Synthesis Of Apigenin-samarium Complex And Its Activity Anti-gouty Arthritis

In this study,apigenin with anti-gout and anti-inflammatory activities was used as ligand and rare earth metal samarium ion was used as coordination center to design and synthesize apigenin-samarium complex（Ap-Sm）.The structure of apigenin-samarium complex was characterized by UV,IR,¹H-NMR,Conductivity and TG-DTA.The anti-gouty arthritis activity,anti-inflammatory mechanism and toxicity of the complex were preliminarily investigated.This has important theoretical and practical significance for the development of new apigenin anti-gouty arthritis drugs with high efficiency and low toxicity.Specific research is as follows:Investigation on synthesis process conditions.In this study,the yield of apigenin-samarium complex was used as the index,and the synthesis process was optimized by orthogonal experiment.In this study,the ratio of apigenin to samarium nitrate,reaction temperature and p H value were taken as investigation factors to investigate the influence of these factors on the yield.The optimal synthesis conditions of the complex were as follows:the molar ratio of apigenin to samarium nitrate was 3:1,the temperature was 15℃,and the p H value was 8.The yield was 92.69%.The purity of apigenin-samarium detected by HPLC was98.56%.Complex structure.Through UV,IR,¹H-NMR,conductance method and TG-DTA analysis,it is speculated that the chemical composition formula of the complex is Sm(C₁₅H₉O₅)₃·2H₂O.The 5-position hydroxyl oxygen atom of apigenin A ring and 4-position carbonyl oxygen atom of C ring are coordinated with rare earth samarium（III）ions to form a complex with coordination ratio of 3.Study on acute toxicity.The semi-lethal dose method was used for the pretest experiment,and the maximum dose method was used for the formal experiment to investigate the acute toxicity of apigenin-samarium.The toxicity of apigenin-samarium complex was determined by intragastric administration to mice.The LD50 of apigenin-samarium complex could not be measured in the experiment,so the maximum dosage method was used.The results showed that the maximum dose of apigenin-samarium was 0.8g/kgbw d.During the 14-day observation period,there was no toxic reaction.Study on anti-gouty arthritis activity.A mouse model of gouty arthritis was established by injecting sodium urate.To investigate the effects of apigenin and apigenin-samarium on inflammatory index,dysfunction index,ankle swelling rate and inflammatory factors（TNF-α,IL-1βand PGE₂）in mice.The results showed that:In terms of inflammation index and dysfunction index of mice,apigenin-samarium has fast effect and strong effect in controlling disease condition,and its inhibitory activity is greatly enhanced compared with apigenin.In terms of joint swelling rate,apigenin-samarium complex can advance the course of disease,reduce the peak swelling degree,and inhibit joint swelling rate with stronger activity than apigenin.On inflammatory factors in serum and ankle cavity of mouse,apigenin-samarium has stronger effect on PGE₂and TNF-αthan ligand apigenin.Apigenin-samarium is similar to high dose apigenin in inhibiting IL-1βlevel.On inflammatory factors in spleen and liver of mice,apigenin-samarium has stronger effects on PGE₂,IL-1βand TNF-αthan ligand apigenin.The inhibitory effects of the complex on inflammatory index,dysfunction index,foot swelling rate and inflammatory factors（TNF-α,IL-1βand PGE₂）in mice are mostly positively correlated with the dose.The larger the dose of the complex,the stronger the inhibitory effect.A few showed the strongest inhibition in medium dose.To sum up,apigenin-samarium complex has stronger anti-gouty arthritis activity than apigenin ligand,meanwhile,apigenin-samarium has no toxic and side effects on experimental mice.This indicates that samarium（Ⅲ）ions have synergistic effect on the biological activity of the ligand apigenin,which greatly improves its anti-gouty arthritis activity.The possible mechanism is related to the reduction of IL-1β,TNF-αand PGE₂ levels in vivo.