Vol.:(0123456789) 1 3 Molecular and Cellular Biochemistry https://doi.org/10.1007/s11010-020-03905-5 Gallic acid ameliorates COPD‑associated exacerbation in mice Esha Singla 1  · Gayatri Puri 1  · Vivek Dharwal 1  · Amarjit S. Naura 1 Received: 3 April 2020 / Accepted: 7 September 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020 Abstract COPD is an infammatory lung disease, which is often exacerbated with microbial infections resulting in worsening of respiratory symptoms. Gallic acid (GA), a naturally occurring phenolic compound is known to possess anti-oxidant/anti- infammatory activity. We have recently reported that GA protects against the elastase (ET) induced lung infammation and emphysema and the present work was designed to investigate the benefcial efects of Gallic acid against ET + Lipopolysach- haride (LPS) induced COPD exacerbation like condition in mice model. Our data showed that i.t. administration of LPS at 21 days after ET instillation resulted in signifcant infltration of infammatory cells particularly neutrophils (p < 0.0001) into the lungs along with elevated levels of pro-infammatory cytokines like TNF-α, IL-1β and IL-6 (p < 0.0001). Interestingly, daily administration of GA (200 mg/Kg b. wt.) starting 7 days before ET instillation, signifcantly blunted the ET + LPS induced infammation as indicated by reduced number of infammatory cells particularly neutrophils (p < 0.0001) in BALF along with suppression of myeloperoxidase activity (p = 0.0009) and production of pro-infammatory cytokines (p < 0.0001). Further, GA also restored the redox imbalance in the lungs towards normal. Additionally, phosphorylation of p65-NF-κB was found to be reduced (p = 0.015), which was associated with downregulation in the gene expression of IL-1β (p = 0.022) and TNF-α (p = 0.04). Conversely, GA treatment resulted in increased protein levels of Nrf2 (p = 0.021) with concomitant increase in transcription of its downstream target genes HO-1 (p = 0.033) and Prdx-1 (p = 0.006). Overall, our data show that GA efectively modulates COPD exacerbation manifestations in mice potentially by restoring redox imbalance in lungs. Keywords Gallic acid · COPD exacerbation · LPS · Nrf2 · NF-κB Introduction Chronic obstructive pulmonary disease (COPD) is a chronic infammatory disease of airways which afects around 328 million people worldwide [1, 2]. In addition to normal course of the disease, patients with COPD often experience exacerbations which results in sudden worsening of patients’ symptoms that may require change in medication and/or hos- pitalization [1, 3]. The repetitive episodes of exacerbation ultimately result in rapid decline of lung functions and are often associated with high mortality amongst patients with COPD [4, 5]. According to Bafadhel et al. around 55% of COPD exacerbations are caused by bacteria such as Strep- tococcus pneumonia, Moraxella catarrhalis Haemophilus influenza which are the major infectious agents isolated from lungs during the episodes of COPD exacerbations [6, 7]. Astonishingly, the current available therapies against the disease primarily reduce the frequency of exacerbations in COPD patients but does not substantially improve the decline in lung function [1, 8–10]. Therefore, continuous research is ongoing to fnd novel therapies to curb the mani- festations of COPD exacerbations. Oxidative stress plays a crucial role in the COPD patho- genesis and progression. Further, there is a clear evidence of increased oxidative stress in COPD patients which further increases during exacerbation of the disease [11]. Interest- ingly, the redox sensitive transcription factor NF-κB, which regulates the transcription of various infammatory factors is also reported to be highly expressed during COPD exac- erbations [12]. On the other hand, transcription factor Nrf2 plays a major role in attenuating oxidative stress by tran- scriptional upregulation of anti-oxidant response. However, despite high oxidative stress in the lungs, Nrf2 mediated anti-oxidant response is decreased in patients with COPD [13]. Thus, targeting oxidative stress through the use of * Amarjit S. Naura anaura@pu.ac.in 1 Department of Biochemistry, Panjab University, Chandigarh 160014, India