Andrographolide Inhibition of Th17-Regulated Cytokines and JAK1/STAT3 Signaling in OVA-Stimulated Asthma in Mice.

Qian Yu,Zhouping Shen,Chang Shu,Yajie Shi,Yafang Lou,Shiping Zhu,Xuchun Ding,Junqing Yang

doi:10.1155/2021/6862073

Qian Yu, Zhouping Shen + Show 6 more

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https://doi.org/10.1155/2021/6862073

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Abstract

Asthma has long been considered a disease of airway inflammation. The excessive or prolonged production of inflammatory mediators can result in airway remodeling and severe clinical syndromes such as dyspnea or even apnea. Therefore, pharmaceutical intervention is required to restrain the excessive release of such inflammatory mediators in control of asthma. Novel therapeutics and mechanistic insight are sought for the management of this chronic inflammatory disease. Andrographolide (AG) is a type of diterpenoid ester compound and is reported to demonstrate multiple properties such as antioxidation and anti-inflammation. However, the anti-inflammatory capacity of AG by regulating immunologic function in airway of asthma has not been fully studied to date. Therefore, this study investigates whether AG is capable of suppressing the inflammatory response of asthma in OVA-stimulated mice and the mechanism by which this is achieved. Animals were randomly divided into 4 groups: control group, OVA model group, OVA + AG (0.1 mg/ml) group, and OVA + dimethylsulfoxide (DMSO) group. The serum, BALF, and lung tissue of the mice were collected separately for the administration of ELISA, rt-PCR, western blot and pathological section and staining. We found that AG attenuated the OVA-induced production of IL-6, IL-17A, IL-17F, and RORγt; inhibited the OVA-mediated phosphorylation of JAK 1 and STAT3; and alleviated airway remodeling and the neutrophil infiltration of lung tissue. We conclude that AG inhibits the inflammatory response of asthma in OVA-stimulated mice by blocking the activation of Th17-regulated cytokines and the JAK1/STAT3 signaling pathway.

Highlights

Asthma has long been considered the disease of chronic airway inflammation with bronchial hyperresponsiveness
We found that AG inhibited the expression of IL-6, IL-17A, and IL-17F in both serum and bronchoalveolar lavage fluid (BALF) of OVA-stimulated mice. ese results clearly confirmed the anti-inflammatory effects of AG
In our research for the mechanism by which AG mediates the airway inflammatory response, we focused on the OVA-stimulated JAK1/STAT3 signaling pathway

Summary

Introduction

Asthma has long been considered the disease of chronic airway inflammation with bronchial hyperresponsiveness. It usually presents with repeated airway spasm which could be relieved spontaneously or by using bronchodilators. Andrographolide (AG) is a kind of diterpenoid ester compound which is extracted from the herb or leaves of Andrographis paniculata as one of the effective components [3]. It proves that AG plays a vital role in the treatment of multiple diseases such as asthma, chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis, hepatitis, cirrhosis, neurodegenerative diseases, and autoimmune diseases with the function of anti-inflammation and antioxidation [4]. It revealed that AG reduced the total white blood cells especially the eosinophils in the bronchoalveolar lavage fluid (BALF) of ovalbumin(OVA-) induced asthmatic mice to relieve the inflammatory reaction and mucous secretion and lowered the airway hyperresponsiveness by inhibiting nuclear factor kappa-light-chain-enhancer of activated B (NF-κB) pathway

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