title: Anabolic effect of the traditional Chinese medicine compound tanshinone IIA on myotube hypertrophy is mediated by estrogen receptor.
abstract: Skeletal muscle loss during menopause is associated with a higher risk of developing diabetes type II and the general development of the metabolic syndrome. Therefore, strategies combining nutritional and training interventions to prevent muscle loss are necessary. Danshen Si Wu is a traditional Chinese medicine used for menopausal complains. One of the main compounds of Danshen Si Wu is tanshinone IIA. Physiological effects of tanshinone IIA have been described as being mediated via the estrogen receptor. Therefore, it was the aim of this study to determine its tissue specific ERα- and ERβ-mediated estrogenic activity, to investigate its antiestrogenic properties, and, particularly, to study estrogen receptor-mediated biological responses to tanshinone IIA on skeletal muscle cells. The purity of tanshinone IIA was analyzed by LC-DAD-MS/MS analysis. ERα/ERβ-mediated activity was dose-dependently analyzed in HEK 239 cells transfected with ERα or ERβ expression vectors and respective reporter genes. Androgenic, antiandrogenic, and antiestrogenic properties of tanshinone IIA were analyzed in a yeast reporter gene assay. The effects of tanshinone IIA on proliferation and cell cycle distribution were investigated in ERα positive T47D breast cancer cells. The ability of tanshinone IIA to stimulate estrogen receptor-mediated myotube hypertrophy was studied in C2C12 myoblastoma cells. Our data show that tanshinone IIA is quite potent at stimulating ERα and ERβ reporter genes with comparable efficacy. Tanshinone IIA displayed antiestrogenic and also antiandrogenic properties in a yeast reporter gene assay. It inhibited the growth of T47D breast cancer cells by suppressing proliferation and arresting the cells in G0/G1. Tanshinone IIA also stimulated the hypertrophy of C2C12 myotubes via an estrogen receptor-mediated mechanism. Summarizing our results, tanshinone IIA can be characterized as an estrogen receptor partial agonist with antiandrogenic properties. It seems to inhibit ERα-mediated cell proliferation but induces ERβ-related biological responses like hypertrophy of myotubes. These findings are interesting with respect to the treatment of a variety of complains of postmenopausal females, including muscle wasting.
authors.affiliation: School of Preclinical Medicine, Beijing University of Chinese Medicine, Beijing, China.
authors.forename: Piwen
authors.initials: P
authors.lastname: Zhao
authors.affiliation: Department of Safety and Quality of Fruit and Vegetables, Max Rubner-Institut, Karlsruhe, Germany.
authors.forename: Sebastian Tobias
authors.initials: ST
authors.lastname: Soukup
authors.affiliation: German Sport University, Cologne, Germany.
authors.forename: Jonas
authors.initials: J
authors.lastname: Hegevoss
authors.affiliation: German Sport University, Cologne, Germany.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Ngueu
authors.affiliation: Department of Safety and Quality of Fruit and Vegetables, Max Rubner-Institut, Karlsruhe, Germany.
authors.forename: Sabine Emma
authors.initials: SE
authors.lastname: Kulling
authors.affiliation: German Sport University, Cologne, Germany.
authors.forename: Patrick
authors.initials: P
authors.lastname: Diel
mesh_terms: D045784:Abietanes / Q000494:pharmacology* / Q000627:therapeutic use; D045930:Anabolic Agents / Q000494:pharmacology / Q000627:therapeutic use; D059002:Androgen Receptor Antagonists / Q000494:pharmacology; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism; D045744:Cell Line, Tumor; D004365:Drugs, Chinese Herbal / Q000494:pharmacology / Q000627:therapeutic use; D004965:Estrogen Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D047629:Estrogen Receptor beta / Q000378:metabolism; D004967:Estrogens / Q000494:pharmacology* / Q000627:therapeutic use; D057809:HEK293 Cells; D006801:Humans; D006984:Hypertrophy; D018485:Muscle Fibers, Skeletal / Q000187:drug effects*; D009133:Muscular Atrophy / Q000378:metabolism* / Q000517:prevention & control; D008517:Phytotherapy; D011960:Receptors, Estrogen / Q000378:metabolism*; D027561:Salvia miltiorrhiza / Q000737:chemistry*; D020845:Selective Estrogen Receptor Modulators / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D045784:Abietanes; D045930:Anabolic Agents; D059002:Androgen Receptor Antagonists; D000972:Antineoplastic Agents, Phytogenic; D004365:Drugs, Chinese Herbal; D004965:Estrogen Antagonists; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D004967:Estrogens; D011960:Receptors, Estrogen; D020845:Selective Estrogen Receptor Modulators; C021751:tanshinone; C028972:dan-shen root extract