Study on Proinflammatory Response and Regulation of JAK2/STAT3 Signaling Pathway of Ethanol Extract of Anacyclus pyrethrum Root (EEAP) in Rats with Cough-Variant Asthma

Objective: To explore the modulation of the proinflammatory response and the tyrosine protein kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) pathway in the lung of rats with cough-variant asthma (CVA) treated with ethanol extract of Anacyclus pyrethrum root (EEAP). Methods: Sixty specific pathogen-free (SPF) male Sprague-Dawley (SD) rats (with a weight range of 220–260 g, eight to ten weeks) were randomly assigned into six different groups, encompassing a control group, a model group, a positive control group (prednisone acetate, the dosage was 2.5 mg/kg, ig), the high EEAP group (640 mg/kg), medium EEAP group (320 mg/kg), and low EEAP group (160 mg/kg), with a total of 10 participants in each group. The medication was provided on a daily basis for 30 days, commencing on the 29th day. The rodents in each cohort were maintained until the 60th day. Following humane euthanasia, lung tissues and peripheral blood samples were collected. Two groups were formed by dividing rat lung epithelial type II cells: the OVA group, which received 2.5 mg/L ovalbumin stimulation and sensitization, and the treatment group, which was administered 640 mg/kg EEAP. The peripheral blood T-lymphocytes of rats in the control group and the high EEAP cohort were designated as CVA group and intervention group, respectively. The concentrations of interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) were measured in each cohort using the enzyme-linked immunosorbent assay (ELISA). Utilizing real-time quantitative polymerase chain reaction (RT-PCR), the levels of IL-6, JAK2, and STAT3 were analyzed within each group. Results: In contrast to the control group, the concentrations of IL-1β, IL-6, and TNF-α in the model group exhibited a substantial rise (P < 0.05). Moreover, the mRNA expression levels of IL-6, JAK2, and STAT3 in the experimental group were observed to be substantially elevated (P < 0.05). In contrast to the control group, the positive controlled group, the elevated EEAP group, and the intermediate EEAP group demonstrated substantial decreases in the mRNA expression of IL-6, JAK2, and STAT3 (P < 0.05), while the low EEAP group exhibited a notable decrease in the mRNA expression of JAK2. The mRNA expression levels of IL-6 and STAT3 did not exhibit any notable variation in the low EEAP group (P > 0.05). The concentrations of IL-1β, IL-6, and TNF-α, along with the mRNA expression levels of IL-6, JAK2, and STAT3, demonstrated an upward trend as EEAP concentration diminished (P < 0.05) across the higher EEAP category, the intermediate EEAP category, and the low EEAP group. In rat type II alveolar epithelial cells, the concentrations of IL-1β, IL-6, and TNF-α, as well as the mRNA expression levels of IL-6, JAK2, and STAT3 were diminished in the intervention cohort in comparison to the OVA cohort (P < 0.05). When compared to the OVA group, the treatment group demonstrated a notable decrease in IL-1β, IL-6, and TNF-α, along with mRNA expression levels of IL-6, JAK2, and STAT3 (P < 0.05). In contrast to the CVA group, the intervention group demonstrated a significant reduction in IL-1β, IL-6, and TNF-α levels, along with the mRNA expression levels of IL-6, JAK2, and STAT3 in T lymphocytes (P < 0.05). Conclusion: The study demonstrated that EEAP effectively suppressed the proinflammatory response mediated by IL-6 and TNF-α, along with the JAK2/STAT3 pathway, in the lungs of rats suffering from cerebral CVA.