Updated: Nov 8, 2019
Urolithin B enhances the growth, and differentiation of C2C12 myotubes via increasing protein synthesis and repressing a certain pathway known as the ubiquitin-proteasome pathway.
It has been hypothesised and supported by certain tests that an implication of the androgen receptor is responsible for some of the effects of Urolithin B.
Signalling analysis suggests a crosstalk between the androgen receptor (AR) and the mTORC1 pathway, possibly via the AMPK pathway.
Experiments, in vivo, confirm that Urolithin B induces muscle hypertrophy in mice and reduces muscle atrophy.
Urolithin B Stimulates Muscle Protein Synthesis:
For the in-vivo experiments, mice were implanted with mini-osmotic pumps delivering 10 μg/day continuously of urolithin B for 28 days.
Muscle atrophy was studied in mice with a sciatic nerve denervation receiving urolithin B in the same way.
Myotubes were incubated with different urolithin concentrations for 24 hours and evaluated the impact of each treatment on their size. They was never affected in the presence of Urolithin A, whereas the low doses of Urolithin B increased the diameter of myotubes.
The most effective concentration was identified at 15 μM, as the effect disappeared with higher doses, which confirms the anabolic properties of urolithin B in myotubes.
The higher fusion index (+16.3%) indicated an enhanced fusion capability of the cells. The up-regulation of the myogenic factor named Myogenin and the marker of differentiation, named Desmin, after 5 days, confirmed the stimulation of cell differentiation in the presence of urolithin B.
To test the hypothesis that Urolithin B stimulates muscle anabolism, we investigated the Akt/mTORC1 pathway.
When Akt is activated, it phosphorylates the mTORC1 complex. 4E-BP1, a repressor of mRNA translation, is then phosphorylated and inactivated by mTORC1.
S6K1 is another downstream target of mTORC1 that is a kinase for the ribosomal protein rpS6.
The phosphorylation of S6K1 correlates with an increase in the translation of mRNA transcripts. There wasn't any change in the phosphorylation of Akt with urolithin B.
Nevertheless, the phosphorylation of mTOR, rpS6, and 4E-BP1 were higher, rapamycin, a well known inhibitor of mTORC1, completely blunted the effects. These results suggest that the mTORC1 pathway was activated independently of Akt in response to urolithin B.
Urolithin B Decreases Muscle Protein Breakdown:
The Akt/mTORC1 pathway regulates two proteolytic systems in muscle cells, the ubiquitin-proteasome and the autophagy-lysosomal pathways.
Akt prevents the nuclear translocation of the forkhead box factors 1 and 3a (FoxO1 and 3a) by phosphorylating multiple sites.
FoxOs are a transcription factor regulating the expression of the muscle-specific ligases MAFbx and MuRF1, which are induced during situations of muscle atrophy.
The phosphorylated form of FoxO1 and 3a were not modified by urolithin B. However, there was a significant reduction of total FoxO3a.
It was also found that the mRNA coding for FoxO1 and FoxO3, as well as mRNA levels for MAFbx and MuRF1 were decreased by Urolithin B. Immunoblotting using an anti-P4D1 antibody also showed a lower amount of ubiquitinated proteins in cells exposed to Urolithin B.
This strongly suggests a lower activity of the ubiquitin–proteasome system in myotubes exposed to urolithin B, these results show that the faster growth of myotubes exposed to Urolithin B is due to higher protein synthesis as well as reduced activity of the ubiquitin–proteasome system, meaning reduced protein breakdown.
The Effects Of Urolithin B Are Mediated By The Androgen Receptor (AR):
Because previous studies showed a link between the androgen receptor (AR) and the mTORC1 pathway which provided evidence for the anti-aromatase properties of urolithin B, it was hypothesised that Urolithin B induces hypertrophy in myogenic cells via the activation of the AR.
Thus, the AR was inactivated genetically by using a set of specific small interfering RNA (siRNAs) and pharmacologically by using a chemical called bicalutamide.
Interestingly, siRNAs totally blocked the hypertrophy induced by both testosterone (and other androgens) and also urolithin B, providing evidence for the implication of the AR in the enhanced growth of myotubes exposed to the Urolithin B supplement.
Muscle Protective Effects Of Urolithin B:
As urolithin B induces muscle hypertrophy, it was hypothesised that this compound could also have a muscular protective effect during atrophy.
Female mice were denervated by transecting the left sciatic nerve and were simultaneously implanted with a mini-osmotic pump delivering Urolithin B (10 μg/day).
After 7 days, the muscle weights were compared between the groups and it was shown that Urolithin B reduced muscle atrophy during denervation.
In order to understand the mechanisms leading to the protective effects of Urolithin B, we performed histological and biochemical analyses in specific muscles.
Urolithin B prevented a decrease in the cross-sectional area of the fibres of denervated TIB muscles.
Collectively, this data indicates that Urolithin B reduces denervation-induced muscle atrophy, indicating a muscle protective effect.
Anti-Aromatase Activity Of Urolithin B:
Urolithin B was also identified as an inhibitor of aromatase and thereby the conversion of testosterone into estradiol. In agreement with this study, we observed a lower level of aromatase in animals having received Urolithin B.
To assess the impact of low aromatase levels on the androgen status of the animals, we measured plasma testosterone. However, plasma testosterone was decreased after 3 days and unchanged after 7 days of treatment with Urolithin B, suggesting that the inhibition of aromatase is likely not the major molecular event in the regulation of muscle mass induced by Urolithin B.
Most people usually take a dosage of around 150mg Urolithin B, in its extracted form, two times a day, however some may take this in higher dosages safely, my recommendation is to not go over 150mg four times a day!
A lot of my information has come from this study.
Overall, similarly to Ursolic Acid, Urolithin B may be a powerful addition to your supplement stack as a natural anabolic for building muscle!
Urolithin B's Benefits:
Stimulates Muscle Protein Synthesis
Reduces Muscle Protein Breakdown
May Have Muscle Protective Effects
May Have Anti-Aromatase Properties
So, there you have it! Another article explaining the benefits of Urolithin B. For more articles visit my articles page on this website!