5‐Hydroxy‐7‐methoxyflavone derivatives from Kaempferia parviflora induce skeletal muscle hypertrophy

Skeletal muscle plays a critical role in locomotion and energy metabolism. Maintenance or enhancement of skeletal muscle mass contributes to the improvement of mobility and prevents the development of metabolic diseases. The extracts from Kaempferia parviflora rhizomes contain at least ten methoxyfl...

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Published in:Food science & nutrition 2019-01, Vol.7 (1), p.312-321
Main Authors: Ono, Shintaro, Yoshida, Naoki, Maekawa, Daisuke, Kitakaze, Tomoya, Kobayashi, Yasuyuki, Kitano, Takehiro, Fujita, Takanori, Okuwa‐Hayashi, Hirotaka, Harada, Naoki, Nakano, Yoshihisa, Yamaji, Ryoichi
Format: Article
Language:English
Subjects:
5‐hydroxy‐7‐methoxyflavone
Animal models
Aprotinin
Ca2
Calcium (extracellular)
Calcium (intracellular)
Calcium ions
Derivatives
Diet
Energy metabolism
Ethylenediaminetetraacetic acid
Exercise
Flavones
Glucose metabolism
Glycogen
Hydroxyl groups
Hypertrophy
Intracellular
Kaempferia
Kaempferia parviflora
Locomotion
Metabolic disorders
Metabolism
Mice
muscle hypertrophy
Muscles
Musculoskeletal system
Myotubes
Original Research
Physical fitness
Protein biosynthesis
Protein synthesis
Proteins
Rhizomes
Senescence
senescence‐accelerated mouse
Skeletal muscle
Soleus muscle
Type 2 diabetes
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Summary:Skeletal muscle plays a critical role in locomotion and energy metabolism. Maintenance or enhancement of skeletal muscle mass contributes to the improvement of mobility and prevents the development of metabolic diseases. The extracts from Kaempferia parviflora rhizomes contain at least ten methoxyflavone derivatives that exhibit enhancing effects on ATP production and glucose uptake in skeletal muscle cells. In the present study, we investigated the effects of ten K. parviflora‐derived methoxyflavone derivatives (six 5,7‐dimethoxyflavone (DMF) derivatives and four 5‐hydroxy‐7‐methoxyflavone (HMF) derivatives) on skeletal muscle hypertrophy. Murine C2C12 myotubes and senescence‐accelerated mouse‐prone 1 (SAMP1) mice treated with methoxyflavones were used as experimental models to determine the effects of HMF derivatives on myotube diameter and size and muscle mass. The four HMF derivatives, but not the six DMF derivatives, increased myotube diameter. The 5‐hydroxyflavone, 7‐methoxyflavone, and 5,7‐dihydroxyflavone had no influence on myotube size, a result that differed from HMF. Dietary administration of the mixture composed of the four HMF derivatives resulted in increase in the soleus muscle size and mass in SAMP1 mice. HMF derivatives also promoted protein synthesis in myotubes, and treatment with the intracellular Ca2+ chelator BAPTA‐AM, which depletes intracellular Ca2+ levels, inhibited this promotion. Furthermore, BAPTA‐AM inhibited HMF‐promoted protein synthesis even when myotubes were incubated in Ca2+‐free medium. These results indicate that HMF derivatives induce myotube hypertrophy and that both the 5‐hydroxyl group and the 7‐methoxy group in the flavones are necessary for myotube hypertrophy. Furthermore, these results suggest that HMF‐induced protein synthesis requires intracellular Ca2+, but not extracellular Ca2+. The structure–activity relationship of the 5‐hydroxy and 7‐methoxy groups of the methoxyflavones was determined on the diameter of the short axis of myotubes and the expression level of myosin heavy chain (MyHC). 5‐Hydroxy‐7‐methoxyflavone (5‐OH‐7‐OCH3), but not 5,7‐dimethoxyflavone (5,7‐diOCH3), 5‐hydroxyflavone (5‐OH), 7‐methoxyflavone (7‐OCH3), and 5,7‐dihydroxyflavone (5,7‐diOH), increased the myotubes size and the expression level of MyHC.
ISSN:2048-7177
2048-7177
DOI:10.1002/fsn3.891