Abstract
Frailty develops due to multiple factors, such as sarcopenia, chronic pain, and dementia. Go-sha-jinki-Gan (GJG) is a traditional Japanese herbal medicine used for age-related symptoms. We have reported that GJG improved sarcopenia, chronic pain, and central nervous system function through suppression of tumor necrosis factor-alpha (TNF-α) production. In the present study, GJG was found to reduce the production of TNF-α in the soleus muscle of senescence-accelerated mice at 12weeks and 36weeks. GJG did not change the differentiation of C2C12 cells with 2% horse serum. GJG significantly decreased the expression of Muscle atrophy F-box protein (MAFbx) induced by TNF-α in C2C12 cells on real-time PCR. TNF-α significantly decreased the expression of PGC-1α and negated the enhancing effect of GJG for the expression of PGC-1α on digital PCR. Examining 20 chemical compounds derived from GJG, cinnamaldehyde from cinnamon bark and Chikusetsusaponin V (CsV) from Achyrantes Root dose-dependently decreased the production of TNF-⍺ in RAW264.7 cells stimulated by LPS. CsV inhibited the nuclear translocation of nuclear factor-kappa B (NF-κB) p65 in RAW264.7 cells. CsV showed low permeability using Caco-2 cells. However, the plasma concentration of CsV was detected from 30min to 6h and peaked at 1h in the CD1 (ICR) mice after a single dose of GJG. In 8-week-old SAMP8 mice fed 4% (w/w) GJG from one week to four weeks, the plasma CsV concentration ranged from 0.0500 to 10.0ng/mL. The evidence that CsV plays an important role in various anti-aging effects of GJG via suppression of TNF-⍺ expression is presented.
Highlights
Frailty is becoming one of the most important problems for clinical practice and public health in the world[1]
Examining 20 chemical compounds derived from GJG, cinnamaldehyde from cinnamon bark and Chikusetsusaponin V (CsV) from Achyrantes Root dose-dependently decreased the production of TNF-⍺ in RAW264.7 cells stimulated by LPS
Examining various chemical compounds derived from the component herbs of GJG, we found that Chikusetsusaponin V (CsV), which is derived from Achyranthes Root, dose-dependently decreased the production of TNF-⍺ and the NF-κB signaling pathway
Summary
Frailty is becoming one of the most important problems for clinical practice and public health in the world[1]. It is an urgent task to establish strategies against frailty to prevent an increase in the bedridden and nursing care population. The physical aspects of the frailty phenotype require attention. Frailty is thought to be multidimensional, involving both physical and psychosocial factors. As to the physical aspects of frailty, sarcopenia has been gaining attention. Sarcopenia is thought to be caused by a variety of factors, such as aging-related decreases in physical activity, in addition to changes in nutrient intake, hormones, and the inflammatory response[5]. With respect to the psychosocial aspects of frailty, depression and dementia induce withdrawal and loneliness, resulting in the development of sarcopenia[1]. Given the multidimensional aspects of frailty, new pharmacotherapies need to be developed
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