Abstract
Liang-Ge-San (LGS) is a classic formula in traditional Chinese medicine, which is widely used to treat acute lung injury (ALI), pharyngitis and amygdalitis in clinic. However, the underlying mechanisms remain poorly defined. In this study, we discovered that LGS exerted potent anti-inflammatory effects in lipopolysaccharide (LPS)-induced inflammation. We found that LGS significantly depressed the production of IL-6 and TNF-α in LPS-stimulated RAW 264.7 macrophage cells. The degradation and phosphorylation of IκBα and the nuclear translocation of NF-κB p65 were also inhibited. Moreover, LGS activated α7 nicotinic cholinergic receptor (α7nAchR). The blockage of α7nAchR by selective inhibitor methyllycaconitine (MLA) or α7nAchR siRNA attenuated the inhibitory effects of LGS on IκBα, NF-κB p65, IL-6 and TNF-α. Critically, LGS significantly inhibited inflammation in LPS-induced ALI rats through the activation of NF-κB signaling pathway. However, these protective effects could be counteracted by the treatment of MLA. Taken together, we first demonstrated anti-inflammatory effects of LGS both in vitro and in vivo through cholinergic anti-inflammatory pathway. The study provides a rationale for the clinical application of LGS as an anti-inflammatory agent and supports the critical role of cholinergic anti-inflammatory pathway in inflammation.
Highlights
The high mortality human diseases, such as acute lung injury (ALI), sepsis and shock, are caused by excessive inflammation [1,2,3]
It has been reported that the activation of cholinergic anti-inflammatory pathway could reduce ALI. α7nAchR agonist can suppress the excess lung water, reduce inflammatory cells, myeloperoxidase and proteins in the bronchoalveolar lavage fluid (BALF), and down-regulate pro-inflammatory chemokines and cytokines, including IL-6, TNF-α, macrophage inflammatory protein-1α (MIP-1α) and macrophage inflammatory protein-2 (MIP-2) in LPS or acid-induced ALI murine model [12, 13]
We found that LGS could significantly inhibit the inflammation in LPS-induced ALI rats through suppressing the rise of wet-to-dry ratio of lung tissue and lung permeability
Summary
The high mortality human diseases, such as acute lung injury (ALI), sepsis and shock, are caused by excessive inflammation [1,2,3]. Recent research indicated that cholinergic anti-inflammatory pathway could significantly suppress peripheral inflammatory responses [4] It potentially originates from activating the vagus nerve to release acetylcholine (Ach), which binds to the α7 cholinergic receptor (α7nAchR) on immune cells and suppresses the production of inflammatory cytokines, including interleukin-6 (IL-6) and tumor necrosis factor (TNF-α), high-mobility group box 1 proteins and matrix metalloproteinase 9 [5,6,7,8,9]. Α7nAchR agonist (nicotine, choline and PNU-282987) can suppress the excess lung water, reduce inflammatory cells, myeloperoxidase and proteins in the bronchoalveolar lavage fluid (BALF), and down-regulate pro-inflammatory chemokines and cytokines, including IL-6, TNF-α, macrophage inflammatory protein-1α (MIP-1α) and macrophage inflammatory protein-2 (MIP-2) in LPS or acid-induced ALI murine model [12, 13] It has been reported that the activation of cholinergic anti-inflammatory pathway could reduce ALI. α7nAchR agonist (nicotine, choline and PNU-282987) can suppress the excess lung water, reduce inflammatory cells, myeloperoxidase and proteins in the bronchoalveolar lavage fluid (BALF), and down-regulate pro-inflammatory chemokines and cytokines, including IL-6, TNF-α, macrophage inflammatory protein-1α (MIP-1α) and macrophage inflammatory protein-2 (MIP-2) in LPS or acid-induced ALI murine model [12, 13]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
