Dataset Information

Liangxue Tongyu Prescription Alleviates Brain Damage in Acute Intracerebral Hemorrhage Rats by Regulating Intestinal Mucosal Barrier Function.

ABSTRACT:

Background

Liangxue Tongyu prescription (LTP) is a commonly used formula for acute intracerebral hemorrhage (AICH) in clinical practice that has significant ameliorative effects on neurological deficits and gastrointestinal dysfunction, yet the mechanism remains elusive. The aim of this study was to investigate the pathway by which LTP alleviates brain damage in AICH rats.

Methods

The AICH rat models were established by autologous caudal arterial blood injection. The neurological function scores were evaluated before and after treatment. The water content and the volume of Evans blue staining in the brain were measured to reflect the degree of brain damage. RT-PCR was used to detect the inflammatory factors of the brain. Western blotting was used to detect the expression of the tight junction proteins zonula occludens 1 (ZO-1), occludin (OCLN), and claudin (CLDN) in the brain and colon, followed by mucin 2 (MUC2), secretory immunoglobulin A (SIgA), and G protein-coupled receptor 43 (GPR43) in the colon. Flow cytometry was used to detect the ratios of helper T cells 17 (Th17) and regulatory T cells (Treg) in peripheral blood, and the vagus nerve (VN) discharge signals were collected.

Results

LTP reduced the brain damage of the AICH rats. Compared with the model group, LTP significantly improved the permeability of the colonic mucosa, promoted the secretion of MUC2, SigA, and GPR43 in the colon, and regulated the immune balance of peripheral T cells. The AICH rats had significantly faster VN discharge rates and lower amplitudes than normal rats, and these abnormalities were corrected in the LTP and probiotics groups.

Conclusion

LTP can effectively reduce the degree of brain damage in AICH rats, and the mechanism may be that it can play a neuroprotective role by regulating the function of the intestinal mucosal barrier.

SUBMITTER: Zhou Y

PROVIDER: S-EPMC9789913 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Publications

Liangxue Tongyu Prescription Alleviates Brain Damage in Acute Intracerebral Hemorrhage Rats by Regulating Intestinal Mucosal Barrier Function.

Zhou Yu Y Zhang Zijian Z Sun Yingying Y Zhou Dandan D Zhao Yang Y Li Jianxiang J Guo Weifeng W

Evidence-based complementary and alternative medicine : eCAM 20221217

<h4>Background</h4>Liangxue Tongyu prescription (LTP) is a commonly used formula for acute intracerebral hemorrhage (AICH) in clinical practice that has significant ameliorative effects on neurological deficits and gastrointestinal dysfunction, yet the mechanism remains elusive. The aim of this study was to investigate the pathway by which LTP alleviates brain damage in AICH rats.<h4>Methods</h4>The AICH rat models were established by autologous caudal arterial blood injection. The neurological ...[more]

PMID: 36573082

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Project description:BackgroundNowadays, acute intracerebral hemorrhage stroke (AICH) still causes higher mortality. Liangxue Tongyu Formula (LXTYF), originating from a traditional Chinese medicine (TCM) prescription, is widely used as auxiliary treatment for AICH.ObjectiveTo dig into the multicomponent, multitarget, and multipathway mechanism of LXTYF on treating AICH via network pharmacology and RNA-seq.MethodsNetwork pharmacology analysis was used by ingredient collection, target exploration and prediction, network construction, and Gene Ontology (GO) and KEGG analysis, with the Cytoscape software and ClusterProfiler package in R. The RNA-seq data of the AICH-rats were analyzed for differential expression and functional enrichments. Herb-Compound-Target-Pathway (H-C-T-P) network was shown to clarify the mechanism of LXTYF for AICH.Results76 active ingredients (quercetin, Alanine, kaempferol, etc.) of LXTYF and 376 putative targets to alleviate AICH (PTGS2, PTGS1, ESR1, etc.) were successfully identified. The protein-protein interaction (PPI) network indicated the important role of STAT3. The functional enrichment of GO and KEGG pathway showed that LXTYF is most likely to influence MAPK and PI3K-Akt signaling pathways for AICH treatment. From the RNA-seq of AICH-rats, 583 differential mRNAs were identified and 14 of them were consistent with the putative targets of LXTYF for AICH treatment. The KEGG pathway enrichment also implied that the MAPK signaling pathway was the most correlated one among all the related signaling pathways. Many important targets with expression changes of LXTYF for AICH treatment and their related pathways are great markers of antioxidation, anti-inflammatory, antiapoptosis, and lowering blood pressure, which indicated that LXTYF may play mutiroles in the mechanisms for AICH treatment.ConclusionThe LXTYF attenuates AICH partially by antioxidation, anti-inflammatory, and antiapoptosis and lowers blood pressure roles through regulating the targets involved MAPK, calcium, apoptosis, and TNF signaling pathway, which provide notable clues for further experimental validation.

