title: Protective effect of platycodin D on liver injury in alloxan-induced diabetic mice via regulation of Treg/Th17 balance.
abstract: Platycodin D is a major pharmacological constituent of Platycodi Radix with immunomodulatory activity. The present study was designed to investigate how platycodin D (PLD) reveals liver injury in diabetic mice and its mechanism. Fifty mice were divided into five groups randomly: control group, model group, rosiglitazone (ROG, 10 mg/kg) group, PLD (50 mg/kg) group, and PLD (100 mg/kg) group. Diabetes was induced with the injection of alloxan monohydrate (150 mg/kg) subcutaneously, and animals with blood glucose level of ≥250 mg/dl were considered as diabetic mice. After the first day of diabetes induction, the treatments were performed for 8 weeks. Then the animals were anaesthetized, and blood and liver samples were also collected for further assay. PLD significantly decreased the serum levels of glucose, insulin, interleukin-6 (IL-6), interleukin-1β, tumor necrosis factor-α (TNF-α), and interleukin (IL)-17A and increased IL-10 level in serum. PLD effectively downregulated aspartate transaminase (AST), alanine aminotransferase (ALT), total cholesterol (TC), and triglycerides (TG) in liver. PLD also attenuated liver histological change. In addition, PLD significantly attenuated IL-17A and IL-10 levels in vitro, flow cytometry (FCM) studies also showed that PLD remarkably inhibited Th17 cells and significantly increased Treg cells in liver tissues and spleen cells. Western blot demonstrated PLD inhibited the phosphorylation of JAK and STAT-3 and the expression of RORγt and increased the expression of Foxp3. The findings showed that PLD exerts beneficial effects on alloxan-induced liver injury in mice.
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China; Department of Pharmacology, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Tong
authors.initials: T
authors.lastname: Chen
authors.affiliation: School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Gao
authors.affiliation: School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Pengjun
authors.initials: P
authors.lastname: Xiang
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China; Department of Pharmacology, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Yongde
authors.initials: Y
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China; Department of Pharmacology, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Ji
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China; Department of Pharmacology, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Xie
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China; Department of Pharmacology, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China; Department of Pharmacology, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Xiao
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China; Department of Pharmacology, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Yidan
authors.initials: Y
authors.lastname: Wei
authors.affiliation: Changchun University of Chinese Medicine, Changchun 130117, China.
authors.forename: Shumin
authors.initials: S
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China; Department of Pharmacology, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Li
authors.initials: L
authors.lastname: Lan
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China; Department of Pharmacology, China Pharmaceutical University, Nanjing 210009, China. Electronic address: huijicpu@163.com.
authors.forename: Hui
authors.initials: H
authors.lastname: Ji
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China. Electronic address: yantianhuabest@126.com.
authors.forename: Tianhua
authors.initials: T
authors.lastname: Yan
mesh_terms: D000410:Alanine Transaminase / Q000235:genetics / Q000378:metabolism; D000496:Alloxan / Q000008:administration & dosage; D000818:Animals; D001219:Aspartate Aminotransferases / Q000235:genetics / Q000378:metabolism; D001786:Blood Glucose / Q000187:drug effects; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy* / Q000276:immunology; D002784:Cholesterol / Q000378:metabolism; D029745:Codonopsis / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000276:immunology; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D007328:Insulin / Q000097:blood; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008815:Mice, Inbred Strains; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism; D012503:Saponins / Q000008:administration & dosage* / Q000009:adverse effects; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000276:immunology; D058504:Th17 Cells / Q000187:drug effects* / Q000276:immunology; D014315:Triterpenes / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D001786:Blood Glucose; D016207:Cytokines; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D018836:Inflammation Mediators; D007328:Insulin; D050796:STAT3 Transcription Factor; D012503:Saponins; C494087:Stat3 protein, mouse; D014315:Triterpenes; D000496:Alloxan; D002784:Cholesterol; C108953:platycodin D; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase
keywords: Diabetic; Liver injury; Platycodin D; Treg/Th17 balance