Sarcopenia is an age-related skeletal muscle atrophy. Exercise is effective in improving sarcopenia via two mechanisms: activation of skeletal muscle satellite cells (SCs) and stimulation of muscle protein synthesis. In contrast, most nutritional approaches for improving sarcopenia focus mainly on muscle protein synthesis, and little is known about SC activation. Here, we investigated the effect of lemon myrtle extract (LM) on SC activation both in vitro and in vivo. Primary SCs or myoblast cell lines were treated with LM or its derived compounds, and incorporation of 5-bromo-2′-deoxyuridine, an indicator of cell cycle progression, was detected by immunocytochemistry. We found that LM significantly activated SCs (p < 0.05), but not myoblasts. We also identified casuarinin, an ellagitannin, as the active compound in LM involved in SC activation. The structure–activity relationship analysis showed that rather than the structure of each functional group of casuarinin, its overall structure is crucial for SC activation. Furthermore, SC activation by LM and casuarinin was associated with upregulation of interleukin-6 mRNA expression, which is essential for SC activation and proliferation. Finally, oral administration of LM or casuarinin to rats showed significant activation of SCs in skeletal muscle (p < 0.05), suggesting that LM and casuarinin may serve as novel nutritional interventions for improving sarcopenia through activating SCs.

The essential oil or extract of Lemon myrtle (Backhousia citriodora F. Muell.), belonging to the family Myrtaceae and the genus Backhousia, exhibits anti-inflammatory and antioxidant properties. However, limited information exists on the safety of water extracts from its leaves. The present study aimed to assess the safety of lemon myrtle water extract as a functional food by performing genotoxicity studies and repeated-dose oral toxicity. Although the bacterial reverse mutation test (Ames test) yielded positive results, in vivo mammalian erythrocyte micronucleus and alkaline comet assays yielded negative results. In a 28-day oral toxicity study, the extract was orally administered to male and female Crl:CD rats at doses of 0, 250, 500, and 1000 mg/kg bw/day. Notably, the extract induced no adverse effects, and the no-observed-adverse-effect level was 1000 mg/kg bw/day in male and female rats. Despite its genotoxicity in vitro, the extract did not exhibit genotoxicity in vivo. Moreover, no signs of toxicity were observed in the general toxicity study. Overall, these results suggest that lemon myrtle water extract does not pose a substantive genotoxic risk at practical oral exposure levels.