Extracellular vesicles (EVs) generated from redox active anticancer drugs are released into the extracellular environment. These EVs contain oxidized molecules and trigger inflammatory responses by macrophages. Using a mouse model of doxorubicin (DOX)-induced tissue injury, we previously found that the major sources of circulating EVs are from heart and liver, organs that are differentially affected by DOX. Here, we investigated the effects of EVs from cardiomyocytes and those from hepatocytes on macrophage activation. EVs from H9c2 rat cardiomyocytes (H9c2 EVs) and EVs from FL83b mouse hepatocytes (FL83 b EVs) have different levels of protein-bound 4-hydroxynonenal and thus different immunostimulatory effects on mouse RAW264.7 macrophages. H9c2 EVs but not FL83 b EVs induced both pro-inflammatory and anti-inflammatory macrophage activation, mediated by NFκB and Nrf-2 pathways, respectively. DOX enhanced the effects of H9c2 EVs but not FL83 b EVs. While EVs from DOX-treated H9c2 cells (H9c2 DOXEVs) suppressed mitochondrial respiration and increased glycolysis of macrophages, EVs from DOX-treated FL83b cells (FL83b DOXEVs) enhanced mitochondrial reserve capacity. Mechanistically, the different immunostimulatory functions of H9c2 EVs and FL83 b EVs are regulated, in part, by the redox status of the cytoplasmic thioredoxin 1 (Trx1) of macrophages. H9c2 DOXEVs lowered the level of reduced Trx1 in cytoplasm while FL83b DOXEVs did the opposite. Trx1 overexpression alleviated the effect of H9c2 DOXEVs on NFκB and Nrf-2 activation and prevented the upregulation of their target genes. Our findings identify EVs as a novel Trx1-mediated redox mediator of immune response, which greatly enhances our understanding of innate immune responses during cancer therapy.

Malaria remains a significant cause of death in tropical and subtropical regions by serious complications with hematological abnormalities consistent with high parasitemia. Hence, this study aimed to determine the efficacy of the Gymnema inodorum leaf extract (GIE) on hematological alteration in Plasmodium berghei infection in mice. Groups of ICR mice were infected intraperitoneally with parasitized red blood cells of P. berghei ANKA (PbANKA). They were administered orally by gavage of 100, 250, and 500 mg/kg of GIE for 4 consecutive days. Healthy and untreated groups were given distilled water, while 10 mg/kg of chloroquine was treated as the positive control. Hematological parameters including RBC count, hemoglobin (Hb), hematocrit (Hct), mean corpuscular volume (MCV), mean cell hemoglobin (MCH), mean cell hemoglobin concentration (MCHC), RBC distribution width (RDW), white blood cell (WBC) count, and WBC differential count were measured. The results showed that significant decreases of RBC count, Hb, Hct, MCV, MCH, MCHC, and reticulocytes were observed in the untreated group, while RDW was significantly increased compared with the healthy control. Furthermore, the WBC, neutrophil, monocyte, basophil, and eosinophil of untreated mice increased significantly, while the lymphocyte was significantly decreased compared with the healthy control. Interestingly, GIE normalized the hematological alteration induced by PbANKA infection in GIE-treated groups compared with healthy and untreated groups. The highest efficacy of GIE was observed at a dose of 500 mg/kg. Our results confirmed that GIE presented the potential role in the treatment of hematological alteration during malaria infection.

Turmeric (Curcuma longa L.), a member of Zingiberacaeae, is used for Thai traditional medicine, flavoring, preservative, and coloring agent. In Southern Thailand, turmeric is a famous ingredient for food recipes. Not only is the ripened rhizome used for cuisine, but also the young rhizomes. Previous studies have indicated that a variety of turmeric products from the ripened rhizome are valuable source of antioxidant compounds. However, there are ambiguous data regarding the level of antioxidant activity of the young rhizome. The aim of this study was to investigate the level of total phenolic content (TPC) and antioxidant activity of the young rhizomes by comparing to the ripened rhizome. TPC and antioxidant activity of aqueous and 80% methanolic extracts from the young turmeric grown in Southern Thailand were estimated using the Folin-Ciocalteu method and DPPH free radical scavenging activity (DPPH-RSA) assay, respectively. Results showed that the concentration of TPC determined in methanolic extract (19.80±0.25 mg GAE/ g extract) from the young rhizome was significantly higher than the corresponding aqueous extract (18.38±0.41 mg GAE/ g extract). The aqueous and methanolic extracts exhibited significant inhibition in DPPH-RSA with the half-maximal inhibitory concentration (IC50) value of 5.88±0.70 mg/mL and 3.00±0.31 mg/mL, respectively. However, in comparison with the ripened rhizome, TPC and DPPH-RSA of the young rhizome were lower. These results indicate that the young rhizome grown in Southern Thailand could be a source of antioxidant compounds, but the ripened rhizome provides better antioxidant properties than the young rhizome.

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