Inhibitory effects of magnolol and honokiol on human calcitonin aggregation.
Amyloid formation is associated with multiple amyloidosis diseases. Human calcitonin (hCT) is a typical amyloidogenic peptide, its aggregation is associated with medullary carcinoma of the thyroid (MTC), and also limits its clinical application. Magnolia officinalis is a traditional Chinese herbal medicine; its two major polyphenol components, magnolol (Mag) and honokiol (Hon), have displayed multiple functions. Polyphenols like flavonoids and their derivatives have been extensively studied as amyloid inhibitors. However, the anti-amyloidogenic property of a biphenyl backbone containing polyphenols such as Mag and Hon has not been reported. In this study, these two compounds were tested for their effects on hCT aggregation. We found that Mag and Hon both inhibited the amyloid formation of hCT, whereas Mag showed a stronger inhibitory effect; moreover, they both dose-dependently disassembled preformed hCT aggregates. Further immuno-dot blot and dynamic light scattering studies suggested Mag and Hon suppressed the aggregation of hCT both at the oligomerization and the fibrillation stages, while MTT-based and dye-leakage assays demonstrated that Mag and Hon effectively reduced cytotoxicity caused by hCT aggregates. Furthermore, isothermal titration calorimetry indicated Mag and Hon both interact with hCT. Together, our study suggested a potential anti-amyloidogenic property of these two compounds and their structure related derivatives.
Tongji School of Pharmacy, Huazhong University of Science and Technology, Wuhan, Hubei, P. R. China, 430030.
Caiao
C
Guo
Tongji School of Pharmacy, Huazhong University of Science and Technology, Wuhan, Hubei, P. R. China, 430030.
Liang
L
Ma
Tongji School of Pharmacy, Huazhong University of Science and Technology, Wuhan, Hubei, P. R. China, 430030.
Yudan
Y
Zhao
Dept. of Pharmacy, The Third Hospital of Wuhan, Wuhan, Hubei, P. R. China, 430060.
Anlin
A
Peng
Dept. of Pharmacy, Central Hospital of Wuhan, Wuhan, Hubei, P. R. China, 430014.
Biao
B
Cheng
Tongji School of Pharmacy, Huazhong University of Science and Technology, Wuhan, Hubei, P. R. China, 430030.
Qiaoqiao
Q
Zhou
College of Life Sciences, Wuhan University, Wuhan, Hubei, P. R. China, 430072.
Ling
L
Zheng
Tongji School of Pharmacy, Huazhong University of Science and Technology, Wuhan, Hubei, P. R. China, 430030.|Centre for Biomedicine Research, Wuhan Institute of Biotechnology, Wuhan, Hubei, P. R. China, 430075.
Kun
K
Huang
D001713:Biphenyl Compounds / Q000737:chemistry / Q000378:metabolism*; D002116:Calcitonin / Q000737:chemistry / Q000378:metabolism*; D002151:Calorimetry; D045744:Cell Line, Tumor; D000067493:Dynamic Light Scattering; D006801:Humans; D017705:Lignans / Q000737:chemistry / Q000378:metabolism*; D031566:Magnolia / Q000737:chemistry / Q000378:metabolism; D008516:Medicine, Chinese Traditional; D046529:Microscopy, Electron, Transmission; D059808:Polyphenols / Q000737:chemistry; D011485:Protein Binding; D000498:Allyl Compounds; D010636:Phenols
D001713:Biphenyl Compounds; D002116:Calcitonin; D017705:Lignans; D059808:Polyphenols; C005498:magnolol; C005499:honokiol; D000498:Allyl Compounds; D010636:Phenols