Shotgun Proteomics and Quantitative Pathway Analysis of the Mechanisms of Action of Dehydroeffusol, a Bioactive Phytochemical with Anticancer Activity from Juncus effusus.

Dehydroeffusol (DHE) is a phenanthrene isolated from the Chinese medicinal plant Juncus effusus. Biological evaluation of DHE reveals in vitro and in vivo anticancer effects. We performed a shotgun proteomic analysis using liquid chromatography-tandem mass spectrometry to investigate the changes in the protein profiles in cancer cells upon DHE treatment.

Identification of "sarsasapogenin-aglyconed" timosaponins as novel Aβ-lowering modulators of amyloid precursor protein processing.

The inhibition of amyloid β (Aβ) peptide production is a key approach in the development of therapeutics for the treatment of Alzheimer's disease (AD). We have identified that timosaponins consisting of sarsasapogenin (SSG) as the aglycone can effectively lower the production of Aβ peptides and stimulate neurite outgrowth in neuronal cell cultures. Structure-activity relationship studies revealed that the -fused AB ring, 3β-configuration, spiroketal F-ring and 25-configuration of SSG are the essential structural features responsible for the Aβ-lowering effects and neurite-stimulatory activity.

Guidelines for the use and interpretation of assays for monitoring autophagy.

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding.

Activation of autophagy of aggregation-prone ubiquitinated proteins by timosaponin A-III.

Chemical modulators of autophagy provide useful pharmacological tools for examination of autophagic processes, and also may lead to new therapeutic agents for diseases in which control of cellular sequestration and degradation capacity are beneficial. We have identified that timosaponin A-III (TAIII), a medicinal saponin reported to exhibit anticancer properties and improve brain function, is a pronounced activator of autophagy. In this work, the salient features and functional role of TAIII-induced autophagy were investigated.

Timosaponin A-III induces autophagy preceding mitochondria-mediated apoptosis in HeLa cancer cells.

Timosaponin A-III (TAIII), a saponin isolated from the rhizome of Anemarrhena asphodeloides, exhibits potent cytotoxicity and has the potential to be developed as an anticancer agent. Here, we provide evidence that TAIII induces autophagy in HeLa cells followed by apoptotic cell death. TAIII-induced autophagy was morphologically characterized by the formation of membrane-bound autophagic vacuoles recognizable at the ultrastructural level.

Terpenoids from the seeds of Artemisia annua.

Fourteen sesquiterpenes, three monoterpenes and one diterpene natural product have been isolated from the seeds of Artemisia annua. The possible biogenesis of some of these natural products are discussed by reference to recently reported experimental results for the autoxidation of dihydroartemisinic acid and other terpenoids from Artemisia annua.

Determination of the absolute stereochemistry of the epoxide group in alpinia epoxide by NMR.

The absolute stereochemistry of the epoxide group in alpinia epoxide [14,15-epoxylabda-8(17),12-dien-16-al (E)] has been determined by simultaneous reduction of the aldehyde and epoxide functional groups in this molecule to primary and secondary alcohols, followed by selective protection of the primary alcohol and derivitization of the secondary alcohol with S(+) and R(-) MTPCl as Mosher esters. Changes in (1)HNMR chemical shifts for all positions in these two esters were determined by 2D-NMR and used to infer the absolute stereochemistry of the epoxide group in the natural product alpinia epoxide.

A prezizaane sesquiterpene from Illicium angustisepalum.

The prezizaane sesquiterpene angustisepalin has been isolated from the aerial parts of Illicium angustisepalum, and its structure determined by 2D-NMR spectroscopy. Angustisepalin is formally the 10-benzoyl ester of neomajucin, previously reported from Illicium majus.