Oleuropein, Chief Constituent of Olive Leaf Extract, Prevents the Development of Morphine Antinociceptive Tolerance through Inhibition of Morphine-induced L-type Calcium Channel Overexpression.
Zare, Leila 1; Esmaeili-Mahani, Saeed 1; Abbasnejad, Mehdi 1; Rasoulian, Bahram 2; Sheibani, Vahid 3; Sahraei, Hedayat 4; Kaeidi, Ayat 2
[Article]
Phytotherapy Research.
26(11):1731-1737, November 2012.
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: It has been shown that blockade of L-type calcium channels could abolish the development of opioid-induced antinociceptive tolerance. Here, the antitolerant effects of olive leaf extract (OLE) and its main component, oleuropein, which have a calcium channel blocker property were determined. Adult male Wistar rats were injected with morphine (20 mg/kg, i.p.) for 8 days to induce antinociceptive tolerance. Then OLE (50-200 mg/kg i.g.) and oleuropein (1-10 mg/kg i.p.) were injected concomitantly with morphine. The tail-flick test was used to assess the nociceptive threshold. The dorsal half of the lumbar spinal cord was assayed for the expression of L-type calcium channel using semiquantitative RT-PCR.
The results showed that OLE (200 mg/kg) completely prevented morphine tolerance development. In addition, oleuropein in dose of 10 mg/kg, but not in 5 mg/kg, prevented the development of morphine antinociceptive tolerance. In addition, a significant increase in the mRNA levels of calcium channel (43.9%) was observed in the lumbar spinal cord of tolerant animals, which was reversed by effective of dose OLE.
In conclusion, the results indicate that olive leaf extract has a potential antitolerant property against the chronic usage of morphine and that its main component, oleuropein, is responsible for such effect. Copyright (C) 2012 John Wiley & Sons, Ltd.
Copyright (C) 2012 John Wiley & Sons, Inc.
