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Ischemic stroke is often associated with a large disease burden. The existence of ischemia-reperfusion injury brings great challenges to the treatment of ischemic stroke. The purpose of this study was to explore the differences of metabolites in different parts of the brain induced by Shuxuetong injection against cerebral ischemia-reperfusion and to extend the corresponding mechanism. The rats were modeled by transient middle cerebral artery occlusion (t-MCAO) operation, and the success of modeling was determined by neurological function score and TTC staining. UPLC-Q/TOF-MS metabolomics technique and multivariate statistical analysis were used to analyze the changes and differences of metabolites in the cortex and hippocampus of cerebral ischemia-reperfusion rats. Compared with the model group, the neurological function score and cerebral infarction volume of the Shuxuetong treatment group were significantly different. There were differences and changes in the metabolic distribution of the cortex and hippocampus in each group, the distribution within the group was relatively concentrated. The separation trend between the groups was obvious, and the distribution of the Shuxuetong treatment group was similar to that of the sham operation group. We identified 13 metabolites that were differentially expressed in the cortex, including glutamine, dihydroorotic acid, and glyceric acid. We also found five differentially expressed metabolites in the hippocampus, including glutamic acid and fumaric acid. The common metabolic pathways of Shuxuetong on the cortex and hippocampus were D-glutamine and D-glutamate metabolism and nitrogen metabolism, which showed inhibition of cortical glutamine and promotion of hippocampal glutamic acid. Specific pathways of Shuxuetong enriched in the cortex included glyoxylate and dicarboxylate metabolism and pyrimidine metabolism, which showed inhibition of glyceric acid and dihydroorotic acid. Specific pathways of Shuxuetong enriched in the hippocampus include arginine biosynthesis and citrate cycle (TCA cycle), which promotes fumaric acid. Shuxuetong injection can restore and adjust the metabolic disorder of the cortex and hippocampus in cerebral ischemia-reperfusion rats. The expression of Shuxuetong in different parts of the brain is different and correlated. [ABSTRACT FROM AUTHOR]

The traditional Chinese medicine decoction FuFangChangTai (FFCT) has been used in the therapy of colon cancer clinically, yielding alleviated toxicity and enhanced immunity. In our previous study, FFCT exerted its antitumor activity not only by inducing apoptosis but also by activating autophagy to eliminate tumor cells. However, its mechanism is not well understood. The purpose of this study was to investigate the relationship between macrophages activation and FFCT-induced autophagy. Results showed that FFCT could induce autophagy in colon cancer, as demonstrated by increased level of intracellular autophagy marker LC3 II in CT26.WT cells by fluorescence microscope and western blot assay. FFCT also facilitated numbers of vesicular bodies with bilayer membrane in CT26.WT cells, which were indicative of autophagosomes formation. Autophagosomes secreted by FFCT-treated CT26.WT cells can activate M1 type macrophages, accompanied with increased expression of costimulatory molecules CD86 and CD40 on the surface of RAW264.7 cells, and more inflammatory cytokines secretion, such as TNF-α, IL-6, MCP-1, and IL-1β. mRNA expressions of M2 macrophages markers, such as IL-10, CD206, Arg-1, and FIZZ-1, were downregulated. And this process helps regulate the polarization of macrophages and promote the immune response. These findings support a mechanism of FFCT-induced autophagy and provide novel evidence demonstrating that macrophages are involved in FFCT-induced autophagy progression. [ABSTRACT FROM AUTHOR]