Synergistic Inhibition of Acetylcholinesterase by Alkaloids Derived from Stephaniae Tetrandrae Radix, Coptidis Rhizoma and Phellodendri Chinensis Cortex
Abstract
:1. Introduction
2. Results
2.1. Determination of Alkaloids in Herbal Extracts
2.2. Herbal Extracts and Their Alkaloids Inhibit AChE
2.3. Herbal Combination Synergistically Inhibits AChE
2.4. Fangchinoline and Coptisine Synergistically Inhibit AChE
2.5. Fangchinoline and Berberine Synergistically Inhibit AChE
2.6. AChE Binding Sites Analysis of Fangchinoline, Coptisine and Berberine
3. Discussion
4. Materials and Methods
4.1. Chemicals and Preparation of Herb Extracts for HPLC Determination
4.2. Determination of Alkaloids in Herbal Extracts
4.3. Preparation of Herbal Extracts and Alkaloids for AChE Assay
4.4. Ellman Assay
4.5. Synergism Calculation by the Median-Effect Principle
4.6. Molecular Docking
4.7. Statistical Analysis
5. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Sample Availability: Samples of the herbal extracts and alkaloids in this work are available from the authors. |
Alkaloids | Linear Equation | R2 | Linear Range (μg/mL) |
---|---|---|---|
Fangchinoline | y = 7541.7x − 5907.9 | 0.9996 | 3.125–200 |
Tetrandrine | y = 6713x − 21313 | 0.9999 | 6.25–400 |
Coptisine | y = 37028x − 14419 | 0.9999 | 1.171875–75 |
Berberine | y = 46365x − 54509 | 0.9998 | 4.6875–300 |
Palmatine | y = 40443x − 19298 | 0.9998 | 1.171875–75 |
Epiberberine | y = 32555x − 8332.1 | 0.9998 | 0.625–40 |
Name | IC50 | AChE Inhibitory Activity 1 |
---|---|---|
STR extract | 570.11 ± 10.41 μg/mL | + |
CR extract | 4.11 ± 0.15 μg/mL | +++ |
PCC extract | 22.19 ± 3.12 μg/mL | ++ |
Fangchinoline | 2.17 ± 0.05 μM | +++ |
Tetrandrine | − | − |
Coptisine | 13.50 ± 1.48 μM | + |
Berberine | 2.33 ± 0.16 μM | +++ |
Palmatine | 6.52 ± 0.84 μM | ++ |
Epiberberine | 18.70 ± 0.83 μM | + |
Tacrine 2 | 0.44 ± 0.12 μM | +++ |
Name | Alkaloids’ Binding Interactions with AChE | Scores 1 | |||
---|---|---|---|---|---|
Ligand | Receptor | Interaction | Distance Å | ||
Fangchinoline | O 4 | O TYR334 (A) | H-donor | 2.59 | −7.11 ± 0.32 |
6-ring | N PHE288 (A) | π–H | 3.56 | ||
Coptisine | C 9 | 6-ring PHE330 (A) | H–π | 3.99 | −6.76 ± 0.02 |
C 30 | 6-ring TRP279 (A) | H–π | 3.90 | ||
Berberine | C 9 | 6-ring PHE330 (A) | H–π | 4.03 | −7.00 ± 0.01 |
C 11 | 6-ring TYR334 (A) | H–π | 3.57 | ||
C 13 | 6-ring TRP279 (A) | H–π | 3.67 | ||
Donepezil 2 | C 2 | 6-ring TYR334 (A) | H–π | 4.13 | −7.99 ± 0.02 |
C 18 | 6-ring TRP279 (A) | H–π | 3.45 | ||
C 20 | 5-ring TRP279 (A) | H–π | 4.03 | ||
C 28 | 6-ring TRP84 (A) | H–π | 4.06 | ||
6-ring | 6-ring PHE330 (A) | π–π | 3.54 |
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Kong, X.-P.; Liu, E.Y.L.; Chen, Z.-C.; Xu, M.L.; Yu, A.X.D.; Wu, Q.-Y.; Xia, Y.-J.; Duan, R.; Dong, T.T.X.; Tsim, K.W.K. Synergistic Inhibition of Acetylcholinesterase by Alkaloids Derived from Stephaniae Tetrandrae Radix, Coptidis Rhizoma and Phellodendri Chinensis Cortex. Molecules 2019, 24, 4567. https://doi.org/10.3390/molecules24244567
Kong X-P, Liu EYL, Chen Z-C, Xu ML, Yu AXD, Wu Q-Y, Xia Y-J, Duan R, Dong TTX, Tsim KWK. Synergistic Inhibition of Acetylcholinesterase by Alkaloids Derived from Stephaniae Tetrandrae Radix, Coptidis Rhizoma and Phellodendri Chinensis Cortex. Molecules. 2019; 24(24):4567. https://doi.org/10.3390/molecules24244567
Chicago/Turabian StyleKong, Xiang-Peng, Etta Y.L. Liu, Zhi-Cong Chen, Miranda Li Xu, Anna X.D. Yu, Qi-Yun Wu, Ying-Jie Xia, Ran Duan, Tina T.X. Dong, and Karl W.K. Tsim. 2019. "Synergistic Inhibition of Acetylcholinesterase by Alkaloids Derived from Stephaniae Tetrandrae Radix, Coptidis Rhizoma and Phellodendri Chinensis Cortex" Molecules 24, no. 24: 4567. https://doi.org/10.3390/molecules24244567