Antihyperalgesic activity of salvianolic acid B and its formulations in the chronic constriction injury of the sciatic nerve (CCI) model of neuropatic pain

Salvianolic acid B (Sal B) is the most abundant and the major active antioxidant from S. miltiorrhiza preventing Aβ25–35-induced reduction in BPRP in PC12 cells [1], having neuronprotective effect against hydrogen peroxide (H₂O₂)-induced rat pheochromocytoma line PC12 injury [2] and inhibiting HIV-1 replication [3]. In the framework of a large screening of natural constituents, the antihyperalgesic activity of Sal B was tested by the Paw-pressure test, in a model of neuropathic pain produced by a chronic constriction injury of the sciatic nerve. Size exclusion chromatography (Sephadex LH-20) was used for a rapid separation and refinement of Sal B from the crude extract of the roots of S. miltiorrizha Bunge (danshen). Hydroalchoholic solutions were used as eluents for a safe and convenient separation obtaining Sal B almost pure by NMR (>96%). Liposomial formulations were prepared using egg phosphatydil choline, cholesterol and 18:0/18:0 PEG 2000 in the case of long circulationg liposome. Encapsulation efficacy of Sal B was evaluated by HPLC-DAD, while size, polydispersion index and zeta potential by dynamic light scattering. Sal B and two formulations, liposomes and long circulating liposomes, administered intraperitoneally at the dose of 100mg/kg, reverted the mechanical hyperalgesia in CCI treated rats, evaluated in the Paw-pressure test. The antihyperalgesic effect started 15min. after administration and in the case of long circulating liposomes the antihyperalgesic effect was still significant at 45min. The prolonged, delayed and increased therapeutic effect of the long circulating liposomes was also supported by preliminary pharmacokinetic studies.

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2. Liu, CS. et al. (2006) Phytomedicine 14:492.

3. Abd-Elazem IS. et al. (2002) Antivir. Res. 55:91.