Pterostilbene suppresses oxidative stress and allergic airway inflammation through AMPK/Sirt1 and Nrf2/HO‐1 pathways

Abstract

Introduction Pterostilbene (Pts) may be used for allergic asthma treatment. The AMPK/Sirt1 and Nrf2/HO‐1 pathways are potential targets for asthma treatement. However, the relationship between Pts and AMPK/Sirt1 and Nrf2/HO‐1 pathways in asthma is unclear. Herein, we aim to explore the pharmacological effects of Pts on oxidative stress and allergic inflammatory response as well as the mechanism involving AMPK/Sirt1 and Nrf2/HO‐1 pathways. Methods Asthma model was established in mice with ovalbumin (OVA). The model mice were treated by different concentrations of Pts. Lung pathological changes were observed through histological staining. In vitro, lipopolysaccharide (LPS)‐stimulated 16HBE cells were treated with Pts. The siAMPKα2, siSirt1 and siNrf2 knockdown, and treatment with compound C, EX‐527 or ML385 were also performed in 16HBE cells. Enzyme‐linked immunosorbent assay was used to detect interleukin‐4 (IL‐4), IL‐13, IL‐5, total and OVA specific immunoglobulin E (IgE), and interferon γ (IFN‐γ). Pneumonography was used to measure the airway hyperreactivity (AHR). Superoxide dismutase (SOD), catalase (CAT), and malondialdehyde (MDA) levels were also detected. Immunohistochemistry, Western blot and immunofluorescence were used to measure protein levels. Results Pts significantly attenuated lung inflammatory cell infiltration and goblet cell proliferation. Meanwhile, Pts treatment could reduce IL‐4, IL‐13, IL‐5, and IgE (total and OVA specific) levels in the asthma model mice. However, IFN‐γ in bronchoalveolar lavage fluid was elevated. In addition, Pts reduced AHR. We also found that Pts treatment promoted serum SOD and CAT, and reduced MDA. In vitro results showed that Pts treatment promoted iNOS, TNF‐α, COX‐2, IL‐1β, and IL‐6 expressions in 16HBE cells, prolonged G0/G1 phase of the cell cycle, and resulted in a shortened G2M phase. Moreover, we found that Pts promoted the phosphorylation of AMPK in 16HBE, and meanwhile inhibited the increase of ROS induced by LPS. Additionally, Pts treatment inhibited p‐AMPK, Sirt1, Nrf2 and HO‐1, which in turn leads to the alleviation of AMPK/Sirt1 and Nrf2/HO‐1 pathways. Conclusion Pts alleviated oxidative stress and allergic airway inflammation via regulation of AMPK/Sirt1and Nrf2/HO‐1 signaling pathways.

Roles of sirtuins in asthma

“…Chen et al demonstrated that resveratrol played a role by upregulating the expression of phosphatase and tensin homolog (PTEN) via activating SIRT1 [ 42 ]. Both gentiopicroside and pterostilbene have anti-inflammatory roles in asthma via upregulating the expression of SIRT1 [ 43 , 44 ]. Additionally, myricetin increases the deacetylase activity of SIRT1, thus inhibiting tumor necrosis factor α (TNF-α)-induced nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activation and reducing the inflammatory response [ 45 ].…”

Exploring the Neuroprotective Mechanism of Curcumin Inhibition of Intestinal Inflammation against Parkinson’s Disease Based on the Gut-Brain Axis

“…In a previous study, it was confirmed that the SIRT1/NRF2 pathway plays an anti-inflammatory protective role in a large number of diseases [ 18 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 ]. Antipyroptosis is one of the roles of this pathway.…”

The Water Extract of Ampelopsis grossedentata Alleviates Oxidative Stress and Intestinal Inflammation

“…There is a growing body of evidence that suggests that various drugs can inhibit oxidative stress and inflammation by activating the Nrf2/Keap1 pathway. For instance, cardamonin, a natural flavone, has been shown to alleviate inflammatory bowel disease by inhibiting NLRP3 inflammasome activation through the Nrf2/NQO1 pathway [ 37 ]; chlorogenic acid, a polyphenolic, ameliorates oxidative stress and improves endothelial function in diabetic mice via Nrf2 activation [ 38 ]; pterostilbene suppresses oxidative stress and allergic airway inflammation through AMPK/Sirt1 and Nrf2/HO-1 pathways [ 39 ]. In the current study, we found that WEA administration significantly elevates the expression of Nrf2 and downstream antioxidants, such as NQO1, and decreases the expression of pro-inflammatory cytokines IL-1β and TNF-α resulting from LPS-induced oxidative stress in mice.…”