Search

Go-sha-jinki-Gan (GJG) is a traditional Japanese herbal medicine. In clinical practice, GJG is effective against neuropathic pain and hypersensitivity induced by chemotherapy or diabetes. In our previous study using a chronic constriction injury mouse model, we showed that GJG inhibited microglia activation by suppressing the expression of tumor necrosis factor-α (TNF-α) and p38 mitogen-activated protein kinase (p38 MAPK) in the peripheral nervous system. To investigate whether GJG can suppress inflammation in the central nervous system (CNS) in the context of neurological disorders, we examined the effect of GJG on the activation of resident glial cells and on p38-TNF signaling in two mouse models of neurological disorders: the experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis and the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of Parkinson's disease. GJG administration relieved the severity of clinical EAE symptoms and MPTP-induced inflammation by decreasing the number of microglia and the production of TNF-α in the spinal cord of EAE mice and the substantia nigra of MPTP-treated mice. Accordingly, GJG suppressed the phosphorylation of p38 in glial cells of these two mouse models. We conclude that GJG attenuates inflammation of the CNS by suppressing glial cell activation, followed by a decrease in the production of TNF-α via p38-TNF signaling. [ABSTRACT FROM AUTHOR]

Sarcopenia is characterized by age-associated skeletal muscle atrophy and reduced muscle strength; currently, no pharmaceutical treatment is available. Go-sha-jinki-Gan (GJG) is a traditional Japanese herbal medicine that is used to alleviate various age-related symptoms, especially motor disorders. Here, we investigated the effect of GJG on aging-associated skeletal muscle atrophy by using senescence-accelerated mice (SAMP8). Immunohistochemical and western blotting analyses clearly showed that GJG significantly reduced the loss of skeletal muscle mass and ameliorated the increase in slow skeletal muscle fibers in SAMP8 mice compared to control mice. The expression levels of Akt and GSK-3β, the phosphorylation of FoxO4, and the phosphorylations of AMPK and mitochondrial-related transcription factors such as PGC-1α were suppressed, while the expression of MuRF1 increased in SAMP8 mice, but approximated that in senescence-accelerated aging-resistant (SAMR1) mice after GJG treatment. We demonstrate for the first time that GJG has a therapeutic effect against sarcopenia. [ABSTRACT FROM AUTHOR]

• Go-sha-jinki-Gan (GJG), a traditional Japanese herbal medicine, reduce the production of TNF-α in the soleus muscle of senescence-accelerated mice. • Cinnamaldehyde and Chikusetsusaponin V (CsV) derived from GJG dose-dependently decreased the production of TNF-⍺ in RAW264.7 cells. • CsV inhibited the nuclear translocation of nuclear factor-kappa B (NF-κB) p65 in RAW264.7 cells. • In 8-week-old SAMP8 mice fed 4% GJG from one week to four weeks, the plasma CsV concentration were detected. 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 12 weeks and 36 weeks. 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 30 min to 6 h and peaked at 1 h 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 10.0 ng/mL. The evidence that CsV plays an important role in various anti-aging effects of GJG via suppression of TNF-⍺ expression is presented. [ABSTRACT FROM AUTHOR]

• Frailty is a decrease in multiple functions associated with aging. • Frailty can be prevented or improved by early diagnosis and intervention. • A simple screening tool for frailty was created based on concepts of Kampo medicine. Frailty is one of the most important problems in a super-aged society. It is necessary to identify frailty quickly and easily at the bedside. We developed a simple patient-reported frailty screening scale, the Japan Frailty Scale (JFS), based on the aging concept of Kampo medicine. Eight candidate questions were prepared by Kampo medicine experts, and a simple prediction model was created in the development cohort (n = 434) and externally validated in an independent validation cohort (n = 276). The physical indicators and questionnaires associated with frailty were also comprehensively evaluated. The reference standard for frailty or pre-frailty was determined based on the Kihon checklist. In the development cohort, four questions, nocturia (0–2), lumbago (0–2), cold sensitivity (0–2), exhaustion (0–4), and age (0–1) were selected by multivariable logistic regression analysis. The total JFS score is 0–11. Receiver-operating characteristic curve analysis of the JFS for identifying frailty status showed moderately good discrimination (area under the curve (AUC) = 0.78, 95 % confidence interval (CI): 0.73–0.82). At the JFS cutoff value of 3/4 for frailty or pre-frailty, the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 86.9 %, 53.3 %, 62.8 %, and 81.7 %, respectively. External validation of the JFS showed moderately good discrimination (AUC = 0.76, 95 % CI: 0.70–0.81). The sensitivity, specificity, PPV, and NPV were 79.9 %, 61.4 %, 69.3 %, and 73.7 %, respectively. These results indicate that the JFS is a promising patient-reported clinical scale for early identification of pre-frail/frail patients at the bedside in primary care. [ABSTRACT FROM AUTHOR]