Elucidating the Synergistic Effect of Multiple Chinese Herbal Prescriptions in the Treatment of Post-stroke Neurological Damage

Abstract

Background: Traditional Chinese medicine (TCM) has been widely used in the treatment of human diseases. However, the synergistic effects of multiple TCM prescriptions in the treatment of stroke have not been thoroughly studied.Objective of the study: This study aimed to reveal the mechanisms underlying the synergistic effects of these TCM prescriptions in stroke treatment and identify the active compounds.Methods: Herbs and compounds in the Di-Tan Decoction (DTD), Xue-Fu Zhu-Yu Decoction (XFZYD), and Xiao-Xu-Ming Decoction (XXMD) were acquired from the TCMSP database. SEA, HitPick, and TargetNet web servers were used for target prediction. The compound-target (C-T) networks of three prescriptions were constructed and then filtered using the collaborative filtering algorithm. We combined KEGG enrichment analysis, molecular docking, and network analysis approaches to identify active compounds, followed by verification of these compounds with an oxygen-glucose deprivation and reoxygenation (OGD/R) model.Results: The filtered DTD network contained 39 compounds and 534 targets, the filtered XFZYD network contained 40 compounds and 508 targets, and the filtered XXMD network contained 55 compounds and 599 targets. The filtered C-T networks retained approximately 80% of the biological functions of the original networks. Based on the enriched pathways, molecular docking, and network analysis results, we constructed a complex network containing 3 prescriptions, 14 botanical drugs, 26 compounds, 13 targets, and 5 pathways. By calculating the synergy score, we identified the top 5 candidate compounds. The experimental results showed that quercetin, baicalin, and ginsenoside Rg1 independently and synergistically increased cell viability.Conclusion: By integrating pharmacological and chemoinformatic approaches, our study provides a new method for identifying the effective synergistic compounds of TCM prescriptions. The filtered compounds and their synergistic effects on stroke require further research.

The mechanisms underlying the actions of Xuefu Zhuyu decoction pretreatment against neurological deficits after ischemic stroke in mice: The mediation of glymphatic function by aquaporin-4 and its anchoring proteins

“…XFZYD contains herbs that have multi-potent properties with significant anticoagulation and anti-inflammation effects. These herbs play an important role in improving blood supply, stimulating blood circulation and controlling the recurrence of thrombosis ( Xing et al, 2016 ; Yeh et al, 2017 ; Xu et al, 2022 ). However, the mechanisms underlying these preconditioning effects have yet to be fully elucidated.…”

“…Mounting evidence indicates that traditional Chinese medicine can ameliorate dysfunction associated with post-ischemic stroke ( Bu et al, 2020 ; Zhu et al, 2021 ). Notably, Xuefu Zhuyu decoction (XFZYD), a traditional Chinese prescription that is recorded in Yilin Gaicuo , contains eleven herbs ( Table 1 ) and has been shown to reverse IS-induced neurological dysfunction ( Lee et al, 2011 ; Shen et al, 2015 ; Xu et al, 2022 ). However, the specific mechanisms and potential targets of XFZYD against neurological deficits have yet to be investigated.…”

Screening of key functional components of Taohong Siwu Decoction on ischemic stroke treatment based on multiobjective optimization approach and experimental validation

“…Cell viability assays were carried out with a Cell Counting Kit-8 (RiboBio, China) following the methods described earlier [ 44 ]. In brief, 10 µl of CCK-8 solution in 100 µl of complete culture medium was added to each well of a 96-well plate and further incubated for 3 h. Then, the absorbance was measured at 450 nm optical density in a microplate reader (KC junior, BioTek, USA).…”

“…The same to the methods described in our earlier study [ 44 ], R statistical software version 4.0.3 was used for the statistical analysis of the experimental data. Outliers in each repeat higher than twofold of the standard deviation were eliminated.…”