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.

[Efficacy of oral cavity care in preventing stomatitis (mucositis) in cancer chemotherapy].

Stomatitis is a common side effect during cancer chemotherapy. We hypothesized that careful oral cavity care using patient guidance and cleanliness index prevents stomatitis in cancer chemotherapy. We introduced oral care patient guidance including teaching good brushing methods, O'Leary's Plaque Control Record(PCR)as a cleanliness index, and Eilers' Oral Assessment Guide(OAG)as an overall index after April 2006. We evaluated the incidence of stomatitis in 20 patients(10 patients between April 2004 to May 2006 and 10 patients after April 2006)with esophageal cancer who received chemotherapy including 5-FU and CDDP. Patients receiving brushing training after 2006 were evaluated regarding cleanliness of their oral cavities using PCR index and OAG index. The rates of stomatitis were 60%(6/10)and 40%(4/10)before and after the introduction of oral care patient guidance. The average of PCR index decreased from 82% to 46% after teaching good brushing method to the patients. The average of OAG index after brushing training was 9.14 which was better score compared with previous reports. Introduction of oral care patient guidance decreased the incidence of stomatitis. Both PCR and OAG indexes were useful in evaluating the objective condition of the oral cavity and in sharing patients' information among a medical team. These indexes encouraged the patients to clean their oral cavities.