The Cholinesterase Inhibitory Properties of Stephaniae Tetrandrae Radix
Stephaniae tetrandrae radix (STR) is a commonly used traditional Chinese medicine in alleviating edema by inducing diuresis. In the clinic, STR extracts or its components are widely used in the treatment of edema, dysuria, and rheumatism for the regulation of water metabolism. Furthermore, STR has b...
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MDPI AG
2020-12-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/25/24/5914 |
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| author | Xiang-Peng Kong Hai-Qin Ren Etta Y. L. Liu Ka-Wing Leung Shu-Chen Guo Ran Duan Tina T. X. Dong Karl W. K. Tsim |
| author_facet | Xiang-Peng Kong Hai-Qin Ren Etta Y. L. Liu Ka-Wing Leung Shu-Chen Guo Ran Duan Tina T. X. Dong Karl W. K. Tsim |
| author_sort | Xiang-Peng Kong |
| collection | DOAJ |
| description | Stephaniae tetrandrae radix (STR) is a commonly used traditional Chinese medicine in alleviating edema by inducing diuresis. In the clinic, STR extracts or its components are widely used in the treatment of edema, dysuria, and rheumatism for the regulation of water metabolism. Furthermore, STR has been used in treating emotional problems for years by combining with other Chinese herbs. However, the material basis and mechanism of STR on the nervous system have not been revealed. Here, the main components of STR extracts with different extracting solvents were identified, including three major alkaloids, i.e., cyclanoline, fangchinoline, and tetrandrine. The cholinesterase inhibitory activity of STR extracts and its alkaloids was determined using the Ellman assay. Both cyclanoline and fangchinoline showed acetylcholinesterase (AChE) inhibitory activity, demonstrating noncompetitive enzyme inhibition. In contrast, tetrandrine did not show enzymatic inhibition. The synergism of STR alkaloids with huperzine A or donepezil was calculated by the median-effect principle. The drug combination of fangchinoline–huperzine A or donepezil synergistically inhibited AChE, having a combination index (CI) < 1 at <i>F<sub>a</sub></i> = 0.5. Furthermore, the molecular docking results showed that fangchinoline bound with AChE residues in the peripheral anionic site, and cyclanoline bound with AChE residues in the peripheral anionic site, anionic site, and catalytic site. In parallel, cyclanoline bound with butyrylcholinesterase (BChE) residues in the anionic site, catalytic site, and aromatic site. The results support that fangchinoline and cyclanoline, alkaloids derived from STR, could account for the anti-AChE function of STR. Thus, STR extract or its alkaloids may potentially be developed as a therapeutic strategy for Alzheimer’s patients. |
| first_indexed | 2024-03-10T14:06:17Z |
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| language | English |
| last_indexed | 2024-03-10T14:06:17Z |
| publishDate | 2020-12-01 |
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| spelling | doaj.art-d5aa4949c7a6405ebe45cfb79aec3fd92023-11-21T00:42:31ZengMDPI AGMolecules1420-30492020-12-012524591410.3390/molecules25245914The Cholinesterase Inhibitory Properties of Stephaniae Tetrandrae RadixXiang-Peng Kong0Hai-Qin Ren1Etta Y. L. Liu2Ka-Wing Leung3Shu-Chen Guo4Ran Duan5Tina T. X. Dong6Karl W. K. Tsim7Institute of Pharmaceutical & Food Engineering, Chinese Medicine Master Studio of Wang Shimin, Shanxi University of Chinese Medicine, 121 Daxue Road, Yuci District, Jinzhong 030619, ChinaShenzhen Key Laboratory of Edible and Medicinal Bioresources, HKUST Shenzhen Research Institute, Hi-Tech Park, Shenzhen 518057, ChinaDivision of Life Science and Center for Chinese Medicine, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, ChinaShenzhen Key Laboratory of Edible and Medicinal Bioresources, HKUST Shenzhen Research Institute, Hi-Tech Park, Shenzhen 518057, ChinaShenzhen Key Laboratory of Edible and Medicinal Bioresources, HKUST Shenzhen Research Institute, Hi-Tech Park, Shenzhen 518057, ChinaShenzhen Key Laboratory of Edible and Medicinal Bioresources, HKUST Shenzhen Research Institute, Hi-Tech Park, Shenzhen 518057, ChinaShenzhen Key Laboratory of Edible and Medicinal Bioresources, HKUST Shenzhen Research Institute, Hi-Tech Park, Shenzhen 518057, ChinaShenzhen Key Laboratory of Edible and Medicinal Bioresources, HKUST Shenzhen Research Institute, Hi-Tech Park, Shenzhen 518057, ChinaStephaniae tetrandrae radix (STR) is a commonly used traditional Chinese medicine in alleviating edema by inducing diuresis. In the clinic, STR extracts or its components are widely used in the treatment of edema, dysuria, and rheumatism for the regulation of water metabolism. Furthermore, STR has been used in treating emotional problems for years by combining with other Chinese herbs. However, the material basis and mechanism of STR on the nervous system have not been revealed. Here, the main components of STR extracts with different extracting solvents were identified, including three major alkaloids, i.e., cyclanoline, fangchinoline, and tetrandrine. The cholinesterase inhibitory activity of STR extracts and its alkaloids was determined using the Ellman assay. Both cyclanoline and fangchinoline showed acetylcholinesterase (AChE) inhibitory activity, demonstrating noncompetitive enzyme inhibition. In contrast, tetrandrine did not show enzymatic inhibition. The synergism of STR alkaloids with huperzine A or donepezil was calculated by the median-effect principle. The drug combination of fangchinoline–huperzine A or donepezil synergistically inhibited AChE, having a combination index (CI) < 1 at <i>F<sub>a</sub></i> = 0.5. Furthermore, the molecular docking results showed that fangchinoline bound with AChE residues in the peripheral anionic site, and cyclanoline bound with AChE residues in the peripheral anionic site, anionic site, and catalytic site. In parallel, cyclanoline bound with butyrylcholinesterase (BChE) residues in the anionic site, catalytic site, and aromatic site. The results support that fangchinoline and cyclanoline, alkaloids derived from STR, could account for the anti-AChE function of STR. Thus, STR extract or its alkaloids may potentially be developed as a therapeutic strategy for Alzheimer’s patients.https://www.mdpi.com/1420-3049/25/24/5914cholinesteraseStephaniae tetrandrae radixalkaloidfangchinoline |
| spellingShingle | Xiang-Peng Kong Hai-Qin Ren Etta Y. L. Liu Ka-Wing Leung Shu-Chen Guo Ran Duan Tina T. X. Dong Karl W. K. Tsim The Cholinesterase Inhibitory Properties of Stephaniae Tetrandrae Radix Molecules cholinesterase Stephaniae tetrandrae radix alkaloid fangchinoline |
| title | The Cholinesterase Inhibitory Properties of Stephaniae Tetrandrae Radix |
| title_full | The Cholinesterase Inhibitory Properties of Stephaniae Tetrandrae Radix |
| title_fullStr | The Cholinesterase Inhibitory Properties of Stephaniae Tetrandrae Radix |
| title_full_unstemmed | The Cholinesterase Inhibitory Properties of Stephaniae Tetrandrae Radix |
| title_short | The Cholinesterase Inhibitory Properties of Stephaniae Tetrandrae Radix |
| title_sort | cholinesterase inhibitory properties of stephaniae tetrandrae radix |
| topic | cholinesterase Stephaniae tetrandrae radix alkaloid fangchinoline |
| url | https://www.mdpi.com/1420-3049/25/24/5914 |
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