TM-4 presented precognitive effect on scopolamine-induced memory impairment. And the regulation of multi-targets for TM-4 were further conformed through transcriptome sequencing. More interesting, the blood, urine and feces metabolism in rat and rat/human liver microsome metabolism towards TM-4 were also investigated. Overall, TM-4 is a promising multi-function candidate for the development of drugs to Alzheimer's disease. According to the latest Global Burden of Disease Study data, non-communicable diseases in general and cardiovascular disease (CVD) in particular are the leading cause of premature death and reduced quality of life. Demographic shifts, unhealthy lifestyles and a higher burden of adverse environmental factors provide an explanation for these findings. The expected growing prevalence of CVD requires enhanced research efforts for identification and characterisation of novel therapeutic targets and strategies. Cardiovascular risk factors including classical (e.g. hypertension, diabetes, hypercholesterolaemia) and non-classical (e.g. environmental stress) factors induce the development of endothelial dysfunction, which is closely associated with oxidant stress and vascular inflammation and results in CVD, particularly in older adults. Most classically successful therapies for CVD display vasoprotective, antioxidant and anti-inflammatory effects, but were originally designed with other therapeutic aims. So far, only a few 'redox drugs' are in clinical use and many antioxidant strategies have not met expectations. With the present review, we summarise the actual knowledge on CVD pathomechanisms, with special emphasis on endothelial dysfunction, adverse redox signalling and oxidative stress, highlighting the preclinical and clinical evidence. In addition, we provide a brief overview of established CVD therapies and their relation to endothelial dysfunction and oxidative stress. Finally, we discuss novel strategies for redox-based CVD therapies trying to explain why, despite a clear link between endothelial dysfunction and adverse redox signalling and oxidative stress, redox- and oxidative stress-based therapies have not yet provided a breakthrough in the treatment of endothelial dysfunction and CVD. Although Tanshinone IIA (Tan IIA) has been associated with inflammation, oxidative stress and apoptosis, the effects of Tan IIA on lung blast injury remain uncertain. In this study, we explored the effects of Tan IIA on lung blast injury, studied its possible molecular mechanisms. Fifty C57BL/6 mice were randomly divided into the control, blast, blast + Tan IIA, blast + LY294002 (a PI3K inhibitor), or blast + Tan IIA + LY294002 groups. Serum and lung samples were collected 48 h after blast injury. The data showed that Tan IIA significantly inhibited blast-induced increases in the lung weight/body weight and wet/dry (W/D) weight ratios, decreased the CD44-and CD163-positive inflammatory cell infiltration in the lungs, reduced the IL-1β, TNF-α and IL-6 expression, and enhanced IL-10 expression. Tan IIA also significantly alleviated the increases in MDA5 and IRE-a and the decrease in SOD-1 and reversed the low Bcl-2 expression and the high Bax and Caspase-3 expressions. Additionally, Tan IIA significantly decreased p-PI3K and p-Akt expression and increased p-FoxO1 expression. More importantly, both LY294002 and Tan IIA pretreatment markedly protected against blast-induced inflammation, oxidative stress and apoptosis in lung blast injury. These results suggest that Tan IIA protects against lung blast injury, which may be partly mediated by inhibiting the PI3K/Akt/FoxO1 signaling pathway. There has been a renewed interest in the enzyme arginase for its role in various physiological and pathological processes that go beyond the urea cycle. One such role ascribed to arginase has been that of regulating nitric oxide (NO) production by a substrate (l-arginine) competition between arginase and nitric oxide synthase (NOS). Several arginase inhibitors have been developed to investigate the biological roles of arginase, of which Nω-hydroxy-l-norarginine (nor-NOHA) is commercially available and is used widely from cell culture models to clinical investigations in humans. check details Despite the prevalence of nor-NOHA to investigate the substrate competition between arginase and NOS, little is known regarding interferences that nor-NOHA could have on common methods to assess NO production. Therefore, we investigated if nor-NOHA has unintended consequences on common NO assessment methods. We show that nor-NOHA spontaneously releases biologically active NO-like molecule in cell culture media by reacting with riboflavin. This NO-like molecule is indistinguishable from an NO donor (NOR-3) using common methods to assess NO. Besides riboflavin, nor-NOHA spontaneously reacts with H2O2 to diminish H2O2 content and produce NO-like molecule in the process. Our investigation provides detailed evidence on unintended artefacts related to nor-NOHA that can limit its use in cell culture, as well as some ex vivo and in vivo models. Future studies on arginase should take into consideration the limitations presented here when using nor-NOHA as a research tool, not only in investigations related to arginase and NOS competition, but also for investigating other biological roles of arginase. Diabetes is a metabolic disorder associated with mitochondrial (mt) dysfunction and oxidative stress. The molecular mechanisms involved in diabetes-associated neurological complications remain elusive. This study aims to investigate the protective effect of metformin (MF) on regulatory networks and integrated stress responses in brain tissue of Streptozotocin (STZ)-induced diabetic mice. STZ-induced diabetic mice were treated with MF (20 mg/kg BW), and whole brain tissue was harvested for further analysis. Protein carbonylation was measured as a marker of neuronal oxidative stress. Protein expression of mt chaperones, maintenance proteins, and regulators of the unfolded protein response (UPR) were measured by Western blot. Transcript levels of antioxidant enzyme GSTA4; mt biogenesis markers, ER stress regulators, and miR-132 and miR-148a were analysed using qPCR. The results showed that MF efficiently reduced protein carbonylation and oxidation. Mt function was improved by MF-treatment through upregulation of chaperone proteins (HSP60, HSP70 and LonP1).