RESUMO
Effects of a Kampo (Japanese herbal) medicine "shoseiryuto (SST, xiao-qing-long-tang in Chinese)", which has been used for the treatment of allergic bronchial asthma clinically, were examined on ovalbumin (OVA)-sensitized allergic airway inflammation model (i.e., bronchial asthma) in a mouse. When SST was orally administered at 0.5 g kg(-1) day(-1) from day 1 to 6 after OVA inhalation, SST reduced the inflammation in lung tissue, the number of eosinophils and the OVA-specific immunoglobulin E (IgE) antibody titer in bronchoalveolar lavage (BAL) fluids at 7 days after the OVA inhalation. SST also reduced the airway hyperreactivity at 6 days after the OVA inhalation. Proteomic analysis with the agarose two-dimensional electrophoresis showed that the expression of spectrin α2 was reduced in the lung tissue of OVA-sensitized mice and SST recovered the expression. Western blot and immunohistochemical analyses of lung tissue also confirmed this result. When prednisolone was orally administered at 3 mg kg(-1) day(-1) from day 1 to 6 after OVA inhalation, the inflammation in lung tissue, the number of eosinophils in BAL fluids and airway hyperreactivity were reduced in the OVA-sensitized mice. However, prednisolone did not reduce the OVA-specific IgE antibody titer in BAL fluids and did not recover the expression of spectrin α2 in lung tissue. These results suggest that at least a part of action mechanism of SST against OVA-sensitized allergic airway inflammation in a mouse model is different from that of prednisolone.
RESUMO
Pinellic acid from the tuber of Pinellia ternata was isolated as an effective oral adjuvant for nasal influenza vaccine, and identified 9S,12S,13S-trihydroxy-10E-octadecenoic acid (9S,12S,13S) by the enantioselective total synthesis [Nagai et al., Int. Immunopharmacol., 2, 1183-93 (2002); Shirahata et al., Tetrahedron, 62, 9483-96 (2006)]. However, present study showed that synthetic 9S,12S,13S that was nearly 100% pure was not effective as an oral adjuvant. HPLC analysis also showed that the adjuvant active pinellic acid fraction from tuber of P. ternata contained the 9S,12S,13S as the main component and at least two minor components. Therefore seven other chemically synthesized stereoisomers were tested in combination with the 9S,12S,13S for oral adjuvant activity. Only the 9S,12S,13S in combination with the 9S,12R,13R isomer in a weight% ratio of 90.4:9.6 (pinellic acid mixture, PAM) was a potent oral adjuvant and elicited both antiviral IgA antibody (Ab) in bronchoalveolar lavage fluids and nasal washes and antiviral IgG(1) Ab in mice sera. Oral administration of the PAM followed by nasal influenza vaccination and infection with A/PR/8/34 virus showed increases in survival rate (22%, control versus 78% test) in mice orally administered PAM as adjuvant. Histopathological examination of lung tissue of mice given oral PAM with vaccine followed by influenza virus infection showed attenuated infiltration of inflammatory cells with decreases in the alveolar spaces and increases in the alveolar septa. The result of this study refutes the our previous study and suggests that the combination of 9S,12S,13S and 9S,12R,13R isomers is necessary for effective oral adjuvant activity when used in conjunction with nasal influenza vaccine.
