Post-stroke treatment of storax improves long-term outcomes of stroke in rats

Ethnopharmacological relevance: The lack of widely applicable pharmacological treatments for ischemic stroke patients has led to a growing interest in traditional medicine. The identification of pharmacologically active components of the clinically used traditional medicine has been considered translationally significant. SuHeXiang Wan is a prescription containing 15 herbs approved by Chinese National Drug Administration (CNDA) for treating ischemic stroke. Storax is one of the main contents in this prescription and is believed to play a significant pharmacological role, which has been used to treat stroke for nearly 1000 years in traditional Chinese medicine. Emerging experimental investigations suggested Storax might be effective for treating ischemic stroke. Aim of the study: This study aimed to test our hypothesis that post-stroke treatment of Storax can improve longterm outcomes of stroke. Materials and methods: Male Wistar rats (250-280 g) subjected to 2 h of MCAO following reperfusion were treated with Storax by intragastric at 1 h and repeated at 3 h, 6 h after stroke. In the first set experiment, an array of neurological function deficits assessments were tested before and after stroke, brain lesion size was examined at 28 days after ischemia. CD31 and synatophysin were analyzed by immunohistochemistry. In the second set experiment, markers of proinflammatory activation were determined at 24 h after stroke. ELISA was performed to analyze brain concentrations of TNF-alpha, IL-18 and circulating levels of iNOS, ET-1, and immunohistochemistry was performed to determine GFAP, IBA-1 and NF-Kappa B p65. Results: Storax significantly alleviated neurological deficits from 7 days after stroke and lasted until 28 days, corresponding to the significantly decreased lesion volume at 28 days after stroke; Meanwhile, Storax increased the density of CD31and SYP in peri-infarct areas. At 24 h after stroke, Storax significantly inhibited brain TNF-alpha, IL-18 expression and circulating iNOS, ET-1 levels, reduced the NF-Kappa B/p65 positive cell number, and decreased activated microglia/macrophages and astrocytes cell numbers alongside reversed their morphological transformations. Conclusion: Our experimental findings demonstrate treatment of Storax at the acute phase significantly improves long-term neurological outcomes in the focal stroke model of rats. We also speculate that inhibition of acute proinflammation activation by Storax might be associated with its beneficial pharmacological effect, but remain to define and elucidate in future investigation.