[Diterpenoid constituents in Pseudolarix amabilis and their antitumor activities in vitro].

By various chromatographic techniques and extensive spectroscopic methods, 17 abietane diterpenoids were isolated from the dichloromethane fraction of the 95% ethanol cold-soak extracts of the seeds of Pseudolarix amabilis, namely pseudoamaol A(1), 12α-hydroxyabietic acid(2), 12-methoxy-7,13-abietadien-18-oic acid(3), 13-hydroxy-8,11,13-podocarpatrien-18-oic acid(4), 15-hydroxy-7,13-abietadien-12-on-18-oic acid(5), 8(14)-podocarpen-13-on-18-oic acid(6), holophyllin K(7), metaglyptin B(8), 7α-hydroxydehydroabietinsaure-methylester(9), 7-oxodehydroabietic acid(10), 15-hydroxy-7-oxodehydroabietinsaure-methy-lester(11), 15-methoxydidehydroabietic acid(12), 7-oxo-15-hydroxy-dehydroabietic acid(13), 15-hydroxydehydroabietic acid(14), 8,11,13-abietatriene-15,18-diol(15), 8,11,13-abietatriene-15-hydroxy-18-succinic acid(16), and 7ß-hydroxydehydroabie-tic acid(17). Compound 1 was a new compound. The isolated compounds were evaluated for their antitumor activities(HepG2, SH-SY5Y, K562), and compounds 8 and 17 showed potential cytotoxic activity against K562 cells, with IC_(50) values of 26.77 and 37.35 µmol·L~(-1), respectively.

Acetylharpagide Protects Mice from Staphylococcus Aureus-Induced Acute Lung Injury by Inhibiting NF-κB Signaling Pathway.

Staphylococcus aureus (S. aureus)-induced acute lung injury (ALI) is a serious disease that has a high risk of death among infants and teenagers. Acetylharpagide, a natural compound of Ajuga decumbens Thunb. (family Labiatae), has been found to have anti-tumor, anti-inflammatory and anti-viral effects. This study investigates the therapeutic effects of acetylharpagide on S. aureus-induced ALI in mice. Here, we found that acetylharpagide alleviated S. aureus-induced lung pathological morphology damage, protected the pulmonary blood-gas barrier and improved the survival of S. aureus-infected mice. Furthermore, S. aureus-induced myeloperoxidase (MPO) activity of lung homogenate and pro-inflammatory factors in bronchoalveolar lavage (BAL) fluid were suppressed by acetylharpagide. Mechanically, acetylharpagide inhibited the interaction between polyubiquitinated receptor interacting protein 1 (RIP1) and NF-κB essential modulator (NEMO), thereby suppressing NF-κB activity. In summary, these results show that acetylharpagide protects mice from S. aureus-induced ALI by suppressing the NF-κB signaling pathway. Acetylharpagide is expected to become a potential treatment for S. aureus-induced ALI.

New lignans, sesquiterpenes and other constituents from twigs and leaves of Rhododendron micranthum.

Rhododendron micranthum is used traditionally as a remedy for the treatment of chronic bronchitis in China. To clarify the chemical basis and provide a reference for the rational use of this medicinal plant, a phytochemical study was carried out on the twigs and leaves of R. micranthum, which afforded eight new compounds (1-8) and eight known compounds (9-16). Their structures were rigorously determined by comprehensive HRESIMS, NMR and electronic circular dichroism (ECD) analyses. The anti-inflammatory activities of these compounds were evaluated. Compounds 3, 13, and 14 suppressed the transcription of the NF-κB-dependent reporter gene in LPS-induced 293T/NF-κB-luc cells at 10 µM, while no effect on cell viability was observed.

Micranthanosides I and II, two novel 1,10-secograyanane diterpenoids and their antinociceptive analogues from the leaves and twigs of Rhododendron micranthum.

Micranthanosides I and II (1-2), two diterpenoid glucosides featuring a new 1,10-secograyanane skeleton, thirteen new diterpenoid glycosides (3-15), and 21 known analogues were obtained from the ethanol extract of the leaves and twigs of Rhododendron micranthum. Micranthanoside XII (12) represent the first example of 3,5-epoxy-4,5-seco-ent-kaurane diterpenoid. The structures of these compounds were determined by spectroscopic data analysis and quantum chemical calculations. To clarify the chemical basis and provide reference for rational use of this medicinal plant, the antinociceptive and the anti-inflammatory activities of the compounds were tested. In the acetic acid-induced writhing test, compounds 17 and 19 showed significant antinociceptive activity at a dose of 3 mg kg-1 and compounds 2, 6 and 32 showed significant antinociceptive activity at a dose of 10 mg kg-1. Toxic reactions such as nausea and convulsion were observed when 17, 19, 29, and 31 at a dose of 10 mg kg-1 or 30 and 33 at a dose of 1 mg kg-1 were administered. The anti-inflammatory activities of the isolated compounds were evaluated by measuring the inhibitory effects of LPS-induced NO production in BV2 cells. At 10 µM, micranthanoside IX (9) and rhodomicranoside F (26) showed moderate anti-inflammatory activities with inhibition rates of 56.31% and 72.43%, respectively.

Antinociceptive Diterpenoids from the Leaves and Twigs of Rhododendron decorum.

Three new leucothane-type (1-3), two new micrathane-type (4, 5), eight new grayanane-type diterpenoids (6-13), and four known compounds were obtained from the ethanol extract of the leaves and twigs of Rhododendron decorum. The structures were determined based on NMR spectra, quantum chemical calculations, and X-ray crystallography. The antinociceptive activities of compounds 1, 3, 4, 6, 8, 10-13, and 15-17 were evaluated via the acetic acid-induced writhing test. Compounds 1, 8, 11-13, and 15 exhibited significant antinociceptive activities. In particular, 12 and 15 were found to be effective at doses of 0.8 and 0.08 mg/kg, respectively.

Reversal of the Apoptotic Resistance of Non-Small-Cell Lung Carcinoma towards TRAIL by Natural Product Toosendanin.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) selectively triggers cancer cell death via its association with death receptors on the cell membrane, but exerts negligible side effects on normal cells. However, some non-small-cell lung carcinoma (NSCLC) patients exhibited resistance to TRAIL treatment in clinical trials, and the mechanism varies. In this study, we described for the first time that toosendanin (TSN), a triterpenoid derivative used in Chinese medicine for pain management, could significantly sensitize human primary NSCLC cells or NSCLC cell lines to TRAIL-mediated apoptosis both in vitro and in vivo, while showing low toxicity against human primary cells or tissues. The underlying apoptotic mechanisms involved upregulation of death receptor 5 (DR5) and CCAAT/enhancer binding protein homologous protein, which is related to the endoplasmic reticulum stress response, and is further associated with reactive oxygen species generation and Ca2+ accumulation. Surprisingly, TSN also induced autophagy in NSCLC cells, which recruited membrane DR5, and subsequently antagonized the apoptosis-sensitizing effect of TSN. Taken together, TSN can be used to sensitize tumors and the combination of TRAIL and TSN may represent a useful strategy for NSCLC therapy; moreover, autophagy serves as an important drug resistance mechanism for TSN.