Studies On The Pharmacodynamic Material Bases Of Traditional Chinese Medicine Seaweed Complex Preparation (SCP)

Tradititonal Chinese medicine preparation (TCMP) was a main form for Chinese medical practice. TCMP was composed according to the compatibility theory and dialectical view. It was very difficult to study on the pharmacodynamic material bases of TCMP due to the complexity of chemical constituents and pharmacodynamic effects. It is significant to elucidate the effective constituents and function mechanisms of TCMP. In this paper, the pharmacodynamic material bases of Seaweed Complex Preparation (SCP), a clinical traditional Chinese medicine preparation with antitumor effects, was investigated by a"whole prescription"research strategy in a view of multicomponents, multitargets and mutiapproaches.SCP was mainly composed by several traditional Chinese herbs, such as seaweed Sargassum pallidum (Turn.) C. Ag., the radix of Astragalus membranaceus (Fisch.) Bge. and the fruits of Ligustrum lucidum Ait. As a clinical preparation, it has been used to treat lung cancer, liver cancer and digestive cancer. The pharmacodynamic material bases of SCP was studied by the"whole prescription"method under the guidance of bioactivities of immunomodulatory, cytotoxic, antioxidant and antibacterial activities in vitro. More than 60 compounds were isolated from the ethyl acetate fraction and n-BuOH fraction of the preparation by chromatography on silica gel, Sephadex LH-20, PTLC and PHPLC. Structures of 49 compounds including 2 novel compounds and 1 new natural product were identified by spectroscopy such as 1H NMR, 13C NMR, 2D NMR, MS, IR and UV. More than 10 structure types were found, such as flavonoid glycoside, flavonoid, phenolic compound, lignan, steroid, terpene and lactone. The petroleum ether fraction was analyzed by GC/MS resulting in the identification of 15 acyclic compounds, 6 other chemical constituents including terpenoid and sterol. The polysaccharide isolated from the water fraction was mainly composed of glucose with a small quantity of rhamnose, mannose, fructose and galactose.The antitumor effects of the chemical constituents of SCP was investgated at cell level for cell proliferation inhibition and cytotoxicity (cell lines P388, BEL7402, KB) and molecule level for immunomodulatory activites (cytokines IL-2, IL-4 and INF-γ). It was found that SCP was an organic unity of complicated chemical constituents with multiple antitumor approaches. Four molecular communities including flavonoid glycosides, flavonoids, phenolic compounds and polysaccharides could be involved in antitumor effects. Flavonoid glycosides and flavonoids exhibited immunomodulatory activites. Flavonoid glycosides and caffeic acid derivatives showed remarkable antioxidant activities. And polysaccharides showed immunological enhancement effects. Synergism of these four molecular communities together with auxiliary effect of other components (such as the weak cytotoxic activities of sesquiterpenes and lipids) embodied the muticompenent and mutitarget features of SCP.The chemical constituents of monarch drug S. pallidum (Turn.) C. Ag. were investgated in order to trace the origin of the compounds obtained from SCP. More than 22 compounds were obtained from the whole plant. Structures of 18 compounds were identified including dipeptides, coumarins, flavonoids and sterols, among which several flavonoids and sterols were the same or similar to that of SCP. The chemical constituents of the fruits of L. lucidum Ait. was also studied to investigate the origin ofβ-D-glucopyranoside, 2-(4-hydroxyphenyl), 6-acetate (44). It was indicated that this compound existed in L. lucidum Ait.. The possible producing approaches of (3-Ethylidene-2-oxo-tetrahydro-pyran-4-yl)-acetic acid methyl ester (42) and [5-(1-Hydroxyl-ethyl)-4-hydroxymethylene- 2-oxo-tetrahydro-pyran-3-yl]-acetic acid methyl ester (43) were deduced as products generated from decoction of the preparation.The acting-pattern of effective molecular communites with muticomponents, mutitargets and mutiapproaches was proposed by using"whole prescription"strategy. The results obtained from our research should provid elemental information for clinical application and further development of SCP. And the strategy and methods used in our experiments should also have an enlightenment and reference significance to the research on pharmacodynamic material bases of traditional Chinese medicine prescription.