Chemical constituents of Isodon melissoides.
Four new diterpenoids, melissoidesin E (1), F (2), G (4) and H (5), together with one known diterpenoid and two lignan glycosides, were isolated from aerial parts of Isodon melissoides. Their structures were established by spectral analysis and comparison with related compounds. The lignan glycosides (compounds 7 and 8) were the first examples to be isolated from the genus Isodon plants.
Melissoidesin G, a diterpenoid purified from Isodon melissoides, induces leukemic‐cell apoptosis through induction of redox imbalance and exhibits synergy with other anticancer agents
Melissoidesin G (MOG) is a new diterpenoid purified from Isodon melissoides, a plant used in Chinese traditional medicine as antitumor and anti‐inflammatory agents. In our study, MOG was shown to specifically inhibit the growth of human leukemia cell lines and primary acute myeloid leukemia (AML) blasts via induction of apoptosis, with the evidence of mitochondrial ΔΨm loss, reactive oxygen species production, caspases activation and nuclear fragmentation. Furthermore, it was shown that thiol‐containing antioxidants completely blocked MOG‐induced mitochondrial ΔΨm loss and subsequent cell apoptosis, while the inhibition of apoptosis by benzyloxy‐carbonyl‐Val‐Ala‐Asp‐fluoromethylketone only partially attenuated mitochondrial ΔΨm loss, indicating that MOG‐induced redox imbalance is an early event upstream to mitochondrial ΔΨm loss and caspase‐3 activation. Consistently, it was found that MOG rapidly decreased the intracellular glutathione (GSH) content in a dose‐dependent manner and the significance of GSH depletion in MOG‐induced apoptosis was further supported by the protective effects of tert‐butylhydroquinone (tBHQ) and the facilitative effects of DL‐buthionine (S,R)‐sulfoximine (BSO). Furthermore, it was showed that GSH depletion induced by MOG rendered some leukemia cell lines more sensitive to arsenic trioxide (As2O3), doxorubicin or cisplatin. Additionally, the synergistic apoptotic effects of MOG with As2O3 were detected in HL‐60 and primary AML cells, but not in normal cells, suggesting the selective toxicity of their combination to the malignant cells. Together, we proposed that MOG alone or administered with other anticancer agents may provide a novel therapeutic strategy for leukemia. © 2007 Wiley‐Liss, Inc.
Diterpenoids from Isodon adenoloma
Abstract Five new ent-kaurene diterpenoids, adenolin A—E, and a known compound, longikaurin D were isolated from the air-dried leaves of Isodon adenoloma. The structures were established by spectroscopic means.