Effects of evodiamine mediating prostaglandin E receptor 2/Nod-like receptor protein 3 pathway on primary dysmenorrhea in rats
Objective To investigate the ameliorative effect of Evodiamine on primary dysmenorrhea in rats and its possible mechanism.Methods Female SD rats were randomly divided into normal group,model group,evodiamine low dose group,evodiamine medium dose group,evodiamine high dose group and positive control group,with 10 rats in each group.The primary dysmenorrhea model was established in all the other groups except the normal group.The rats in evodiamine low,medium and high dose groups were intragaically given 10,20 and 40 mg·kg-1 evodipine,respectively.Rats in positive control group were given 2.1 g·kg-1 Tongjingbao granules every day,and rats in normal group and model group were given the same amount of 0.9%NaCl.The times and latency of twisting were recorded in each group.The expression level of serum related factors and the content of Ca2+in uterine tissue were detected by enzyme-linked immunosorbent assay(ELISA).Serum malondialdehyde(MDA)and superoxide dismutase(SOD)levels were detected by thiobarbituric acid method and xanthine oxidase method.Hematoxylin-eosin(HE)staining was used to observe the pathological changes of uterus in each group.The expression of uterine tissue protein was detected by Western blot.Results The prostaglandin F2α(PGF2α)/prostaglandin E2(PGE2)values of normal group,model group,evodiamine low dose group,evodiamine medium dose group,evodiamine high dose group and positive control group were 0.73±0.07,2.35±0.44,1.84±0.18,1.40±0.17,1.04±0.12,and 0.97±0.14;Ca2+content were(1.00±0.17),(2.57±0.33),(2.01±0.24),(1.68±0.11),(1.38±0.16)and(1.78±0.10)nmol·gprot-1;MDA levels were(3.11±0.19),(5.07±0.19),(4.54±0.18),(4.01±0.13),(3.37±0.25)and(4.25±0.37)nmol·mL-1;prostaglandin E receptor 2(EP2)protein levels were 0.25±0.03,0.75±0.09,0.62±0.06,0.53±0.06,0.32±0.03,0.72±0.07,respectively;the Nod-like receptor protein 3(NLPP3)protein levels were 0.35±0.04,0.87±0.07,0.71±0.03,0.58±0.04,0.42±0.03 and 0.82±0.05;the protein levels of cysteine aspartic acid specific protease-1(caspase-1)were 0.40±0.06,0.90±0.07,0.73±0.07,0.59±0.06,0.45±0.03 and 0.86±0.07,respectively.The above indicators,comparison between model group and normal group,comparison between evodiamine low,medium,high dose groups and model group,comparison between different dosage groups of evodiamine,the differences were all statistically significant(all P<0.05).Conclusion Evodiamine may improve primary dysmenorrhea in rats by inhibiting EP2/NLRP3/caspase-1 pathway.
evodiamineprimary dysmenorrheaprostaglandin F2α6-keto prostaglandin F1-αprostaglandin E receptor 2/Nod-like receptor protein 3 pathway