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Pharmacological Comparison of Flavonoid Glycosides and Aglycones on Their Anti-oxidation and Anti-fatigue Activities

Author: LiuQiuWei
Tutor: LiangJu
School: Henan University of Science and Technology
Course: Pharmacology
Keywords: Baicalein Liposomes Antioxidant Anti-fatigue Sustained-release HPLC
CLC: R285
Type: Master's thesis
Year: 2011
Downloads: 111
Quote: 1
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Abstract

Free radicals are intermediate metabolism, has a strong oxidizing ability. When the people of free radicals produce too much or too slow to clear the body of the oxidation - antioxidant balance is broken free radicals by oxidation, peroxide and nitration reactions lead to protein denaturation, nucleic acid degradation and lipid peroxidation, thereby induce a variety of diseases. Therefore, screening free radical scavengers and antioxidants on the prevention and treatment of related diseases is of great significance, is the hot topic of the medical profession and academic medicine research. Natural flavonoid compounds are widespread in nature, with the structure of various types, a notable feature of the antioxidant activity in vitro and in vivo, a variety of free radicals potent scavenging effect. In recent years, for the class of compounds reported antioxidant activity and antioxidant mechanism after another, more and more in-depth study of their structure-activity relationship of antioxidant, but it still lacks the class of compounds antioxidant capacity, the formulations, in vivo efficacy system of the school and pharmacokinetic studies. General structure-activity law based on the antioxidant activity of flavonoids, the thesis structure representative flavonoid glycosides and their aglycone of 8 compounds, a comparative study of its in vitro antioxidant capacity, choose one antioxidant capacity the strong - baicalein, the formulations, pharmacodynamic and pharmacokinetic system provided the experimental basis for the development of clinical potent antioxidants. Specific work includes the following aspects: (1) the use of ultraviolet spectroscopy of flavonoids in vitro ONOO-of · OH and O2 · - scavenging ability. The results showed that the eight kinds of flavonoids on ONOO-induced protein nitration there is a certain extent - have a significant role in the removal of · OH and O2 ·. Eight kinds of flavonoids ONOO-reaction dynamics and free radical scavenging ability of comprehensive evaluation found that baicalein has the most significant antioxidant capacity. In order to improve the stability of flavonoids drug enhanced pharmacodynamic effect in the body, we prepared liposomes baicalein. The comparison results indicate that of the three liposome preparation method, ether injection baicalein liposomes prepared having higher and more consistent drug encapsulation efficiency. The preparation process of the method of orthogonal experimental optimization, the optimal conditions were as follows: lecithin: cholesterol = 8:1,0.020 g baicalein PBS (pH 6.7) used in an amount of 20 mL of 0.060 g of cholesterol ether amount of 15 mL. Baicalein the process obtained under average liposome encapsulation efficiency was 41.5 ± 4.77%, particle size distribution range of 400-600 nm, when sustained-release time to reach 24 h, the cumulative release amount of drug baicalein 91.2%. 3 acute toxicity in mice, and medium-and long-term toxicity experimental evaluation baicalein drug safety. By gavage once observed experimental mice poisoning and death. The results showed that 24 for 48 h, the baicalein the LD50 3000 mg / kg for 14 d, baicalein LD50 gt; 2000 mg / kg. The organ coefficient weight change baicalein mouse liver, spleen and kidney have toxic effects, including kidney damage is most significant. 4 consecutive treatment, 14 d, the experimental study of anti-fatigue baicalein liposomes. The results show that, compared with the movement of the control group of drug-treated mice serum LD and MDA content were decreased SOD activity increased, swim to exhaustion time, this is closely related to the antioxidant effect and baicalein. Compared with the movement of the control group, baicalein the liposomes low dose group showed significant differences, suggesting that baicalein liposomes has significant anti-fatigue effect. Determination of Biochemical show, baicalein also has the hypoglycemic, lipid-lowering effects, the latter effect is more significant. 5. HPLC method was used to establish the method of determination of mouse plasma baicalein concentration. HPLC assay of concentration mouse plasma baicalein, high specificity, simple operation, separated completely reliable results relative recoveries were in the range of 85 to 115%, the intraday and interday coefficients of variation were less than 10. %, in line with the requirements of bioequivalence studies for baicalein pharmacokinetic study. An HPLC method, we study the pharmacokinetics of baicalein liposome. The results showed that 3 h after administration, the plasma concentration peak drug absorption and elimination rate roughly equal to 3 to 6 h interval, for drug stabilization period, after the growth over time, the plasma concentration gradually decreased until 24 h after administration, there is still a small amount of the drug was released. In summary, we prepared liposomes baicalein efficiency and sustained release characteristics suitable for clinical development and utilization.

Pharmacological Comparison of Flavonoid Glycosides and Aglycones on Their Anti-oxidation and Anti-fatigue Activities

Abstract

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