Reversibility of sarcopenia by Ishige okamurae and its active derivative Diphloroethohydroxycarmalol: Aging rodent and human clinical study

Jimin Hyun, Jun-Geon Je, Sang-Woon Lee, and You-Jin Jeon*

Department of Marine Life Science, Jeju National University, Jeju 63243, Korea

*Corresponding author (You-Jin Jeon): Tel: +82-64-754-3475; Fax: +82-64-756-3493; E-mail: youjin2014@gmail.com

 

With the rapid increase in the elderly population worldwide, the number of people with sarcopenia has also increased significantly, and this disease is emerging as a medical and social issue. The development of pharmaceutics targeting sarcopenia is limited owing to the occurrence of side effects, and exercise therapy also has a limited scope of application. Therefore, it is necessary to develop safe and biocompatible agents to treat age-related sarcopenia. Ishige okamurae (IO), an edible brown alga, and its active substance, diphloroethohydroxycarmalol (DPHC), have been reported to have various physiological functions, including skeletal muscle regeneration ability. However, this effect has not been verified in an in vivo aging model. As an aging model, the oral IO extracts and DPHC supplemented 14-month-old female C57BL/6J mice were compared to the young group in this study; the mice model showed a substantial restoration of physical exercise ability with the imbalance of famine hormone and senescence-associated secretary phenotypes compared with those in young mice. Regarding the lean mass increase in aging mice following IO extract and DPHC administration, the muscular characteristics and molecular alterations in the gastrocnemius and soleus muscles, which are sensitive to the damage that occurs during the aging process, were significantly improved. Interestingly, the improved physical performance and androgen hormone imbalance, and enhanced gastrocnemius muscular characteristics were reproduced in 12-month-old aging male mice. In addition, the clinical trial (Age: 50-85, period: 12-weeks) showed a significant increase in quadriceps muscle strength (right) was observed in IO extract treatment group via ITT and PP analysis, and no hazards were found in safety assessment for participants. Collectively, the current study reveals that the natural agent IO extract and its derivative DPHC can reverse sarcopenia that occurs during the process of aging by improving the imbalance of muscle regeneration in vivo.

Keywords: Sarcopenia, Ishige okamurae, DPHC, Aging mice, Human clinical trials, Skeletal muscle regeneration