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Published on: April 28, 2016
Rikkunshito ameliorates the aging-associated decrease in ghrelin receptor reactivity via phosphodiesterase III
Hiroshi Takeda1, Shuichi Muto, Tomohisa Hattori
1Department of Pathophysiology and Therapeutics, Hokkaido University Faculty of Pharmaceutical Sciences, N12 W6, Kita-ku, Sapporo 060-0812, Japan. h_takeda@pharm.hokudai.ac.jp
Endocrinology
|November 13, 2009
Summary
Aging reduces food intake, causing anorexia. This study found rikkunshito, a Japanese medicine, combats this by inhibiting phosphodiesterase 3 (PDE3) in aged mice, restoring appetite.
Area of Science:
- Gerontology
- Neuroendocrinology
- Pharmacology
Background:
- Aging is linked to reduced food intake, known as anorexia of aging.
- Appetite regulation involves complex peripheral and central factors, including hormones and gene expression.
- Traditional Japanese medicines like rikkunshito may offer therapeutic potential for age-related conditions.
Purpose of the Study:
- To investigate age-related changes in appetite-regulating factors in mice.
- To determine the efficacy of rikkunshito in ameliorating age-related anorexia.
- To elucidate the molecular mechanisms underlying rikkunshito's effects on appetite.
Main Methods:
- Comparison of food intake, ghrelin/leptin levels, and gene expression in young (6-wk) and aged (75-wk) C57BL/6J mice.
- Administration of ghrelin, rikkunshito, phosphoinositide 3-kinase (PI3K) inhibitors, and phosphodiesterase 3 (PDE3) inhibitors.
- Analysis of rikkunshito's active components and their effects on PDE3.
Main Results:
- Aged mice exhibited significantly decreased food intake, lower fasting acylated ghrelin, and higher feeding leptin levels.
- Hypothalamic expression of appetite-related genes (preproghrelin, NPY, AgRP) was altered in aged mice.
- Ghrelin failed to stimulate appetite in aged mice, but PI3K and PDE3 inhibitors, along with rikkunshito, increased food intake.
- Rikkunshito's components inhibited PDE3 activity.
Conclusions:
- Aged mice develop anorexia due to dysregulated ghrelin secretion and central ghrelin resistance.
- Rikkunshito ameliorates aging-associated anorexia by inhibiting PDE3, suggesting a novel therapeutic strategy.
- Targeting PDE3 offers a potential pathway to manage age-related appetite decline.
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