Synthesis of cordycepin: Current scenario and future perspectives.

Cordyceps genus, such as C. militaris and C. kyushuensis, is a source of a rare traditional Chinese medicine that has been used for the treatment of numerous chronic and malignant diseases. Cordycepin, 3'-deoxyadenosine, is a major active compound found in most Cordyceps. Cordycepin exhibits a variety of biological activities, including anti-tumor, immunomodulation, antioxidant, and anti-aging, among others, which could be applied in health products, medicine, cosmeceutical etc. fields. This review focuses on the synthesis methods for cordycepin. The current methods for cordycepin synthesis involve chemical synthesis, microbial fermentation, in vitro synthesis and biosynthesis; however, some defects are unavoidable and the production is still far from the demand of cordycepin. For the future study of cordycepin synthesis, based on the illumination of cordycepin biosynthesis pathway, genetical engineering of the Cordyceps strain or introducing microbes by virtue of synthetic biology will be the great potential strategies for cordycepin synthesis. This review will aid the future synthesis of the valuable cordycepin.

S-Adenosylmethionine regulates connexins sub-types expressed by hepatocytes.

Intercellular communication via GAP Junctions plays an important role in tissue homeostasis, apoptosis, carcinogenesis, cell proliferation and differentiation. Hepatocyte connexins (Cx) 26 and 32 levels are decreased during the de-differentiation process of primary hepatocytes in culture, a situation that is also characterized by a decrease in S-Adenosylmethionine (SAMe) levels. In this current study, we show that SAMe supplementation in cultured hepatocytes every 12h, leads to an up-regulation of Cx26 and 32 mRNA and protein levels and blocks culture-induced Cx43 expression, although it failed to increase Cx26 and 32 membrane localization and GAP junction intracellular communication. SAMe reduced nuclear ß-catenin accumulation, which is known to stimulate the TCF/LEF-dependent gene transcription of Cx43. Moreover SAMe-induced reduction in Cx43 and ß-catenin was prevented by the proteasome inhibitor MG132, and was not mediated by GSK3 activity. SAMe, and its metabolite 5'-methylthioadenosine (MTA) increased Cx26 mRNA in a process partially mediated by Adenosine A(2A) receptors but independent of PKA. Finally livers from MAT1A knockout mice, characterized by low hepatic SAMe levels, express higher Cx43 and lower Cx26 and 32 protein levels than control mice. These results suggest that SAMe maintains a characteristic expression pattern of the different Cxs in hepatocytes by differentially regulating their levels.