Effects of Rhizome Extract of Dioscorea batatas and Its Active Compound, Allantoin, on the Regulation of Myoblast Differentiation and Mitochondrial Biogenesis in C2C12 Myotubes

Junnan Ma,Xianglong Meng,An Na Kang,Seok Yong Kang,Jong Hun Park,Hyo Won Jung,Yong-Ki Park

doi:10.3390/molecules23082023

Abstract

With the aging process, a loss of skeletal muscle mass and dysfunction related to metabolic syndrome is observed in older people. Yams are commonly use in functional foods and medications with various effects. The present study was conducted to investigate the effects of rhizome extract of Dioscorea batatas (Dioscoreae Rhizoma, Chinese yam) and its bioactive compound, allantoin, on myoblast differentiation and mitochondrial biogenesis in skeletal muscle cells. Yams were extracted in water and allantoin was analyzed by high performance liquid chromatography (HPLC). The expression of myosin heavy chain (MyHC) and mitochondrial biogenesis-regulating factors, peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), sirtuin-1 (Sirt-1), nuclear respiratory factor-1 (NRF-1) and transcription factor A, mitochondrial (TFAM), and the phosphorylation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) were determined in C2C12 myotubes by reverse transcriptase (RT)-polymerase chain reaction (RT-PCR) or western blot. The glucose levels and total ATP contents were measured by glucose consumption, glucose uptake and ATP assays, respectively. Treatment with yam extract (1 mg/mL) and allantoin (0.2 and 0.5 mM) significantly increased MyHC expression compared with non-treated myotubes. Yam extract and allantoin significantly increased the expression of PGC-1α, Sirt-1, NRF-1 and TFAM, as well as the phosphorylation of AMPK and ACC in C2C12 myotubes. Furthermore, yam extract and allantoin significantly increased glucose uptake levels and ATP contents. Finally, HPLC analysis revealed that the yam water extract contained 1.53% of allantoin. Yam extract and allantoin stimulated myoblast differentiation into myotubes and increased energy production through the upregulation of mitochondrial biogenesis regulators. These findings indicate that yam extract and allantoin can help to prevent skeletal muscle dysfunction through the stimulation of the energy metabolism.

Highlights

Dietary glucose is supplied by meals, and glucose is stored as glycogen in the liver, kidney, and muscle to enable metabolic energy function [1]
We observed myosin heavy chain (MyHC) expression in C2C12 myotubes using immunocytochemistry (Figure 1C), which revealed that MyHC-positive myotubes with an elongated and widened cylinder-shape and multiple nuclei were present in greater numbers in yam extract and allantoin-treated cells than non-treated cells
Metformin-treated cells as a positive control group were shown to exhibit an increase of MyHC. Expression, but this was lower than for treatment with yam extract or allantoin. These results indicate that yam extract and allantoin can induce myoblast differentiation into myotubes in skeletal muscle cells

Summary

Introduction

Dietary glucose is supplied by meals, and glucose is stored as glycogen in the liver, kidney, and muscle to enable metabolic energy function [1]. Skeletal muscle function deficit, in particular, age-related and disease-related muscle loss, is associated with. Molecules 2018, 23, 2023 many chronic diseases including sarcopenia, diabetes and obesity [3]. Such conditions are still difficult to control because causes of muscle loss are multifactorial and influenced by genetics. Natural dietary compounds have gained increasing attention as adjuvant therapy due to their relative low toxicity and synergistic effects with current chemotherapeutic agents [19]

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Discussion

Conclusion