title: Administration of Danhong Injection to diabetic db/db mice inhibits the development of diabetic retinopathy and nephropathy.
abstract: Danhong Injection (DHI), a Chinese medicine for treatment of patients with coronary heart disease, inhibits primary abdominal aortic aneurysms in apoE deficient (apoE(-/-)) mice. Formation of microaneurysms plays an important role in the development of diabetic retinopathy and nephropathy. It remains unknown if DHI can reduce these diabetic complications. In this study, diabetic db/db mice in two groups were injected with saline and DHI, respectively, for 14 weeks. Blood and tissue samples were collected to determine serum glucose, lipids and tissue structure. DHI reduced diabetes-induced body weight gain, serum cholesterol and glucose levels. In retinas, DHI blocked the shrink of whole retina and retinal sub-layers by inhibiting expression of caspase 3, matrix metalloproteinase 2 (MMP-2) and MMP-9, accumulation of carbohydrate macromolecules and formation of acellular capillaries. DHI improved renal functions by inhibiting mesangial matrix expansion, expression of vascular endothelial growth factor A, fibronectin and advanced glycation end products in kidneys. Mechanistically, DHI induced expression of glucokinase, AMPKα/phosphorylated AMPKα, insulin receptor substrate 1, fibroblast growth factor 21 and peroxisome proliferator-activated γ. Expression of genes responsible for energy expenditure was also activated by DHI. Therefore, DHI inhibits diabetic retinopathy and nephropathy by ameliorating glucose metabolism and demonstrates a potential application in clinics.
authors.affiliation: 1] State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin 300071, China [2] College of Life Sciences, Nankai University, Tianjin 300071, China.
authors.forename: Mengyang
authors.initials: M
authors.lastname: Liu
authors.affiliation: 1] State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin 300071, China [2] College of Life Sciences, Nankai University, Tianjin 300071, China.
authors.forename: Quan
authors.initials: Q
authors.lastname: Pan
authors.affiliation: 1] State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin 300071, China [2] Collaborative Innovation Center for Biotherapy, Nankai University, Tianjin 300071, China.
authors.forename: Yuanli
authors.initials: Y
authors.lastname: Chen
authors.affiliation: 1] State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin 300071, China [2] College of Life Sciences, Nankai University, Tianjin 300071, China.
authors.forename: Xiaoxiao
authors.initials: X
authors.lastname: Yang
authors.affiliation: Buchang Pharmaceutical Co. Ltd., Xi'an 712000, China.
authors.forename: Buchang
authors.initials: B
authors.lastname: Zhao
authors.affiliation: Buchang Pharmaceutical Co. Ltd., Xi'an 712000, China.
authors.forename: Lifu
authors.initials: L
authors.lastname: Jia
authors.affiliation: Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China.
authors.forename: Boli
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China.
authors.forename: Xiumei
authors.initials: X
authors.lastname: Gao
authors.affiliation: College of Life Sciences, Nankai University, Tianjin 300071, China.
authors.forename: Xiaoju
authors.initials: X
authors.lastname: Li
authors.affiliation: 1] State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin 300071, China [2] Collaborative Innovation Center for Biotherapy, Nankai University, Tianjin 300071, China.
authors.forename: Jihong
authors.initials: J
authors.lastname: Han
authors.affiliation: 1] State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin 300071, China [2] Collaborative Innovation Center for Biotherapy, Nankai University, Tianjin 300071, China.
authors.forename: Yajun
authors.initials: Y
authors.lastname: Duan
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism / Q000652:urine; D053148:Caspase 3 / Q000378:metabolism; D061945:Caspase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D003928:Diabetic Nephropathies / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology / Q000517:prevention & control; D003930:Diabetic Retinopathy / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology / Q000517:prevention & control; D004195:Disease Models, Animal; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage* / Q000494:pharmacology; D004734:Energy Metabolism / Q000187:drug effects; D017127:Glycation End Products, Advanced / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D051379:Mice; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D015415:Biomarkers; D061945:Caspase Inhibitors; D004365:Drugs, Chinese Herbal; D017127:Glycation End Products, Advanced; D061965:Matrix Metalloproteinase Inhibitors; D042461:Vascular Endothelial Growth Factor A; C540581:danhong; D053148:Caspase 3; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9