title: Inhibitory effect of baicalin on collagen-induced arthritis in rats through the nuclear factor-κB pathway.
abstract: This study focused on the potential therapeutic effect of baicalin on collagen-induced arthritis (CIA) in rats and the underlying mechanisms. The CIA rats were injected with baicalin (50, 100, or 200 mg/kg) once daily for 30 days. The rats were monitored for clinical severity of arthritis, and joint tissues were used for radiographic assessment and histologic examination. We quantified tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in experimental animals and used Western blots to assess levels of protein abundance, phosphorylation, and acetylation of nuclear factor (NF)-κB p65 and sirtuin 1 (sirt1) protein expression in joint tissues. Human fibroblast-like synoviocytes from rheumatoid arthritis (HFLS-RA) were adopted in further mechanistic investigations. Baicalin intraperitoneal injection for 30 days dose-dependently blocked clinical manifestations of CIA, such as functional impairment and swollen red paws. Meanwhile, it alleviated collagen-induced joint inflammation injury and inhibited the secretion of TNF-α and IL-1β in both rat synovium and HFLS-RA. Further mechanistic investigations revealed that baicalin suppresses NF-κB p65 protein expression and phosphorylation in synovial tissue and human-derived synoviocytes. Moreover, the acetylation of NF-κB p65 was downregulated by baicalin, which negatively correlates with the baicalin-induced upregulation of sirt1 expression in the same conditions. The data indicate that CIA in rats can be alleviated by baicalin treatment via relieving joint inflammation, which is related to the suppression of synovial NF-κB p65 protein expression and the elevation of its deacetylation by sirt1.
authors.affiliation: Department of Laboratory Diagnosis (H.-Z.W., Y.-H.L.), The Second Affiliated Hospital of Harbin Medical University, Harbin, China; Departments of Laboratory Diagnosis (H.-Z.W., G.-Z.W.,), Department of Respiratory Medicine (H.Z.), and Department of Orthopaedic Surgery (D.W.), The Fifth Affiliated Hospital of Harbin Medical University, Daqing, China; College of Medical Laboratory Science and Technology and the Key Laboratory of Molecular Diagnosis in Laboratory Medicine (H.-H.W., S.-S.H., Z.-G.W.), and Department of Pharmacology (Y.-G.C.), Harbin Medical University, Daqing, China.
authors.forename: Hong-Zhi
authors.initials: HZ
authors.lastname: Wang
authors.affiliation: Department of Laboratory Diagnosis (H.-Z.W., Y.-H.L.), The Second Affiliated Hospital of Harbin Medical University, Harbin, China; Departments of Laboratory Diagnosis (H.-Z.W., G.-Z.W.,), Department of Respiratory Medicine (H.Z.), and Department of Orthopaedic Surgery (D.W.), The Fifth Affiliated Hospital of Harbin Medical University, Daqing, China; College of Medical Laboratory Science and Technology and the Key Laboratory of Molecular Diagnosis in Laboratory Medicine (H.-H.W., S.-S.H., Z.-G.W.), and Department of Pharmacology (Y.-G.C.), Harbin Medical University, Daqing, China.
authors.forename: Hai-He
authors.initials: HH
authors.lastname: Wang
authors.affiliation: Department of Laboratory Diagnosis (H.-Z.W., Y.-H.L.), The Second Affiliated Hospital of Harbin Medical University, Harbin, China; Departments of Laboratory Diagnosis (H.-Z.W., G.-Z.W.,), Department of Respiratory Medicine (H.Z.), and Department of Orthopaedic Surgery (D.W.), The Fifth Affiliated Hospital of Harbin Medical University, Daqing, China; College of Medical Laboratory Science and Technology and the Key Laboratory of Molecular Diagnosis in Laboratory Medicine (H.-H.W., S.-S.H., Z.-G.W.), and Department of Pharmacology (Y.-G.C.), Harbin Medical University, Daqing, China.
