Escin ameliorates the impairments of neurological function and blood brain barrier by inhibiting systemic inflammation in intracerebral hemorrhagic mice.

This study aims to investigate whether escin ameliorates the impairments of neurological function by ameliorating systemic inflammation instead of targeting the brain directly in intracerebral hemorrhage (ICH) mice. It showed that escin did not cross the blood brain barrier (BBB). Compared with the ICH group, the Garcia test scores in the escin groups were significantly increased. Brain water contents and Evans blue extravasation of the right basal ganglia in the ICH group were augmented, and significantly reduced by escin. Escin abated the increases of monocyte counts and serum IL-1ß levels induced by ICH. IL-1ß administration reversed the effect of escin on Garcia test scores, the brain water contents, and the Evans blue extravasation. Escin ameliorated the increasing levels of RhoA, ROCK1, nuclear NF-κB and the decreasing expression of IκBα, cytosolic NF-κB, occludin, claudin-5 in the ICH group. IL-1ß administration blocked not only escin-mediated increases of IκBα, cytosolic NF-κB, occludin, and claudin-5, but also escin-caused decreases of RhoA, ROCK1, and nuclear NF-κB. The results indicate that escin improves neurological outcomes and the BBB function in ICH mice, which is associated with attenuating ICH-induced peripheral system inflammation, and therefore, inhibiting IL-1ß/RhoA/NF-κB signaling pathway in BBB, at least in part. These findings suggest that it may be useful to ameliorate brain injury by inhibiting systemic inflammation instead of aiming to target the brain directly after ICH.

Coadministration of hydroxysafflor yellow A with levodopa attenuates the dyskinesia.

Levodopa (L-DOPA) is used as the most effective drug available for the symptomatic treatment of Parkinson's disease (PD). However, long-term treatment of L-DOPA frequently causes complications, including abnormal involuntary movements such as dyskinesia and response fluctuations in PD patients. In the present work, we investigated whether hydroxysafflor yellow A (HSYA) ameliorates L-DOPA-induced dyskinesia and motor fluctuations in the 6-hydroxydopamine-lesioned rat model of PD. Valid PD rats were treated daily with vehicle, HSYA alone, L-DOPA, or a combination of HSYA plus L-DOPA for 21days, respectively. L-DOPA (8mg/kg) and benserazide (15mg/kg) were treated intraperitoneally. HSYA was administrated intraperitoneally at a dose of 10mg/kg. The abnormal involuntary movements and rotational behavior were evaluated. The expression of the dopamine D3 receptor in the striatum was also assayed. The results demonstrated that daily administration of L-DOPA to PD rats for 21days induced a steady expression of dyskinesia. Coadministration of HSYA with L-DOPA significantly ameliorated L-DOPA-induced dyskinesia. The combination treatment also prevented the shortening of the motor response duration that defines wearing off motor fluctuations. HSYA also inhibited the increase of expression of the dopamine D3 receptor in the striatum. These findings demonstrated that HSYA provided anti-dyskinetic relief against L-DOPA in a preclinical model of PD via regulating the expression of the dopamine D3 receptor. The combination of L-DOPA and HSYA also reduced the likelihood of wearing off development, and may thus support the utility of such compounds for the improved treatment of PD.