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Luteolin attenuates cognitive dysfunction induced by chronic cerebral hypoperfusion through the modulation of the PI3K/Akt pathway in rats

Haitao He
Haitao He
 oraz 
Xi Chen
Xi Chen
   | 05 lip 2021
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Data publikacji: 05 lip 2021
Zakres stron: 341 - 349
Otrzymano: 19 lis 2020
Przyjęty: 16 cze 2021
DOI: https://doi.org/10.2478/jvetres-2021-0037
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© 2021 H. He, X. Chen. published by Sciendo
This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Fig. 1a

Effects of luteolin on learning and memory impairment in 2-VO rats evaluated by the object recognition test one month after 2-VO surgery. Discrimination index was measured at one month after 2-VO surgery. Data are expressed as mean ± SEM. n = 15 in each groupSham – group subjected to sham two-vessel occlusion surgery; Model – group subjected to two-vessel occlusion surgery without drug treatment; Lut 50 – group subjected to two-vessel occlusion surgery and administered luteolin at 50 mg/kg b.w.; Lut 100 – group subjected to two-vessel occlusion surgery and administered luteolin at 100 mg/kg b.w.; Nimodipine – group subjected to two-vessel occlusion surgery and administered nimodipine at 16 mg/kg b.w.; ** – P < 0.01, model group vs. sham group; ## – P < 0.01, luteolintreated groups vs. model group; ns – non-significant
Effects of luteolin on learning and memory impairment in 2-VO rats evaluated by the object recognition test one month after 2-VO surgery. Discrimination index was measured at one month after 2-VO surgery. Data are expressed as mean ± SEM. n = 15 in each groupSham – group subjected to sham two-vessel occlusion surgery; Model – group subjected to two-vessel occlusion surgery without drug treatment; Lut 50 – group subjected to two-vessel occlusion surgery and administered luteolin at 50 mg/kg b.w.; Lut 100 – group subjected to two-vessel occlusion surgery and administered luteolin at 100 mg/kg b.w.; Nimodipine – group subjected to two-vessel occlusion surgery and administered nimodipine at 16 mg/kg b.w.; ** – P < 0.01, model group vs. sham group; ## – P < 0.01, luteolintreated groups vs. model group; ns – non-significant

Fig. 1b

Effects of luteolin on learning and memory impairment in 2-VO rats evaluated by the object recognition test three months after 2-VO surgery. Discrimination index was measured at three months after 2-VO surgery. Data are expressed as mean ± SEM. n = 15 in each groupSham – group subjected to sham two-vessel occlusion surgery; Model – group subjected to two-vessel occlusion surgery without drug treatment; Lut 50 – group subjected to two-vessel occlusion surgery and administered luteolin at 50 mg/kg b.w.; Lut 100 – group subjected to two-vessel occlusion surgery and administered luteolin at 100 mg/kg b.w.; Nimodipine – group subjected to two-vessel occlusion surgery and administered nimodipine at 16 mg/kg b.w.; *– P < 0.05;** – P < 0.01, model group vs. sham group; * –P < 0.05, all three treatment groups vs. model group; ## –P < 0.01, luteolin-treated groups vs. model group
Effects of luteolin on learning and memory impairment in 2-VO rats evaluated by the object recognition test three months after 2-VO surgery. Discrimination index was measured at three months after 2-VO surgery. Data are expressed as mean ± SEM. n = 15 in each groupSham – group subjected to sham two-vessel occlusion surgery; Model – group subjected to two-vessel occlusion surgery without drug treatment; Lut 50 – group subjected to two-vessel occlusion surgery and administered luteolin at 50 mg/kg b.w.; Lut 100 – group subjected to two-vessel occlusion surgery and administered luteolin at 100 mg/kg b.w.; Nimodipine – group subjected to two-vessel occlusion surgery and administered nimodipine at 16 mg/kg b.w.; *– P < 0.05;** – P < 0.01, model group vs. sham group; * –P < 0.05, all three treatment groups vs. model group; ## –P < 0.01, luteolin-treated groups vs. model group

