Abstract
Traditional uses and current results highlight the neuroprotective properties of Rosmarinus officinalis L. The compelling need for novel strategies able to relieve neuropathic pain encouraged us to analyze different rosemary leaf extracts in rats following chronic constriction injury (CCI) of sciatic nerve. Ethanol, acetone, and the innovative ultrasound-hexane extractive methods were used to obtain: EE, AE, and for hexane extracts UREprel and URE. Extracts were characterized in terms of typical constituents and repeatedly administered to CCI-rats (13-days treatment, from the day of surgery). URE showed the best efficacy and potency in reducing hypersensitivity to noxious- and non-noxious stimuli and spontaneous pain. URE contained the higher quantity of the terpenoid carnosic acid (CA) and its efficacy was compared to pure CA. Histological analysis of the sciatic nerve revealed that URE prevented axon and myelin derangement, edema and inflammatory infiltrate. In the dorsal horn of the spinal cord, URE did not reduce astrocyte activation. Both the pain reliever and the neuroconservative effects of URE were significantly prevented by the nicotinic receptor (nAChR) antagonist mecamylamine. In conclusion, the hexane-ultrasound rosemary extract is able to reduce neuropathic hypersensitivity and protect nervous tissues. Effectiveness is mainly related to the terpenoid fraction by mechanisms involving nAChRs.
Highlights
Rosmarinus officinalis L. (Lamiaceae), commonly called rosemary, is woody perennial herb native of the Mediterranean region and widely spread in European countries
As previously assessed[25] the total phenolic extract was obtained using ethanol (EE), the acetone extract was applied to selectively recover terpenoids and several lipophilic flavonoids without containing rosmarinic acid (AE); extracts enriched in terpenoids, in carnosic acid (CA), were obtained by n-hexane extraction assisted by ultrasounds (UREprel and URE)
EE (Fig. 1a) typically contains all the components that characterize the phenolic fraction: rosmarinic acid and other minor cinnamoyl derivatives, a group of glycosylated and methoxylated flavonoids and the diterpenoid fraction mainly constituted by CA and derivatives[25]
Summary
Rosmarinus officinalis L. (Lamiaceae), commonly called rosemary, is woody perennial herb native of the Mediterranean region and widely spread in European countries. The efficacy against acute pain is most closely related to the muscarinic component[20,21], on the contrary the cholinergic relevance in neuropathic pain management is imputable to the nicotinic acetylcholine receptors (nAChRs)[22]. Both the anti-hypersensitive and neuroprotective effects of the ACh synthesis promoter acetyl-l-carnitine are blocked by mecamylamine, a nonselective nAChR antagonist[22]. Aim of this study was to investigate the efficacy of novel extracts of Rosmarinus officinalis leaves on Chronic Constriction Injury (CCI) induced neuropathic pain in the rat, a model of trauma-induced neuropathy representative of compressive damage. The pharmacodynamic relevance of nAChRs in rosemary anti-neuropathic activity was assessed
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