TY - JOUR
T1 - Effects of rikkunshito supplementation on resistance to oxidative stress and lifespan in mice
AU - Wang, Zi
AU - Komatsu, Toshimitsu
AU - Ohata, Yoshihisa
AU - Watanabe, Yukari
AU - Yuan, Yiwen
AU - Yoshii, Yuki
AU - Park, Seongjoon
AU - Mori, Ryoichi
AU - Satou, Motoyasu
AU - Kondo, Yoshitaka
AU - Shimokawa, Isao
AU - Chiba, Takuya
N1 - Funding Information:
The work was supported by Grants‐in‐Aid for Scientific Research from the Japan Society for the Promotion of Science (TK, no. 22790620; TC, nos. 24659181 and 25282027) and Waseda University IBUKA Foundation (TC). The work was supported by a Grant‐in‐Aid for the Cooperative Research Project from Institute of Natural Medicine, University of Toyama in 2010. We are grateful to the staff at the Laboratory Animal Center for Biomedical Research at the Center for Frontier Life Sciences, Nagasaki University for their animal care and technical assistance. We thank Maho Kumagai, Yutaka Araki, Yuko Moriyama and Rieko Tahara for their excellent technical assistance. We thank Edanz Group ( www.edanzediting.com/ac ) for editing a draft of this manuscript.
Funding Information:
The work was supported by Grants-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (TK, no. 22790620; TC, nos. 24659181 and 25282027) and Waseda University IBUKA Foundation (TC). The work was supported by a Grant-in-Aid for the Cooperative Research Project from Institute of Natural Medicine, University of Toyama in 2010. We are grateful to the staff at the Laboratory Animal Center for Biomedical Research at the Center for Frontier Life Sciences, Nagasaki University for their animal care and technical assistance. We thank Maho Kumagai, Yutaka Araki, Yuko Moriyama and Rieko Tahara for their excellent technical assistance. We thank Edanz Group (www.edanzediting.com/ac) for editing a draft of this manuscript.
PY - 2020/3/1
Y1 - 2020/3/1
N2 - Aim: Caloric restriction (CR), which limits the caloric intake to 60–70% of ad libitum (AL) amounts in various experimental animals, delays aging and extends the lifespan. We previously showed that neuropeptide Y (NPY), an appetite-stimulating peptide, is essential for the anti-oxidative and life-extending effects of CR. Here, we investigated whether a Japanese traditional herbal medicine, rikkunshito (RKT), which induces NPY activation, has CR-like life-extending effects. Methods: First, we evaluated the life-extending activity of RKT by examining the effect of long-term RKT administration on wild-type and NPY knockout mice. Furthermore, we tested whether RKT enhances CR-mediated beneficial effects under AL conditions with a normal diet and under mild CR conditions with a high-fat diet. We then used 3-nitropropionic acid or doxorubicin to induce oxidative stress, and analyzed the differences in survival rate, weight loss, gene expression and cellular oxidative damage among groups. Results: RKT administration did not extend the lifespan of wild-type or NPY knockout mice. In the oxidative stress models, RKT treatment upregulated anti-oxidative gene expression in the liver. Furthermore, RKT administration reduced the oxidative damage in the liver compared to the CR conditions alone. However, on induction of oxidative stress by 3-nitropropionic acid or doxorubicin, RKT administration did not affect the survival rate. Conclusions: These results show that RKT administration only partially mimics the effects of CR at the cellular level, but not at the organismal level to increase the lifespan of mice. Geriatr Gerontol Int 2019; ••: ••–••.
AB - Aim: Caloric restriction (CR), which limits the caloric intake to 60–70% of ad libitum (AL) amounts in various experimental animals, delays aging and extends the lifespan. We previously showed that neuropeptide Y (NPY), an appetite-stimulating peptide, is essential for the anti-oxidative and life-extending effects of CR. Here, we investigated whether a Japanese traditional herbal medicine, rikkunshito (RKT), which induces NPY activation, has CR-like life-extending effects. Methods: First, we evaluated the life-extending activity of RKT by examining the effect of long-term RKT administration on wild-type and NPY knockout mice. Furthermore, we tested whether RKT enhances CR-mediated beneficial effects under AL conditions with a normal diet and under mild CR conditions with a high-fat diet. We then used 3-nitropropionic acid or doxorubicin to induce oxidative stress, and analyzed the differences in survival rate, weight loss, gene expression and cellular oxidative damage among groups. Results: RKT administration did not extend the lifespan of wild-type or NPY knockout mice. In the oxidative stress models, RKT treatment upregulated anti-oxidative gene expression in the liver. Furthermore, RKT administration reduced the oxidative damage in the liver compared to the CR conditions alone. However, on induction of oxidative stress by 3-nitropropionic acid or doxorubicin, RKT administration did not affect the survival rate. Conclusions: These results show that RKT administration only partially mimics the effects of CR at the cellular level, but not at the organismal level to increase the lifespan of mice. Geriatr Gerontol Int 2019; ••: ••–••.
KW - calorie restriction
KW - ghrelin
KW - longevity
KW - metabolism
KW - oxidative stress
UR - http://www.scopus.com/inward/record.url?scp=85077025839&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85077025839&partnerID=8YFLogxK
U2 - 10.1111/ggi.13848
DO - 10.1111/ggi.13848
M3 - Article
C2 - 31855319
AN - SCOPUS:85077025839
VL - 20
SP - 238
EP - 247
JO - Geriatrics and Gerontology International
JF - Geriatrics and Gerontology International
SN - 1447-0594
IS - 3
ER -