Abstract

BackgroundNaoshuantong capsule (NSTC) is an oral Chinese medicine formula composed of Typhae Pollen, Radix Paeoniae Rubra, Curcumae Radix, Gastrodiae Rhizoma and Radix Rhapontici. It has been widely used at the acute and recovery stage of ischemic stroke since 2001. Comparing with its wide clinical application, there are only few studies emphasize on investigating its pharmacological effects.MethodsTo more generally elucidate the underlying mechanisms in this study, we identified active ingredients in NSTC by a network pharmacology approach based on transcriptomics analysis and pharmacological experiments. Modified neurological severity scores and morphometric analysis using Nissl staining were employed to evaluate the neuroprotective effects of NSTC on ischemia stroke in mice.ResultsThe results showed that NSTC had preventive and protective effects on ischemia stroke, featuring repair of brain tissue during the sub-acute stage of stroke. This may attribute to the underlying mechanisms including anti-inflammatory, antioxidant, and anti-apoptotic activities, as well as an attenuation of excitatory amino acids (EAAs) toxicity of the active ingredients, especially the most active apigenin, from NSTC. Specifically, naringenin, calycosin, gastrodin, caffeic acid, paeoniflorin, and β-elemene seem to be also pharmacological active substances responsible for the anti-inflammatory effects. Meanwhile, 13-hydroxygemone, gastrodin, and p-hydroxybenzyl alcohol contributed to the attenuation of EAAs toxicity Furthermore, apigenin, naringenin, calycosin, gastrodin, and β-elemene accelerated the repair of brain ischemic tissue by up-regulating the expression of TGF-β1 levels.ConclusionsThe present study identifies the active ingredients of NSTC and illustrates the underlying mechanism using a combination of network pharmacology, transcriptomics analysis, and pharmacological experiments.

Highlights

  • Naoshuantong capsule (NSTC) is an oral Chinese medicine formula composed of Typhae Pollen, Radix Paeoniae Rubra, Curcumae Radix, Gastrodiae Rhizoma and Radix Rhapontici

  • Luo et al Chin Med (2020) 15:119 oral Traditional Chinese medicine (TCM) formula Naoshuantong capsule (NSTC) is an oral Chinese medicine formula composed of Typhae Pollen (TP), Radix Paeoniae Rubra (PR), Curcumae Radix (CR), Gastrodiae Rhizoma (GR) and Radix Rhapontici (RR) was approved by the China Food and Drug Administration (CFDA) as a clinical drug for stroke in 2001

  • Fifty-four signaling pathways were enriched for differentially expressed genes (DEGs) between the NSTC and IS groups, covering signal transductions, inflammatory responses, neurotransmitters and synapses, as well as cell apoptosis. These results suggested that NSTC started to exert therapeutic effects within 4 h after stroke, and the main mechanism that the TCM formula repressed acute inflammatory responses, curbed cell apoptosis in neurons, restored signal transmission and regulated neurotransmitters synapses

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Summary

Introduction

Naoshuantong capsule (NSTC) is an oral Chinese medicine formula composed of Typhae Pollen, Radix Paeoniae Rubra, Curcumae Radix, Gastrodiae Rhizoma and Radix Rhapontici. It has been widely used at the acute and recovery stage of ischemic stroke since 2001. Comparing with its wide clinical application, there are only few studies emphasize on investigating its pharmacological effects. Luo et al Chin Med (2020) 15:119 oral TCM formula Naoshuantong capsule (NSTC) is an oral Chinese medicine formula composed of Typhae Pollen (TP), Radix Paeoniae Rubra (PR), Curcumae Radix (CR), Gastrodiae Rhizoma (GR) and Radix Rhapontici (RR) was approved by the China Food and Drug Administration (CFDA) as a clinical drug for stroke in 2001. The constituents [7] and metabolic profile [8] of NSTC have been fully investigated, not much research has been done in pharmacological mechanism of NSTC, which is an emerging bottleneck restraining its clinical application

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