Perilla Fruit Water Extract Attenuates Inflammatory Responses and Alleviates Neutrophil Recruitment via MAPK/JNK-AP-1/c-Fos Signaling Pathway in ARDS Animal Model

Abstract

Airway respiratory distress syndrome (ARDS) is usually caused by a severe pulmonary infection. However, there is currently no effective treatment for ARDS. Traditional Chinese medicine (TCM) has been shown to effectively treat inflammatory lung diseases, but a clear mechanism of action of TCM is not available. Perilla fruit water extract (PFWE) has been used to treat cough, excessive mucus production, and some pulmonary diseases. Thus, we propose that PFWE may be able to reduce lung inflammation and neutrophil infiltration in a lipopolysaccharide (LPS)-stimulated murine model. C57BL/6 mice were stimulated with LPS (10 μg/mouse) by intratracheal (IT) injection and treated with three doses of PFWE (2, 5, and 8 g/kg) by intraperitoneal (IP) injections. To investigate possible mechanisms, A549 cells were treated with PFWE and stimulated with LPS. Our results showed that PFWE decreased airway resistance, neutrophil infiltration, vessel permeability, and interleukin (IL)-6 and chemokine (C-C motif) ligand 2 (CCL2/MCP-1) expressions in vivo. In addition, the PFWE inhibited the expression of IL-6, CCL2/MCP-1, chemokine (CXC motif) ligand 1 (CXCL1/GROα), and IL-8 in vitro. Moreover, PFWE also inhibited the MAPK/JNK-AP-1/c-Fos signaling pathway in A549 cells. In conclusion, we demonstrated that PFWE attenuated pro-inflammatory cytokine and chemokine levels and downregulated neutrophil recruitment through the MAPK/JNK-AP-1/c-Fos pathway. Thus, PFWE can be a potential drug to assist the treatment of ARDS.

Depicting the regulatory role of JZOL on TRP channels in the treatment of Acute Bronchitis based on the combination of clinical trials, computational analysis and in vivo experiments

“…It has been established that the effective ingredients of AHCHOS are ambroxol hydrochloride and clenbuterol hydrochloride, which are representative drugs for symptomatic treatment. AHCHOS, as a mucus motility enhancer, can promote airway cilia oscillation, improve mucus clearance kinetics, and help expel phlegm 55 .…”

“…It has been established that the effective ingredients of AHCHOS are ambroxol hydrochloride and clenbuterol hydrochloride, which are representative drugs for symptomatic treatment. AHCHOS, as a mucus motility enhancer, can promote airway cilia oscillation, improve mucus clearance kinetics, and help expel phlegm 55 . According to the Chinese Children’s Medication Guidelines, AHCHOS is recommended for children with wet coughs, including bronchial asthma complicated with infection, persistent bacterial bronchitis, and pertussis 22,60 , and is one of the most important cough and phlegm relieving compound formulations suitable for children.…”

“…Then TRPV1 played a regulatory role on TRPA1. Numerous molecules within the network targeted by JZOL for cough treatment have been previously linked to cough, for example, JNK was a common molecule in many respiratory diseases, like asthma and acute lung injury, and participated in many pathogenic molecular pathways [54][55][56] . PKA and PKC activation of TRPV1 induced cough and served as an inflammatory marker in evaluating the airway in a postoperative chronic cough model 57,58 .…”

Network analysis-based strategy to investigate the protective effect of cepharanthine on rat acute respiratory distress syndrome

“…Traditional Chinese medicine (TCM) has been widely used to treat lung diseases ( Tsai et al, 2013 ). Relevant studies have shown that TCM has obvious effects in alleviating ARDS pulmonary inflammation, reducing mortality and improving prognosis ( Yeh et al, 2021 ; Ting et al, 2022 ). Cepharanthine (CEP), a monomer component of TCM, is a natural alkaloid extracted from Step hania cepharantha Hayata , which has anti-inflammation, immunomodulation, antioxidation, anti-parasitic and anti-virus effects ( Murakami et al, 2000 ; Furusawa and Wu, 2007 ; Kudo et al, 2011 ).…”