| Fulvic acid is a kind of complicated organic compound with weak acid, its raw material multiplicity different decay process and different extraction process can lead to its composition complexity and functional difference, which greatly limits its research in medical advances, so it is necessary to make efforts on its source, purification, standardization and treatment mechanism study. In traditional medicine study fulvic acid showed antiulcer, improve microcirculation, hemostatic and invigorate the circulation of blood activity etc., the pharmacological mechanism may be involved in angiogenesis, how about the effects of lignite fulvic acid on angiogenesis are still not be reported, in addition there are some controversial of fulvic acid on cancer cells effects, some one reported that fulvic acid could promote cancer cell transformation and proliferation, there are also some reports that fulvic acid has antioxidant and antitumor activity, did this relation to its resouces and angiogenesis promoting need to be researched.On this basis, we studied the pharmacological activity of lignite fulvic acid with multiple samples of different places at the same condition, explored the effect of lignite sodium fulvate on angiogenesis and its in vitro anticancer activity, and compared the similarities and differences of pharmacological activity of sodium fulvate, finally provides some basic data for the lignite resources and make it could be developed and utilized according to the actual situation.In this study we got young brown coal form Eshan, Xundian, Zhaotong region of Yunnan province, using H2O2oxidative degradation and001x7type cation exchange resin purifying method finally obtained the purified products. We explored the angiogenesis effects and mechanism of sodium fulvate through HUVEC MTT assay, scratch assay and VEGF detection assay, and CAM model. We also study the effects of sodium fulvate on cancer cell line A549and KYSE510by MTT assay. The main results showed as follows:1. The pharmacological effects trend on HUVEC model of sodium fulvate of Eshan region and Xundian region was similar. Both of them could promoting the viability and migration of HUVEC at low concentration, and up regulate the expression of VEGF as well, with the sodium fulvate concentration increased the proliferation and migration of HUVEC was inhibited, and the expression of VEGF was also reduced. But both of them also have some differences, Eshan sodium fulvate appeared strongest promotion effects at50μg·ml-1, Xundian sodium fulvate appeared strongest promotion effects at25μg·ml-1, at the same time no matter promotion or inhibiting effects Xundian sodium fulvate is better than Eshan sodium fulvate. Zhaotong sodium fulvate has no obvious effects on HUVEC at low concentrations, and Zhaotong sodium fulvate has inhibiting effect at high concentrations, the inhibiting ability is similar to Eshan sodium fulvate.2. The CAM assay results showed that Eshan lignite sodium fulvate could promote blood vessel growth at200μg·ml-1,400μg·ml-1, with the concentration increased at1200μg·ml-1the angiogenesis of CAM could be significantly inhibited. Xundian lignite sodium fulvate can obviously promote the angiogenesis of CAM at200μg·ml-1,and at800μg·ml-1it could significantly inhibit the angiogenesis. Zhaotong lignite sodium fulvate can’t promote the CAM blood vessel growth at low concentration, but at the concentration of800μg·ml-1could inhibit the angiogenesis of CAM. Xundian lignite sodium fulvate showed the best active on promotion effects or inhibiting effects of angiogenesis compared with the other two places.3. The MTT assay results of human lung cancer cell A549showed that the sodium fulvate from Eshan and Xundian could inhibit the A549proliferation, with the increase of concentration and the prolong of time the pharmacological effects become more stronger, compared with Xundian sodium fulvate Eshan sodium fulvate has better effect. Zhaotong sodium fulvate almost has no effect on A549, only when the concentration was increased to800μg·ml-1it could show inhibitory effects on A549at42h or72h. The MTT assay results of human esophageal cancer cell KYSE510showed, Xundian lignite sodium fulvate at low concentrations of S0μg·ml-1、100μg·ml-1can promote cell proliferation, only when the concentration increased to400μg·ml-1inhibition effect appeared, Eshan and Zhaotong lignite sodium fulvate could inhibit the cell growth, with the increase of concentration and the prolong of time the pharmacological effects become more stronger as well.The results of the study showed that the angiogenesis effects of lignite sodium fulvate at the three places are different, and the effects on cancer cell proliferation also showed differences, and there is no necessary connection between angiogenesis and cancer cell proliferation.this study further illustrated the research on fulvic acid should according to its resources and physical background, we also confirmed the mechanism of sodium fulvate is complexed with multicomponent, multi-target, and multi-factor process. The development and utilization of Yunnan lignite should according to the actual situation. |
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