Protective effect of dihydromyricetin on hyperthermia-induced apoptosis in human myelomonocytic lymphoma cells.

Dihydromyricetin (DMY) is a traditional herbal medicine, with a wide range of biological activities. Extreme hyperthermia (HT) can suppress the immune system; thus, protection of the immune system is beneficial in heat-related diseases, including heatstroke. In our study, we revealed the protective effect of DMY against HT-induced apoptosis and analysed the underlying molecular mechanisms. We incubated human myelomonocytic lymphoma U937 cells at 44 °C for 30 min with or without DMY and followed by further incubation for 6 h at 37 °C. Cell viability was determined by the CCK-8 assay. DMY did not cause any cytotoxic effects in U937 cells even at high doses. HT treatment alone induced significant apoptosis, which was detected by DNA fragmentation and Annexin V/PI double staining. Mitochondrial dysfunction was identified by loss of mitochondrial membrane potential (MMP) during heat stimulation. Apoptotic related proteins were involved, truncated Bid and caspase-3 were upregulated, and Mcl-1 and XIAP were downregulated. We also identified the related signalling pathways, such as the MAPK and PI3K/AKT pathways. However, changes in HT were dramatically reversed when the cells were pretreated with DMY before exposure to HT. Overall, MAPKs and PI3K/AKT signalling, mitochondrial dysfunction, and caspase-mediated pathways were involved in the protective effect of DMY against HT-induced apoptosis in U937 cells, which was totally reversed by DMY pretreatment. These findings indicate a new clinical therapeutic strategy for the protection of immune cells during heatstroke.

Three New Abietane-Type Diterpenoids from Callicarpa macrophylla Vahl.

Three new abietane-type diterpenoids, named callicapoic acid M3 (1), callicapoic acid M4 (2) and callicapoic acid M5 (3), were isolated from the Callicarpa macrophylla Vahl. Their structures were established by spectroscopic techniques (IR, UV, MS, 1D and 2D NMR). All the isolated three compounds were evaluated for inhibitory activity on NO production in LPS-activated RAW 264.7 macrophage cells by using MTT assays. Compounds 1, 2 and 3 showed potent inhibitory activity, with inhibition rates of 34.47-40.13%.

[Effect of 5-fluorouracil in combination with Astragalus membranaceus on amino acid metabolism in mice model of gastric carcinoma].

OBJECTIVE: To study the effect of 5-fluorouracil-FU in combination with astragalus membranaceus(AM) on amino acid metabolism in mice model of gastric carcinoma induced by 3-methylcholanthrene(MC). METHODS: Mice gastric carcinoma models were established by 3-methylcholanthrene induction and randomly divided into different groups, and received 5-FU treatment (group A) 5-FU plus AM (group B), 5-FU plus a high dose of AM(group C), no treatment (group D). Normal mice were used as control (group N). Free amino acid in the tumor specimens were examined. RESULTS: The levels of free Valine, Methionine, Leucine, Arginine and cystine in the tumor specimens in group D were significantly higher than that in group N(P< 0.05). The levels of free serine in group A, B, C, D were significantly higher than that in group N. The levels of free glutamic acid in group A, B were significantly higher than that in group N(P< 0.05). The levels of free proline in group C, D were significantly higher than that in group P, N(P< 0.05). CONCLUSIONS: The increasing levels of free serine and proline in tumor specimens in gastric cancer mice model reveals metabolic disturbance of amino acid. 5-FU plus astragalus membranaceus can decrease the level of free glutamic acid in the mice models, and inhibit tumor growth.