Inhibitory effect of xanthohumol on the growth of Echinococcus multilocularis metacestode in the liver of mice

doi:10.12140/j.issn.1000-7423.2021.03.003

Abstract

Abstract:

Objective To explore the inhibitory effect of xanthohumol on the growth of hepatic Echinococcus multilocularis metacestode in mice.Methods Thirty C57BL/6 mice with liver infection of E. multilocularis metacestode 30 d post infection were randomly assigned into the infection group, solvent group, and xanthohumol group (10 mice in each group); a health control group of 10 mice was also set. Mice in the xanthohumol group received weekly intraperitoneal injection of xanthohumol (10 mg/kg), while those in the solvent group were intraperitoneally injected with an equal volume of dimethyl sulfoxide (DMSO). The mice in the health control group and infection group received no any treatment. After 60 days of treatment, the mice of each group were euthanized. The wet weights of liver and the multilocular hydatid cysts in each group were recorded, and the inhibition rate of cyst wet weight was calculated. ELISA was performed to examine the serum content of vascular endothelial growth factor (VEGF) in the mice in each group. The histopathological changes of hepatic multilocular hydatid cysts were observed by HE staining. Immunohistochemistry and Western blotting were used to detect the protein levels of nuclear factor kappa-B P65 (NF-κB P65), VEGF and microvessel density-highly glycosylated type I transmembrane glycoprotein (MVD-CD34) in the hepatic multilocular metacestode tissues in mice, with the glyceraldehyde-3-phosphate dehydrogenase（GAPDH） as internal control.Results After 60 days of xanthohumol treatment, the cyst wet weight in the xanthohumol group was (0.458 ± 0.068) g, which was lower than in the infection group (1.088 ± 0.274) g and the solvent group (1.973 ± 0.213) g (bothP < 0.05); the cyst inhibition rate of the xanthohumol group was 57.7% (63/109), which was higher than 10.4% (11.5/109.8) in the solvent group and 0 in the infection group (both P < 0.05). ELISA results showed that the serum level of VEGF in the xanthohumol group was (45.24 ± 1.93) pg/ml, which was lower than (58.00 ± 5.56) pg/ml in the infection group and (57.85 ± 16.00) pg/ml in the solvent group, but higher than (40.20 ± 3.24) pg/ml in the health control group (all P < 0.05). The liver pathological examination of the infected mice liver tissues showed that the xanthohumol group had narrow inflammatory reaction bands and disordered germinal layers. The results of immunohistochemistry showed that the score of NF-κB P65 in the multilocular metacestode tissue in the xanthohumol group was (2.65 ± 1.14), which was lower than that of the infection group (9.46 ± 2.60) and the solvent group (9.20 ± 1.64) (both P < 0.05). The VEGF score in the xanthohumol group (1.80 ± 0.83) was significantly lower than that of the infection group (7.20 ± 1.30) and the solvent group (7.43 ± 2.96) (both P < 0.05). The MVD-CD34 score in the xanthohumol group was (16.40 ± 1.14), which was significantly lower than that of the infection group (40.60 ± 1.14) and the solvent group (40.83 ± 2.16) (both P < 0.05). Western blotting results showed that the VEGF/GAPDH ratio in the xanthohumol group was (0.76 ± 0.82), which was lower than that of the infection group (2.84 ± 0.33) and the solvent group (2.47 ± 0.12), but was higher than that of the health control group (0.63 ± 0.02) (all P < 0.05), but there was no significant difference between the infection group and the solvent group ( P > 0.05). The MVD-CD34/GAPDH ratio in the xanthohumol group was (0.40 ± 0.02), which was lower than that of the infection group (1.11 ± 0.07) and the solvent group (1.02 ± 0.14), but was higher than that of the health control group (0.14 ± 0.02) (all P < 0.05). There was no significant difference between the infection group and the solvent group ( P > 0.05). The NF-κB P65/GAPDH ratio in the xanthohumol group was (0.24 ± 0.03), which was lower than that of the infection group (0.61 ± 0.05) and the solvent group (0.66 ± 0.13), but was higher than that of the health control group (0.02 ± 0.01) (all P < 0.05). Conclusion The growth and angiogenesis of hepatic multilocular metacestode in mice were inhibited after treatment with xanthohumol for 60 days.

Key words: Echinococcus metacestode, Xanthohumol, Vascular endothelial growth factor, Microvessel density, Nuclear factor kappa-B

CLC Number:

R383.33

TAN Xiao-wu, YU Xiao-fan, JIANG Hui-jiao, XING Zhi-kun, CHEN Xue-ling, WU Xiang-wei. Inhibitory effect of xanthohumol on the growth of Echinococcus multilocularis metacestode in the liver of mice[J]. CHINESE JOURNAL OF PARASITOLOGY AND PARASITIC DISEASES, 2021, 39(3): 304-310.

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