title: 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.
authors.affiliation: Laboratory of Liver Injury and Repair Molecular Medicine, Guilin Medical University, Affiliated Hospital, Guilin, Guangxi, People's Republic of China; Department of Infectious Diseases, Guilin Medical University, Affiliated Hospital, Guilin, Guangxi, People's Republic of China.
authors.forename: Xingsi
authors.initials: X
authors.lastname: Liang
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, People's Republic of China.
authors.forename: Bin
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital of Liaoning Medical University, Jinzhou, Liaoning, People's Republic of China.
authors.forename: Quan
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Laboratory of Liver Injury and Repair Molecular Medicine, Guilin Medical University, Affiliated Hospital, Guilin, Guangxi, People's Republic of China; Department of Hepatobiliary Surgery, Guilin Medical University, Affiliated Hospital, Guilin, Guangxi, People's Republic of China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Laboratory of Liver Injury and Repair Molecular Medicine, Guilin Medical University, Affiliated Hospital, Guilin, Guangxi, People's Republic of China; Department of Hepatobiliary Surgery, Guilin Medical University, Affiliated Hospital, Guilin, Guangxi, People's Republic of China.
authors.forename: Biao
authors.initials: B
authors.lastname: Lei
authors.affiliation: Department of Hepatobiliary Surgery, Guilin Medical University, Affiliated Hospital, Guilin, Guangxi, People's Republic of China.
authors.forename: Bo
authors.initials: B
authors.lastname: Li
authors.affiliation: Laboratory of Liver Injury and Repair Molecular Medicine, Guilin Medical University, Affiliated Hospital, Guilin, Guangxi, People's Republic of China; Department of Hepatobiliary Surgery, Guilin Medical University, Affiliated Hospital, Guilin, Guangxi, People's Republic of China.
authors.forename: Yangchao
authors.initials: Y
authors.lastname: Wei
authors.affiliation: Laboratory of Liver Injury and Repair Molecular Medicine, Guilin Medical University, Affiliated Hospital, Guilin, Guangxi, People's Republic of China; Department of Hepatobiliary Surgery, Guilin Medical University, Affiliated Hospital, Guilin, Guangxi, People's Republic of China.
authors.forename: Run
authors.initials: R
authors.lastname: Zhai
authors.affiliation: Department of Infectious Diseases, Guilin Medical University, Affiliated Hospital, Guilin, Guangxi, People's Republic of China.
authors.forename: Zhiqing
authors.initials: Z
authors.lastname: Liang
authors.affiliation: Laboratory of Liver Injury and Repair Molecular Medicine, Guilin Medical University, Affiliated Hospital, Guilin, Guangxi, People's Republic of China; Department of Hepatobiliary Surgery, Guilin Medical University, Affiliated Hospital, Guilin, Guangxi, People's Republic of China.
authors.forename: Songqing
authors.initials: S
authors.lastname: He
authors.affiliation: Laboratory of Liver Injury and Repair Molecular Medicine, Guilin Medical University, Affiliated Hospital, Guilin, Guangxi, People's Republic of China; Department of Hepatobiliary Surgery, Guilin Medical University, Affiliated Hospital, Guilin, Guangxi, People's Republic of China.
authors.forename: Bo
authors.initials: B
authors.lastname: Tang
mesh_terms: D055371:Acute Lung Injury / Q000150:complications* / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D032429:Alpinia / Q000737:chemistry; D000818:Animals; D051398:Aquaporin 1 / Q000172:deficiency / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D042783:Endothelial Cells / Q000187:drug effects; D044950:Flavanones / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008516:Medicine, Chinese Traditional; D010195:Pancreatitis / Q000150:complications* / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: C496020:AQP1 protein, human; D004365:Drugs, Chinese Herbal; D044950:Flavanones; D014409:Tumor Necrosis Factor-alpha; C436748:alpinetin; D051398:Aquaporin 1
keywords: HPMVEC; acute lung injury; alpinetin; aquaporin-1; severe acute pancreatitis; tumor necrosis factor-α