Studies On The Chemical Constituents Of Ramulus Mori And Their Phosphodiesterase-4 Inhibitory Activity

Ramulus Mori is a twig which belong to the genus Morus of Moraceae, Mulberry leaves, roots, branches and fruits all can be used as medicinal. Ramulus Mori is commonly used in shoulder joint pain and numbness in the fingers, rheumatism, paralysis and other diseases. Phytochemical investigationson Morus alba L. reported occurrences of polyphenolic constituents(flavonoids, flavanone, dihydro flavonols, chalcones, Diels-Alder adducts, benzofuran derivatives, stilbene and its derivatives) and alkaloids, polysacc harides, etc,in which polyphenolic constituents are the main chemical constituents and also the main active ingredients. Modern pharmacological studies have shown that it has anti-inflammatory and other pharmacological activity, their pharmacological activity is closely related to the active ingredient of them.The phosphodiesterases-4(PDE4) is a part of superfamily of phosphodiesterases enzymes. They are mainly distributed in a variety of inflammatory cells so that we can inhibit the activity of PDE4 to suppress the inflammatory cells. Therefore, PDE4 is considered to be a new type of anti-inflammatory targets. In central of PDE4 inhibition, this topic selected PDE4 inhibitory activities of 95% ethanol extract of the organic phase extraction of Ramulus Mori. Then study on the composition of the ethyl acetate active fraction in order to obtain chemical constituents of PDE4 inhibitory activity. This paper will provide strong scientific certification for the research of PDE4 active ingredients and confirm Ramulus Mori. is an important medicinal resource for anti-inflammatory active ingredients.The present study focus on the PDE4 inhibitive activity, on the basis of previous studies on the chemical constituents of Cortex Mori, this thesis further studied on the chemical constituents of Ramulus Mori. which is as the same plant source as Cortex Mori and choosed typical chemical components to discuss their PDE4 inhibitory activity, in order to obtain chemical constituents of PDE4 inhibitory activity. This paper will provide strong scientific support for the reserarch of PDE4 active ingredients and useful data for the deeper investigation of the structure-activity relationship of PDE4 active ingredients.This study based on PDE4 inhibitory activity tracking method and by means of a variety of chemical methods of various color developing agent while the use of a combination of normal phase silica gel, reverse phase silica gel and semi-preparative high performance liquid chromatography method,the branchs of Morus alba L. were studied systemically in chemistry. Based on the organic mass spectrometry, nuclear magnetic resonance (NMR) spectrometry and other modern means as well, the compounds which isolated from ethyl acetate fractionof the branchs of Morus alba L. were elucidated and related biological activity test were done. The compounds are: 5,7-dihydroxy coumarin (compound 1)、Noratocarpanone (compound 2) Dihydromorin(compound 3)、Moracin M(compound 4)、Oxyresveratrol(compound 5)、Ursolic acid (compound 6)、Kuwanon C (compound 7)、Morusin (compound 8)、2,4-dihydroxybenzaldehyde (compound 9)、Umbelliferone (compound 10) Dibutyl phthalate(compound 11),Moracin M-3’-O-β-D-glucopyranos ide(compound 12), cis-oxyreseratrol-4-O-β-D-glucopyranoside (compound 13*),2’,4’-dihydroxy-7,8-(2"-isopropenylfuranyl)-6-prenyl-flavonol] (compound 14*), Mornigrol E (compound 15), Mornigrol F (compound 16), Among the sixteen compounds isolated from the branchs of Morus alba L., which include two coumarin (1,10), atriterpenoid (6), seven flavonoids (2,3,7,8,14,15,16), four stilbene compound (4,5,12,13), two other classes (9,11).Using[3H] tag liquid scintillation counting method to get PDE4 inhibitory activity of thirteen compounds in vitro test. The PDE4 inhibitory activity tests showed four phenolic compounds (4,7,8,16) have significant inhibitory activity against PDE4, with IC50 values of 2.90,0.38,1.02 and 0.50μM, respectively.