Glavonoid, a possible supplement for prevention of ATTR amyloidosis
Hiroaki Matsushita,
Aito Isoguchi,
Masamitsu Okada,
Teruaki Masuda,
Yohei Misumi,
Chiharu Tsutsui,
Narumi Yamaguchi,
Yuko Ichiki,
Jinko Sawashita,
Mitsuharu Ueda,
Mineyuki Mizuguchi,
Yukio Ando
Affiliations
Hiroaki Matsushita
Department of Amyloidosis Research, Faculty of Pharmaceutical Sciences, Nagasaki International University, 2825-7 Huis Ten Bosch Sasebo, Nagasaki 859-3298, Japan; Corresponding author.
Aito Isoguchi
Department of Neurology, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto 860-0811, Japan
Masamitsu Okada
Department of Neurology, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto 860-0811, Japan
Teruaki Masuda
Department of Neurology, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto 860-0811, Japan
Yohei Misumi
Department of Neurology, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto 860-0811, Japan
Chiharu Tsutsui
Department of Amyloidosis Research, Faculty of Pharmaceutical Sciences, Nagasaki International University, 2825-7 Huis Ten Bosch Sasebo, Nagasaki 859-3298, Japan
Narumi Yamaguchi
Department of Amyloidosis Research, Faculty of Pharmaceutical Sciences, Nagasaki International University, 2825-7 Huis Ten Bosch Sasebo, Nagasaki 859-3298, Japan
Yuko Ichiki
Department of Amyloidosis Research, Faculty of Pharmaceutical Sciences, Nagasaki International University, 2825-7 Huis Ten Bosch Sasebo, Nagasaki 859-3298, Japan
Jinko Sawashita
Pharma & Supplemental Nutrition Solutions Vehicle, Kaneka Corporation, Osaka, Japan
Mitsuharu Ueda
Department of Neurology, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto 860-0811, Japan
Mineyuki Mizuguchi
Faculty of Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama 930-0914, Japan
Yukio Ando
Department of Amyloidosis Research, Faculty of Pharmaceutical Sciences, Nagasaki International University, 2825-7 Huis Ten Bosch Sasebo, Nagasaki 859-3298, Japan; Department of Neurology, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto 860-0811, Japan; Corresponding author.
Transthyretin (TTR) is an amyloidogenic protein associated with hereditary and nonhereditary transthyretin amyloidoses (ATTR). Dissociation of the tetramer of TTR to the monomer induces TTR misfolding, which leads to amyloid fibril formation and triggers the onset of ATTR amyloidosis. Stabilizers of tetrameric TTR have been accepted as an effective ATTR amyloidosis treatment while effect is limited and they are too expensive. The aim of our study was to find more effective and cheep natural compound to suppress TTR amyloid formation. Glabridin, a prenylated isoflavan isolated from Glycyrrhiza glabra L., stabilized the TTR tetramer in vitro. The effects of licorice-derived flavonoid oil—Glavonoid, a natural substance that includes glabridin and several polyphenols—on stabilizing the TTR tetramer must still be elucidated. To examine plasma TTR stabilization by Glavonoid in vitro, we investigated the feasibility of utilizing glabridin plus Glavonoid to prevent TTR amyloid fibril formation. Glavonoid mixed with human plasma samples at 24 h incubation in vitro increased the tetramer level (P < 0.05) and reduced the monomer level (P < 0.01) and the monomer/tetramer ratio (P < 0.05) of TTR compared to those without Glavonoid by immunoblot analysis, such effect could not observe in the presence of glabridin. Oral Glavonoid (300 mg for 12 weeks) in 7 healthy volunteers effectively increased the plasma glabridin concentration. Glavonoid increased the TTR tetramer level and reduced the monomer/tetramer ratio of TTR (P < 0.05) in plasma at 12 weeks in healthy volunteers compared to those of age matched control subjects without the supplement. Thus, oral Glavonoid may effectively prevent TTR amyloid fibril formation via TTR tetramer stabilization. Glavonoid may become a promising supplement before onset of ATTR amyloidosis.
