcriptomic Analysis of Zebrafish Glucagon Receptor Mutant Reveals Its Regulated Metabolic Network.

The invention discloses application of ruscogenin in preparing a blood sugar reduction medicine and relates to the technical field of natural medicines. Experiments show that ruscogenin has a remarkable blood sugar reduction function on a mouse suffering from hyperglycemia induced by high fat, is capable of remarkably reducing the level of blood sugar of a mouse suffering from diabetes, and has the main mechanism that utilization and conversion of glucose are intensified by promoting absorption of glucose in muscle tissue, so that formation of HbA1c can be interfered, and the blood sugar of the mouse suffering from hyperglycemia can be reduced. Therefore, the ruscogenin has good application prospects in preparing diabetes medicines and medicine compositions of the diabetes medicines. The ruscogenin is simple and convenient in extraction method, wide in source, small in side effect and wide in application. The whole screening operation is simple, the method is convenient and rapid, anda theoretic basis can be provided for further development of the ruscogenin in the field of diabetes.

Wu Zhiqiang

Papers

Staprexanthones, Xanthone-Type Stimulators of Pancreatic β-Cell Proliferation from a Mangrove Endophytic Fungus.

Global Transcriptomic Analysis of Zebrafish Glucagon Receptor Mutant Reveals Its Regulated Metabolic Network.

Application of ruscogenin in preparing blood sugar reduction medicine