Limits...
Inhibitory effects of magnolol and honokiol on human calcitonin aggregation.

Guo C, Ma L, Zhao Y, Peng A, Cheng B, Zhou Q, Zheng L, Huang K - Sci Rep (2015)

Bottom Line: In this study, these two compounds were tested for their effects on hCT aggregation.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.Together, our study suggested a potential anti-amyloidogenic property of these two compounds and their structure related derivatives.

View Article: PubMed Central - PubMed

Affiliation: Tongji School of Pharmacy, Huazhong University of Science and Technology, Wuhan, Hubei, P. R. China, 430030.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus

Size distribution of hCT aggregates detected by dynamic light scattering in the absence or presence of different compounds.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4555095&req=5

f4: Size distribution of hCT aggregates detected by dynamic light scattering in the absence or presence of different compounds.

Mentions: The particle size distribution of amyloid aggregates was further determined by dynamic light scattering (DLS). For hCT, the observed average diameter of aggregates was 580 nm after 24 h of incubation, and was increased to over 5000 nm after 72 h (Fig. 4). The addition of an equimolar amount of EGCG decreased the average diameter to 1300 nm after 72 h (Fig. 4). The presence of equimolar amounts of Mag and Hon showed no significant effect on the size of hCT aggregates, which displayed an average diameter of 2000 nm and 4200 nm after 72 h, respectively (Fig. 4). However, when a 5-fold molar excess of Mag and Hon was added, the average diameters of hCT aggregates were significantly decreased to 680 and 1630 nm after 72 h, respectively (Fig. 4).


Inhibitory effects of magnolol and honokiol on human calcitonin aggregation.

Guo C, Ma L, Zhao Y, Peng A, Cheng B, Zhou Q, Zheng L, Huang K - Sci Rep (2015)

Size distribution of hCT aggregates detected by dynamic light scattering in the absence or presence of different compounds.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4555095&req=5

f4: Size distribution of hCT aggregates detected by dynamic light scattering in the absence or presence of different compounds.
Mentions: The particle size distribution of amyloid aggregates was further determined by dynamic light scattering (DLS). For hCT, the observed average diameter of aggregates was 580 nm after 24 h of incubation, and was increased to over 5000 nm after 72 h (Fig. 4). The addition of an equimolar amount of EGCG decreased the average diameter to 1300 nm after 72 h (Fig. 4). The presence of equimolar amounts of Mag and Hon showed no significant effect on the size of hCT aggregates, which displayed an average diameter of 2000 nm and 4200 nm after 72 h, respectively (Fig. 4). However, when a 5-fold molar excess of Mag and Hon was added, the average diameters of hCT aggregates were significantly decreased to 680 and 1630 nm after 72 h, respectively (Fig. 4).

Bottom Line: In this study, these two compounds were tested for their effects on hCT aggregation.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.Together, our study suggested a potential anti-amyloidogenic property of these two compounds and their structure related derivatives.

View Article: PubMed Central - PubMed

Affiliation: Tongji School of Pharmacy, Huazhong University of Science and Technology, Wuhan, Hubei, P. R. China, 430030.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus