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Aims: Pseudoginsenoside-F11 (PF11), an ocotillol-type ginsenoside, has been reported to exert wide-ranging neuroprotective properties. The aim of this study was to investigate the effect and potential mechanisms of PF11 on the autophagic/lysosomal pathway following ischemic stroke., Methods: Male Sprague-Dawley rats underwent permanent middle cerebral artery occlusion (pMCAO). Cerebral ischemia outcome, TUNEL staining, Fluoro-Jade B staining were carried out 24 hours poststroke. The autophagic/lysosomal-related proteins were measured., Results: A single administration of PF11 significantly decreased the infarct area, reduced the brain water content, and improved neurological functions, even 4 hours after the onset of pMCAO. Meanwhile, PF11 lessened the ischemic insult-mediated loss of neurons and activation of astrocytes and microglia. Furthermore, PF11 attenuated pMCAO-induced accumulations of autophagosomes and apoptosis. We further observed a remarkable effect of PF11 in reversing the ischemic insult-induced accumulation of autophagosomes (LC3-II) and abnormal aggregation of autophagic proteins (SQSTM1 and ubiquitin). Furthermore, PF11 was capable of improving lysosomal function and lysosome/autophagosome fusion following pMCAO, and this change was reversed by the lysosomal inhibitor chloroquine. Also, the improvement of ischemic outcome and the antiapoptotic effect induced by PF11 was reversed by CQ., Conclusion: These findings indicate that the autophagic flux is impaired in a rat model of pMCAO, and that PF11 exerts an excellent protective effect against ischemic stroke by alleviating autophagic/lysosomal defects., (© 2017 John Wiley & Sons Ltd.)

Background and Purpose: IL‐1β produced by macrophages via the NOD‐, LRR‐ and pyrin domain‐containing 3 (NLRP3) inflammasome, mediates the inflammatory crosstalk between macrophages and adipocytes. In our previous study, (16S,20S,24R)‐12β‐acetoxy‐16,23‐epoxy‐24,25‐dihydroxy‐3β‐(β‐D‐xylopyranosyloxy)‐9,19‐cyclolanost‐22(23)‐ene (AEDC), a cycloartane triterpenoid isolated from Actaea vaginata (Ranunculaceae), was found to possess anti‐inflammatory effect on LPS‐treated RAW264.7 macrophages. This study was designed to investigate whether AEDC modulates macrophage–adipocyte crosstalk to alleviate adipose tissue inflammation. Experimental Approach The anti‐inflammatory effect of AEDC was evaluated on LPS plus ATP‐induced THP‐1 macrophages and C57BL/6J mice. The expression of autophagy‐related and NLRP3 inflammasome complex proteins was analysed by western blots, immunofluorescence staining and co‐immunoprecipitation. The pro‐inflammatory cytokines levels were determined by ELISA kits. The adipose tissue inflammation was evaluated by histological analysis and immunohistochemical staining. Key Results: AEDC (5 and 10 μM) activated autophagy, which in turn suppressed the NLRP3 inflammasome activation and IL‐1β secretion in THP‐1 macrophages. AEDC increased the expression of SIRT3 deacetylase and enhanced its deacetylating activity to reverse mitochondrial dysfunction and activate AMP‐activated protein kinase, which together induced autophagy. Moreover, AEDC (10 μM) attenuated macrophage conditioned medium‐induced inflammatory responses in adipocytes and blocked THP‐1 macrophages migration towards 3T3‐L1 adipocytes. In inflammation mice, AEDC (5 and 20 mg·kg−1) treatment reduced the levels of pro‐inflammatory cytokines in serum and epididymal adipose tissue and reduced macrophage infiltration to alleviate adipose tissue inflammation. Conclusion and Implications: AEDC attenuated the inflammatory crosstalk between macrophages and adipocytes through SIRT3‐autophagy‐mediated NLRP3 inflammasome inhibition, which might used for the treatment of adipose tissue inflammation‐related metabolic disorders. [ABSTRACT FROM AUTHOR]