Inulooligosaccharides in Atractylodis lanceae rhizoma and Atractylodis rhizoma of hochuekkito formula are essential for regulation of the pulmonary immune system of immuno‐compromised mice

Abstract

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.

Basic pharmacological mechanisms and clinical evidence of the efficacy of hochuekkito against infectious diseases and its potential for use against COVID‐19

“…HET has an effect on innate immunity as shown by increases in NK activity and cytokines. In infection models of bacterial [23,26–30] and viral infection [31–36], HET also increased cytokines. The effects on various cytokines are recognized for the whole body, notably the lung and alveoli (Fig.…”

“…In animal models of immune deficiency by age [20], steroids [21], cyclophosphamide [22], mitomycin C [23], and restraint stress [24,25], HET improved reduced immune function by both innate and acquired immunity. Related to these immuno‐stimulatory effects, HET exhibited a preventive effect from infection by Salmonella enteritidis [26], Listeria monocytogenes [27,28], Helicobacter pylori [29], methicillin‐resistant Staphylococcus aureus (MRSA) [30], influenza virus [31–35], cytomegalovirus [36], and Plasmodium chabaudi [37]. HET also exhibited a protective effect on cancer caused by inoculation of cancer cells [38,39] or carcinogenic substances [40–42].…”

Hochuekkito comprising Atractylodis lanceae rhizoma prevents pulmonary infection of Streptococcus pneumoniae in cyclophosphamide‐treated mice through acceleration of anti‐bacterial protein production

“…(a) Immuno-compromised mice: Female BALB/c mice (six weeks old) were orally administered anaqueous solution (500 μl/mice) of decocted extracts of HR/ALR-hochuekkito formula (1.5 g/kg) once daily for seven days before and for five days after CY injection. The dose of the decocted extract was determined as described previously [12]. A saline solution (200 μl/mouse) of CY (200 mg/kg) was intraperitroneally injected into the mice, and then the mice were intranasally inoculated with LPS (25, 50 or 100 μg/ mouse) five days after CY treatment (Day 0) in accordance with the procedure of S. pneumoniae infection.…”

“…Serum, BALF and lung were collected using GBS instead of phosphate-buffered saline containing 0.05% bovine serum albumin according to the procedures described previously [12,14]. The samples were kept at −80 C prior to use.…”

“…The formula consists of 10 component herbs, and of these, Atractylodis rhizoma (AtR) and Atractylodis lanceae rhizoma (ALR) or Hedysari radix (HR) and Astragali radix (ASR) are respectively swapped in the formula according to patient symptoms in Japan. In our previous study, hochuekkito formula comprising ALR, and HR or ASR (HR/ALR‐ or ASR/ALR‐hochuekkito formula) successfully enhanced the adaptive immune response in both the upper and lower respiratory tracts whereas those comprising AtR (HR/AtR‐ or ASR/AtR‐formula) stimulated the immune response only in the upper respiratory tract [12]. It has also been reported that commercially available hospital‐grade extract of hochuekkito formula comprising ALR shows a clinical efficacy on prevention of MRSA respiratory infection of inpatients with disturbance of consciousness [13].…”