Dataset Information

Modified Si-Jun-Zi-Tang Attenuates Airway Inflammation in a Murine Model of Chronic Asthma by Inhibiting Teff Cells via the mTORC1 Pathway.

ABSTRACT: Background: Modified Si-Jun-Zi-Tang (MSJZT), a multi-herb formulation, is frequently used in traditional Chinese medicine for patients during the remission stage of asthma. However, the pharmacological basis underlying the effects of MSJZT on asthma has yet to be elucidated. This study aims at evaluating the anti-asthmatic effects of MSJZT and investigating its possible mechanism. Methods: A chronic murine model of asthma was established by sensitization and repeated challenge with ovalbumin (OVA) in female BALB/c mice, followed with oral administration of MSJZT during remission, and then mouse were re-challenged by OVA. The chemical profile of MSJZT was analyzed by high-performance liquid chromatography. The characteristic features of allergic asthma, including airway hyperreactivity, histopathology, cytokine levels (IL-4, -5, -13, -17, and INF-?), T regulatory (Treg) lymphocytes (Foxp3+CD4+CD25+), and T effector (Teff) lymphocytes (Foxp3-CD25+CD4+) in bronchoalveolar lavage fluid (BALF), and downstream proteins of mTORC1/2 signaling pathway were examined. Results: MSJZT markedly suppressed airway hyper-responsiveness to aerosolized methacholine, and reduced levels of IL-4, IL-5, and IL-13 in the BALF. Histological studies showed that MSJZT significantly reduced inflammatory infiltration in lung tissues. The percentage and absolute number of Teff cells were suppressed to a remarkable level by MSJZT without affecting Treg cells. Furthermore, MSJZT effectively inhibited the mTORC1 activity, but exerted limited effects on mTORC2, as assessed by the phosphorylation of the mTORC1 and mTORC2 substrates, S6 ribosomal protein, p70 S6 kinase, mTOR S2481, and Akt, respectively. Conclusion: MSJZT attenuated chronic airway inflammation in a mouse model of asthma by inhibiting Teff cells, which occurred, at least in part, via modulation of the mTORC1 signaling pathway.

SUBMITTER: Jin H

PROVIDER: S-EPMC6400882 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Publications

Modified Si-Jun-Zi-Tang Attenuates Airway Inflammation in a Murine Model of Chronic Asthma by Inhibiting Teff Cells via the mTORC1 Pathway.

Jin Hualiang H Cai Cui C Li Bei B Jin Weizhong W Xia Junbo J Wang Limin L Ma Shenglin S

Frontiers in pharmacology 20190227

<b>Background:</b> Modified Si-Jun-Zi-Tang (MSJZT), a multi-herb formulation, is frequently used in traditional Chinese medicine for patients during the remission stage of asthma. However, the pharmacological basis underlying the effects of MSJZT on asthma has yet to be elucidated. This study aims at evaluating the anti-asthmatic effects of MSJZT and investigating its possible mechanism. <b>Methods:</b> A chronic murine model of asthma was established by sensitization and repeated challenge with ...[more]

PMID: 30873032

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Project description:Intestinal mucositis is a common toxicity of many anti-neoplastic therapies that negatively influences health, the quality of life, economic outcomes, and even the success of cancer treatment. Unfortunately, there is presently no optimal medicine that is able to effectively manage this condition. l-glutamine is one of the most frequently used agent in practice among the limited treatment choices due to its safety and inexpensiveness despite there being a lack of evidence. Previous studies indicated that l-glutamine may alleviate mucositis and mucosal atrophy but failed to improve patients' macroscopic conditions, such as the occurrence of diarrhea. A compound glutamine capsule (G-SJZ), composed of l-glutamine and the traditional Chinese herbal formula Si-Jun-Zi-Tang, has been used in China for 23 years to treat many types of gastrointestinal diseases, including gastrointestinal reactions induced by radiotherapy and chemotherapy. However, the exact effect of G-SJZ on intestinal mucositis is unclear, and moreover, whether l-glutamine combined with Si-Jun-Zi-Tang is more effective than l-glutamine alone have not been studied. In the current study, we explored the effects of G-SJZ and l-glutamine in a mouse model of intestinal mucositis induced by 5-fluorouracil (5-Fu). The results revealed that pretreatment with G-SJZ ameliorated the physical manifestations of weight loss and the severity of diarrhea following continuous 5-Fu injections in mice. Likewise, the histopathological damage and the destruction of villus and crypt structures in the intestinal mucosa as well as the increase in circulating intestinal injury markers caused by 5-Fu were reversed with G-SJZ pretreatment. Furthermore, the protective effect of G-SJZ was accompanied by modulations in the immunohistochemical expression of tight junction proteins. Interestingly, although treatment with a dose of l-glutamine alone that was equivalent to the dose in G-SJZ also showed a protective effect, it did not appear to be as strong as treatment with G-SJZ. Si-Jun-Zi-Tang in G-SJZ may compensate for the deficiencies of l-glutamine in this model which seems not to be related to the regulation of tight junction proteins. Our study is the first to suggest that the combined use of l-glutamine and Si-Jun-Zi-Tang might be more effective than l-glutamine alone despite exact mechanism still needs further study. Because of the limited number of therapeutic agents, G-SJZ is likely to be a preferable choice for intestinal mucositis.

Dataset Information

Modified Si-Jun-Zi-Tang Attenuates Airway Inflammation in a Murine Model of Chronic Asthma by Inhibiting Teff Cells via the mTORC1 Pathway.

Publications

Modified Si-Jun-Zi-Tang Attenuates Airway Inflammation in a Murine Model of Chronic Asthma by Inhibiting Teff Cells via the mTORC1 Pathway.

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