Effect of crocus sativus L. (saffron) stigma and its constituents, crocin and safranal, on morphine withdrawal syndrome in mice

Abstract

Crocus sativus L. has been shown to interact with the opioid system. Thus, the effects of aqueous and ethanolic extracts of stigma and its constituents were evaluated on morphine-withdrawal syndrome in mice. Dependence was induced using subcutaneous (s.c.) injections of morphine for 3 days. On day 4, morphine was injected 0.5 h prior the interaperitoneal (i.p.) injections of the extracts, crocin, safranal, clonidine (0.3 mg/kg) or normal saline. Naloxone was injected (5 mg/kg i.p.) 2 h after the final dose of morphine and the number of episodes of jumping during 30 mm was considered as the intensity of the withdrawal syndrome. Clonidine, the aqueous and ethanolic extracts of saffron reduced the jumping activity. Safranal was injected (s.c.) 30 mm prior and 1 and 2 h after the injection of morphine. It potentiated some signs of withdrawal syndrome. The aqueous extract decreased the movement in all of the doses (80, 160, 320 mg/kg) and the ethanolic extract decreased it in the dose of 800 mg/kg in open field test. But crocin and the dose of 400 mg/kg ethanolic extract showed no effect on activity in this test. It is concluded that the extracts and crocin may have interaction with the opioid system to reduce withdrawal syndrome.

Neuroinflammation and Endoplasmic Reticulum Stress Are Coregulated by Crocin To Prevent Demyelination and Neurodegeneration

“…Crocin is the active ingredient in saffron, a natural spice commonly used in northern Indian and Persian cooking (65), and has been shown to prevent TNF-a-induced cell death of neuronally differentiated PC-12 cells (50). Crocin also diminishes free radical-induced stress, evidenced by the suppression of NO and malondialdehyde, in the brain after cerebral ischemia (52).…”

Saffron: a natural product with potential pharmaceutical applications

“…[50,51] More specifically, Imenshahidi et al reported that pretreatment of mice with intraperitoneal injection of crocin at a dose of 600 mg/kg for 4 days and 30 min before morphine administration, blocked the acquisition of morphine conditioned place preference (CPP). [51] Similarly, Hosseinzadeh and Jahanian have shown that both aqueous and higher doses of ethanolic saffron extracts suppressed morphine withdrawal syndrome in mice by reducing the number of jumping episodes.…”

“…Interestingly, they also reported that the inhibitory effect of crocin alone on locomotor parameters was significantly lower than that of the aqueous extract, indicating a more specific effect of crocin on opioid system with reduced adverse effect rate. [50] Learning and memory effects: impact on Alzheimer's and Parkinson's diseases Concerning spatial cognitive abilities after chronic cerebral hypoperfusion, the administration of saffron extract or crocin solution significantly improved memory skills in rats compared with controls. [52] Several studies have been published by Abe's Research Group indicating the favourable effect of saffron extract, crocin and crocetin on memory and learning skills, in ethanol-induced learning behaviour impairments in swine.…”

Medicinal plants with central nervous effects (part 2): plant based review

“…In addition, there was an ameliorative change with saffron extract and honey syrup against AlCl 3 neurotoxicity. The obtained molecular results suggested that AlCl 3 made induction for BCL-W gene, which was an anticancer gene or belonged to the DNA repair system in the brain cells, as well as for R-spondin and inositol polyphosphate 4-phosphatase genes, which helped in cell proliferation [113].…”