Synergy Between Borneol and Extract of Ligusticum chuanxiong Hort Against Cortex and Striatum Ischemia

Background and Objective: Ligusticum Chuanxiong Hort (LC) is often prescribed with borneol (BO) for a better effect in treating ischemic stroke in Asia. However, the mechanism of their combination is unclear till now. This study was aim to explore the synergy between BO and extract of LC (ELC) in protecting cortex and striatum against ischemia attack. Materials and Methods: The rats were divided into sham, model, ELC, BO and ELC+BO groups. Four-vessel occlusion surgery was employed for rat global cerebral ischemia/reperfusion (GCIR) model. After the treatment, the microcirculation, anti-oxidative ability, apoptosis index (Al), levels of apoptosis-related genes, intracellular [Ca2+] and autophagy-related proteins expressions were measured respectively. Results:In cortex, the superiority of ELC was on anti-oxidation, while that of BO was on improvement of brain microcirculation. Both of them inhibited Ca2+ overload and apoptosis in cortex via regulating p53, caspase-3, Bcl-2 and Bax. In striatum, ELC had the superiorities in regulating Al, mTOR, LC3 II/I, besides their common modulation on p53, Beclin 1 and [Ca2+]. Surprisingly, the combined group produced some new targets, including ULK1 in cortex and including CAT, GSH-Px, MDA, iNOS, NO, Bcl-2, Bax, caspase-3 and ULK1in striatum. Conclusion: The superiorities of ELC against cerebral ischemia were in inhibiting oxidation and apoptosis and promoting autophagy, while those of BO were in improving microcirculation and autophagy and inhibiting apoptosis. Their combinative therapy brought some new mechanisms in treating brain ischemia.