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NIS - libdoc.who.int - World Health Organization

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Folium Salviae<br />

This study was an extension of earlier studies by Yasukawa et al. (81) and<br />

Okuyama et al. (80).<br />

Cholinergic activity<br />

Studies were carried out to evaluate the cholinergic receptor-binding activity<br />

of ethanol extracts prepared from leaves of S. officinalis. Plant extracts<br />

were screened for their ability to displace [ 3 H]-(N)-nicotine from nicotinic<br />

receptors and [ 3 H]-(N)-scopolamine from muscarinic receptors, in homogenates<br />

of human cerebral cortical cell membranes. The most potent extracts,<br />

prepared from three Salvia species had a median inhibitory concentration<br />

(IC 50<br />

) of < 1 mg/ml. The displacement curves of some of these extracts were<br />

comparable with that of carbamylcholine chloride, a potent acetylcholine<br />

analogue. Choline, a weak nicotinic ligand (IC 50<br />

, 3 × 10-4 M) was found in<br />

extracts at concentrations of 10 -6 – 10 -5 M. However, at the concentrations<br />

studied, choline accounted for only 5% of the displacement activity observed.<br />

Although most extracts screened expressed some nicotinic and muscarinic<br />

activity, only a few showed dose-dependent receptor activity typical<br />

of compounds with genuine cholinergic activity (57). Mnemogenic effects of<br />

the ethanol extract from the leaves of S. officinalis (50 mg/kg, administered<br />

<strong>int</strong>raperitoneally) were tested in rats. Interactions of the extract with the<br />

cholinergic system in memory retention of passive avoidance learning were<br />

investigated. Administration of the extract increased memory retention.<br />

Stimulation of muscarinic and nicotinic cholinoreceptors by pilocarpine (0.5<br />

and 1 mg/rat) and nicotine (0.1 and 1 µg/rat) potentiated the response of the<br />

extract and increased memory retention (F 4,25<br />

= 7.67, p < 0.001) (83).<br />

Neuroprotective effect<br />

The effect of a standardized extract of the leaves of S. officinalis and its<br />

active ingredient rosmarinic acid on Alzheimer amyloid-β peptide (Aβ)-<br />

induced toxic effects in cultured rat pheochromocytoma PC12 cells was<br />

evaluated. Incubation of PC12 cells with Aβ (fragment 1-42) for 24 hours<br />

caused cell death and this effect was reduced by the extract, and by rosmarinic<br />

acid. Rosmarinic acid reduced a number of events induced by Aβ.<br />

These included formation of reactive oxygen species, lipid peroxidation,<br />

DNA fragmentation, caspase-3 activation, and tau protein hyperphosphorylation.<br />

Moreover, rosmarinic acid inhibited p-p38 mitogen-activated<br />

protein kinase, but not glycogen synthase kinase-3 activation. These<br />

data demonstrated a neuroprotective effect of Salvia leaf extract against<br />

Aβ-induced toxicity, which could support the use of this plant in the<br />

treatment of Alzheimer disease. Rosmarinic acid could contribute, at least<br />

in part, to the extract-induced neuroprotective effect (84).<br />

351

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