Identification of Molecules from Coffee Silverskin That Suppresses Myostatin Activity and Improves Muscle Mass and Strength in Mice

Abstract

Coffee has been shown to attenuate sarcopenia, the age-associated muscle atrophy. Myostatin (MSTN), a member of the TGF-β growth/differentiation factor superfamily, is a potent negative regulator of skeletal muscle mass, and MSTN-inhibition increases muscle mass or prevents muscle atrophy. This study, thus, investigated the presence of MSTN-inhibitory capacity in coffee extracts. The ethanol-extract of coffee silverskin (CSE) but not other extracts demonstrated anti-MSTN activity in a pGL3-(CAGA)12-luciferase reporter gene assay. CSE also blocked Smad3 phosphorylation induced by MSTN but not by GDF11 or Activin A in Western blot analysis, demonstrating its capacity to block the binding of MSTN to its receptor. Oral administration of CSE significantly increased forelimb muscle mass and grip strength in mice. Using solvent partitioning, solid-phase chromatography, and reverse-phase HPLC, two peaks having MSTN-inhibitory capacity were purified from CSE. The two peaks were identified as βN-arachinoyl−5-hydroxytryptamide (C20−5HT) and βN-behenoyl−5-hydroxytryptamide (C22−5HT) using mass spectrometry and NMR analysis. In summary, the results show that CSE has the MSTN-inhibitory capacity, and C20−5HT and C22−5HT are active components of CSE-suppressing MSTN activity, suggesting the potential of CSE, C20−5HT, and C22−5HT being developed as agents to combat muscle atrophy and metabolic syndrome.

Age Is Just a Number: Progress and Obstacles in the Discovery of New Candidate Drugs for Sarcopenia

“…Coffee silver skin (the thin layer that covers coffee seeds) is known to possess antioxidant and neuroprotective properties [152,153]. With the aim of characterizing novel natural products with the potential to treat sarcopenia, Kim et al applied activity-guided fractionation to coffee silver skin extracts [154]. Only the ethanol extract was effective at myostatin inhibition in a cell-based assay using HEK293 cells.…”

“…Further, 6-week-old ICR outbred male mice were orally administered the ethanol extract diluted in saline for 29 days, which produced increases in grip strength and forelimb muscle mass (calculated by subtracting bone mass from the weight of the forelimbs). Solvent partitioning, chromatography, and HPLC were used in conjunction with the myostatin inhibition assay to characterize two active compounds in the extract: β N-arachinoyl-5-hydroxytryptamide and β N-behenoyl-5-hydroxytryptamide [154].…”

Toxicological Assessment of Roasted Coffee Silver Skin (Testa of Coffea sp.) as Novel Food Ingredient

“…Kim et al [ 83 ] investigated the effect of silver skin extract on muscle growth. They administered the extract to mice for 29 days orally.…”