title: Oridonin exerts protective effects against hydrogen peroxide‑induced damage by altering microRNA expression profiles in human dermal fibroblasts.
abstract: The aim of the present study was to evaluate the protective effects of oridonin on hydrogen peroxide-induced cytotoxicity in normal human dermal fibroblasts (NHDFs) using microRNA (miRNA) expression profile analysis. Oridonin was not cytotoxic at low doses (≤5 µM) in the NHDFs, and pre-treatment of the cells with oridonin significantly reduced hydrogen dioxide (H2O2)-mediated cytotoxicity and cell death. Whereas oridonin showed no free radical scavenging activity in in vitro and in vivo antioxidant assays, treatment of the NHDFs with oridonin was associated with intracellular scavenging of reactive oxygen species. High-density miRNA microarray analysis revealed alterations in the expression profiles of specific miRNAs (5 upregulated and 22 downregulated) following treatment with oridonin in the H2O2-treated NHDFs. Moreover, the use of a miRNA target-gene prediction tool and Gene Ontology analysis demonstrated that these miRNAs are functionally related to the inhibition of apoptosis and cell growth. These data provide valuable insight into the cellular responses to oridonin in H2O2-induced damage in NHDFs.
authors.affiliation: Molecular-Targeted Drug Research Center, Konkuk University, Seoul 143-701, Republic of Korea.
authors.forename: Eun-Jin
authors.initials: EJ
authors.lastname: Lee
authors.forename: Hwa Jun
authors.initials: HJ
authors.lastname: Cha
authors.forename: Kyu Joong
authors.initials: KJ
authors.lastname: Ahn
authors.forename: In-Sook
authors.initials: IS
authors.lastname: An
authors.forename: Sungkwan
authors.initials: S
authors.lastname: An
authors.forename: Seunghee
authors.initials: S
authors.lastname: Bae
mesh_terms: D000975:Antioxidants / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D019295:Computational Biology; D020405:Dermis / Q000473:pathology*; D045786:Diterpenes, Kaurane / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D020869:Gene Expression Profiling; D063990:Gene Ontology; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity*; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D020011:Protective Agents / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
chemical_list: D000975:Antioxidants; D045786:Diterpenes, Kaurane; D035683:MicroRNAs; D020011:Protective Agents; C011959:oridonin; D006861:Hydrogen Peroxide