Disuse muscle atrophy-improving effect of ninjin'yoeito in a mouse model

Takemoto, Risa; Sejima, Takehiro; Han, Li; Michihara, Seiwa; Takahashi, Ryuji

doi:10.1016/j.npep.2021.102199

Cited by 5 publications

(5 citation statements)

References 14 publications

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“…But, in this experiment, the change over time in body weight of the 5% NYT group was not different from that of the NT group or showed an increasing trend, and spontaneous locomotion and survival rates were similar, suggesting that the 5% NYT concentration is not optimal but is not toxic. In contrast, in our previous study of disuse muscle atrophy of C57BL/6, which is a background of kl/kl, a 5% NYT concentration was more effective than 3% NYT concentration (Takemoto et al, 2021). Which concentration is the optimal treatment dose against the frailty?…”

Section: Discussionmentioning

confidence: 64%

“…The 1% NYT group showed no change trend from NT in survival rate, so the 3% and 5% concentrations were selected. In addition, in our previous study on NYT for disuse muscle atrophy (Takemoto et al, 2021), a 5% NYT concentration of mixed feed was more effective than 3%, and other studies have reported that 3% NYT was effective in maintaining muscle and alveolar integrity in COPD Model Mice (Miyamoto et al, 2020). The kl/kl mouse is a model that exhibits emphysema, which also led us to select these two doses.…”

Section: Discussionmentioning

confidence: 97%

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Impact of Ninjin’yoeito on frailty and short life in klotho-hypomorphic (kl/kl) mice

Amitani

Chiba²,

Amitani³

et al. 2022

Front. Pharmacol.

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With the recent aging of society, the prevention of frailty has become an important issue because people desire both a long and healthy lifespan. Klotho-hypomorphic (kl/kl) mice are known to show phenotypes of premature aging. Ninjin’yoeito (NYT) is a traditional Japanese Kampo medicine used to treat patients with vulnerable constitution, fatigue or physical exhaustion caused by aging and illness. Recent studies have reported the potential efficacy of NYT against frailty. We therefore evaluated the effect of NYT on the gait function, activity, the histopathological status of organs and survival using kl/kl mice as a model of aging-related frailty. Two sets of 28-day-old male kl/kl mice were assigned to the vehicle (non-treated; NT), 3% or 5% NYT dietary groups. One set of groups (NT, n = 18; 3% NYT, n = 11; 5% NYT, n = 11) was subjected to the analysis of free walking, rotarod, and spontaneous activity tests at approximately 58 days old. Thereafter, we measured triceps surae muscles weight and myofiber cross-sectional area (CSA), and quantified its telomere content. In addition, we evaluated bone strength and performed histopathological examinations of organs. Survival was measured in the second set of groups (NT, 3% NYT and 5% NYT group, n = 8 each). In the walking test, several indicators such as gait velocity were improved in the NYT 3% group. Similar results were obtained for the latency to fall in the rotarod test and spontaneous motor activity. Triceps muscle mass, CSA and its telomere content were significantly improved in the NYT 3% group. Bone density, pulmonary alveolus destruction and testicular atrophy were also significantly improved in the NYT 3% group. Survival rate and body weight were both significantly improved in the NYT3% group compared with those in the NT group. Continuous administration of NYT from the early stage of aging improved not only gait performance, but also the survival in the aging-related frailty model. This effect may be associated with the improvements in aging-related organ changes such as muscle atrophy. Intervention with NYT against the progression of frailty may contribute to a longer, healthier life span among the elderly individuals.

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Section: Discussionmentioning

confidence: 64%

Section: Discussionmentioning

confidence: 97%

Impact of Ninjin’yoeito on frailty and short life in klotho-hypomorphic (kl/kl) mice

Amitani

Chiba²,

Amitani³

et al. 2022

Front. Pharmacol.

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“…Previous studies indicated that NYT exerted ghrelinneuropeptide Y (NPY) pathway-mediated appetiteenhancing effects [81][82][83] and increased blood albumin levels [84], thereby improving the nutritional state. Experiments using older mice and mouse aging models revealed that NYT inhibited muscle strength [85][86][87] and volume loss [85,88], and also prevented muscular telomere shortening [85]. Muscle protein synthesis was promoted and degradation was inhibited.…”

Section: Physical Frailtymentioning

confidence: 99%

“…Muscle protein synthesis was promoted and degradation was inhibited. NYT has been suggested to inhibit muscle volume loss through the Akt/mTOR pathway-mediated hyperphosphorylation of 4E-BP1 (muscle protein synthesis) and FoxO1-mediated Atrogin-1 (muscle protein degradation) [85,88] (Figure 3). A recent study reported that FoxO is essential in sarcopenia [89].…”

