Tanshinone IIA

Ann Plast Surg. 2015 Jun 20.

Tanshinone IIA Inhibits Proliferation and Induces Apoptosis Through the Downregulation of Survivin in Keloid Fibroblasts.[Pubmed: 26101974]

Keloids are considered benign dermal fibroproliferative tumors. Keloid fibroblasts (KFs) persistently proliferate and fail to undergo apoptosis, and no treatment is completely effective against these lesions. Tanshinone IIA induces apoptosis and inhibits the proliferation of various tumor cell types. In this study, we investigated the effect of Tanshinone IIA on the regulation of proliferation, cell cycle, and apoptosis in KFs, and investigated potential mechanisms involved in the effects.
METHODS AND RESULTS:
First, KFs and normal skin fibroblasts (NSFs) were treated with various concentrations of Tanshinone IIA. Cell counting kit-8 (CCK-8) was used to assess the proliferative activity of KFs and NSFs, and flow cytometry was used to investigate the cell cycle and apoptosis in KFs. We found that the proliferation of all Tanshinone IIA-treated KFs was significantly decreased after treatment for 72 hours (P < 0.001). Also, NSFs treated with Tanshinone IIA did not exhibit noticeable effects compared with KFs. In addition, the percentages of G0/G1 cells in all Tanshinone IIA-treated KFs were significantly increased after treatment for 72 hours (P < 0.001). And the percentages of cells undergoing early apoptosis in all Tanshinone IIA-treated KFs were significantly increased after treatment for 120 hours (P < 0.001). Furthermore, the apoptosis antibody array kit and Western blot analysis revealed that Tanshinone IIA decreased survivin expression in KFs (P < 0.001).
CONCLUSIONS:
In conclusion, Tanshinone IIA downregulates survivin and deactivates KFs, thus suggesting that Tanshinone IIA could serve as a potential clinical keloid treatment.

Planta Med. 2015 May;81(7):578-85.

Anabolic Effect of the Traditional Chinese Medicine Compound Tanshinone IIA on Myotube Hypertrophy Is Mediated by Estrogen Receptor.[Pubmed: 26018796]

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.
METHODS AND RESULTS:
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.
CONCLUSIONS:
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.

Eur J Pharmacol. 2007 Jul 30;568(1-3):213-21.

Tanshinone IIA protects cardiac myocytes against oxidative stress-triggered damage and apoptosis.[Pubmed: 17537428]

Tanshinone IIA (tan), a derivative of phenanthrenequinone, is one of the key components of Salvia miltiorrhiza Bunge. Previous reports showed that tan inhibited the apoptosis of cultured PC12 cells induced by serum withdrawal or ethanol. However, whether tan has a cardioprotective effect against apoptosis remains unknown.
METHODS AND RESULTS:
In this study, we investigated the effects of tan on cardiac myocyte apoptosis induced both by in vitro incubation of neonatal rat ventricular myocytes with H(2)O(2) and by in vivo occlusion followed by reperfusion of the left anterior descending coronary artery in adult rats. In vitro, as revealed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium (MTT) assay, treatment with tan prior to H(2)O(2) exposure significantly increased cell viability. Tan also markedly inhibited H(2)O(2)-induced cardiomyocyte apoptosis, as detected by ladder-pattern fragmentation of genomic DNA, chromatin condensation, and hypodioloid DNA content. In vivo, tan significantly inhibited ischemia/reperfusion-induced cardiomyocyte apoptosis by attenuating morphological changes and reducing the percentage of terminal transferase dUTP nick end-labeling (TUNEL)-positive myocytes and caspase-3 cleavage. These effects of tan were associated with an increased ratio of Bcl-2 to Bax protein in cardiomyocytes, an elevation of serum superoxide dismutase (SOD) activity and a decrease in serum malondialdehyde (MDA) level.
CONCLUSIONS:
Taken together, these data for the first time provide convincing evidence that tan protects cardiac myocytes against oxidative stress-induced apoptosis. The in vivo protection is mediated by increased scavenging of oxygen free radicals, prevention of lipid peroxidation and upregulation of the Bcl-2/Bax ratio.

