The mechanism underlying alpinetin-mediated alleviation of pancreatitis-associated lung injury through upregulating aquaporin-1

Abstract

Characterized by its acute onset, critical condition, poor prognosis, and high mortality rate, severe acute pancreatitis (SAP) can cause multiple organ failure at its early stage, particularly acute lung injury (ALI). The pathogenesis of ALI is diffuse alveolar damage, including an increase in pulmonary microvascular permeability, a decrease in compliance, and invasion of many inflammatory cells. Corticosteroids are the main treatment method for ALI; however, the associated high toxicity and side effects induce pain in patients. Recent studies show that the effective components in many traditional Chinese medicines can effectively inhibit inflammation with few side effects, which can decrease the complications caused by steroid consumption. Based on these observations, the main objective of the current study is to investigate the effect of alpinetin, which is a flavonoid extracted from Alpinia katsumadai Hayata, on treating lung injury induced by SAP and to explore the mechanism underlying the alpinetin-mediated decrease in the extent of ALI. In this study, we have shown through in vitro experiments that a therapeutic dose of alpinetin can promote human pulmonary microvascular endothelial cell proliferation. We have also shown via in vitro and in vivo experiments that alpinetin upregulates aquaporin-1 and, thereby, inhibits tumor necrosis factor-α expression as well as reduces the degree of lung injury. Overall, our study shows that alpinetin alleviates SAP-induced ALI. The likely molecular mechanism includes upregulated aquaporin expression, which inhibits tumor necrosis factor-α and, thus, alleviates SAP-induced ALI.

Aquaporin-1 attenuates macrophage-mediated inflammatory responses by inhibiting p38 mitogen-activated protein kinase activation in lipopolysaccharide-induced acute kidney injury

“…In a model of acute lung inflammation induced by crystals, AQP1 ablation in macrophages was associated with a marked reduction in IL-1β release and neutrophilic inflammation in the lungs [30]. Liang et al [31] showed that AQP1 expression can decrease the extent of injury in lung cells by inhibiting TNF-α.…”

Aquaporin Membrane Channels in Oxidative Stress, Cell Signaling, and Aging: Recent Advances and Research Trends

“…The modulatory effects exerted by beneficial dietary patterns, food phytochemicals, and herbal compounds on AQPs, in both health and disease, is a fast growing topic as their exploitation may help support current medical treatment options to improve the prognosis of several diseases. Flavonoid modulation of AQPs has been reported to ameliorate forms of cerebral and retinal edemas of different origins (AQP4) [ 132 – 135 ], lung injuries (AQP1) [ 136 ], and Sjögren syndrome-associated xerostomia (AQP5) [ 137 ], to inhibit ovarian tumor growth (AQP5) [ 89 ] and protect against UV-induced skin damage (AQP3) [ 63 ]. Curcumin influences choroid plexus AQP1 [ 138 ], ovarian AQP3 [ 139 ], and brain AQP4 and AQP9, reducing intracranial pressure in brain injury, inhibiting ovarian cancer cell migration, and reducing brain edema, respectively [ 140 – 142 ].…”

Aquaporins as Targets of Dietary Bioactive Phytocompounds

“…Considerable AQP1 downregulation, a condition negatively correlated with pulmonary edema, has been described in acute lung injury (ALI) and, associated with severe acute pancreatitis (SAP). Interestingly, alpinetin has been found to inhibit TNF-α expression, promote human pulmonary microvascular endothelial cell proliferation and increase the expression level of AQP1 thereby improving the SAP-induced ALI symptoms (Liang et al, 2016 ). Overall, these findings propose alpinetin as possible therapeutical tool against lung inflammation diseases.…”