Traditional Chinese medicine Zhusha Anshen Wan: protective effects on liver, kidney, and intestine of the individual drugs using 1H NMR metabolomics.

Introduction: Zhusha Anshen Wan (ZSASW) is a traditional Chinese medicine compound mainly composed of mineral drugs. In clinical practice, ZSASW did not show the toxicity of administering equal doses of cinnabar alone, suggesting that the four combination herbs in ZSASW can alleviate the damage of cinnabar. The effect of each herb on reducing the toxicity of cinnabar has not been fully explained. Methods: In our study, we utilized a metabonomics approach based on high-resolution 1H nuclear magnetic resonance spectroscopy to investigate the reduction of toxicity by each herb in ZSASW. Liver, kidney and intestinal histopathology examinations and biochemical analysis of the serum were also performed. Results: Partial least squares-discriminant analysis (PLS-DA) was conducted to distinct different metabolic profiles in the urine and serum from the rats. Liver and kidney histopathology examinations, as well as analysis of serum clinical chemistry analysis, were also carried out. The metabolic profiles of the urine and serum of the rats in the CGU (treated with cinnabar and Glycyrrhiza uralensis Fisch) and CCC (treated with cinnabar and Coptis chinensis French) groups were remarkably similar to those of the control group, while those of the CRG (treated with cinnabar and Rehmannia glutinosa Libosch) and CAS (treated with cinnabar and Angelica sinensis) groups were close to those of the cinnabar group. The metabolic profiles of the urine and serum of the rats in the CGU and CCC groups were remarkably similar to those of the control group, while those of the CRG and CAS groups were close to those of the cinnabar group. Changes in endogenous metabolites associated with toxicity were identified. Rehmannia glutinosa, Rhizoma Coptidis and Glycyrrhiza uralensis Fisch could maintain the dynamic balance of the intestinal flora. These results were also verified by liver, kidney and intestinal histopathology examinations and biochemical analysis of the serum. The results suggested that Discussion: The metabolic mechanism of single drug detoxification in compound prescriptions has been elucidated. Coptis chinensis and Glycyrrhiza uralensis serve as the primary detoxification agents within ZSASW for mitigating liver, kidney, and intestinal damage caused by cinnabar. Detoxification can be observed through changes in the levels of various endogenous metabolites and related metabolic pathways.

The significance of the levels of IL-4, IL-31 and TLSP in patients with asthma and/or rhinitis.

AIM: To investigate the clinical significance of the levels of IL-4, IL-33 and thymic stromal lymphopoietin (TLSP) in patients with asthma and/or rhinitis, then do the simple verification in animals. METHODS: Levels of IL-4 IL-31, IL-33 and TLSP were detected by ELISA and real-time PCR in 64 asthma patients (sIgE[+]: 32 cases, sIgE[-]: 32 cases), 64 rhinitis patients (sIgE[+]: 32 cases, sIgE[-]: 32 cases), 64 asthma complicated with allergic rhinitis patients (sIgE[+]: 32 cases, sIgE[-]: 32 cases) and 32 healthy controls. Then we detected the IL-4, IL-31, IL-33 and TLSP in the sensitized mice. RESULTS: Results showed that levels of IL-4, IL-31, IL-33 and TSLP in asthma and rhinitis patients, and those complicated with allergic rhinitis, had significant differences compared with the control group (p < 0.05). It was found that the indicators of mugwort and dust mite allergic patients were significantly higher than that of other allergic patients (p < 0.05). We got the same tendency in in vivo experiments. CONCLUSION: IL-4, IL-31, IL-33 and TSLP may be involved in the pathogenesis of asthma and rhinitis; dust mite and mugwort allergy could increase them significantly.

A prophylactic effect of an oligodeoxynucleotide containing a cytidine-guanosine motif against Japanese cedar pollen-induced T-helper type 2 allergic response.

BACKGROUND: Over 10% of entire population in Japan suffer from allergic diseases induced by Japanese cedar pollen (JCP) every spring. In terms of preventive medicine, it has become a matter of urgency to establish successful prophylactic and therapeutic strategies for controlling the disorders. The effect of an oligodeoxynucleotide containing a cytidine-guanosine motif (CpG ODN) on the regulation of immune responses induced by JCP was investigated in this study. METHODS: BALB/c mice were inoculated with CpG ODN intraperitoneally before intranasal sensitization to JCP. Cellular infiltration in the lung of BALB/c mice after treatment with CpG ODN or JCP was performed by hematoxylin and eosin (H&E) staining. Antibody titers and cytokines levels were determined by ELISA. RESULTS: Intranasal inoculation of BALB/c mice with JCP induced a T-helper type 2 (Th2-type) dominant immune response, as characterized by the production of interleukin (IL)-4 and IL-5 in the lung and of JCP-specific IgE antibody in serum. Prior intraperitoneal administration of CpG ODN to mice suppressed the subsequent JCP-induced antibody production and infiltration of inflammatory cells in the lung. The inhibitory mechanism of CpG ODN seemed to be attributable to a CpG ODN-induced Th1-type dominant environment, which down-regulated Th2-type response subsequently induced by JCP allergen sensitization. Furthermore, administration with CpG ODN decreased the production of JCP-induced IL-17, which has been found to play a pivotal role in several inflammatory diseases including allergic asthma. The decreased production of IL-17, together with reduced secretion of IL-4 and IL-5, may contribute to diminish the inflammation in the lung of JCP-sensitized mice. CONCLUSION: This work provides evidence that the CpG ODN has a prophylactic effect on the JCP-induced Th2-type allergic responses by establishing or restoring a Th1-type shift of immune environments.

Respiratory syncytial virus protects against the subsequent development of Japanese cedar pollen-induced allergic responses.

Respiratory syncytial virus (RSV) infection has been hypothesized to be a risk factor for the development of allergy and asthma, but epidemiologic studies in humans still remain inconclusive. The association between RSV infection and allergic diseases may be dependent on atopic background and previous history of RSV infection. In this study, the influence of the timing of RSV infection on the development of Japanese cedar pollen (JCP)-induced allergic responses was examined. BALB/c mice were intranasally infected with RSV before or after sensitization to JCP. Production of cytokines in the culture fluid of lung parenchyma cells and the level of antigen-specific antibodies in the serum were determined. It became clear that JCP was a strong inducer for the elicitation of Th2-type responses, characterized by production of interleukin (IL)-4 and IL-5 in the lung and JCP-specific IgE antibody in the serum. RSV infection, however, suppressed JCP-induced allergic responses by decreasing the production of Th2-like cytokines and Th2-type antibodies. This phenomenon was observed more clearly in the groups that were infected with RSV, 2 weeks or 2 days before sensitization to JCP. The inhibitory mechanism of RSV infection seems to be due to RSV-induced Th1 type dominant environment, which down-regulated the Th2-type responses subsequently induced by allergen sensitization. On the other hand, JCP-inoculation altered RSV-induced immune responses to shift from Th1- to Th2-type dominance, by inhibiting RSV-induced Th1-like cytokine production. These data provide evidence that under a certain condition, RSV infection may play a protective role in JCP-induced allergic responses.