Section: Physical Frailtymentioning

confidence: 99%

Review of frequently used Kampo prescriptions: Part 4, Ninjin'yoeito

Takayama,

Michihara,

Kimura

et al. 2023

Traditional & Kampo Medicine

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BackgroundThe source of ninjin'yoeito (NYT) is considered the ‘Formulary of Bureau of Taiping People's Welfare Pharmacy’, written around 1241–52 AD. NYT is used to treat patients with chronic fatigue, malaise with qi deficiency, and exhaustion of all five parenchymatous viscera with difficulty in recovering.Key FindingsNYT formula consists of 12 crude drugs. NYT extract for medical use is covered by the National Health Insurance system of Japan for convalescence after recovery from diseases, fatigue and malaise, anorexia, perspiration during sleep, cold limbs, and anemia. Studies have shown clinical effects of NYT: treatment of anemia, cancer treatment support, frailty, cognitive dysfunction, apathy, fatigue/malaise, anorexia, and lung diseases. Preclinical studies support clinical studies; activating ghrelin‐neuropeptide Y pathway‐mediated appetite‐enhancing effects, inhibiting muscle volume loss through the Akt/mTOR pathway‐mediated hyperphosphorylation of 4E‐BP1 and FoxO1‐mediated Atrogin‐1, suppressing the hypothalamic–pituitary–adrenal axis by downregulating the sympathetic‐adrenal‐medullary axis and GABA neurons for improving sociability, promoting recovery from skeletal muscle atrophy through the activation of PGC‐1α, hematopoiesis‐promoting effects, and increasing the number of immune cells in immunocompromised models. The incidence of adverse events of NYT was reported as 3.09 or 2.03%. The most significant adverse effects of NYT are gastrointestinal disorders.ConclusionRecently, NYT has been widely used to treat several symptoms and conditions under the National Health Insurance System of Japan. Clinical studies showed the efficacy of NYT to treat anemia, frailty, cognitive dysfunction, anorexia, apathy, and fatigue/malaise, as well as for long‐term cancer treatment support. The pharmacological mechanisms supporting its effects are also being reported.

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“…Clinical trials have reported that NYT is effective on several conditions related to aging, such as decreased muscle strength, deterioration of muscle quality, and muscle atrophy ( Sakisaka et al, 2017 ; Naoya et al, 2018 ). We have previously reported that NYT exerted an anti-muscle atrophy action in a variety of experimental animal models ( Takahashi et al, 2018 ; Takemoto et al, 2021 ). It has also been reported that NYT was beneficial in an autoimmune disease model ( Nakai et al, 1993 ).…”

Section: Introductionmentioning

confidence: 97%

Ninjin’yoeito suppressed the onset of arthritis, pain, and muscle atrophy in rheumatoid arthritis model mice

et al. 2022

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Rheumatoid arthritis is one of the most common diseases in orthopedic surgery. The main symptoms are joint pain and systemic symptoms. In recent years, rheumatoid arthritis is known to cause sarcopenia. Ninjin’yoeito (NYT), a traditional Japanese medicine, has been prescribed for patients with post-illness or post-operative weakness, fatigue, loss of appetite, rash, cold limbs, and anemia. In addition to its traditional use, NYT has been prescribed for treating frailty in gastrointestinal, respiratory, and urinary functions. Further, NYT is known to be effective in suppressing muscle atrophy in the prior literature. The present study aimed to investigate whether NYT suppresses various symptoms of the Collagen-induced arthritis (CIA) model. Long-term administration of NYT inhibited the increases in arthritis scores, decreases pain threshold, and muscle atrophy in the CIA model. In addition, NYT inhibited the elevation of the plasma IL-6 level. These results suggest that NYT may have therapeutic effects on symptoms, muscle atrophy and increase in plasma IL-6 level caused by rheumatoid arthritis.

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Disuse muscle atrophy-improving effect of ninjin'yoeito in a mouse model

Cited by 5 publications

References 14 publications

Impact of Ninjin’yoeito on frailty and short life in klotho-hypomorphic (kl/kl) mice

Impact of Ninjin’yoeito on frailty and short life in klotho-hypomorphic (kl/kl) mice

Review of frequently used Kampo prescriptions: Part 4, Ninjin'yoeito

Ninjin’yoeito suppressed the onset of arthritis, pain, and muscle atrophy in rheumatoid arthritis model mice

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