title: A combination of the main constituents of Fufang Xueshuantong Capsules shows protective effects against streptozotocin-induced retinal lesions in rats.
abstract: BACKGROUND
  Fufang Xueshuantong Capsule, an herbal formula licensed for clinical use in China, which is composed of Panax notoginseng (Burkill) F.H. Chen, Salvia miltiorrhiza Bunge, Astragalus membranaceus (Fisch.) Bunge, and Scrophularia ningpoensis Hemsl, has proven effective for the treatment of diabetic retinopathy. However, its bioactive constituents are still ambiguous. In this study, the therapeutic effects of a combination of the main constituents of Fufang Xueshuantong Capsule (cFXT) were evaluated in streptozotocin (STZ)-induced retinal lesions to identify the bioactive constituents.
  
  
  METHODS
  Sprague-Dawley rats, except for those in the control group (vehicle+vehicle), were administered a single injection of 60mg/kg STZ. One-week later, STZ-treated rats were randomly divided into three groups-one STZ group (STZ+vehicle) and two cFXT treatment groups (STZ+cFXT). The rats in the latter two groups received cFXT 44.8mg/kg or cFXT 22.4mg/kg by intragastric gavage once per day, for 24 consecutive weeks. The rats in the control and STZ groups received the vehicle in the same way. Body weights and fasting blood glucose levels were recorded every four weeks. After treatment, hemorheological tests were performed to record the erythrocyte aggregation indexes, blood viscosity, and plasma viscosity. The trypsin digestion method was used to observe pericyte and acellular capillary counts in the retina. Ultraviolet spectrophotometry was utilized to measure the activity of aldose reductase (AR) by measuring the nicotinamide adenine dinucleotide phosphate (NADPH) consumption at 340nm. An immunohistochemical assay was used to observe the expressions of vascular endothelial growth factor (VEGF) and pigment epithelium-derived factor (PEDF) in the retina. The expression levels of intercellular adhesion molecule-1 (ICAM-1), endothelin-1 (RT-1),and occludin in the retina were tested by the western blot assay.
  
  
  RESULTS
  cFXT is composed of 991.44mg/g saponins of Panax notoginseng, 1.62mg/g harpagoside, 0.70mg/g cryptotanshinone, 0.74mg/g tanshinone I, and 5.50mg/g astragaloside A. Although it showed no effects on the increased body weight and blood glucose levels induced by STZ in rats. However, it showed a tendency to attenuate the increase in erythrocyte aggregation, plasma viscosity, and acellular vessel and pericyte loss, paralleled with a reversal of the hyper-activation of AR, the hyper-expression of VEGF, ICAM-1, and ET-1, and the hypo-expression of PEDF and occludin in the retinas of STZ-treated rats.
  
  
  CONCLUSIONS
  The saponins of Panax notoginseng, harpagoside, cryptotanshinone, tanshinone I, and astragaloside A are the main bioactive constituents of Fufang Xueshuantong Capsule and contribute to the attenuation of STZ-induced retinal lesions in rats. These constituents can be used as the base to optimize a new drug for the treatment of diabetic retinopathy, and can be selected for quality control of Fufang Xueshuantong Capsules.
authors.affiliation: School of Chinese Material Medica, Beijing University of Chinese Medicine, 6#, Wangjing Zhonghuan Nanlu, Chaoyang District, Beijing 100102, China.
authors.forename: Weijie
authors.initials: W
authors.lastname: Jian
authors.affiliation: School of Chinese Material Medica, Beijing University of Chinese Medicine, 6#, Wangjing Zhonghuan Nanlu, Chaoyang District, Beijing 100102, China.
authors.forename: Suyun
authors.initials: S
authors.lastname: Yu
authors.affiliation: School of Chinese Material Medica, Beijing University of Chinese Medicine, 6#, Wangjing Zhonghuan Nanlu, Chaoyang District, Beijing 100102, China.
authors.forename: Minke
authors.initials: M
authors.lastname: Tang
authors.affiliation: School of Chinese Material Medica, Beijing University of Chinese Medicine, 6#, Wangjing Zhonghuan Nanlu, Chaoyang District, Beijing 100102, China.
authors.forename: Huihui
authors.initials: H
authors.lastname: Duan
authors.affiliation: School of Chinese Material Medica, Beijing University of Chinese Medicine, 6#, Wangjing Zhonghuan Nanlu, Chaoyang District, Beijing 100102, China. Electronic address: huangjm@bucm.edu.cn.
authors.forename: Jianmei
authors.initials: J
authors.lastname: Huang
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D002214:Capsules; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D003930:Diabetic Retinopathy / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D004365:Drugs, Chinese Herbal / Q000494:pharmacology / Q000627:therapeutic use*; D019332:Endothelin-1 / Q000378:metabolism; D005136:Eye Proteins / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008297:Male; D009414:Nerve Growth Factors / Q000378:metabolism; D062793:Occludin / Q000378:metabolism; D008517:Phytotherapy; D051381:Rats; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000187:drug effects / Q000378:metabolism; D012503:Saponins / Q000494:pharmacology / Q000627:therapeutic use; D015843:Serpins / Q000378:metabolism; D013311:Streptozocin; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D000099174:Pigment Epithelium-Derived Factor
chemical_list: D001786:Blood Glucose; D002214:Capsules; D004365:Drugs, Chinese Herbal; D019332:Endothelin-1; D005136:Eye Proteins; D007004:Hypoglycemic Agents; D018799:Intercellular Adhesion Molecule-1; D009414:Nerve Growth Factors; D062793:Occludin; D012503:Saponins; D015843:Serpins; D013311:Streptozocin; D042461:Vascular Endothelial Growth Factor A; D000099174:Pigment Epithelium-Derived Factor; C568987:Ocln protein, rat; C519374:Panax notoginseng extract; C467498:vascular endothelial growth factor A, rat
keywords: Astragaloside A (CAS NO., 83207-58-3); Cryptotanshinone (CAS NO., 35825-57-1); Diabetic retinopathy; Endothelin-1; Fufang Xueshuantong Capsule; Ginsenoside Rb(1) (CAS NO., 41753-43-9); Ginsenoside Rg(1) (CAS NO., 22427-39-0); Harpagoside (CAS NO., 19210-12-9); Intercellular adhesion molecule-1; Notoginsenoside R1 (CAS NO., 80418-24-2); Occludin; Pigment epithelium derived factor; Tanshinone I (CAS NO., 568-73-0)