title: Effects of Tanshinone IIA on the modulation of miR‑33a and the SREBP‑2/Pcsk9 signaling pathway in hyperlipidemic rats.
abstract: Tanshinone IIA is the active compound isolated from Salvia miltiorrhiza bunge, which is a traditional Chinese medicine known as Danshen. The aim of the present study was to assess the effect of Tanshinone IIA on the regulation of lipid metabolism in the livers of hyperlipidemic rats and the underlying molecular events. An in vivo model of hyperlipidemia was established in rats, with the animals receiving a daily dose of Tanshinone IIA. The serum lipid profiles were analyzed using an automatic biochemical analyzer, and the histopathological alterations and lipid deposition in liver tissue were assessed using hematoxylin and eosin staining, and oil red O staining, respectively. The mRNA expression levels of microRNA (miR)‑33a, ATP‑binding cassette transporter (ABC)A1, ABCG1, sterol regulatory element‑binding protein 2 (SREBP‑2), proprotein convertase subtilisin/kexin type 9 (Pcsk9) and low‑density lipoprotein receptor (LDL‑R) in liver tissues were measured using reverse transcription‑quantitative polymerase chain reaction, and the protein expression levels of ABCA1, ABCG1, SREBP‑2, Pcsk9, and LDL‑R were analyzed using western blotting. Tanshinone IIA reduced lipid deposition and improved histopathology in the rat liver tissue, however, did not alter the lipid profile in rat serum. In addition, Tanshinone IIA treatment suppressed the expression of miR‑33a, whereas the protein expression levels of ABCA1, SREBP‑2, Pcsk9 in addition to LDL‑R mRNA and protein were upregulated. In conclusion, the present study indicated that Tanshinone IIA attenuated lipid deposition in the livers of hyperlipidemic rats and modulated the expression of miR‑33a and SREBP‑2/Pcsk9 signaling pathway proteins.
authors.affiliation: Key Laboratory of Ministry of Education for Traditional Chinese Medicine Viscera‑State Theory and Applications, Liaoning University of Traditional Chinese Medicine, Shenyang, Liaoning 110847, P.R. China.
authors.forename: Lianqun
authors.initials: L
authors.lastname: Jia
authors.affiliation: Key Laboratory of Ministry of Education for Traditional Chinese Medicine Viscera‑State Theory and Applications, Liaoning University of Traditional Chinese Medicine, Shenyang, Liaoning 110847, P.R. China.
authors.forename: Nan
authors.initials: N
authors.lastname: Song
authors.affiliation: Key Laboratory of Ministry of Education for Traditional Chinese Medicine Viscera‑State Theory and Applications, Liaoning University of Traditional Chinese Medicine, Shenyang, Liaoning 110847, P.R. China.
authors.forename: Guanlin
authors.initials: G
authors.lastname: Yang
authors.affiliation: Graduate School, Liaoning University of Traditional Chinese Medicine, Shenyang, Liaoning 110847, P.R. China.
authors.forename: Yixin
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Key Laboratory of Ministry of Education for Traditional Chinese Medicine Viscera‑State Theory and Applications, Liaoning University of Traditional Chinese Medicine, Shenyang, Liaoning 110847, P.R. China.
authors.forename: Xuetao
authors.initials: X
authors.lastname: Li
authors.affiliation: Key Laboratory of Ministry of Education for Traditional Chinese Medicine Viscera‑State Theory and Applications, Liaoning University of Traditional Chinese Medicine, Shenyang, Liaoning 110847, P.R. China.
authors.forename: Ren
authors.initials: R
authors.lastname: Lu
authors.affiliation: The First Clinical College, Liaoning University of Traditional Chinese Medicine, Shenyang, Liaoning 110847, P.R. China.
authors.forename: Huimin
authors.initials: H
authors.lastname: Cao
authors.affiliation: The First Clinical College, Liaoning University of Traditional Chinese Medicine, Shenyang, Liaoning 110847, P.R. China.
authors.forename: Ni
authors.initials: N
authors.lastname: Zhang
authors.affiliation: Graduate School, Liaoning University of Traditional Chinese Medicine, Shenyang, Liaoning 110847, P.R. China.
authors.forename: Meilin
authors.initials: M
authors.lastname: Zhu
authors.affiliation: Key Laboratory of Ministry of Education for Traditional Chinese Medicine Viscera‑State Theory and Applications, Liaoning University of Traditional Chinese Medicine, Shenyang, Liaoning 110847, P.R. China.
authors.forename: Junyan
authors.initials: J
authors.lastname: Wang
authors.affiliation: Key Laboratory of Ministry of Education for Traditional Chinese Medicine Viscera‑State Theory and Applications, Liaoning University of Traditional Chinese Medicine, Shenyang, Liaoning 110847, P.R. China.
authors.forename: Xue
authors.initials: X
authors.lastname: Leng
authors.affiliation: Key Laboratory of Ministry of Education for Traditional Chinese Medicine Viscera‑State Theory and Applications, Liaoning University of Traditional Chinese Medicine, Shenyang, Liaoning 110847, P.R. China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Cao
authors.affiliation: Key Laboratory of Ministry of Education for Traditional Chinese Medicine Viscera‑State Theory and Applications, Liaoning University of Traditional Chinese Medicine, Shenyang, Liaoning 110847, P.R. China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Du
authors.affiliation: Graduate School, Liaoning University of Traditional Chinese Medicine, Shenyang, Liaoning 110847, P.R. China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Xu
mesh_terms: D064286:ATP Binding Cassette Transporter 1 / Q000235:genetics / Q000378:metabolism; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1 / Q000235:genetics / Q000378:metabolism; D045784:Abietanes / Q000494:pharmacology*; D000818:Animals; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000187:drug effects; D006949:Hyperlipidemias / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism*; D050356:Lipid Metabolism / Q000187:drug effects; D008055:Lipids / Q000097:blood; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D000071449:Proprotein Convertase 9 / Q000378:metabolism*; D051381:Rats; D011973:Receptors, LDL / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D051782:Sterol Regulatory Element Binding Protein 2 / Q000378:metabolism*
chemical_list: D064286:ATP Binding Cassette Transporter 1; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D045784:Abietanes; D008055:Lipids; C580642:MIRN33 microRNA, rat; D035683:MicroRNAs; D011973:Receptors, LDL; D051782:Sterol Regulatory Element Binding Protein 2; C021751:tanshinone; C510804:PCSK9 protein, rat; D000071449:Proprotein Convertase 9