Abstract
Stroke is a cerebrovascular disease that results in decreased blood flow. Although Panax notoginseng (PN), a Chinese herbal medicine, has been proven to promote stroke recovery, its molecular mechanism remains unclear. In this study, middle cerebral artery occlusion (MCAO) was induced in rats with thrombi generated by thread and subsequently treated with PN. After that, staining with 2,3,5-triphenyltetrazolium chloride was employed to evaluate the infarcted area, and electron microscopy was used to assess ultrastructural changes of the neurovascular unit. RNA-Seq was performed to determine the differential expressed genes (DEGs) which were then verified by qPCR. In total, 817 DEGs were identified to be related to the therapeutic effect of PN on stroke recovery. Further analysis by Gene Oncology analysis and Kyoto Encyclopedia of Genes and Genomes revealed that most of these genes were involved in the biological function of nerves and blood vessels through the regulation of neuroactive live receptor interactions of PI3K-Akt, Rap1, cAMP, and cGMP-PKG signaling, which included in the 18 pathways identified in our research, of which, 9 were reported firstly that related to PN's neuroprotective effect. This research sheds light on the potential molecular mechanisms underlying the effects of PN on stroke recovery.
Highlights
Stroke is a major cause of death in the world, and it can lead to long-term disability [1]
In order to evaluate the protective effect of PN on cerebral ischemia, on the seventh day of the experiment, the neurological functions were assessed blindly using the Longa Neurological Severity Score; the brain was removed after anesthesia (Figure 1) and subjected to triphenyltetrazolium chloride (TTC) staining in order to evaluate the scope of infarction (Figure 2)
Comparing with the middle cerebral artery occlusion (MCAO) group treated with saline, PN-treated animals showed decreased disease score (Figure 2(a)) and significantly less infarct area (Figures 2(b) and 2(c))
Summary
Stroke is a major cause of death in the world, and it can lead to long-term disability [1]. It has been reported that at least twenty saponins were contained in this material, including notoginsenoside R1, ginsenoside Rb1, and ginsenoside Rg1 [5, 6] It is anti-inflammatory and antioxidative, and it is able to regulate the balance of neurotransmitters and promoting the regeneration of nerves and blood vessels [7,8,9]. It has been reported that PN exerted neuroprotective effect in stroke through antioxidative and anti-inflammatory properties [11]; in combination with Angelica sinensis, it could inhibit NF-κΒ signaling and DNA binding activity, downregulate NO, NLRP3 inflammasome formation, and influence microglial pyroptosis [12, 13]. Further studies need to be conducted to explore underlying mechanism(s) of PN’s protective effects on NVU, especially in stroke
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