A good quality of life requires maintaining adequate skeletal muscle mass and strength, but therapeutic agents are lacking for this. We developed a bioassay-guided fractionation approach to identify molecules with hypertrophy-promoting effect in human skeletal muscle cells. We found that extracts from rosemary leaves induce muscle cell hypertrophy. By bioassay-guided purification we identified the phenolic diterpene carnosol as the compound responsible for the hypertrophy-promoting activity of rosemary leaf extracts. We then evaluated the impact of carnosol on the different signaling pathways involved in the control of muscle cell size. We found that activation of the NRF2 signaling pathway by carnosol is not sufficient to mediate its hypertrophy-promoting effect. Moreover, carnosol inhibits the expression of the ubiquitin ligase E3 Muscle RING Finger protein-1 that plays an important role in muscle remodeling, but has no effect on the protein synthesis pathway controlled by the protein kinase B/mechanistic target of rapamycin pathway. By measuring the chymotrypsin-like activity of the proteasome, we found that proteasome activity was significantly decreased by carnosol and Muscle RING Finger 1 inactivation. These results strongly suggest that carnosol can induce skeletal muscle hypertrophy by repressing the ubiquitin-proteasome system-dependent protein degradation pathway through inhibition of the E3 ubiquitin ligase Muscle RING Finger protein-1.

Lentinus edodes (shiitake) is an edible mushroom cultivated and marketed due to its nutritional and medicinal values. L. edodes is appreciated for its unique fragrant taste and its high dietetic potential. Its bioactive molecules explain its interest as medicinal mushroom. This mushroom can be grown using various substrates and culture conditions. Thus, our work focused on the comparison of chemical constituents (i.e., amino acids and ergosterol) of L. edodes fruit bodies cultivated in organic or nonorganic growing conditions in the French region of Occitanie. Sequential extraction was performed on freeze-dried fungal materials. Quantitative evaluation of amino acids was done using high performance thin layer chromatography. Assay of ergosterol was carried out using high performance liquid chromatography. For both ergosterol and amino acids, differences were highlighted between extracts (depending on the nature of the solvents) and between growing conditions (organic versus nonorganic). Extracts from organically produced shiitake contained the highest content of ergosterol, isoleucine and alanine. In conclusion, this work demonstrated that culture conditions influence the chemical profile of L. edodes as far as ergosterol and amino acids are concerned, which could improve nutrition and human health.

Propolis produced by honeybees, Apis mellifera, has been valued since ancient times as a remedy for different ailments for its broad medicinal properties. This wide range of biological activities may arise from the production of distinct propolis types within the hive, each serving specific functions and containing unique molecular compositions. In this study, we investigated the effects of four propolis types—masonry, sealing, brood-protection, and intruder-neutralizing—on hydrogen peroxide (H₂O₂)-induced oxidative injury in human skeletal muscle cells. Among these, only brood-protection propolis significantly prevented the H₂O₂-induced loss of cell viability. Bio-guided fractionation of this active propolis identified five major compounds: benzyl caffeate (BC), caffeic acid phenethyl ester (CAPE), cinnamyl caffeate (CC), prenyl caffeate (PC), and (E)-3-methyl-3-butenyl caffeate (MBC), all displaying stronger cytoprotective effects than their ferulate equivalents. We finally demonstrated that propolis extract and its active compounds reduced lipid peroxidation in post-mortem minced mouse skeletal muscle and compared their efficacy to other natural compounds. Chemical analysis of resins from neighboring flora suggested that black poplar (Populus nigra) buds are the primary botanical source of these caffeate derivatives. Collectively, these results highlight the functional diversity of hive propolis and its potential applications in food preservation as well as in complementary and preventive medicine.