Extracellular polysaccharides purified (Polycan) from Aureobasidium pullulans SM‑2001 improves pathophysiology of dystrophin-deficient mdx mice

Abstract

Background Duchenne muscular dystrophy is a hereditary muscular disease involving degeneration (i.e. atrophy and loss of muscle fibres) of skeletal muscles, including the diaphragm, and progressively severe functional decline. A previous study shows Polycan, a type of β-glucan derived from the black yeast Aureobasidium pullulans (SM-2001), promotes osteogenicity and bone loss, and possesses anti-inflammatory activity to induce inflammatory cytokines in human immune and cancer cells. Objective In this study, we evaluated changes in exercise load behaviour measurements and changes in muscle-related physiological indicators following oral administration of Polycan in mdx mice, an experimental animal model of Duchenne muscular dystrophy. Result In mdx mice, Polycan prevented weight loss and thickness of skeletal muscle. In addition, by monitoring increases in running time of mice on treadmills and performing a grip strength test, we confirmed reduced muscle function was recovered to some extent after administering Polycan to mdx mice. In addition, we confirmed that Polycan significantly altered mRNA expression in a concentration-dependent manner, whereby myogenic transcription factors (MyoD, Myf5 and Myogenin) increased and FoxO3α, MuRF1 and Atrogin-1 decreased. We aimed to investigate the mechanism of action in Polycan on energy metabolism of p-AMPK, SIRT1 and PGC1α with apoptosis expression levels as factors related to signalling pathways. Expression ratios of cleaved-caspase-3/caspase-3 and Bax/Bcl-2 in the Polycan extract-administered group increased compared with the control group. Conclusion These results demonstrate that Polycan can improve and protect muscle atrophy by preventing apoptosis via pathway regulation related to myogenic transcription factors and energy metabolism in mdx mice.

Combined effect of polycan, a β-glucan from Aureobasidium pullulans, and regular resistance exercise on muscle strength, biomarkers, and fitness profiles in adults with relatively low skeletal muscle mass: a randomised controlled trial

“…As an extension of previous experimental and human pilot studies, 15,16,29,30 the present human study showed that APβG does not affect CK, IGF-1, and GH concentrations. Such differences compared to those reported in previous animal studies could be partly explained by the fact that the participants in this study were adults with relatively low skeletal muscle mass.…”

“…16 In another pilot study, β-glucan administration (2 g per day) for 4 weeks showed no difference in lower extremity muscle strength; however, it improved grip strength in professional table tennis players. 31 As an extension of previous experimental and human pilot studies, 15,16,29,30 the present human study showed that APβG does not affect CK, IGF-1, and GH concentrations. Such differences compared to those reported in previous animal studies could be partly explained by the fact that the participants in this study were adults with relatively low skeletal muscle mass.…”

“…15 The researchers further confirmed that APβG activated myogenic transcription (mRNA expression levels of Myf5, MyoD, myogenin, and MEF2) and inhibited muscle proteolytic factors (mRNA expression levels of FoxO3α, MuRF1, and atrogin-1), resulting in the improvement and protection of muscle atrophy in mdx (C57BL/10ScSn-Dmdmdx/J) mice models for Duchenne-type muscular dystrophy. 29 A previous pilot study 16 reported that the group administered a combination of high-dosage intake of APβG and resistance exercise group became more flexible than the control group. In addition, the 10 m obstacle walking time in the high-dose intake and resistance exercise group was shorter than that of the control group, and the grip strength of both hands in the group was higher than that of the control group at week 12.…”

“…13 The mechanism underlying the effects of β-glucan on muscle health has been reported in in vitro and animal models. 15,[27][28][29] Recently, Hwang et al 30 reported that APβG induced the suppression of C2C12 myotube atrophy by activating the phosphoinositide 3-kinase/protein kinase B pathway in in vitro models. In addition, APβG was observed to exhibit a potential for skeletal muscle-preserving therapy in dexamethasone-induced catabolic muscle atrophy by exhibiting the anti-inflammatory and antioxidant effects of APβG, which were mediated by upregulating the expression of genes related to muscle protein synthesis (Akt1, PI3K, A1R, and TRPV4) and inhibiting the expression of genes related to muscle protein degradation (atrogin-1, MuRF1, myostatin, and SIRT1) in mice.…”

Effect of Polycan, a β-Glucan from Aureobasidium pullulans SM-2001, on Inflammatory Response and Intestinal Barrier Function in DSS-Induced Ulcerative Colitis

“…This is because, unlike common β-1,3-glucan, β-1,3/1,6-glucan produced by A. pullulans has unique physiological activity not found in plant polymers and has comparable physical properties [14]. It effectively promotes bone formation and bone loss [15][16][17]. Recently, studies have shown that Polycan can reduce the expression of inflammatory cytokines in osteoarthritis models and atopy models [18].…”