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Arctigenin (ARG) is a functional active component that has important physiological and pharmacological activities. The anti-tumour and anti-inflammatory activities of ARG show good potential for application and development, but this material has the defect of low water solubility. In this experiment, the valine derivative of ARG (ARG-V) was designed and synthesized to overcome this disadvantage. The ARG amino acid, EDCI and DMAP were raw materials in the addition reaction, with a molar ratio of 1:2:2:0.5. The yield of ARG-V was up to 80%. ARG-V has strong anti-tumour activity in vivo and in vitro. The inhibitory rate of ARG-V was 69.2%, with less damage to the immune organs and different degrees of increased serum cytotoxicity. Moreover, the pharmacokinetics of ARG following oral administration and ARG-V following oral administration in rats were also studied. The Cmax and AUC values of ARG-V showed significant differences compared to ARG. The relative bioavailabilities of three doses of ARG-V compared to ARG were 664.7%, 741.5% and 812.9%. These pharmacokinetic results may be useful for further studies of the bioactive mechanism of ARG and provide a theoretical basic for clinical use.

The use of arctigenin (ARG), a traditional medicine with many pharmacological activities, has been restricted due to its poor solubility in water. Five amino acid derivatives of ARG have been synthesized using glycine, o-alanine, valine, leucine, and isoleucine, which have t-butyloxy carbonyl (BOC) as a protective group. In this study, we examined the effects of removing these protective groups. The results showed that the amino acid derivatives have better solubility and nitrite-clearing ability than ARG. Among the compounds tested, the amino acid derivatives without protective group were the best. Based on these results, ARG and its two amino acid derivatives without protective group (ARG8, ARG10) were selected to evaluate their anti-tumor activity in vivo at a dosage of 40 mg/kg. The results indicated that ARG8 and ARG10 both exhibit more anti-tumor activity than ARG in H 22 tumor-bearing mice. The tumor inhibition rates of ARG8 and ARG10 were 69.27 and 43.58%, which was much higher than ARG. Furthermore, the mice treated with these compounds exhibited less damage to the liver, kidney and immune organs compared with the positive group. Furthermore, ARG8 and ARG10 improved the serum cytokine levels significantly compared to ARG. In brief, this study provides a method to improve the water solubility of drugs, and we also provide a reference basis for new drug development.

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ABSTRACT.We investigated the effect of atorvastatin on vascular endothelial growth inhibitor (VEGI) expression in rats with diabetic retinopathy. Wistar rats were divided into a blank group and diabetic model group, which was further randomly divided into treatment and control groups. Rats in the treatment group received 10 mg/kg atorvastatin daily, while rats in the blank and control groups received normal saline. Rats were randomly euthanized at 3 or 6 months. Immunohistochemical staining was used to determine changes in VEGI and vascular endothelial growth factor, interleukin-4, and tumor necrosis factor α levels in rats with diabetic retinopathy. Survival rate in the treatment group was 84% (63/75) after 6 months, which was significantly higher than that in the control group (P < 0.05); rats in the control group showed the lowest survival rate. Survival in the treatment group was higher than that in the control group but not significant compared with the blank group after 3 months. VEGI, vascular endothelial growth factor, tumor necrosis factor α, and interluekin-4 expression was lower than that in the control group, but higher than the blank group after 3 months. The (2015) expression of each factor decreased to the blank group level in the treatment group and was significantly lower than that in the control group after 6 months (P < 0.05). Expression in control and blank groups was similar at 3 and 6 months. Atorvastatin can inhibit VEGI and vascular endothelial growth factor expression to protect rats from diabetic retinopathy.