title: Oridonin ameliorates lupus-like symptoms of MRL(lpr/lpr) mice by inhibition of B-cell activating factor (BAFF).
abstract: Oridonin, a pharmacologically safe agent extracted from Isodon Serra, has been shown to possess potent anti-inflammatory properties. However, it is not clear whether Oridonin affects B-cell activating factor (BAFF) expression, thereby exerting beneficial effects in the treatment of BAFF-associated autoimmune diseases such as systemic lupus erythematosus (SLE). Thus, the current study aimed to find the function of Oridonin in regulation of BAFF and amelioration of SLE. In vitro, we explored the effect of Oridonin on BAFF expression and production in mouse macrophages. Moreover, using a spontaneous murine SLE model, we investigated the role of Oridonin delivery in the treatment of lupus-like disease in MRL(lpr/lpr) mice, by measuring the changes in lupus symptoms, renal damage, BAFF expression, and B cell subsets. Our results showed that Oridonin significantly inhibited BAFF expression in mouse macrophages by suppressing the transcriptional activation of its promoter. And in vivo administration of Oridonin efficiently ameliorated the serological and clinical manifestations of SLE in MRL(lpr/lpr) mice, as shown by increased survival benefit, reduced proteinuria levels, diminished production of specific auto-antibodies, and attenuated renal damage, in association with down-regulation of BAFF and a lower rate of B-cell maturation and differentiation. Thus, it suggests that Oridonin will serve as a novel natural therapeutic strategy for SLE by inhibition of BAFF.
authors.affiliation: Department of Laboratory Medicine, Changzhen Hospital, Second Military Medical University, 415 Fengyang Road, Shanghai 200003, China. gracelin_zhou@yahoo.com.cn
authors.forename: Lin
authors.initials: L
authors.lastname: Zhou
authors.forename: Lijuan
authors.initials: L
authors.lastname: Sun
authors.forename: Hongkun
authors.initials: H
authors.lastname: Wu
authors.forename: Lingzhen
authors.initials: L
authors.lastname: Zhang
authors.forename: Mingcang
authors.initials: M
authors.lastname: Chen
authors.forename: Jianwen
authors.initials: J
authors.lastname: Liu
authors.forename: Renqian
authors.initials: R
authors.lastname: Zhong
mesh_terms: D000818:Animals; D000906:Antibodies / Q000097:blood / Q000276:immunology; D053264:B-Cell Activating Factor / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D001402:B-Lymphocytes / Q000187:drug effects / Q000473:pathology; D002452:Cell Count; D002460:Cell Line; D003404:Creatinine / Q000097:blood; D004247:DNA / Q000276:immunology; D045786:Diterpenes, Kaurane / Q000494:pharmacology* / Q000627:therapeutic use; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D007668:Kidney / Q000187:drug effects; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism* / Q000652:urine; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D019463:Mice, Inbred MRL lpr; D011401:Promoter Regions, Genetic / Q000187:drug effects; D011507:Proteinuria / Q000188:drug therapy; D016019:Survival Analysis
chemical_list: D000906:Antibodies; D053264:B-Cell Activating Factor; D045786:Diterpenes, Kaurane; C011959:oridonin; D004247:DNA; D003404:Creatinine
keywords: B cell; BAFF; Isodon Serra; MRL(lpr/lpr) mice; Oridonin; Systemic lupus erythematosus