MOTHERWORT PLAYS A PROTECTIVE ROLE IN CEREBRAL ISCHEMIA MODEL MICE BY ACTIVATING NRF-2/HO-1 SIGNALING PATHWAY

Shuai Wang¹, Junye Shen^{2, *}, Yingsong Zhou³

¹Department of Rehabilitation Medicine, Hwa Mei Hospital, University of Chinese Academy of Sciences, Ningbo, PR China - ²Department of Traditional Chinese Medicine, Hwa Mei Hospital, University of Chinese Academy of Sciences, Ningbo, PR China - ³Faculty of Physical Education, Ningbo University, Ningbo, PR China

Objective: To study the protective effect of leonurine has on cerebral-ischemia-modelling mice through activating the Nrf-2/HO-1 signalling pathway. 

Methods: Sixty healthy and clean adult male Sprague Dawley mice were randomly divided into four groups: false-operation group, control group, low-dosage group and high-dosage group. A right middle cerebral artery occlusion was established in the control group, low-dosage group and high-dosage group according to the thread thrombus method of Zea-Longe. After the success of the modelling was determined by scored behavioural observations, the mice in the low-dosage group and the high-dosage group began to being intravenously injected with 5mg/kg and 10mg/kg of leonurine solution, beginning two hours after the operation and continuing once per day for seven days. The control group was injected with saline of the same volume once a day for seven days, beginning two hours after the operation. A modified neurological deficit score (Longa score) was used to evaluate the behaviour of all of the mice. The water content of brain tissue was measured using a dry-and-wet-weight method: the brain tissue of mice was collected following killing mice, the volume of cerebral infarction was calculated after TTC staining, and the levels of nuclear respiratory factor 2 (Nrf-2) and heme oxygenase-1 (HO-1) in the ischemic-side tissue of mice in each group were measured using a real-time quantitative fluorescence method.

Results: The Longa scores and brain-tissue water content of the control group were significantly higher than for the false-operation group. The Longa scores and brain-tissue water content in the dosed groups were significantly lower than for the control group and decreased with the increase of dose (P<0.05). The blood flow perfusion and the total power of the cerebral cortex for the control group were significantly lower than for the false-operation group. The blood perfusion and the total power of the cerebral cortex in the dosed groups were significantly higher than for the control group; this increased with the increase of dose, the differences being statistically significant (P<0.05). In the control group, the number of Nissl corpuscles in the hippocampal CA1 areas and CA3 areas decreased sharply, the volume decreased and the shape was very irregular; the number of Nissl corpuscles in the low-dosage group was higher than in the control group, the neurons were orderly and the nerve cells were less damaged; the number of Nissl corpuscles in the high-dosage group was higher than in the low-dosage group, and nerve injuries were alleviated. The levels of Nrf-2 and HO-1 in the ischemic-side tissue of the mice in the low-dosage group and the high-dosage group were significantly higher than the levels in the false-operation group. The levels of Nrf-2 and HO-1 on the ischemic-side tissue of the mice treated with leonurine were significantly higher than the levels for the control group; the difference was statistically significant with the increase of dose (P<0.05). 

Conclusion: Leonurine has certain protective effects on the brain tissue of cerebral-ischemia-modelling mice; this protective effect may be enacted by activating Nrf-2/HO-1 signalling pathway.