Reversal of NADPH Oxidase-Dependent Early Oxidative and Inflammatory Responses in Chronic Obstructive Pulmonary Disease by Puerarin

Abstract

In the present study, we investigated effects of Puerarin on the early oxidative and inflammatory responses in the lung triggered by acute cigarette smoking (ACS). C57BL/6 mice were exposed to ACS for 1 hr in the presence or absence of Puerarin and harvested at 2, 6, and 24 hours. ACS induced significant increases in superoxide production in mouse lungs at 2 and 6 hours; and superoxide production was also elevated in a time and concentration dependent manner in cigarette smoke extract (CSE) stimulated human small airway epithelial cells (HSAECs), which was dose-dependently abrogated by Puerarin. ACS exposure upregulated NOX1, NOX2, and NOX4 protein expression in mouse lungs. Likewise, NOX1 and NOX4 were upregulated in CSE-stimulated HSAECs. These responses were significantly or completely attenuated by Puerarin. ACS induced significant infiltrations of neutrophils and macrophages in mouse lung parenchyma and BAL fluid, which were completely or significantly abrogated by Puerarin, so was the activation of the NF-кB pathway and the upregulation in inflammatory mediators including TNF-α, KC (murine homolog of IL-8), COX-2, IL-6 and MCP-1. Nuclear translocation of p65, IL-8 secretion, and upregulation of COX-2 in CSE stimulated HSAECs were also markedly attenuated by Puerarin. Moreover, ACS or CSE stimulated upregulation in reactive oxygen species (ROS) production and expression of inflammatory mediators were alleviated by ROS scavenger TEMPO in vivo and vitro, with no synergy combining with Puerarin, indicating that the effects of Puerarin are redox-sensitive following activation of NOX. In summary, our data for the first time demonstrate that Puerarin robustly attenuates NOX isoform-dependent ROS production and inflammatory activation in ACS exposed mice and CSE treated HSAECs, indicating that Puerarin might be used as a robust therapeutic agent for early or early stage COPD.

Integrating RNA-seq and scRNA-seq to explore the mechanism of macrophage ferroptosis associated with COPD

“…CYBB, also referred to as NOX2, is mainly expressed in lung macrophages (Seimetz et al, 2020). And NOX2 protein expression is found to be upregulated in the lungs of COPD mice and is involved in the oxidative and inflammatory response in the early stages of COPD (Zhang et al, 2022). Heat shock protein (HSP) is a potent inducer of natural and adaptive immunity, and the association between increased expression levels of HSPB1 and the risk of COPD has been reported and verified (Cui et al, 2015).…”

Progression of the PI3K/Akt signaling pathway in chronic obstructive pulmonary disease

“…In addition to some of these molecular targeted drugs, natural compounds, traditional Chinese medicine formulations, and some anti-inflammatory agents also inhibit the progression of COPD by inhibiting the PI3K/Akt pathway. It has been shown recently that puerarin can relieve over-oxidation in cells ( Zhang P. et al, 2022 ). Wang L. et al (2022) found that puerarin reverses apoptosis in HBEC stimulated by cigarette smoke extract (CSE) via the PI3K/Akt signaling pathway.…”

HDAC6 inhibition alleviates acute pulmonary embolism: a possible future therapeutic option

“…The fixed lung samples were embedded in paraffin as previously described [26], and sectioned serially at 5 μm slices by using a rotary microtome (Leica, Nussloch, Germany). Subsequently, the samples were stained with hematoxylin and eosin (H&E) [27,28]. Finally, the stained sections were observed and photographed under a BX53 microscope (Olympus, Tokyo, Japan).…”