2016 Jul 15;8(7):3124-32.

Tanshinone IIA inhibits apoptosis in the myocardium by inducing microRNA-152-3p expression and thereby downregulating PTEN[Pubmed: 27508033]

Progressive loss of cardiac myocytes through apoptosis contributes to heart failure (HF). In this study, we tested whether Tanshinone IIA, one of the most abundant constituents of the root of Salvia miltiorrhiza, protects rat myocardium-derived H9C2 cells against apoptosis. Treatment of H9C2 cells with Tanshinone IIA inhibited angiotensin II-induced apoptosis by downregulating the expression of PTEN (phosphatase and tensin homolog), a tumor suppressor that plays a critical role in apoptosis. Furthermore, Tanshinone IIA was found to inhibit PTEN expression by upregulating the microRNA miR-152-3p, a potential PTEN regulator that is highly conserved in both rat and human. Notably, the antiapoptotic effect of Tanshinone IIA was partially reversed when H9C2 cells were transfected with an inhibitor of miR-152-3p. Collectively, our findings reveal a previously unrecognized mechanism underlying the cardioprotective role of Tanshinone IIA, and further suggest that Tanshinone IIA could represent a promising drug candidate for HF therapy.

J Neurol Sci. 2015 Jan 15;348(1-2):142-52.

Tanshinone IIA prevents the loss of nigrostriatal dopaminergic neurons by inhibiting NADPH oxidase and iNOS in the MPTP model of Parkinson's disease.[Pubmed: 25491263 ]

Tanshinone IIA is one of the major constituents of Salvia miltiorrhiza Bunge known as Danshen. Recent reports have shown that Tanshinone IIA has neuroprotective effects against cerebral ischemia/reperfusion injury and traumatic injury of the spinal cord in rats. However, whether Tanshinone IIA has any neuroprotective effect in Parkinson's disease remains unknown.
METHODS AND RESULTS:
In this study, we evaluated whether Tanshinone IIA promotes the survival of nigrostriatal dopaminergic (DA) neurons in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson's disease. MPTP induced degeneration of nigrostriatal DA neurons and microglial activation as visualized by tyrosine hydroxylase and CD11b immunoreactivity. The results of Western blot and immunohistochemistry showed upregulation of NADPH oxidase and iNOS in the MPTP-treated substantia nigra pars compacta. Treatment with Tanshinone IIA prevented degeneration of nigrostriatal DA neurons and increased the level of striatal dopamine content. This neuroprotection afforded by Tanshinone IIA was associated with the suppression of microglial activation and reduced expression of NADPH oxidase and iNOS.
CONCLUSIONS:
The present findings show that Tanshinone IIA may possess anti-inflammatory and anti-oxidative properties and may have therapeutic value in the treatment of Parkinson's disease.

Int J Clin Exp Med. 2015 Feb 15;8(2):1985-92.

Tanshinone IIA protects against methylglyoxal-induced injury in human brain microvascular endothelial cells.[Pubmed: 25932127]

Tanshinone IIA is one of the major diterpenes from Salvia miltiorrhiza Bunge and has been shown to possess a protective effect on the endothelial cells. The present study aimed to investigate whether Tanshinone IIA could protect against methylglyoxal (MGO)-induced injury in human brain microvascular endothelial cells (HBMEC).
METHODS AND RESULTS:
Using cultured HBMEC, cell viability was measured by MTT assay and trypan blue dye exclusion test. Cellular oxidative stress was measured by production of reactive oxygen species (ROS), thiobarbituric acid reactive substances (TBARS) and H2O2. AnnexinV/PI staining and western blot were performed to determine cell apoptosis and protein expression. We found that MGO treatment caused a concentration and time-dependent decrease in cell viability, which was inhibited by pretreatment with Tanshinone IIA. Exposure to MGO promoted the accumulation of AGEs, and production of ROS, TBARS and H2O2 in the cultured HBMEC, which were inhibited by Tanshinone IIA pretreatment. Addition of Tanshinone IIA significantly reduced MGO-induced cell apoptosis as shown by flow cytometry. On the molecular level, Tanshinone IIA administration altered the expression of apoptosis-related proteins such as p53, Bax, Bcl-2 and cyto C. In addition, MGO treatment remarkably increased the phosphorylation of MAPK family including p38, JNK and ERK. By contrast, addition of Tanshinone IIA inhibited the activation of MAPK family members.
CONCLUSIONS:
These data indicated that Tanshinone IIA could protect against MGO-induced cell injury through inhibiting MAPK activation in HBMEC.

