ligustilide and Stroke

Stroke is a result of cerebral ischemia that triggers a cascade of both physiological and biochemical events. No effective treatment is available for stroke; however, stem cells have the potential to rescue tissue from the effects of stroke. Adipose-derived stem cells (ADSCs) are an abundant source of adult stem cells; therefore, ADSC therapy can be considered as a future strategy for regenerative medicine. However, more research is required to improve the effectiveness of transplanted ADSCs as a treatment for stroke in the mouse stroke model. Ligustilide, isolated from the herb Angelica sinensis, exhibits a protective effect on neurons and inhibits inflammation. We also demonstrated that ligustilide treatment increases the expression levels of homing factors such as SDF-1 and CXCR4. In the present study, we evaluated the therapeutic effects of ADSC transplantation and ligustilide treatment in a mouse thromboembolic stroke model by behavioral tests, including beam walking, locomotor activity, and rotarod analysis. ADSCs pretreated with ligustilide were transplanted into the brains of stroke mice. The results showed that the therapeutic effect of ADSCs pretreated with ligustilide was better than that of ADSCs without ligustilide pretreatment. There was no difference between the recovery of mice treated by ADSC transplantation combined with subcutaneous ligustilide injection and that of mice treated only with ADSCs. The TUNEL assay showed fewer apoptotic cells in the brains of mice transplanted with ADSCs pretreated with ligustilide as well as in those without pretreatment. In summary, pretreatment of ADSCs with ligustilide improves the therapeutic efficacy of ADSC transplantation. The results of this study will help improve stem cell therapies being developed for future clinical applications.

Topics: 4-Butyrolactone; Adipose Tissue; Animals; Apoptosis; Cell- and Tissue-Based Therapy; Cells, Cultured; Chemokine CXCL12; Disease Models, Animal; Mice; Mice, Inbred BALB C; Receptors, CXCR4; Stem Cell Transplantation; Stem Cells; Stroke; Thromboembolism

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