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Protective mechanism of rhubarb anthraquinone glycosides in rats with cerebral ischaemia-reperfusion injury: interactions between medicine and intestinal flora.

ABSTRACT: Background:Anthraquinone glycosides extracted from rhubarb have been proven to have significant therapeutic effects on ischaemic stroke. It is well known that anthraquinone glycosides are not easily absorb. Thus, how can rhubarb anthraquinone glycosides (RAGs) exert protective effects on the brain? Is this protective effect related to interactions between RAGs and intestinal flora? Methods:The model used in this study was established by middle cerebral artery occlusion (MCAO) and reperfusion. Twenty-seven adult male Sprague-Dawley (SD) rats were randomly divided into 3 groups: the normal group (A) (non-MCAO?+?0.5% sodium carboxymethyl cellulose (CMC-Na)), model group (B) (MCAO?+?0.5% CMC-Na) and medicine group (C) (MCAO?+?RAGs (15 mg/(kg day)). The rats were fed by gavage once a day for 7 days. Fresh faeces were collected from the normal group to prepare the intestinal flora incubation liquid. Add RAGs, detect the RAGs and the corresponding anthraquinone aglycones by HPLC-UV at different time points. On the 8th day, the rats were euthanized, and the colonic contents were collected and analysed by high-throughput sequencing. In addition, 12 adult male SD rats were randomly divided into 2 groups: the normal group (D) (non-MCAO?+?RAGs (15 mg/(kg day)) and model group (E) (MCAO?+?RAGs (15 mg/(kg day)). The rats were fed by gavage immediately after reperfusion. Blood was collected from the orbital venous plexus, and the RAGs and anthraquinone aglycones were detected by HPLC-UV. Results:The abundance and diversity of the intestinal flora in rats decreased after cerebral ischaemia-reperfusion injury (CIRI). RAGs could effectively improve the abundance of the intestinal flora. In addition, in vitro metabolism studies showed that RAGs were converted into anthraquinone aglycones by intestinal flora. In the in vivo metabolism studies, RAGs could not be detected in the plasma; in contrast, the corresponding anthraquinone aglycones could be detected. Absorption of RAGs may be inhibited in rats with CIRI. Conclusions:CIRI may lead to intestinal flora disorder in rats, and after the administration of RAGs, the abundance of intestinal flora can be improved. RAGs can be metabolized into their corresponding anthraquinone aglycones by intestinal flora so that they can be absorbed into the blood.

SUBMITTER: Li Q

PROVIDER: S-EPMC7275394 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Protective mechanism of rhubarb anthraquinone glycosides in rats with cerebral ischaemia-reperfusion injury: interactions between medicine and intestinal flora.

Li Qiuying Q Guo Ying Y Yu Xiahui X Liu Wenhong W Zhou Liping L

Chinese medicine 20200605

<h4>Background</h4>Anthraquinone glycosides extracted from rhubarb have been proven to have significant therapeutic effects on ischaemic stroke. It is well known that anthraquinone glycosides are not easily absorb. Thus, how can rhubarb anthraquinone glycosides (RAGs) exert protective effects on the brain? Is this protective effect related to interactions between RAGs and intestinal flora?<h4>Methods</h4>The model used in this study was established by middle cerebral artery occlusion (MCAO) and ...[more]

