Four cucurbitane glycosides, momordicosides Q, R, S, and T, and stereochemistry-established karaviloside XI, were isolated from the vegetable bitter melon (Momordica charantia). These compounds and their aglycones exhibited a number of biologic effects beneficial to diabetes and obesity. In both L6 myotubes and 3T3-L1 adipocytes, they stimulated GLUT4 translocation to the cell membrane--an essential step for inducible glucose entry into cells. This was associated with increased activity of AMP-activated protein kinase (AMPK), a key pathway mediating glucose uptake and fatty acid oxidation. Furthermore, momordicoside(s) enhanced fatty acid oxidation and glucose disposal during glucose tolerance tests in both insulin-sensitive and insulin-resistant mice. These findings indicate that cucurbitane triterpenoids, the characteristic constituents of M. charantia, may provide leads as a class of therapeutics for diabetes and obesity.

Five new stemoninine-type alkaloids, bisdehydrostemoninine (1), isobisdehydrostemoninine (2), bisdehydroneostemoninine (3), and bisdehydrostemoninines A (4) and B (5), were isolated from the crude-alkaloid extract of the roots of Stemona tuberosa. Their structures were elucidated on the basis of one- and two-dimensional NMR and other spectroscopic studies. The relative configuration of 4 was determined by X-ray diffraction. Alkaloid 1 displayed significant antitussive activity in the citric acid-induced guinea pig cough model.

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Protein tyrosine kinase (PTK) inhibitors represent emerging therapeutics for cancer chemoprevention. In our study, hematoxylin (26) was identified as one of the most remarkable c-Src inhibitors in an orthogonal compound-mixing library (32200 compounds) by using an ELISA-based automated high-throughput screening (HTS) strategy. Interestingly, hematoxylin was found to be an ATP competitive broad-spectrum PTK inhibitor in vitro, with IC50 values ranging from nanomolar to micromolar level. Further studies showed that such inhibition was associated with the PTK phosphorylation and subsequent downstream signaling pathways. The structure-activity relationship assessment of the PTK inhibitory potency of hematoxylin analogues isolated from Heamatoxylon campechianum was in good agreement with the result of concurrent molecular docking simulation: the catechol moiety in ring A and the hematoxylin-like three-dimensional structure were essential for c-Src-targeted activities. Hematoxylin and its natural analogues were substantially validated to function as a new class of PTK inhibitors.

Investigation of the roots of Stemona tuberosa afforded five minor constituents, stemoenonine (1), 9a- O-methylstemoenonine (2), oxystemoenonine (3), 1,9a- seco-stemoenonine (4), and oxystemoninine (5), along with the known compound stemoninoamide (6). Their structures were elucidated by 1D and 2D NMR spectra and other spectroscopic studies. Alkaloids 1, 2, and 6, as well as the representative stemoninine-type alkaloid, stemoninine (7), were screened for antitussive activity in the citric acid-induced guinea pig cough model. Compounds 6 and 7 exhibited strong antitussive activity after oral and intraperitoneal administrations.

A new seco-kalmane-type diterpenoid, seco-rhodomollone (1), five new grayanane-type diterpenoids, rhodomollein XXI (2), 6-O-acetylrhodomollein XXI (3), 6,14-di-O-acetylrhodomollein XXI (4), rhodomollein XXII (5), and 2-O-methylrhodomollein XI (6), and two new kalmane-type diterpenoids, rhodomolleins XXIII (7) and XXIV (8), together with seven known compounds, were isolated from the flowers of Rhododendron molle collected in Guangxi Province, China. The absolute configurations of 1 and 3 were defined by single-crystal X-ray diffraction experiments. Compound 1 possesses an unprecedented 1,5-seco-kalmane skeleton presumably derived by cleavage of the C-1-C-5 bond of the kalmane skeleton. Compounds 2-4 represent the first examples from a natural source of grayanane-type diterpenoids with a chlorine substituent.

Three new dimeric sesquiterpenoids, chloramultilides B-D ( 1- 3), along with 10 known sesquiterpenoids, were isolated from the whole plant of Chloranthus spicatus. Their structures were established by physical data (1D and 2D NMR, MS). The structure and absolute configuration of 1 was confirmed by X-ray crystallography. Compound 1 exhibited moderate in vitro antifungal activity.

Five new alkaloids, 6beta-hydroxystemofoline (1), 16-hydroxystemofoline (2), neostemofoline (3), protostemodiol (4), and 13-demethoxy-11(S*),12(R*)-dihydroprotostemonine (5), along with 10 known alkaloids, were isolated from stems and leaves of Stemona japonica. Their structures were elucidated by 1D and 2D NMR and other spectroscopic studies. The insecticidal activity of the agonist 16-hydroxystemofoline (2) and antagonist 13-demethoxy-11(S*),12(R*)-dihydroprotostemonine (5) was demonstrated by electrophysiological in vitro tests on the insect nicotinic acetylcholine receptor and by in vivo screenings against relevant agricultural insect pests.