Identification of target proteins of mangiferin in mice with acute lung injury using functionalized magnetic microspheres based on click chemistry.
Prevention of the occurrence and development of inflammation is a vital therapeutic strategy for treating acute lung injury (ALI). Increasing evidence has shown that a wealth of ingredients from natural foods and plants have potential anti-inflammatory activity. In the present study, mangiferin, a natural C-glucosyl xanthone that is primarily obtained from the peels and kernels of mango fruits and the bark of the Mangifera indica L. tree, alleviated the inflammatory responses in lipopolysaccharide (LPS)-induced ALI mice. Mangiferin-modified magnetic microspheres (MMs) were developed on the basis of click chemistry to capture the target proteins of mangiferin. Mass spectrometry and molecular docking identified 70 kDa heat-shock protein 5 (Hspa5) and tyrosine 3-monooxygenase (Ywhae) as mangiferin-binding proteins. Furthermore, an enzyme-linked immunosorbent assay (ELISA) indicated that mangiferin exerted its anti-inflammatory effect by binding Hspa5 and Ywhae to suppress downstream mitogen-activated protein kinase (MAPK) signaling pathways. Thoroughly revealing the mechanism and function of mangiferin will contribute to the development and utilization of agricultural resources from M. indica L.
State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy, Tianjin Key Laboratory of Molecular Drug Research, Nankai University , Tianjin 300071, People's Republic of China.|State Key Laboratory of Natural and Biomimetic Drugs, Peking University , Beijing 100871, People's Republic of China.
Jiajia
J
Wang
State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy, Tianjin Key Laboratory of Molecular Drug Research, Nankai University , Tianjin 300071, People's Republic of China.
Yan
Y
Nie
Guangxi University of Chinese Medicine , Nanning, Guangxi 530001, People's Republic of China.
Yunjuan
Y
Li
State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy, Tianjin Key Laboratory of Molecular Drug Research, Nankai University , Tianjin 300071, People's Republic of China.|State Key Laboratory of Natural and Biomimetic Drugs, Peking University , Beijing 100871, People's Republic of China.
Yuanyuan
Y
Hou
State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy, Tianjin Key Laboratory of Molecular Drug Research, Nankai University , Tianjin 300071, People's Republic of China.
Wei
W
Zhao
Guangxi University of Chinese Medicine , Nanning, Guangxi 530001, People's Republic of China.
Jiagang
J
Deng
State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy, Tianjin Key Laboratory of Molecular Drug Research, Nankai University , Tianjin 300071, People's Republic of China.
Peng George
PG
Wang
State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy, Tianjin Key Laboratory of Molecular Drug Research, Nankai University , Tianjin 300071, People's Republic of China.
Gang
G
Bai
D048948:14-3-3 Proteins / Q000235:genetics / Q000378:metabolism; D055371:Acute Lung Injury / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D057930:Click Chemistry / Q000295:instrumentation / Q000379:methods; D000091342:Endoplasmic Reticulum Chaperone BiP; D005638:Fruit / Q000737:chemistry; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008297:Male; D031022:Mangifera / Q000737:chemistry*; D051379:Mice; D008807:Mice, Inbred BALB C; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D010936:Plant Extracts / Q000008:administration & dosage*; D044004:Xanthones / Q000008:administration & dosage*
D048948:14-3-3 Proteins; D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; C000717248:Hspa5 protein, mouse; D010936:Plant Extracts; D044004:Xanthones; C576823:Ywhae protein, mouse; C013592:mangiferin; D020928:Mitogen-Activated Protein Kinases
Hspa5; MAPK; Ywhae; acute lung injury; click chemistry; mangiferin