Gosha-jinki-Gan (GJG) shows anti-aging effects through suppression of TNF-α production by Chikusetsusaponin V.

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 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.

• Authors: Keisuke Hagihara, Kazuto Nunomura, Bangzhong Lin, Megumi Fumimoto, Junko Watanabe, Yasuharu Mizuhara
• Journal: Gene (Gene) Vol. 815 Pg. 146178 (Mar 20 2022) ISSN: 1879-0038 [Electronic] Netherlands
• PMID: 34995733 (Publication Type: Journal Article)
• Copyright: Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.

Chemical References

• Drugs, Chinese Herbal
• Muscle Proteins
• Saponins
• Transcription Factor RelA
• Tumor Necrosis Factor-alpha
• chikusetsusaponin V
• gosha-jinki-gan
• Fbxo32 protein, mouse
• SKP Cullin F-Box Protein Ligases

Topics

• Active Transport, Cell Nucleus (drug effects)
• Administration, Oral
• Aging (drug effects)
• Animals
• Dose-Response Relationship, Drug
• Drug Stability
• Drugs, Chinese Herbal (chemistry, pharmacology)
• Male
• Mice
• Mice, Inbred ICR
• Muscle Proteins (metabolism)
• Muscle, Skeletal (drug effects, metabolism)
• RAW 264.7 Cells
• SKP Cullin F-Box Protein Ligases (metabolism)
• Saponins (administration & dosage, blood, pharmacology)
• Solubility
• Transcription Factor RelA (metabolism)
• Tumor Necrosis Factor-alpha (metabolism, pharmacology)