Additional file 1: Figure S1. of Asiatic acid attenuates methamphetamine-induced neuroinflammation and neurotoxicity through blocking of NF-kB/STAT3/ERK and mitochondria-mediated apoptosis pathway

Effects of AA and METH on the viability and morphology of SH-SY5Y cells. (a) SH-SY5Y cells were treated with AA (1, 5, 10, 15, 20, and 30 μM) for 24 h, and then, MTT assays were conducted (n = 4). (b) SH-SY5Y cells were treated with METH (0.5, 1, 1.5, 2, and 5 mM) and then, MTT (n = 4) and ELISA assays (n = 4) were conducted. (c) SH-SY5Y cells were pretreated with AA (1, 10, and 20 μM) for 1 h and then stimulated with 1 mM METH for 24 h. AA significantly increased the viability of 1 mM METH-stimulated SH-SY5Y cells in a concentration dependent (n = 4). (d) Cell morphology changes (magnifications ×200, n = 4/group). The data are representative of three independent experiments and quantified as mean values ± SEM. Tukey’s multiple comparison test, *p < 0.05 compared to normal control, † p < 0.05 compared to METH treatment. (PDF 197 kb

Additional file 3: Figure S3. of Asiatic acid attenuates methamphetamine-induced neuroinflammation and neurotoxicity through blocking of NF-kB/STAT3/ERK and mitochondria-mediated apoptosis pathway

Effects of AA on METH-induced translocation of NF-κB and TH expression in mesencephalic neurons. Immunofluorescence double staining for TH (green) and p-NF-κB p65 (red) localization. Cells were counterstained with Hoechst 33342 (blue). Magnifications ×200. The data are representative of three independent experiments. (PDF 154 kb

Hair Metabolomics in Animal Studies and Clinical Settings

Metabolomics is a powerful tool used to understand comprehensive changes in the metabolic response and to study the phenotype of an organism by instrumental analysis. It most commonly involves mass spectrometry followed by data mining and metabolite assignment. For the last few decades, hair has been used as a valuable analytical sample to investigate retrospective xenobiotic exposure as it provides a wider window of detection than other biological samples such as saliva, plasma, and urine. Hair contains functional metabolomes such as amino acids and lipids. Moreover, segmental analysis of hair based on its growth rate can provide information on metabolic changes over time. Therefore, it has great potential as a metabolomics sample to monitor chronic diseases, including drug addiction or abnormal conditions. In the current review, the latest applications of hair metabolomics in animal studies and clinical settings are highlighted. For this purpose, we review and discuss the characteristics of hair as a metabolomics sample, the analytical techniques employed in hair metabolomics and the consequence of hair metabolome alterations in recent studies. Through this, the value of hair as an alternative biological sample in metabolomics is highlighted

Development of Thiazolidinedione-Based HDAC6 Inhibitors to Overcome Methamphetamine Addiction

Thiazolidinedione is a five-membered heterocycle that is widely used in drug discovery endeavors. In this study, we report the design, synthesis, and biological evaluation of a series of thiazolidinedione-based HDAC6 inhibitors. In particular, compound 6b exerts an excellent inhibitory activity against HDAC6 with an IC50 value of 21 nM, displaying a good HDAC6 selectivity over HDAC1. Compound 6b dose-dependently induces the acetylation level of &alpha;-tubulin via inhibition of HDAC6 in human neuroblastoma SH-SY5Y cell line. Moreover, compound 6b efficiently reverses methamphetamine-induced morphology changes of SH-SY5Y cells via regulating acetylation landscape of &alpha;-tubulin. Collectively, compound 6b represents a novel HDAC6-isoform selective inhibitor and demonstrates promising therapeutic potential for the treatment of methamphetamine addiction