Abstract
BackgroundAnthraquinone 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?MethodsThe 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.ResultsThe 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.ConclusionsCIRI 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.
Highlights
Anthraquinone glycosides extracted from rhubarb have been proven to have significant therapeutic effects on ischaemic stroke
rhubarb anthraquinone glycosides (RAGs) increased the abundance of intestinal flora in rats with cerebral ischaemia–reperfusion injury (CIRI) To assess the effect of RAGs on intestinal flora in rats with CIRI, we analysis the colonic contents in different groups by high-throughput sequencing
The main findings of this study are as follows: (1) CIRI can reduce the abundance and diversity of the intestinal flora, and the structure of the intestinal flora is different from that of normal rats; (2) RAGs can effectively regulate the structure of the intestinal flora in rats with CIRI and inhibit the disorder of the intestinal flora caused by cerebral ischaemia injury; (3) RAGs need to be metabolized into anthraquinone aglycones by the intestinal flora so that they can absorb into the blood; and (4) the changes in the intestinal flora caused by cerebral ischaemia injury can interfere with the absorption of anthraquinones compounds
Summary
Anthraquinone glycosides extracted from rhubarb have been proven to have significant therapeutic effects on ischaemic stroke. How can rhubarb anthraquinone glycosides (RAGs) exert protective effects on the brain? According to the theory of TCM, cerebral ischaemia, which is called stroke, can be induced by hyperactivity of liver Yang, disordered diet, stagnation of blood, etc. The main cause is blood stasis [3]. Prescriptions are commonly used to improve blood stasis in order to treat stroke, and these prescriptions include Xiexin Decoction (recorded in the Synopsis of the Golden Chamber), Didang Decoction (recorded in the Treatise on Febrile Diseases) and Dahuang Zhechong pill (recorded in the Synopsis of the Golden Chamber), all of which use rhubarb as the main ingredient. The main active components of rhubarb are RAGs and the corresponding free anthraquinone [6, 7]
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