Recuperating Lung Decoction Attenuates the Oxidative Stress State of Chronic Obstructive Pulmonary Disease by Inhibiting the MAPK/AP‐1 Signal Pathway and Regulating γ‐GCS

Abstract

Purpose/Objective. To evaluate the effects of Recuperating Lung Decoction (RLD) on the indices of oxidative stress in a rat model of COPD and detect the indices of the MAPK/AP-1/γ-GCS signal pathway for a further survey of the possible targeting site of RLD. Methods/Materials. The rats of COPD were treated with RLD. The protein levels of glutathione (GSH), oxidized glutathione (GSSG), 8-hydroxy-2-deoxyguanosine (8-OHdG), and 4-hydroxynonenal (4-HNE) were measured. In addition, the levels of key signaling molecules (extracellular signal-regulated kinases [ERK], the c-jun N-terminal kinase [JNKs signal pathway], and p38 MAP kinase [p38MAPK], AP-1 proteins [C-fos, C-jun], and γ-glutamyl-cysteine synthetase [γ-GCS-h]) of the MAPK/AP-1/γ-GCS-h signal pathway were assessed. Results. After treatment, the protein level of GSH and the ratio of GSH/GSSG were increased and the amounts of 8-OHdG and 4-HNE were decreased significantly in lung tissues when compared with the nontreated COPD group. Further results showed that the RLD could effectively inhibit the MAPK pathway by inactivation of p38MAPK and ERK and could also downregulate the AP-1 and the γ-GCS-h genes expressions in both protein and mRNA levels. Conclusion. RLD might improve the state of oxidative stress by downregulation of the expression of γ-GCS-h gene by inhibition of the MAPK/AP-1 pathway, thereafter enhancing the ability of antioxidation in COPD.

The Mechanism of Penehyclidine Hydrochloride and Its Effect on the Inflammatory Response of Lung Tissue in Rats with Chronic Obstructive Pulmonary Disease During Mechanical Ventilation

“…On the one hand, it can activate downstream target gene c-Jun to help cells cope with a variety of stimuli, such as cytokines, bacteria, and diseases. 19 On the other hand, p38 can enhance the activity of transcription factors c-fos and c-jun, participate in the expression of apoptosis-promoting proteins such as TNF-a, and regulate the inflammatory process. The results showed that the expression of JNK and p-JNK in group H was lower than that in group N, which indicated that penehyclidine hydrochloride could inhibit the JNK/MAPK pathway in mechanically ventilated rats with COPD, improve the inflammatory response mediated by the JNK/MAPK pathway, improve the inflammatory edema of lung tissue caused by neutrophil activation and aggregation in airway mucosa, and improve airflow restriction, all of which would protect the lung function of the rats.…”

“…On the one hand, it can activate downstream target gene c-Jun to help cells cope with a variety of stimuli, such as cytokines, bacteria, and diseases. 19 On the other hand, p38 can enhance the activity of transcription factors c-fos and c-jun, participate…”

Determining Pharmacological Mechanisms of Chinese Incompatible Herbs Fuzi and Banxia in Chronic Obstructive Pulmonary Disease: A Systems Pharmacology‐Based Study

“…For example, Recuperating Lung Decoction could inhibit the MAPK/AP-1 signaling pathway to downregulate oxidative stress, resulting in the improvement of antioxidation of COPD. [ 32 ] Indeed, apoptosis was the second most indicated pathway in KEGG analysis. Whether in p53 signaling way, Kaposi sarcoma-associated herpesvirus infection pathway, or human immunodeficiency virus 1 infection pathway, the genes were primarily involved in apoptosis pathway ( Figure 10 ).…”

The PPI network analysis of mRNA expression profile of uterus from primary dysmenorrheal rats

“…AP-1 family plays essential roles in cell proliferation and survival 28 , which critically involves in MAP kinases pathways in various cellular types 29 – 31 . Previous data revealed that the extracellular signal-regulated kinases (ERK) and the c-Jun NH2-terminal kinases (JNK), two essential members of MAP kinases, can be activated in VSMCs from the acutely induced hypertensive rats, with the up-regulated gene expression of c-Fos and c-Jun , as well as the enhanced AP-1 DNA-binding activity 32 .…”