Structural Stabilization of Human Transthyretin by Centella asiatica (L.) Urban Extract: Implications for TTR Amyloidosis
Abstract
:1. Introduction
2. Materials and Methods
2.1. Purification of huTTR from Plasma
2.2. Preparation of CAB
2.3. Nitroblue Tetrazolium (NBT) Redox-Cycling Assay
2.4. Determination of the Stability of huTTR in the Presence of CAB
2.4.1. Against Urea-Mediated Denaturation
2.4.2. Against Acid-Mediated Denaturation
2.5. Determination of 8,1-ANS Binding Displacement from huTTR by CAB
2.6. Determination of the Influence of CAB on huTTR Fibrillation by Transmission Electron Microscopy (TEM)
2.7. Determination of CAB Antioxidant Properties
2.7.1. DPPH (1,1-Diphenyl-2-picrylhydrazyl) Radical Scavenging Activity
2.7.2. Ferric Reducing Antioxidant Power (FRAP)
2.8. Determination of the Chemical Composition of CAB
2.8.1. Total Phenolic Content
2.8.2. Total Flavonoid Content
2.8.3. Thin-Layer Chromatography (TLC) Profile of CAB
2.8.4. High-Performance Liquid Chromatography-Mass Spectrometry (HPLC-MS) Fingerprint of CAB
2.9. Statistical Analysis
3. Results
3.1. CAB Directly Binds to huTTR
3.2. CAB Binds to the T4-Binding Sites of huTTR
3.3. CAB Increases huTTR Structural Stability
3.4. CAB Prevents huTTR Fibril Formation
3.5. Antioxidant Activity of CAB
3.6. Chemical Characterization of CAB
3.6.1. Total Phenolic and Flavonoid Contents
3.6.2. TLC Profile of CAB
3.6.3. HPLC-QTOF-MS Analysis of CAB
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Acknowledgments
Conflicts of Interest
References
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Peak No. | Retention Time | Observed Accurate Mass (m/z) | Predicted Formula | Calculated Mass (Da) | Tentative Identity of Compound |
---|---|---|---|---|---|
4 | 2.0 | 503.1527 [M − H]− | C21H28O14 | 504.1479 | Caffeic acid dihexoside |
12 | 15.1 | 353.0877 [M − H]− | C16H18O9 | 354.0951 | 3-O-Caffeoylquinic acid |
14 | 17.0 | 353.088 [M − H]− | C16H18O9 | 354.0951 | 5-O-Caffeoylquinic acid |
21 | 21.3 | 693.2790 [M − H2O − H]− | C34H48O16 | 712.2942 | Nominilic acid 17-glucoside |
22 | 21.6 | 477.0685 [M − H]− | C21H18O13 | 478.0747 | Quercetin 3-O-glucoronide |
23 | 22.4 | 5151195 [M − H]− | C25H24O12 | 516.1268 | 3,4-O-Dicaffeoylquinic acid |
24 | 22.9 | 515.1209 [M − H]− | C25H24O12 | 516.1268 | 3,5-O-Dicaffeoylquinic acid |
25 | 23.3 | 601.1226 [M − H]− | C28H26O15 | 602.1272 | 3,5-O-Dicaffeoyl-4-malonylquinic acid |
26 | 23.6 | 515.1203 [M − H]− | C25H24O12 | 516.1268 | 4,5-O-Dicaffeoylquinic acid |
27 | 24.0 | 601.1209 [M − H]− | C28H26O15 | 602.1272 | 3,5-O-Dicaffeoyl-4-malonylquinic acid isomer |
28 | 24.4 | 601.1228 [M − H]− | C28H26O15 | 602.1272 | Eriodictyol 7-(6-galloylglucoside) |
29 | 24.7 | 1019.5149 [M + Formate]− | C49H79O22 | 1019.5063 | Asiaticoside B |
30 | 24.8 | 1019.5149 [M + Formate]− | C49H79O22 | 1019.5063 | Madecassoside |
31 | 25.1 | 529.1351 [M − H]− | C26H26O12 | 530.1424 | 3-Caffeoyl-4-feruloylquinic acid |
32 | 25.2 | 873.4522 [M + Formate − H]− | C43H69O18 | 874.4562 | Centellasaponin B |
33 | 25.7 | 1003.5166 [M + Formate − H]− | C49H79O21 | 1004.5192 | Centellasaponin A |
34 | 26.1 | 957.5088 [M − H]− | C48H78O19 | 958.5137 | Asiaticoside |
36 | 27.8 | 1061.5180 [M − H]− | C51H82O23 | 1062.5247 | Avenacoside A |
39 | 29.8 | 987.5213 [M − H]− | C49H79O20 | 988.5243 | Soyasaponin I |
40 | 30.2 | 571.0881 [M − H2O − H]− | C30H20O12 | 572.0955 | Manniflavanone |
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Eze, F.N.; Leelawatwattana, L.; Prapunpoj, P. Structural Stabilization of Human Transthyretin by Centella asiatica (L.) Urban Extract: Implications for TTR Amyloidosis. Biomolecules 2019, 9, 128. https://doi.org/10.3390/biom9040128
Eze FN, Leelawatwattana L, Prapunpoj P. Structural Stabilization of Human Transthyretin by Centella asiatica (L.) Urban Extract: Implications for TTR Amyloidosis. Biomolecules. 2019; 9(4):128. https://doi.org/10.3390/biom9040128
Chicago/Turabian StyleEze, Fredrick Nwude, Ladda Leelawatwattana, and Porntip Prapunpoj. 2019. "Structural Stabilization of Human Transthyretin by Centella asiatica (L.) Urban Extract: Implications for TTR Amyloidosis" Biomolecules 9, no. 4: 128. https://doi.org/10.3390/biom9040128
APA StyleEze, F. N., Leelawatwattana, L., & Prapunpoj, P. (2019). Structural Stabilization of Human Transthyretin by Centella asiatica (L.) Urban Extract: Implications for TTR Amyloidosis. Biomolecules, 9(4), 128. https://doi.org/10.3390/biom9040128