A homologous series of α-glucans from Hemicentrotus pulcherrimus and their immunomodulatory activity.

Seven macromolecular polysaccharides (HPP-2S-HPP-8S) were purified from the gonads of sea urchin Hemicentrotus pulcherrimus. They were characterized as α-glucan homologues, sharing the same α-1,4-glucan backbone substituted at C-6 positions by glucose with HPP-1S that occurs as the major polysaccharide in H. pulcherrimus, while with higher degrees of branching, and additionally possessing minor amounts of mannose and ribose. The branching degree and amounts of non-glucose branches showed a generally increasing tendency across HPP-2S - HPP-8S. These polysaccharides exhibited significant macrophage-activating effects by augmenting the secretion of NO, TNF-α and IL-6, which probably involves the activation of NF-κB and MAPKs signaling pathways. Notably, the polysaccharides with a higher degree of branching exhibited markedly enhanced immunomodulatory capacity with a lowest effective concentration of 1.95 µg/mL. This work provides new cases of bioactive α-glucans and reveals their potential application as immunomodulating agents.

Selective Inhibition of PTP1B by New Anthraquinone Glycosides from Knoxia valerianoides.

Protein tyrosine phosphatase 1B (PTP1B) is highly validated as a therapeutic target for type 2 diabetes. However, active site-directed PTP1B inhibitors generally suffer from poor selectivity and bioavailability. Inspired by the identification of a unique anthraquinone-coumarin hybrid from Knoxia valerianoides exhibiting good specificity for PTP1B over the highly homologous T-cell protein tyrosine phosphatase (TCPTP), further chemical investigation of this plant species led to the isolation of nine new anthraquinone glycosides (1-9) and two known ones (10 and 11). Structures were characterized by a combination of spectroscopic analyses and chemical methods. All compounds showed PTP1B inhibitory activities with IC50 values ranging from 1.05 to 13.74 µM. Compounds 4 and 8 exhibited greater than 64-fold selectivity over TCPTP. Enzyme kinetic studies revealed that compounds 4 and 7 behaved as mixed-type inhibitors. Docking studies predicted similar binding modes of these compounds at the allosteric site positioned between helices α3 and α6.