AimHochuekkito formula includes four kinds of prescriptions in Japan. It is not known whether all the formulas express the same stimulating effect on the mucosal immune systems of the upper and lower respiratory tracts.MethodsBy using influenza virus‐sensitized BALB/c mice, which are immuno‐compromised with cyclophosphamide, effects of administration of decocted extracts of four kinds of hochuekkito formulas were compared on anti‐influenza antibody titers in nasal cavity and bronchoalveolar fluids. The contribution of inulooligosaccharides to immuno‐modualting effects on T lymphocyes in Peyer's patches and pulmonary immune responses in poly(I:C)‐induced pneumonia mice was also analyzed.ResultsHochuekkito formulas with either Atractylodis lanceae rhizoma (ALR‐hochuekkito) or Atractylodis rhizoma (AtR‐hochuekkito) stimulated anti‐influenza virus‐specific antibody titers in the nasal cavity; however, ALR‐hochuekkito stimulated the production of the antibody titer in lung but AtR‐hochuekkito did not. Longer‐size inulooligosaccharides in ALR‐hochuekkito induced more IFN‐γ‐producing T lymphocytes in Peyer's patches whereas the intermediate‐size inulooligosaccharides in AtR‐hochuekkito induced more IL‐10‐producing T lymphocytes. Oral administration of the intermediate‐size inulooligosaccharides reduced pulmonary inflammation in poly(I:C)‐inoculated mice but not the longer‐size inulooligosaccharides.ConclusionsAll the hochuekkito formulas stimulate the mucosal immune system in upper respiratory tracts whereas the formula with Atractylodis lanceae rhizoma up‐regulates the pulmonary immune system, and inulooligosaccharides from Atractylodis lanceae rhizoma and Atractylodis rhizoma play a crucial role in regulating the pulmonary immune system with the hochuekkito formula.
Aim: Few pharmacological prophylactics have been developed to prevent lower respiratory tract infection before the onset. Because hochuekkito formula containing Atractylodis lanceae rhizoma (ALR formula) has been shown to enhance the adaptive mucosal immune system of both the upper and lower respiratory tracts, the effect of the formula was investigated on pulmonary infection with Streptococcus pneumoniae and productions of anti-bacterial proteins as innate protective immunity in lung of immuno-compromised mice. Methods: Cyclophosphamide (CY)-treated BALB/c mice were intranasally infected with S. pneumoniae, and effects of hochuekkito formula comprising Hedysari radix and ALR (HR/ALR formula) were evaluated on bacterial counts in lung and lung damage. CY-treated and untreated mice were stimulated by intranasal inoculation of lipopolysaccharide (LPS), and the effect of administrating HR/ALR-hochuekkito on the production of anti-bacterial proteins in the lung was also analyzed. Results: Oral administration of HR/ALR-hochuekkito (1.5 g/kg) reduced cell counts of S. pneumoniae in bronchoalveolar fluids (BALF) of CY-treated mice. Bactericidal activity of BALF and mRNA expression of surfactant protein D gene (Sftpd) in the lung were significantly increased by HR/ALR-hochuekkito prior to S. pneumoniae infection. Intestinal manipulation decreased mRNA expression of surfactant protein A gene (Sftpa1) in the lung, and HR/ALR formula improved this impairment. The formula enhanced the production of surfactant protein D and chitinase-3-like-1 in both CY-treated and untreated mice under LPS stimulation. ALR-hochuekkito containing Astragali radix (ASR) (ASR/ALR formula) also increased the production of these anti-bacterial proteins. Conclusion: Prophylactic treatment with ALR-hochuekkito formula protected immuno-compromised mice from bacterial pneumonia by enhancing the production of anti-bacterial proteins such as surfactant protein A/D and chitinase-3-like-1 in the lung.
Aim Inulooligosaccharides in a Kampo formula, hochuekkito, have been shown to participate in the regulation of the pulmonary immune system. Difference in chain length distribution of the oligosaccharides strongly affects their immunopharmacological activities. This phenomenon cannot be explained by bifidogenic activity and/or short‐chain fatty acids produced by intestinal microflora from the oligosaccharides. Effects of intermediate‐size inulooligosaccharides, which have a similar chain length distribution as the oligosaccharides obtained from hochuekkito containing Atractylodis rhizoma, were analyzed on immunocompetent cells in Peyer’s patches. Methods Effect of intermediate‐size inulooligosaccharide preparation (degree of polymerization (d.p.) 3–15) on mRNA expression of genes of markers and functional molecules of stromal cells and type 3 innate lymphoid cells (ILC3) in Peyer’s patches was analyzed. Results Oral administration of intermediate‐size inulooligosaccharide preparation significantly up‐regulated expression of mRNAs of genes of not only marker molecules of fibroblastic reticular cells (FRC) and ILC3 but also immunological factors for positive and negative regulatory functions of FRC in addition to genes of auto‐immune regulator (AIRE), DEAF‐1 transcription factor, and some AIRE‐dependent tissue‐related antigens (TRA). Conclusion FRC and ILC3 are suggested to be target cell candidates in Peyer’s patches for inulooligosaccharides in hochuekkito formula containing Atractylodis rhizoma.
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