Testing anabolic activity, potency and mechanisms of action of the phyto-derived beta 2 agonist higenamine.
Study Goal
The researchers aimed to investigate the anabolic activity and molecular mechanisms of Higenamine in C2C12 myotubes, focusing on its potential performance-enhancing effects.
Results Summary
Higenamine significantly increased myotube diameters and stimulated mRNA expression of hypertrophy-related genes. Its effects were antagonized by ER and AR inhibitors but not by an ADRB2 inhibitor, suggesting interactions with AR and ER pathways rather than β2-adrenoceptor activation.
Population
Differentiated C2C12 myotubes (in vitro cell model).
Effective Dosage
Dose-dependent effects were analyzed, but specific dosage amounts are not provided.
Duration
Not specified.
Interactions
Antagonistic activity with AR and ER; potential cross-talk with these receptors.
| Intervention | Direction | Endpoint | Population | Dosage | Impact | Claim # |
|---|---|---|---|---|---|---|
Higenamine (Hige) | increase | myotube diameters | C2C12 myotubes | - | significantly increased | #1 |
Higenamine (Hige) | increase | mRNA expression of hypertrophy-involved genes | C2C12 myotubes | - | stimulated | #2 |
ER inhibitor ZK 191703 | decrease | Hige-induced increase of myotube diameter | C2C12 myotubes | - | were able to antagonize | #3 |
AR inhibitor Flutamide (Flu) | decrease | Hige-induced increase of myotube diameter | C2C12 myotubes | - | were able to antagonize | #4 |
dexamethasone (Dexa) | decrease | Hige-induced increase of myotube diameter | C2C12 myotubes | - | were able to antagonize | #5 |
ADRB2 inhibitor (ICI 118551) | no change | Hige-induced increase of myotube diameter | C2C12 myotubes | - | In contrast to | #6 |
Higenamine (Hige) | decrease | AR and ER yeast transactivation assay | yeast transactivation assay | - | has antagonistic activity | #7 |
Higenamine (Hige), a plant derived alkaloid is classified as β2 agonist by the World Anti-Doping Agency (WADA). However, pharmacologic mechanisms of its performance-enhancing activity have not been investigated so far. Therefore, we investigate the anabolic activity and associated molecular mechanisms of Hige in C2C12 myotubes. In differentiated C2C12 cells dose-dependent effects of Hige on myotube size were analyzed. The mRNA expression of genes involved in hypertrophy was measured. For mechanistic studies, β2-adrenoceptor (ADRB2), androgen receptor (AR), and estrogen receptor (ER) inhibitors and dexamethasone (Dexa) were co-incubated and myotube diameter was evaluated. The interaction of Hige with the AR and ER was investigated. Hige treatment significantly increased myotube diameters and stimulated the mRNA expression of hypertrophy-involved genes. In contrast to the ADRB2 inhibitor (ICI 118551), the ER inhibitor ZK 191703, the AR inhibitor Flutamide (Flu), and treatment with Dexa were able to antagonize the Hige-induced increase of myotube diameter. Hige has antagonistic activity in the AR and ER yeast transactivation assay. Our results demonstrate that Hige induces anabolic effects in C2C12 cells but not via the ADRB2. There are indications for a cross talk between Hige and the AR and ER. Future studies are necessary to investigate the involved molecular mechanisms.