A Gedunin-Type Limonoid, 7-Deacetoxy-7-Oxogedunin, from Andiroba (Carapa guianensis Aublet) Reduced Intracellular Triglyceride Content and Enhanced Autophagy in HepG2 Cells.

The seed oil of Carapa guianensis Aublet (Andiroba) has been used in folk medicine for its insect-repelling, anti-inflammatory, and anti-malarial activities. This study aimed to examine the triglyceride (TG) reducing effects of C. guianensis-derived limonoids or other commercially available limonoids in human hepatoblastoma HepG2 cells and evaluate the expression of lipid metabolism or autophagy-related proteins by treatment with 7-deacetoxy-7-oxogedunin (DAOG; 1), a principal limonoid of C. guianensis. The gedunin-type limonoids, such as DAOG (% of control at 20 µM: 70.9 ± 0.9%), gedunin (2, 74.0 ± 1.1%), epoxyazadiradione (4, 73.4 ± 2.0%), 17ß-hydroxyazadiradione (5, 79.9 ± 0.6%), 7-deacetoxy-7α-hydroxygedunin (6, 61.0 ± 1.2%), andirolide H (7, 87.4 ± 2.2%), and 6α-hydroxygedunin (8, 84.5 ± 1.1%), were observed to reduce the TG content at lower concentrations than berberine chloride (BBR, a positive control, 84.1 ± 0.3% at 30 µM) in HepG2 cells pretreated with high glucose and oleic acid. Andirobin-, obacunol-, nimbin-, and salannin-type limonoids showed no effect on the intracellular TG content in HepG2 cells. The TG-reducing effect of DAOG was attenuated by the concomitant use of compound C (dorsomorphin), an AMPK inhibitor. Further investigation on the detailed mechanism of action of DAOG at non-cytotoxic concentrations revealed that the expressions of autophagy-related proteins, LC3 and p62, were upregulated by treatment with DAOG. These findings suggested that gedunin-type limonoids from Andiroba could ameliorate fatty liver, and that the action of DAOG in particular is mediated by autophagy.

Bayesian prediction of anxiety level in aged people at rest using 2-channel NIRS data from prefrontal cortex.

The aim of this study was to predict mental stress levels of aged people at rest from two-channel near-infrared spectroscopy (NIRS) data from the prefrontal cortex (PFC). We used the State-Trait Anxiety Inventory (STAI) for the mental stress index.We previously constructed a machine learning algorithm to predict mental stress level using two-channel NIRS data from the PFC in 19 subjects aged 20-24 years at rest (Sato et al., Adv Exp Med Biol 765:251-256, 2013). In the present study, we attempted the same prediction for aged subjects aged 61-79 years (10 women; 7 men). The mental stress index was again STAI. After subjects answered the STAI questionnaire, the NIRS device measured oxy- and deoxy-hemoglobin concentration changes during a 3-min resting state. The algorithm was formulated within a Bayesian machine learning framework and implemented by Markov Chain Monte Carlo. Leave-one-subject-out cross-validation was performed.Average prediction error between the actual and predicted STAI values was 5.27. Prediction errors of 12 subjects were lower than 5.0. Since the STAI score ranged from 20 to 80, the algorithm appeared functional for aged subjects also.

Bayesian STAI anxiety index predictions based on prefrontal cortex NIRS data for the resting state.

Several distinctive activity patterns have been observed in the brain at rest. The aim of this study was to determine whether the STAI index can be predicted from changes in the oxy- and deoxy-hemoglobin (Hb) concentrations by using two-channel prefrontal cortex (PFC) NIRS data for the resting state. The study population comprised 19 subjects. Each subject performed four trials, each of which consisted of resting with no task for 3 min. Data were acquired using a portable NIRS device equipped with two channels. The prediction algorithm was derived within a Bayesian machine learning framework. The prediction errors for seven subjects were not greater than 5.0. Because the STAI index varied between 20 and 80, these predictions appeared reasonable. The present method allowed prediction of mental status based on the NIRS data at resting condition obtained in the PFC.

New method of analyzing NIRS data from prefrontal cortex at rest.

The aim of this study was to develop a simple technique for objective assessment of mental stress levels by measuring hemoglobin concentration changes in the bilateral prefrontal cortex (PFC) at rest, employing two-channel near-infrared spectroscopy (NIRS). Each subject was instructed to think about nothing in particular for 3 min and then to complete the State-Trait Anxiety Inventory (STAI) test. Next, NIRS measurements were taken and the left/right asymmetry of PFC activity at rest was evaluated by calculating the proposed Laterality Index at Rest (LIR). There was a significant positive correlation between the LIR and STAI score in 39 subjects. The present method allowed evaluation of mental stress level from NIRS data in the PFC at rest.

Correlation between asymmetry of spontaneous oscillation of hemodynamic changes in the prefrontal cortex and anxiety levels: a near-infrared spectroscopy study.

According to the valence asymmetry hypothesis, the left/right asymmetry of prefrontal cortex (PFC) activity is correlated with specific emotional responses to mental stress and personality traits. Here, we evaluated the relation between emotional state and asymmetry in PFC activity at rest by using near-infrared spectroscopy (NIRS). We measured spontaneous oscillation of oxyhemoglobin (oxy-Hb) concentrations in the bilateral PFC at rest in normal adults employing two-channel NIRS. In order to analyze left/right asymmetry of PFC activity at rest, we calculated the laterality index at rest (LIR) (see text). We investigated the correlation between the LIR and anxiety levels evaluated by the State-Trait Anxiety Inventory (STAI) test. We found that the right PFC was more active at rest than the left PFC, corresponding to a higher anxiety level measured by the STAI; that is, subjects with right-dominant activity at rest showed higher STAI scores, while those with left-dominant oxy-Hb changes at rest showed lower STAI scores. Aging had no significant effect on the relation. The present results obtained by NIRS are consistent with the valence asymmetry hypothesis. We emphasize NIRS may be a useful tool for objective assessment of anxiety levels.