Beneficial effects of horsetail (Equisetum arvense) in in vitro models of sarcopenia and osteoporosis

Sarcopenia, defined as loss of skeletal muscle mass (muscle atrophy) and strength with aging, is strictly connected to the decrease of bone mass (osteoporosis), predisposing to frailty, bone fractures and loss of personal independence in over-60s [1,2]. Due to the growing life expectancy, sarcopenia and osteoporosis represent primary social and financial problem for western countries [2,3]. The imbalance between myofibrillary protein breakdown (especially, type II myosin heavy chain, MyHC-II) and synthesis, and the excessive presence of osteoclasts, responsible of bone resorption [1-3], are recognized causes of the loss of muscle and bone tissues. Low-grade chronic inflammation and excessive treatment with glucocorticoids (GCs) are common processes underlying the pathogenesis of sarcopenia and osteoporosis [2,3]. Horsetail (Equisetum arvense) is traditionally recommended for the maintenance of bone homeostasis [4]. We tested a standardized dry extract of horsetail on well-characterized in vitro experimental models mimicking i) muscle atrophy, i.e., C2C12 myotubes treated with proinflammatory cytokines (TNFα/IFNγ) or excess GCs (dexamethasone, Dex) [1]; or ii) osteoclastogenesis, i.e., RAW 264.7 cells treated with RANKL [5]. We found that horsetail extract, not toxic for myotubes up to 600 μg/mL, protects myotubes against MyHC-II degradation under atrophying stimuli, as indicated by the analysis of myotube diameters and MyHC-II expression. Horsetail reduces the activity of the catabolic pathways, p38 MAPK and STAT3 in the presence of TNFα/IFNγ. Moreover, it blunts the activation of FoxO3a-dependent ubiquitin-proteasome system and the reduction of anabolic Akt-mTOR pathway in the presence of Dex. Interestingly, horsetail rescues MyHC-II expression and Akt activity in myotubes derived from muscle biopsies of sarcopenic subjects. When tested on RAW 264.7 cells, horsetail shows marked inhibition of RANKL-dependent osteoclast formation, as demonstrated by dose-dependent reduction of TRAP-positive cells and TRAP enzymatic activity, and by down-regulation of osteoclastogenic markers. Based on our results, horsetail is a promising source of active compounds to sustain muscle functionality and balanced bone remodelling in aged people and in diffuse atrophying conditions, improving the quality of life and reducing health-care costs.