Acteoside from Conandron ramondioides Reduces Microcystin-LR Cytotoxicity by Inhibiting Intracellular Uptake Mediated by OATP1B3.

The hepatotoxin microcystin-LR is a strong inhibitor of serine/threonine protein phosphatase (PP) 1 and PP2A. The onset of its cytotoxicity depends on its selective uptake via the hepatocyte uptake transporters, organic anion transporting polypeptide (OATP) 1B1 and OATP1B3. Understanding and preventing the cytotoxicity of microcystin-LR is crucial to maintain human health. This chemoprevention study demonstrates that the herbal plant extract of iwajisha (20 µg/mL) reduced microcystin-LR cytotoxicity in OATP1B3-expressing cells by approximately six times. In addition, 20 µM acteoside, which is one of the major compounds in iwajisha, reduced microcystin-LR cytotoxicity by approximately 7.4 times. Acteoside could also reduce the cytotoxicity of other compounds, such as okadaic acid and nodularin, which are both substrates of OATP1B3 and inhibitors of PP1/PP2A. To investigate the mechanism by which the cytotoxicity of microcystin-LR is attenuated by acteosides, microcystin-LR and microcystin-LR-binding proteins in cells were examined after microcystin-LR and acteosides were co-exposed. Thus, acteoside noncompetitively inhibited microcystin-LR uptake by OATP1B3-expressing cells. Furthermore, acteoside inhibited the intracellular interaction of microcystin-LR with its binding protein(s), including the 22 kDa protein. Furthermore, using immunoblot analysis, acteoside induced the phosphorylation of extracellular signal-regulated kinase (ERK), which is one of the survival signaling molecules. These results suggest that acteoside reduces microcystin-LR cytotoxicity through several mechanisms, including the inhibition of microcystin-LR uptake via OATP1B3, and decreased interaction between microcystin-LR and its binding protein(s), and that ERK signaling activation contributes to the attenuation effect of acteoside against microcystin-LR cytotoxicity.

The Mindful Self: A Mindfulness-Enlightened Self-view.

This paper analyzes studies of mindfulness and the self, with the aim of deepening our understanding of the potential benefits of mindfulness and meditation for mental health and well-being. Our review of empirical research reveals that positive changes in attitudes toward the self and others as a result of mindfulness-enabled practices can play an important role in modulating many mental and physical health problems. Accordingly, we introduce a new concept-the "mindful self"-and compare it with related psychological constructs to describe the positive changes in self-attitude associated with mindfulness meditation practices or interventions. The mindful self is conceptualized as a mindfulness-enlightened self-view and attitude developed by internalizing and integrating the essence of Buddhist psychology into one's self-system. We further posit that the mindful self will be an important intermediary between mindfulness intervention and mental health problems, and an important moderator in promoting well-being. More generally, we suggest that the mindful self may also be an applicable concept with which to describe and predict the higher level of self-development of those who grow up in the culture of Buddhism or regularly engage in meditation over a long period of time.