authors.forename: Shi-Shun
authors.initials: SS
authors.lastname: Huang
authors.affiliation: Department of Laboratory Diagnosis (H.-Z.W., Y.-H.L.), The Second Affiliated Hospital of Harbin Medical University, Harbin, China; Departments of Laboratory Diagnosis (H.-Z.W., G.-Z.W.,), Department of Respiratory Medicine (H.Z.), and Department of Orthopaedic Surgery (D.W.), The Fifth Affiliated Hospital of Harbin Medical University, Daqing, China; College of Medical Laboratory Science and Technology and the Key Laboratory of Molecular Diagnosis in Laboratory Medicine (H.-H.W., S.-S.H., Z.-G.W.), and Department of Pharmacology (Y.-G.C.), Harbin Medical University, Daqing, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Department of Laboratory Diagnosis (H.-Z.W., Y.-H.L.), The Second Affiliated Hospital of Harbin Medical University, Harbin, China; Departments of Laboratory Diagnosis (H.-Z.W., G.-Z.W.,), Department of Respiratory Medicine (H.Z.), and Department of Orthopaedic Surgery (D.W.), The Fifth Affiliated Hospital of Harbin Medical University, Daqing, China; College of Medical Laboratory Science and Technology and the Key Laboratory of Molecular Diagnosis in Laboratory Medicine (H.-H.W., S.-S.H., Z.-G.W.), and Department of Pharmacology (Y.-G.C.), Harbin Medical University, Daqing, China.
authors.forename: Yong-Gang
authors.initials: YG
authors.lastname: Cao
authors.affiliation: Department of Laboratory Diagnosis (H.-Z.W., Y.-H.L.), The Second Affiliated Hospital of Harbin Medical University, Harbin, China; Departments of Laboratory Diagnosis (H.-Z.W., G.-Z.W.,), Department of Respiratory Medicine (H.Z.), and Department of Orthopaedic Surgery (D.W.), The Fifth Affiliated Hospital of Harbin Medical University, Daqing, China; College of Medical Laboratory Science and Technology and the Key Laboratory of Molecular Diagnosis in Laboratory Medicine (H.-H.W., S.-S.H., Z.-G.W.), and Department of Pharmacology (Y.-G.C.), Harbin Medical University, Daqing, China.
authors.forename: Guang-Zhi
authors.initials: GZ
authors.lastname: Wang
authors.affiliation: Department of Laboratory Diagnosis (H.-Z.W., Y.-H.L.), The Second Affiliated Hospital of Harbin Medical University, Harbin, China; Departments of Laboratory Diagnosis (H.-Z.W., G.-Z.W.,), Department of Respiratory Medicine (H.Z.), and Department of Orthopaedic Surgery (D.W.), The Fifth Affiliated Hospital of Harbin Medical University, Daqing, China; College of Medical Laboratory Science and Technology and the Key Laboratory of Molecular Diagnosis in Laboratory Medicine (H.-H.W., S.-S.H., Z.-G.W.), and Department of Pharmacology (Y.-G.C.), Harbin Medical University, Daqing, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Wang
authors.affiliation: Department of Laboratory Diagnosis (H.-Z.W., Y.-H.L.), The Second Affiliated Hospital of Harbin Medical University, Harbin, China; Departments of Laboratory Diagnosis (H.-Z.W., G.-Z.W.,), Department of Respiratory Medicine (H.Z.), and Department of Orthopaedic Surgery (D.W.), The Fifth Affiliated Hospital of Harbin Medical University, Daqing, China; College of Medical Laboratory Science and Technology and the Key Laboratory of Molecular Diagnosis in Laboratory Medicine (H.-H.W., S.-S.H., Z.-G.W.), and Department of Pharmacology (Y.-G.C.), Harbin Medical University, Daqing, China.
authors.forename: Zhi-Gang
authors.initials: ZG
authors.lastname: Wang
authors.affiliation: Department of Laboratory Diagnosis (H.-Z.W., Y.-H.L.), The Second Affiliated Hospital of Harbin Medical University, Harbin, China; Departments of Laboratory Diagnosis (H.-Z.W., G.-Z.W.,), Department of Respiratory Medicine (H.Z.), and Department of Orthopaedic Surgery (D.W.), The Fifth Affiliated Hospital of Harbin Medical University, Daqing, China; College of Medical Laboratory Science and Technology and the Key Laboratory of Molecular Diagnosis in Laboratory Medicine (H.-H.W., S.-S.H., Z.-G.W.), and Department of Pharmacology (Y.-G.C.), Harbin Medical University, Daqing, China hrb_liuyanhong@126.com.
authors.forename: Yan-Hong
authors.initials: YH
authors.lastname: Liu
mesh_terms: D000107:Acetylation; D000818:Animals; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000276:immunology; D005260:Female; D005419:Flavonoids / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction; D056564:Sirtuin 1 / Q000378:metabolism; D013583:Synovial Membrane / Q000187:drug effects; D051996:Transcription Factor RelA / Q000037:antagonists & inhibitors*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D005419:Flavonoids; D053583:Interleukin-1beta; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; C038044:baicalin; C488368:Sirt1 protein, rat; D056564:Sirtuin 1