PMID: 32518585

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Project description:BackgroundRhubarb is an important Chinese medicinal herb with a long history of over 2000 years and has been commonly used as a laxative. It is the radix and rhizome of Rheum officinale Baill., R. palmatum L. and R. tanguticum Maxim, all of which are mainly distributed in a broad region in the Tibetan plateau. Anthraquinone glycosides are a series of major active ingredients found in all three species. They are key intermediates in the anthraquinone secondary metabolism and the sennnoside biosynthesis. The variation of the anthraquinone glycoside content in rhubarb in response to specific factors remains an attractive topic.ResultsA simple and sensitive Ultra Performance Liquid Chromatography with Photo-Diode Array (UPLC-PDA) detector was developed for the simultaneous determination of six anthraquinone glycosides in rhubarb, i.e., aloeemodin-8-O-glucoside, rhein-8-O-glucoside, chrysophanol-1-O-glucoside, emodin-1-O-glucoside, chrysophanol-8-O-glucoside, emodin-8-O-glucoside. Twenty-seven batches from three species were submitted to the multi-component analysis. The results showed that the anthraquinone glycoside content varied significantly even within the same species. The results showed that the anthraquinone glycoside content varied significantly within the same species but not between different species. The PCA and content analysis results confirmed that the plant species has no obvious effect on the content variation. Neither was any significant correlation observed between the anthraquinone glycoside content and the geographic distribution of the rhubarb. Through correlational analysis, altitude was found to be the main factor that affects the anthraquinone glycoside content in rhubarb. Rhubarb grown at higher altitude has higher anthraquinone glycoside content.ConclusionsThis work provides a rapid, sensitive and accurate UPLC-PDA method for the simultaneous determination of six anthraquinone glycosides in rhubarb. The anthraquinone glycoside content varied significantly within the same species. The relationship of the anthraquinone glycoside content with plant species, geographic distribution and altitude were studied using correlational analysis, principal component analysis and spatial autocorrelation analysis through SPSS and ArcGIS. Plant species and geographic distribution were found not to affect the content of the six anthraquinone glycosides in rhubarb. The variations in the anthraquinone glycoside content were primarily due to the different altitude where the plant was grown.

Project description:Background and aimsAlthough type 2 innate lymphoid cells (ILC2s) were originally found to be liver-resident lymphocytes, the role and importance of ILC2 in liver injury remains poorly understood. In the current study, we sought to determine whether ILC2 is an important regulator of hepatic ischaemia/reperfusion injury (IRI).MethodsILC2-deficient mice (ICOS-T or NSG) and genetically modified ILC2s were used to investigate the role of ILC2s in murine hepatic IRI. Interactions between ILC2s and eosinophils or macrophages were studied in coculture. The role of human ILC2s was assessed in an immunocompromised mouse model of hepatic IRI.ResultsAdministration of IL-33 prevented hepatic IRI in association with reduction of neutrophil infiltration and inflammatory mediators in the liver. IL-33-treated mice had elevated numbers of ILC2s, eosinophils, and regulatory T cells. Eosinophils, but not regulatory T cells, were required for IL-33-mediated hepatoprotection in IRI mice. Depletion of ILC2s substantially abolished the protective effect of IL-33 in hepatic IRI, indicating that ILC2s play critical roles in IL-33-mediated liver protection. Adoptive transfer of ex vivo-expanded ILC2s improved liver function and attenuated histologic damage in mice subjected to IRI. Mechanistic studies combining genetic and adoptive transfer approaches identified a protective role of ILC2s through promoting IL-13-dependent induction of anti-inflammatory macrophages and IL-5-dependent elevation of eosinophils in IRI. Furthermore, in vivo expansion of human ILC2s by IL-33 or transfer of ex vivo-expanded human ILC2s ameliorated hepatic IRI in an immunocompromised mouse model of hepatic IRI.ConclusionsThis study provides insight into the mechanisms of ILC2-mediated liver protection that could serve as therapeutic targets to treat acute liver injury.Impact and implicationsWe report that type 2 innate lymphoid cells (ILC2s) are important regulators in a mouse model of liver ischaemia/reperfusion injury (IRI). Through manipulation of macrophage and eosinophil phenotypes, ILC2s mitigate liver inflammation and injury during liver IRI. We propose that ILC2s have the potential to serve as a therapeutic tool for protecting against acute liver injury and lay the foundation for translation of ILC2 therapy to human liver disease.

Dataset Information

Protective mechanism of rhubarb anthraquinone glycosides in rats with cerebral ischaemia-reperfusion injury: interactions between medicine and intestinal flora.

Publications

Protective mechanism of rhubarb anthraquinone glycosides in rats with cerebral ischaemia-reperfusion injury: interactions between medicine and intestinal flora.

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