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. 2018 Sep;16(3):2229-2234.
doi: 10.3892/etm.2018.6457. Epub 2018 Jul 17.

Morroniside protects against cerebral ischemia/reperfusion injury by inhibiting neuron apoptosis and MMP2/9 expression

Guoyong Zeng  1 , Weijiang Ding  2 , Yin Li  2 , Meiying Sun  3 , Liying Deng  2
Affiliations

Morroniside protects against cerebral ischemia/reperfusion injury by inhibiting neuron apoptosis and MMP2/9 expression

Guoyong Zeng et al. Exp Ther Med. 2018 Sep.

Abstract

The aim of the present study was to investigate the effect of morroniside against matrix metalloproteinase (MMP)2/9 and focal cerebral ischemia/reperfusion (I/R) injury in rats. A rat model of focal cerebral I/R injury rats was established and rats were administered with 30, 90 or 270 mg/kg/day morroniside for 7 days. The expression of MMP2/9 and neuronal apoptosis were assessed. In addition, the expression of active caspase-3, B-cell lymphoma 2 (Bcl-2) and Bcl-2-associated X protein (Bax) were measured. The results revealed that MMP2 and MMP9 expression was upregulated and the percentage of apoptotic neurons was increased in rats with focal cerebral I/R injury compared with the control. However, treatment with morroniside significantly inhibited I/R-induced MMP2/9 expression and neuron apoptosis compared with the untreated I/R injury group. Morroniside administration also decreased the expression of active caspase-3 and increased the Bcl-2/Bax ratio compared with untreated rats with focal cerebral I/R injury. The inhibitory effect of morroniside on MMP2/9 expression and neuron apoptosis was dose dependent. In summary, the results of the present study suggest that morroniside is able to protect against cerebral I/R injury in the brain and may have potential as a therapeutic treatment for patients who have suffered a stroke.

Keywords: cerebral ischemia/reperfusion injury; matrix metalloproteinase-2; matrix metalloproteinase-9; morroniside.

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Figures

Figure 1.
Figure 1.
Western blotting and reverse transcription-quantitative polymerase chain reaction were performed to measure MMP2 and MMP9 (A) protein and (B) mRNA, respectively, in rat brain tissues (n=10). **P<0.01 vs. Con, &P<0.05 an &&P<0.01 vs. Model. MMP, matrix metalloproteinase; Con, control; Low, 30 mg/kg morroniside; Mod, 90 mg/kg morroniside; High, 270 mg/kg morroniside.
Figure 2.
Figure 2.
An immunofluorescence assay was performed to assess the expression of (A) MMP2 and (B) MMP9 in rat brain tissues (n=10). Magnification, ×200. MMP, matrix metalloproteinase; Con, control; Low, 30 mg/kg morroniside; Mod, 90 mg/kg morroniside; High, 270 mg/kg morroniside.
Figure 3.
Figure 3.
(A) A TUNEL assay was performed to quantify apoptotic neurons in a cerebral ischemia/reperfusion injury model (n=10 rats). (B) Western blotting was performed to measure the expression of active caspase-3, Bcl-2 and Bax protein. Magnification, ×200. **P<0.01 vs. Con, &P<0.05 an &&P<0.01 vs. Model. Bcl-2, B-cell lymphoma 2; Bax, Bcl-2-associated X protein; Con, control; Low, 30 mg/kg morroniside; Mod, 90 mg/kg morroniside; High, 270 mg/kg morroniside.
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