Oncol Rep. 2009 Apr;21(4):1075-81.

Tanshinone IIA inhibits leukemia THP-1 cell growth by induction of apoptosis.[Pubmed: 19288011]

Tanshinone IIA, a diterpene quinone extracted from the traditional herbal medicine, Salvia miltiorrhiza Bunge, has been reported to have anti-tumor effects on a large variety of cancer cells. The present study was undertaken to investigate the in vitro antiproliferation and apoptosis inducing effects of Tanshinone IIA on leukemia THP-1 cell lines and its mechanisms of action.
METHODS AND RESULTS:
MTT assay was used to detect the cell growth inhibitory rate; cell apoptotic rate and the mitochondrial membrane potential (Deltapsim) were investigated by flow cytometry (FCM), apoptotic morphology was observed by Hoechst 33258 staining and DNA fragmentation analysis. The expression of caspase-3 and different apoptosis modulators were analyzed by Western blotting. The results revealed that Tanshinone IIA inhibited the growth of THP-1 cells and caused significant apoptosis, the suppression was both in time- and dose-dependent manner. After treatment by Tanshinone IIA for 48 h, the percentage of disruption of Deltapsim gradually increased in a dose-dependent manner along with marked changes of cell apoptosis. Western blotting showed cleavage of the caspase-3 zymogen protein (32-kDa) with the appearance of its 20-kDa subunit and a dose-dependent cleavage of PARP, with the appearance of 89-kDa fragment; The expression of Bcl-2 and survivin was down-regulated remarkably while Bax expression was up-regulated concurrently after the cells were treated with Tanshinone IIA for 48 h.
CONCLUSIONS:
We therefore conclude that Tanshinone IIA has significant growth inhibition effects on THP-1 cells by induction of apoptosis, and that Tanshinone IIA-induced apoptosis on THP-1 cells is mainly related to the disruption of Deltapsim and activation of caspase-3 as well as down-regulation of anti-apoptotic protein Bcl-2, survivin and up-regulation of pro-apoptotic protein Bax. The results indicate that Tanshinone IIA may serve as a potential anti-leukemia reagent.

Genet Mol Res. 2015 Mar 20;14(1):2133-8.

Effect of Tanshinone IIA intrathecal injections on pain and spinal inflammation in mice with bone tumors.[Pubmed: 25867360]

The study aimed to investigate the effect of intrathecal injections of Tanshinone IIA on thermal hyperalgesia in a mouse model of bone cancer-pain.
METHODS AND RESULTS:
Spinal IL-1β, IL-6, TNF-α expression levels were analyzed. C3H/HeNCrlVr male mice were assigned to groups that either received dose-dependent injections of Tanshinone IIA, or the DMSO + Sham, Tanshinone IIA + Sham, DMSO + Tumor, and Control groups. Paw withdrawal thermal latency (PWTL) was measured with a radiant heat stimulus and mRNA expression levels were determined using real-time PCR. Fourteen days post-injection, PWTL in the DMSO + Tumor group was lower than that in the controls (P < 0.05). Twenty-one days post-injection, compared with the Control group, there was no significant difference in PWTL and IL-1β, IL-6, and TNF-α expression levels between the Tanshinone IIA + Sham and DMSO + Sham groups (P > 0.05). PWTL in the DMSO + Tumor group was significantly lower than the Control group (P < 0.05), while the expression levels of IL-1β, IL-6, and TNF-α were significantly higher than controls. Compared with the DMSO + Tumor group, PWTLs were higher in the Tanshinone IIA - 20-μg and 40-μg groups, while expression levels of IL-1β, IL-6, and TNF-α were significantly lower (P < 0.05). These measures were not significantly different between the Tanshinone IIA 10 μg and the DMSO + Tumor groups (P > 0.05).
CONCLUSIONS:
In conclusion, Tanshinone IIA may inhibit the release of inflammatory cytokines, such as, IL-1 β, IL-6 α, TNF-α.