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3-Dehydroandrographolide Protects Against Lipopolysaccharide-Induced Inflammation Through the Cholinergic Anti-Inflammatory Pathway

3-Dehydroandrographolide Protects Against Lipopolysaccharide-Induced Inflammation Through the Cholinergic Anti-Inflammatory Pathway

Zibin Lu, Pei Xie, Dongmei Zhang, Pinghua Sun, Huayi Yang, Jiaxi Ye, Huihui Cao, Chuying Huo, Hongling Zhou, Yuyao Chen, Wencai Ye, Linzhong Yu, Junshan Liu

Biochem Pharmacol. 2018 Dec;158:305-317.

PMID: 30391477

Abstract:

Acute lung injury (ALI) is a deadly disease without effective chemotherapy, so far. Traditional Chinese medicine andrographis herba is frequently used in the treatment of respiratory diseases. In searching for natural anti-ALI components from andrographis herba, the activities of 3-dehydroandrographolide (3-DA), a new natural andrographolide product from andrographis herba were evaluated. In this study, murine macrophage RAW 264.7 cells and BALB/c mice were treated with LPS (lipopolysaccharide, 100 ng/ml in vitro; 3 mg/kg, intratracheal) to establish inflammation models. 3-DA attenuated the release of pro-inflammatory cytokines IL-6 and TNF-α, inhibited the degradation and phosphorylation of IκBα, and suppressed the nuclear translocation of NF-κB p65 as well as the phosphorylation of Akt at Ser473 in LPS-stimulated RAW 264.7 macrophage cells. Furthermore, 3-DA increased α7nAchR expression level and bound with α7nAchR. More importantly, the anti-inflammatory effects of 3-DA were counteracted in the presence of α7nAchR siRNA or methyllycaconitine (MLA, a α7nAchR specific inhibitor), suggesting that α7nAchR is a potential target in the anti-inflammatory effects of 3-DA. Besides, 3-DA significantly inhibited inflammation in LPS-induced ALI mice, which was associated with the decrease of lung water content and inflammatory cytokines, the inhibition of neutrophil and macrophage infiltration, and activation of the NF-κB/Akt signaling pathway. Moreover, these protective effects were attenuated by the treatment of MLA. Taken together, 3-DA alleviates LPS-induced inflammation via the cholinergic anti-inflammatory pathway in vitro and in vivo. These findings provide a rationale for the role of the cholinergic anti-inflammatory pathway in inflammation and the promising clinical application of 3-DA to treat ALI.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP134418283	Dehydroandrographolide		134418-28-3	Price

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