Anti-inflammatory activities of several diterpenoids isolated from Hemionitis albofusca.

Hemionitis albofusca (Baker) Christenh is a plant that grows in various regions of China. Although it is not recognized as a traditional medicine, it is often mistakenly labelled and used as Aleuritopteris argentea (S. G. Gmél.) Fée to alleviate menstruation-related issues. Recently, several diterpenoids such as ent-16-oxo-17-norkauran-19-oic acid (Compound A), 14-oxy-7ß,20-dihydroxycyath-12,18-diene (Compound B), ent-8(14),15-pimaradiene-2ß,19-diol (Compound C), ent-kaurane-16-ene-2ß,18α-diol (Compound D), ent-kaurane-2ß,16α,18α-triol (Compound E), and onychiol B have been extracted from H. albofusca. In this study, we investigated the anti-inflammatory activity of these diterpenes. We confirmed that compounds A ~ D suppressed the amount of cellular NO production by inhibiting the expression and transcription of iNOS protein. They also significantly inhibited the expression and transcription of inflammatory factors TNF-α and IL-6. Additionally, Compounds A and C suppressed the activation of the NF-κB signaling pathway and inhibited the phosphorylation level of p38, ultimately down-regulating inflammation. Compound B suppressed the activation of the NF-κB signaling pathway, while Compound D inhibited the phosphorylation level of p38 and down-regulated the activation of the p38 MAPK signaling pathway. In a word, our investigation supports the potential application of natural diterpenes as lead compounds for developing anti-inflammatory agents.

Sublethal hyperthermia enhances anticancer activity of doxorubicin in chronically hypoxic HepG2 cells through ROS-dependent mechanism.

Thermal ablation in combination with transarterial chemoembolization (TACE) has been reported to exert a more powerful antitumor effect than thermal ablation alone in hepatocellular carcinoma patients. However, the underlying mechanisms remain unclear. The purpose of the present study was to evaluate whether sublethal hyperthermia encountered in the periablation zone during thermal ablation enhances the anticancer activity of doxorubicin in chronically hypoxic (encountered in the tumor area after TACE) liver cancer cells and to explore the underlying mechanisms. In the present study, HepG2 cells precultured under chronic hypoxic conditions (1% oxygen) were treated in a 42°C water bath for 15 or 30 min, followed by incubation with doxorubicin. Assays were then performed to determine intracellular uptake of doxorubicin, cell viability, apoptosis, cell cycle, mitochondrial membrane potential (MMP), reactive oxygen species (ROS), and total antioxidant capacity. The results confirmed that sublethal hyperthermia enhanced the intracellular uptake of doxorubicin into hypoxic HepG2 cells. Hyperthermia combined with doxorubicin led to a greater inhibition of cell viability and increased apoptosis in hypoxic HepG2 cells as compared with hyperthermia or doxorubicin alone. In addition, the combination induced apoptosis by increasing ROS and causing disruption of MMP. Pretreatment with the ROS scavenger N-acetyl cysteine significantly inhibited the apoptotic response, suggesting that cell death is ROS-dependent. These findings suggested that sublethal hyperthermia enhances the anticancer activity of doxorubicin in hypoxic HepG2 cells via a ROS-dependent mechanism.

Comparative transcriptomic analysis of resistant and susceptible tea cultivars in response to Empoasca onukii (Matsuda) damage.

MAIN CONCLUSION: Transcriptomic studies in resistant and susceptible tea cultivars have been performed to reveal the different defense molecular mechanisms of tea after E. onukii feeding. The molecular mechanism by which tea plants respond to small green leafhopper Empoasca onukii (Matsuda) damage is unclear. Using the resistant tea plant cultivar Juyan (JY) and the susceptible tea plant cultivar Enbiao (EB) as materials, this study performed RNA-seq on tea leaf samples collected at three time points (6 h, 12 h, 24 h) during exposure of the plants to leafhopper to reveal the molecular mechanisms that are activated in susceptible and resistant tea plant cultivars in response to leafhopper damage. The numbers of DEGs in the susceptible tea cultivar during early (6 h) and late (24 h) stages of leafhopper induction were higher than those in the resistant cultivar at the same time points. The stress responses to leafhopper were most intense at 12 h in both tea cultivars. Pathway enrichment analysis showed that most up-regulated DEGs and their related metabolic pathways were similar in the two tea cultivars. However, during the early stage of leafhopper induction (6 h), jasmonic acid (JA)-related genes were significantly up-regulated in the resistant cultivar. The terpenoid biosynthetic pathway and the α-linolenic acid metabolic pathway were activated earlier in the resistant cultivar and remained activated until the late stage of leafhopper damage. Our results confirmed that after leafhopper damage, the resistant tea cultivar activated its defense responses earlier than the susceptible cultivar, and these defense responses were mainly related to terpenoid metabolism and JA biosynthetic pathway. The results provide important clues for further studies on resistance strategy of tea plants to pest.