Hupercumines A and B, <i>Lycopodium</i> Alkaloids from <i>Huperzia cunninghamioides</i>, Inhibiting Acetylcholinesterase

A novel class of C₃₈N₄ <i>Lycopodium</i> alkaloid, hupercumine A (<b>1</b>), consisting of two octahydroquinolines, a decahydroquinoline, and a piperidine, and a new C₂₇N₃-type alkaloid, hupercumine B (<b>2</b>), were isolated from <i>Huperzia cunninghamioides</i> (Hayata) Holub. The structures and absolute configurations of <b>1</b> and <b>2</b> were elucidated on the basis of spectroscopic data, chemical means, and biogenetic point of view. Hupercumines A (<b>1</b>) and B (<b>2</b>) showed moderate inhibitory activity against acetylcholinesterase

Bisleuconothine A Induces Autophagosome Formation by Interfering with AKT-mTOR Signaling Pathway

We have previously reported that bisleuconothine A (Bis-A), a novel bisindole alkaloid isolated from <i>Leuconotis griffithii</i>, showed cytostatic activity in several cell lines. In this report, the mechanism of Bis-A-induced cytostatic activity was investigated in detail using A549 cells. Bis-A did not cause apoptosis, as indicated by analysis of annexin V and propidium iodide staining. Expression of all tested apoptosis-related proteins was also unaffected by Bis-A treatment. Bis-A was found to increase LC3 lipidation in MCF7 cells as well as A549 cells, suggesting that Bis-A cytostatic activity may be due to induction of autophagy. Subsequent investigation via Western blotting and immunofluorescence staining indicated that Bis-A induced formation but prevented degradation of autophagosomes. Mechanistic studies showed that Bis-A down-regulated phosphorylation of protein kinase B (AKT) and its downstream kinase, PRAS40, which is an mTOR repressor. Moreover, phosphorylation of p70S6K, an mTOR-dependent kinase, was also down-regulated. Down-regulation of these kinases suggests that the increase in LC3 lipidation may be due to mTOR deactivation. Thus, the cytostatic activity shown by Bis-A may be attributed to its induction of autophagosome formation. The Bis-A-induced autophagosome formation was suggested to be caused by its interference with the AKT-mTOR signaling pathway

Bisleuconothine A Induces Autophagosome Formation by Interfering with AKT-mTOR Signaling Pathway

We have previously reported that bisleuconothine A (Bis-A), a novel bisindole alkaloid isolated from <i>Leuconotis griffithii</i>, showed cytostatic activity in several cell lines. In this report, the mechanism of Bis-A-induced cytostatic activity was investigated in detail using A549 cells. Bis-A did not cause apoptosis, as indicated by analysis of annexin V and propidium iodide staining. Expression of all tested apoptosis-related proteins was also unaffected by Bis-A treatment. Bis-A was found to increase LC3 lipidation in MCF7 cells as well as A549 cells, suggesting that Bis-A cytostatic activity may be due to induction of autophagy. Subsequent investigation via Western blotting and immunofluorescence staining indicated that Bis-A induced formation but prevented degradation of autophagosomes. Mechanistic studies showed that Bis-A down-regulated phosphorylation of protein kinase B (AKT) and its downstream kinase, PRAS40, which is an mTOR repressor. Moreover, phosphorylation of p70S6K, an mTOR-dependent kinase, was also down-regulated. Down-regulation of these kinases suggests that the increase in LC3 lipidation may be due to mTOR deactivation. Thus, the cytostatic activity shown by Bis-A may be attributed to its induction of autophagosome formation. The Bis-A-induced autophagosome formation was suggested to be caused by its interference with the AKT-mTOR signaling pathway