Moracin M from Morus alba L. is a natural phosphodiesterase-4 inhibitor |
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Authors: | Chen Shang-Ke Zhao Peng Shao Yong-Xian Li Zhe Zhang Cuixian Liu Peiqing He Xixin Luo Hai-Bin Hu Xiaopeng |
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Institution: | School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou 510006, China. |
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Abstract: | Phosphodiesterase-4 (PDE4) has been identified to be a promising target for treatment of asthma. Moracin M extracted from Chinese herbal drug 'Sang-Bai-Pi' (Morus alba L.) was studied for the inhibitory affinity towards PDE4. It inhibited PDE4D2, PDE4B2, PDE5A1, and PDE9A2 with the IC(50) values of 2.9, 4.5, >40, and >100 μM, respectively. Our molecular docking and 8ns molecular dynamics (MD) simulations demonstrated that moracin M forms three hydrogen bonds with Gln369, Asn321, and Asp318 in the active site and stacks against Phe372. In addition, comparative kinetics analysis of its analog moracin C was carried out to qualitatively validate their inhibitory potency as predicted by the binding free energy calculations after MD simulations. |
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