Fig. 2

Effects of luteolin on the PI3K/Akt pathway in the cerebral cortex (A) and hippocampus (B) of 2-VO rats shown in the relative intensity of PI3K subunits of p110α and representative Western blot images of important factors in the PI3K pathway three months after 2-VO surgery. Data are expressed as mean ± SEM. n = 4 in each groupSham – group subjected to sham two-vessel occlusion surgery; Model – group subjected to two-vessel occlusion surgery without drug treatment; Lut 50 – group subjected to two-vessel occlusion surgery and administered luteolin at 50 mg/kg b.w.; Lut 100 – group subjected to two-vessel occlusion surgery and administered luteolin at 100 mg/kg b.w.; Nimodipine – group subjected to two-vessel occlusion surgery and administered nimodipine at 16 mg/kg b.w.; PI3K – phosphatidylinositol 3-kinase; β-actin – total protein amount normaliser; # – P < 0.05, model group vs. sham group; * – P < 0.05, luteolin-treated groups vs. model group; ns – non-significant
Effects of luteolin on the PI3K/Akt pathway in the cerebral cortex (A) and hippocampus (B) of 2-VO rats shown in the relative intensity of PI3K subunits of p110α and representative Western blot images of important factors in the PI3K pathway three months after 2-VO surgery. Data are expressed as mean ± SEM. n = 4 in each groupSham – group subjected to sham two-vessel occlusion surgery; Model – group subjected to two-vessel occlusion surgery without drug treatment; Lut 50 – group subjected to two-vessel occlusion surgery and administered luteolin at 50 mg/kg b.w.; Lut 100 – group subjected to two-vessel occlusion surgery and administered luteolin at 100 mg/kg b.w.; Nimodipine – group subjected to two-vessel occlusion surgery and administered nimodipine at 16 mg/kg b.w.; PI3K – phosphatidylinositol 3-kinase; β-actin – total protein amount normaliser; # – P < 0.05, model group vs. sham group; * – P < 0.05, luteolin-treated groups vs. model group; ns – non-significant

Fig. 3

Effects of Luteolin on the PI3K/Akt pathway in the cerebral cortex (A) and hippocampus (B) of 2-VO rats shown as the relative intensity of PI3K subunits of p85 and representative Western blot images of important factors in the PI3K pathway three months after 2-VO surgery. Data are expressed as mean ± SEM. n = 3 in each groupSham – group subjected to sham two-vessel occlusion surgery; Model – group subjected to two-vessel occlusion surgery without drug treatment; Lut 50 – group subjected to two-vessel occlusion surgery and administered luteolin at 50 mg/kg b.w.; Lut 100 – group subjected to two-vessel occlusion surgery and administered luteolin at 100 mg/kg b.w.; Nimodipine– group subjected to two-vessel occlusion surgery and administered nimodipine at 16 mg/kg b.w.; PI3K – phosphatidylinositol 3-kinase; β-actin – total protein amount normaliser;# – P < 0.05, model group vs. sham group; * – P < 0.05, luteolin-treated groups vs. model group; ns – non-significant
Effects of Luteolin on the PI3K/Akt pathway in the cerebral cortex (A) and hippocampus (B) of 2-VO rats shown as the relative intensity of PI3K subunits of p85 and representative Western blot images of important factors in the PI3K pathway three months after 2-VO surgery. Data are expressed as mean ± SEM. n = 3 in each groupSham – group subjected to sham two-vessel occlusion surgery; Model – group subjected to two-vessel occlusion surgery without drug treatment; Lut 50 – group subjected to two-vessel occlusion surgery and administered luteolin at 50 mg/kg b.w.; Lut 100 – group subjected to two-vessel occlusion surgery and administered luteolin at 100 mg/kg b.w.; Nimodipine– group subjected to two-vessel occlusion surgery and administered nimodipine at 16 mg/kg b.w.; PI3K – phosphatidylinositol 3-kinase; β-actin – total protein amount normaliser;# – P < 0.05, model group vs. sham group; * – P < 0.05, luteolin-treated groups vs. model group; ns – non-significant

