In response to a growing trend towards health consciousness in recent years, an increasing number of persons are engaging in aerobic exercise training in order to eliminate obesity and other lifestyle diseases, and there is a growing understanding and awareness of recovery from muscle fatigue and other physiological effects on the body imparted by nutritional supplements taken before, during and after exercise training not only among athletes, but also members of the general public as well. In view of these circumstances, there is a desire for the development of supplements that support improvement of muscle endurance and recovery from muscle fatigue in order to efficiently engage in aerobic exercise training.
However, muscle damage or muscle fatigue caused by excessive exercise loading as well as diseases attributable thereto have only been treated using methods involving recuperation or simply waiting for muscle to recover while engaging in light exercise or rehabilitation, and drugs used for this purpose merely consisted of the use of anti-inflammatory drugs, analgesics and poultices for the purpose of symptomatic treatment.
Muscle dystrophy is the generic term for a hereditary disease presenting with symptoms mainly consisting of progressive muscle weakness and atrophy caused by degeneration and necrosis of muscle fibers, and is currently categorized into more than ten types based on its mode of inheritance and clinical characteristics, examples of which include Duchenne type, Becker type, limb-girdle type, congenital type, distal type, facioscapulohumeral type and myotonic type. Among these, the number of patients of the Duchenne type is largest, and research has been conventionally proceeded mainly on the Duchenne type.
At present, an effective treatment for muscular dystrophy has not yet to be found with the exception of steroid therapy, and the only benefit from steroid therapy is extension of the workable period of about two years. In addition, rehabilitation for the purpose of delaying progression of symptoms and respiratory care through the use of a ventilator are considered to have important significance at the present time.
Damage occurs to the sarcolemma when muscle is subjected to an excessive load brought on by exercise or other mechanical stress. When the sarcolemma is damaged, Ca2+ present in extracellular fluid flows into the cells and is thought to accelerate the progression of muscle breakdown. Calpain-1 is known to be a proteolytic enzyme that is the key to the progression of muscle breakdown. Calpain-1 is a cysteine protease that is activated by Ca2+, and activated calpain-1 causes muscle breakdown by limited decomposition of cytoskeletal proteins such as α-spectrin. Under normal physiological conditions, since activation of calpain-1 is inhibited by an endogenous inhibitor thereof in the form of calpastatin, muscle breakdown is considered to occur following the loss of inhibition of calpain-1 activation by calpastatin (Non-Patent Document 1).
The mdx mice, a model mouse of Duchenne muscular dystrophy are known to exhibit increased activation of calpain-1, and calpain-1 levels are known to be increased in the skeletal muscle of Duchenne patients. Consequently, calpain inhibitors are being developed as therapeutic drugs for Duchenne muscular dystrophy. For example, activation of calpain in muscle tissue and muscle breakdown have been reported to be inhibited as a result of administering leupeptin, which is a protease inhibitor known to have an inhibitory action on calpain, to mdx mice by intramuscular injection (Non-Patent Document 1). Although calpain inhibitors are continuing to be developed, their development is on the decline due to serious problems with toxicity and adverse side effects.
Sarcopenia is characterized by progressive and systemic reductions in skeletal muscle mass and skeletal muscle strength accompanying physical disabilities or decreases in quality of life caused by such factors as aging. Reduced muscle mass due to aging has been reported to be caused by muscle breakdown (Non-Patent Document 2).
6-methylsulfinylhexyl isothiocyanate (abbreviated as 6-MSITC) is a type of aromatic essence contained in Japanese horseradish (Wasabia japonica), and has been previously determined to have anti-oxidative and anti-inflammatory actions (Non-Patent Documents 3 and 4).
Patent Document 1 suggests that 6-methylsulfinylhexyl isothiocyanate can be used to decrease muscle-related diseases such as myopathy, muscle atrophy, myoglobinuria, hypotonia, muscle pain or exercise tolerance related to mitochondrial dysfunction by adjusting the NAD(P)+/NAD(P)H ratio as a result of activating NAD(P)H:quinone oxidoreductase (NQO1) (Patent Document 1).
Patent Document 2 describes that 6-methylsulfinylhexyl isothiocyanate inhibits the production of TNF-α, and suggests that it can be used to treat muscle-related diseases such as dermatomyositis or polymyositis (Patent Document 2).
Patent Document 3 describes that 6-methylsulfinylhexyl isothiocyanate inhibits increases in the concentration of adrenocorticotropic hormone (ACTH) in the blood as well as increases in blood cytokine and chemokine levels following mental or physical stress loading, and suggests that it can be used to treat muscle-related diseases such as dermatomyositis, myocarditis, fasciitis or myasthenia gravis (Patent Document 3).
However, ω-methylsulfinylalkyl isothiocyanate has previously not been known to have an inhibitory action on muscle damage caused by exercise loading by inhibiting activation of calpain-1.
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