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.
Highlights
Myostatin (MSTN), known as growth and differentiation factor-8 (GDF8), is mainly expressed in skeletal muscle and acts as a negative regulator of skeletal muscle growth in animals [1]
Our results show that ethanol extracts of coffee silverskin (CSE) suppressed MSTN activity, and its administration to mice increased muscle mass and grip strength along with a decrease in blood fatty acid concentration. βN-arachinoyl-5-hydroxytryptamide (C20-5HT) and βN-behenoyl-5-hydroxytryptamide (C22-5HT) were identified as the active constituents of CSE suppressing MSTN activity
This study first introduces a novel function of the ethanol extract of coffee silverskin (CSE)TbhyissshtouwdiynfgirtshtaitnCtrSoEdsuucpespraenssoevdelthfue naccttiivonityofofthMeSeTthNa,naopl oetxetnratcnteogfactiovfefereegsiulvlaetrosrkoinf sl(ouCkfceSilsEfeket)eraballeysmteasulrhesompcwloeuirsnmtceglaretsghsme.antTaeChssaeS.sEMsTasShuyTepwNpMarisenSshfTsuiNebrdtihtitonehrrheyicabcocainttpoifivarricytmiytyceoadofpfMbaCycSiStCTEyNSmEo, ’faesapCbsoluSotrEecekndmitnbnegyeagospuafGtrSiLevmd-e(aCrbdeAy3gGuppAlhaGo)t1Los2r-p(ChAorGyAla)t1i2onlu, caifcerritaiscealrceopmorptoernegnetnoef athsseacyanwoansicfaul rMthSeTrNcosnigfinramliendg bpyathCwSEa’ys
Summary
Myostatin (MSTN), known as growth and differentiation factor-8 (GDF8), is mainly expressed in skeletal muscle and acts as a negative regulator of skeletal muscle growth in animals [1]. MSTN plays an important role in the growth and maintenance of adult skeletal muscle mass [4,5]. Many studies have shown that suppressing MSTN activity using various approaches, such as administration of MSTNblocking proteins and peptides, delivery of MSTN-blocking genes, and RNAi method increases muscle mass in adult animals [10]. MSTN suppression improved the insulin sensitivity and whole-body metabolism accompanied by a decrease in fat mass in mice and pigs [17,18,19,20], indicating that MSTN plays a role in the regulation of muscle mass but, in the regulation of fat mass and energy metabolism
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