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.

Cytotoxicity of Tanshinone IIA combined with Taxol on drug‐resist breast cancer cells MCF‐7 through inhibition of Tau

“…Moreover, Tanshinone IIA was also reported with antitumor activities in many kinds of carcinomas (Jeon et al, ; Jing et al, ; Lin et al, ; Yu, Xue, Zhou, Li, & Zhou, ; Yun et al, ). The antibreast cancer ability of tanshinone is related to its antiestrogenic properties (Zhao et al, ), which is one of the main targets of estrogen positive breast cancer.…”

Antifatigue properties of tanshinone IIA in mice subjected to the forced swimming test

“…Tan IIA has been reported to selectively induce oestrogen receptor β (ERβ)-related myotube hypertrophy in vitro through an anabolic effect (Zhao et al. 2015 ). ERβ is involved in skeletal muscle hypertrophy, which is beneficial for muscle building and exercise tolerance and is inducible by the phytoecdysteroid ecdysterone (Parr et al.…”

Tanshinone IIA Stimulates Cystathionine γ-Lyase Expression and Protects Endothelial Cells from Oxidative Injury

“…Note the reduced fluorescent intensity after DTT treatment in both control and Tan IIA-treated samples. Because some of the actions of Tan IIA are mediated by estrogen receptor (ER) [22,24,27], we, therefore, also tested its involvement. Figure 4C shows that ER inhibitor ICI also prevented the CSE elevation.…”

“…It has estrogen-like activity. Some of the pharmacological effects of Tan IIA are via its stimulation on estrogen receptors [22,24,27]. Interestingly, the induction of CSE expression and endogenous H 2 S production by estrogen has been reported [28][29][30].…”