Fig. 4

Effects of luteolin on the P-Akt/Akt pathway in the cerebral cortex (A) and hippocampus (B) of 2-VO rats shown as the relative intensity of P-Akt and total Akt and representative Western blot images of important factors in the Akt pathway three months after 2-VO surgery. Data are expressed as mean ± SEM. n = 3 in each groupSham – group subjected to sham two-vessel occlusion surgery; Model – group subjected to two-vessel occlusion surgery without drug treatment; Lut 50 – group subjected to two-vessel occlusion surgery and administered luteolin at 50 mg/kg b.w.; Lut 100 – group subjected to two-vessel occlusion surgery and administered luteolin at 100 mg/kg b.w.; Nimodipine – group subjected to two-vessel occlusion surgery and administered nimodipine at 16 mg/kg b.w.; P-Akt – phosphorylated protein kinase B; Akt – protein kinase B; β-actin – total protein amount normaliser; # – P < 0.05, model group vs. sham group; * – P < 0.05, luteolin-treated groups vs. model group; ns – non-significant
Effects of luteolin on the P-Akt/Akt pathway in the cerebral cortex (A) and hippocampus (B) of 2-VO rats shown as the relative intensity of P-Akt and total Akt and representative Western blot images of important factors in the Akt pathway three months after 2-VO surgery. Data are expressed as mean ± SEM. n = 3 in each groupSham – group subjected to sham two-vessel occlusion surgery; Model – group subjected to two-vessel occlusion surgery without drug treatment; Lut 50 – group subjected to two-vessel occlusion surgery and administered luteolin at 50 mg/kg b.w.; Lut 100 – group subjected to two-vessel occlusion surgery and administered luteolin at 100 mg/kg b.w.; Nimodipine – group subjected to two-vessel occlusion surgery and administered nimodipine at 16 mg/kg b.w.; P-Akt – phosphorylated protein kinase B; Akt – protein kinase B; β-actin – total protein amount normaliser; # – P < 0.05, model group vs. sham group; * – P < 0.05, luteolin-treated groups vs. model group; ns – non-significant

Escape latencies in the Morris water maze test in all groups of rats at 1 month after 2-VO surgery (seconds)

Group N Day 1 Day 2 Day 3 Day 4 Day 5
Sham 12 91.18 ± 5.87 52.32 ± 6.03 33.38 ± 5.67 20.09 ± 4.83 22.34 ± 2.1
Model 12 93.2 ± 8.53 53.62 ± 6.04 34.58 ± 5.61 20.89 ± 4.98 24.26 ± 4.56
Lut 50 13 100.9 ± 5.65 55.26 ± 5.52 32.75 ± 5.49 30.63 ± 3.08 24.71 ± 4.98
Lut 100 12 94.35 ± 5.99 60.45 ± 2.76 37.57 ± 6.13 26.48 ± 6.15 23.08 ± 3.36
Nimodipine 12 105.4 ± 5.49 64.91 ± 3.4 39.98 ± 9.33 24.78 ± 6.65 25.28 ± 4.94

Escape latencies in the Morris water maze test in all groups of rats at 3 months after 2-VO surgery (seconds)

Group N Day 1 Day 2 Day 3 Day 4 Day 5
Sham 12 19.6 ± 5.85 10.08 ± 4.81 9.367 ± 4.51 8.49 ± 4.34 6.21 ± 2.22
Model 12 44.34 ± 5.88 37.96 ± 5.59## 27.61 ± 5.55## 35.3 ± 5.40## 37.37 ± 6.07##
Lut 50 13 20.6 ± 5.40 8.553 ± 4.16** 7.66 ± 3.52** 6.93 ± 3.33** 5.77 ± 2.36**
Lut 100 12 26.76 ± 5.84 10.76 ± 4.56** 10.18 ± 4.77** 9.89 ± 5.07** 6.52 ± 3.02**
Nimodipine 12 56.24 ± 5.76 35.33 ± 5.60 35.52 ± 5.82 29.72 ± 7.65 34.48 ± 5.85

Swimming speed of rats on the fifth day in the Morris water maze test (cm/s)

Group N 1 month after 2-VO 3 months after 2-VO
Sham 12 14.25 ± 4.71 16.64 ± 5.70
Model 12 13.12 ± 3.26 15.31 ± 5.46
Lut 50 13 16.42 ± 5.09 17.18 ± 6.07
Lut 100 12 15.07 ± 5.24 16.09 ± 5.93
Nimodipine 12 13.25 ± 3.87 16.21 ± 6.01
eISSN:
2450-8608
Język:
Angielski
Częstotliwość wydawania:
4 razy w roku
Dziedziny czasopisma:
Life Sciences, Molecular Biology, Microbiology and Virology, other, Medicine, Veterinary Medicine
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