Adenosine ameliorated Aß25-35-induced brain injury through the inhibition of apoptosis and oxidative stress via an ERα pathway.

Previous studies have shown that adenosine has estrogen-like activity mediated by estrogen receptor α (ERɑ). This study aimed to examine the effects of adenosine on Aß25-35-induced brain injury and the underlying mechanisms involved. Adenosine (Ade, 20 mg/kg, i.g.) was administered for four weeks, followed by the induction of Alzheimer's disease (AD) by Aß25-35 (200 µM, 3 µL/20 g, i.c.v.). Furthermore, a specific ERα blocker (MPP, 0.3 mg/kg, i.p.) was administered 30 min before the treatments of adenosine to evaluate whether the observed effects elicited by adenosine were mediated via ERα. In addition, the learning and memory ability, neuronal damage, and the levels of amyloid ß-protein (Aß), phosphorylated Tau Protein (p-Tau), apoptosis, oxidative stress, immune cells, and ERα were examined. The antagonistic effect of MPP (1 µM) against adenosine (5 µM) in Aß25-35 (20 µM, 24 h)-induced N9 and PC-12 cells was also investigated. Adenosine improved learning and memory ability, reduced neuronal damage, downregulated Aß42/Aß40, p-Tau, apoptosis, and oxidative stress, transformed immune cells, and increased the expression of ERα following Aß25-35 challenge. MPP could block these effects. Moreover, MPP also blocked the effects of adenosine on the levels of apoptosis and reactive oxygen species (ROS) in Aß25-35-induced N9 and PC-12 cells. Adenosine ameliorated Aß25-35-induced brain injury by inhibiting apoptosis and oxidative stress, possibly via an ERα pathway.

Chrysosplenol D protects mice against LPS-induced acute lung injury by inhibiting oxidative stress, inflammation, and apoptosis via TLR4-MAPKs/NF-κB signaling pathways.

This study investigated the effect and mechanism of chrysosplenol D (CD) on LPS-induced acute lung injury in mice. Histological changes in the lungs were measured by hematoxylin-eosin staining. The levels of IL-6, IL-1ß, and TNF-α in the bronchoalveolar lavage fluid were detected by ELISA. The levels of oxidative stress were detected by the cuvette assay. Immune cells in peripheral blood, the levels of reactive oxygen species, and apoptosis of primary lung cells were detected by flow cytometry. The mRNA levels of TLR4, MyD88, IL-1ß, and NLRP3 were measured by quantitative real-time polymerase chain reaction. The levels of proteins in apoptosis and the TLR4-MAPKs/NF-κB signaling pathways were detected by Western blot. Hematoxylin-eosin staining showed that CD could improve lung injury; decrease the levels of inflammatory factors, oxidative stress, reactive oxygen species, and cell apoptosis; and regulate the immune system. Moreover, CD could down-regulate the mRNA levels of TLR4, MyD88, NLRP3, and IL-1ß in lung, and the protein levels of Keap-1, Cleaved-Caspase-3/Caspase-3, Cleaved-Caspase-9/Caspase-9, TLR4, MyD88, p-ERK/ERK, p-JNK/JNK, p-p38/p38, p-p65/p65, NLRP3, and IL-1ß, and up-regulated the levels of Bcl-2/Bax, p-Nrf2/Nrf2, and HO-1. The results suggested that CD could protect mice against LPS-induced acute lung injury by inhibiting oxidative stress, inflammation, and apoptosis via the TLR4-MAPKs/NF-κB signaling pathways.