ligustilide and Brain-Edema

Essential oil (EO) of Kelussia odoratissima Mozaff, whose main composition is Z-ligustilide, has been shown to have strong antioxidant and anti-inflammatory effects and potent neuroprotective properties.. This study examined whether or not the EO could ameliorate brain damage and behavioural dysfunction in a thromboembolic model of stroke in rats and compare its effects to that of the purified Z-ligustilide.. Stroke was induced in rats by middle cerebral artery occlusion using an autologous pre-formed clot. EO (10 mg kg(-1) and 45 mg kg(-1)) and Z-ligustilide (20 mg kg(-1)) were injected intraperitoneally 1 h prior to embolization. Behavioural scores, infarct size and brain oedema, as well as the level of tumour necrosis factor-alpha (TNF-α), malondialdehyde, glutathione, catalase and superoxide dismutase activity were determined in the ipsilateral cortex 24 hours following stroke induction.. EO (45 mg kg(-1)), statistically similar to Z-ligustilide (20 mg kg(-1)), curtailed brain infarction and oedema, improved behavioural scores and prevented enhanced oxidative stress and TNF-α level in the ischaemic brain tissues.. The findings provide the first evidence of effectiveness of the extract in a thromboembolic model of stroke, whose action can be mediated, at least in part, by the antioxidative and anti-inflammatory mechanisms.

Topics: 4-Butyrolactone; Animals; Antioxidants; Apiaceae; Brain Edema; Catalase; Cerebral Cortex; Disease Models, Animal; Glutathione; Infarction, Middle Cerebral Artery; Male; Malondialdehyde; Oxidative Stress; Plant Extracts; Rats; Rats, Wistar; Stroke; Superoxide Dismutase; Tumor Necrosis Factor-alpha

Subarachnoid hemorrhage (SAH) is a devastating stroke subtype accounting for approximately 3 to 7% of cases each year. Despite its rarity among the various stroke types, SAH is still responsible for approximately 25% of all stroke fatalities. Although various preventative and therapeutic interventions have been explored for potential neuroprotection after SAH, a considerable percentage of patients still experience serious neurologic and/or cognitive impairments as a result of the primary hemorrhage and/or secondary brain damage that occurs. Z-ligustilide (LIG), the primary lipophilic component of the Chinese traditional medicine radix Angelica sinensis, has been shown to reduce ischemic brain injury via antiapoptotic pathways. Accordingly, in our study, we investigated the neuroprotective potential of LIG after experimental SAH in rats. Rats with SAH that was induced using the established double hemorrhage model were studied with and without LIG treatment. Mortality, neurobehavioral evaluation, brain water content, blood-brain barrier (BBB) permeability, and vasospasm assessment of the basilar artery were measured on days 3 and 7 after injury. Additional testing was done to evaluate for apoptosis using TdT-mediated dUTP-biotin nick end labeling staining as well as immunohistochemistry and Western blotting to identify key proapoptotic/survival proteins, i.e., p53, Bax, Bcl-2, and cleaved caspase-3. The results showed that LIG treatment reduced mortality, neurobehavioral deficits, brain edema, BBB permeability, and cerebral vasospasm. In addition, treatment reduced the number of apoptotic cells in the surrounding brain injury site, which accompanied a marked down-regulation of proapoptotic proteins, p53, and cleaved caspase-3. Our data suggest that LIG may be an effective therapeutic modality for SAH victims by altering apoptotic mechanisms.

Topics: 4-Butyrolactone; Angelica sinensis; Animals; Blood-Brain Barrier; Brain Edema; Disease Models, Animal; Dose-Response Relationship, Drug; In Situ Nick-End Labeling; Male; Neuroprotective Agents; Phytotherapy; Plant Oils; Random Allocation; Rats; Rats, Sprague-Dawley; Subarachnoid Hemorrhage; Vasospasm, Intracranial

The present study investigated the effect of Z-Ligustilide (LIG), a characterized 3-n-alkyphthalide derivative existed in many medical Umbelliferae plants, on permanent focal ischemic brain injury in rats. Focal cerebral ischemia was induced by the occlusion of middle cerebral artery (MCA) for 24 h. LIG (20, or 80 mg/kg), orally administered at 2 h after ischemia, reduced the cerebral infarct volumes by 48.29% and 84.87% respectively compared to control group as visualized by 2,3,5-triphenyltetrazolium chloride (TTC) staining (p<0.01). Treatment with LIG could dose-dependently reduce brain swelling by 68.62% and 82.08% (p<0.01), and significantly improve behavioral deficits (p<0.01). In addition, LIG at the above used doses had no significant effect on rat body temperature. These data, along with previous findings in our lab demonstrating the neuroprotective effects of LIG in transient cerebral ischemia, suggest that LIG may be a potential neuroprotective agent for the treatment of ischemic stroke in future.

Topics: 4-Butyrolactone; Animals; Body Temperature; Brain Edema; Brain Ischemia; Infarction, Middle Cerebral Artery; Male; Neurologic Examination; Neuroprotective Agents; Rats; Rats, Sprague-Dawley