Effects of luteolin on CaM-CaMPK signaling pathway in hippocampus in epileptic rats / 国际中医中药杂志

ABSTRACT

Objective To explore the effects of luteolin on cognition function in pentylenetetrazol (PTZ)-induced epileptic rats and related mechanism.Methods Fifty male SD rats were randomly divided into a normal control group(n=8), a model group(n=12), and groups of 25, 50 mg/kg luteolin(both ofn=11), as well as 100 mg/kg luteolin group(n=8). Those rats were given different doses of luteolin (25, 50 and 100 mg/kg, daily, intragastric administration) for 36 consecutive days. Similarly, rats of the normal control group and the model group were given 0.5% sodium carboxymethyl cellulose suspension liquid via intragastric administration. Thirty minutes later, a model of epilepsy was induced using PTZ (40 mg/kg, daily) via intraperitoneal injection except the control group. Learning and memory of rats were evaluated by Morris water maze and novel objective recognition trials(including escape latency and recognition index). The levels of CaM and CaMPK were determined by ELISA methods, and expression of Ras proteins in the hippocampus were detected by Western Blot.Results Compared with the model group, luteolin treatment groups significantly shorten the escape latency(28.51 ± 3.84 s, 19.77 ± 5.41 s, 14.86 ± 2.76 svs. 37.08 ± 5.18 s) in the Morris water maze, and increased recognition index(18.77% ± 2.02%, 25.06% ± 4.32%, 31.92% ± 2.65%vs. 13.87% ± 2.14%) in the novel objection trial(P<0.05 orP<0.01). Meanwhile, CaM(140.33 ± 13.52 ng/L, 124.26 ± 9.97 ng/L, 113.52 ± 11.57 ng/Lvs. 158.36 ± 10.68 ng/L) and CaMPK(8.25 ± 1.37 ng/ml, 7.69 ± 0.84 ng/ml, 6.74 ± 0.93 ng/mlvs. 9.87 ± 1.02 ng/ml) were significantly decreased(P<0.05 orP<0.01). What’s more, the expression of Ras proteins(0.99 ± 0.08, 0.76 ± 0.07, 0.52 ± 0.07vs. 1.58 ± 0.12) was obviously decreased compared with the model group(P<0.05 orP<0.01).Conclusion Luteolin could effectively improve the cognition dysfunction of epileptic rats, and the mechanism might be relevant to regulate the CaM-CaMPK signaling pathway via down-regulation of CaM, CaMPK, as well as Ras protein.