Oral administration of baicalein-enriched fraction during pre- and post-ischemic stroke alleviated cognitive impairments in rat models

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Abstract
In recent years, numerous studies have discovered the potential of natural compounds extracted from medicinal plants as a promising alternative treatment for ischemic stroke (IS). Oroxylum indicum is among the plants that has been widely proven to contain a beneficial flavonoid compound known as baicalein. However, the therapeutic potential of this compound for IS disease has yet to be demonstrated. In this study, a baicalein-enriched fraction (BEF) was harvested from the leaves of O. indicum and tested on neural stem cells (NSCs) to determine its effects on the cell viability and gene expression prior to an in vivo animal study. NSCs were chosen because they are the primitive brain cells that play important roles in neurogenesis after IS injury. It was found that NSCs treated with BEF at concentration of 3.125 µg/mL for 48 hours showed a significant higher cell proliferation rate. Moreover, these cells expressed high NSC markers (Nestin and SOX2) and genes responsible for antioxidant (SOD2) and angiogenesis (ANGPT1) mechanisms, indicating that the BEF treatment could enhance the progenitor brain cells viability and the expression of cytokines that are beneficial to reduce oxidative stress and reinstate blood flow in an ischemic brain. Subsequently, the in vivo therapeutic effects of BEF for IS disease was tested by administering 50 mg/kg b.wt of BEF to male Sprague Dawley (SD) rats via oral gavage before and after induction of IS. Assessments of neurological impairments were performed using a modified neurological severity score (mNSS) and the quantification of the total infarct volume was evaluated as the endpoint of this study. Results showed that an oral administration of BEF improved the behavioral scoring for motor functions (forelimb flexion and forelimb twisting), contralateral sensory functions (paw-whiskers test), motor coordination, balance functions (beam balance test) and reflex functions (pinna, corneal, startle and tail reflex) within 24–72 h; alternatively, the non-treated rats showed continuously lower scores for all the tests throughout the study, indicating that the BEF-treated rats exhibited a faster recovery rate as compared to the non-treated rats. Such improvements were observed up to two weeks. In addition, histological assessment also revealed a reduction of infarct volume in the BEF-treated rats as compared to the control rats. In summary, the present study demonstrated the potential of BEF extracted from the O. indicum as a supplement to improve preclinical IS models.