Project description:Background: One of the severely debilitating and fatal subtypes of hemorrhagic stroke is intracerebral hemorrhage (ICH), which lacks an adequate cure at present. The Zhilong Huoxue Tongyu (ZLHXTY) capsule has been utilized effectively since last decade to treat ICH, in some provinces of China but the scientific basis for its mechanism is lacking. Purpose: To investigate the neuroprotective role of ZLHXTY capsules for ICH-induced oxidative injury through the regulation of redox imbalance with the Nrf2 signaling pathway. Methods: Autologous blood injection model of ICH in C57BL/6J mice was employed. Three treatment groups received ZLHXTY once daily through oral gavage at doses 0.35 g/kg, 0.7 g/kg, and 1.4 g/kg, started after 2 h and continued for 72 h of ICH induction. The neurological outcome was measured using a balance beam test. Serum was tested for inflammatory markers IL-1β, IL-6, and TNF-α through ELISA, oxidative stress through hydrogen peroxide content assay, and antioxidant status by total antioxidant capacity (T-AOC) assay. Nuclear extract from brain tissue was assayed for Nrf2 transcriptional factor activity. RT-qPCR was performed for Nfe2l2, Sod1, Hmox1, Nqo1, and Mgst1; and Western blotting for determination of protein expression of Nrf2, p62, Pp62, Keap, HO1, and NQO1. Fluoro-jade C staining was also used to examine neuronal damage. Results: ZLHXTY capsule treatment following ICH demonstrated a protective effect against oxidative brain injury. Neurological scoring showed improvement in behavioral outcomes. ELISA-based identification demonstrated a significant decline in the expression of serum inflammatory markers. Hydrogen peroxide content in serum was found to be reduced. The total antioxidant capacity was also reduced in serum, but the ZLHXTY extract showed a concentration-dependent increase in T-AOC speculating at its intrinsic antioxidant potential. Nrf2 transcriptional factor activity, mRNA and protein expression analyses revealed normalization of Nrf2 and its downstream targets, which were previously elevated as a result of oxidative stress induced by ICH. Neuronal damage was also reduced markedly after ZLHXTY treatment as revealed by Fluoro-jade C staining. Conclusion: ZLHXTY capsules possess an intrinsic antioxidant potential that can modulate the ICH-induced redox imbalance in the brain as revealed by the normalization of Nrf2 and its downstream antioxidant targets.

Project description:Lung infection is a common complication induced by stroke and seriously affects the prognosis and life quality of patients. However, effective therapeutic strategies are still lacking. In the present study, the herb formula GCis was confirmed to prevent pulmonary infection induced by intracerebral hemorrhage (ICH). The animal model of lung infection induced by ICH, GCis (Ginseng Radix et Rhizoma, Aconiti Lateralis Radix Praeparata, and Cistanches Herba) was orally administrated every day for 7 days. Lung microbial biomass and pathological results showed that the GCis formula pretreatment significantly reduced lung bacterial biomass and alleviated pathological abnormalities. These results indicated that the GCis formula has a clear pharmacological effect on preventing lung infection induced by ICH. Immunosuppression induced by ICH seemed to be the main mechanism of lung infection. Our results showed that the spleen and thymus indexes, WBC, and LY% contents were significantly increased in the GCis formula group. Moreover, bone marrow cells were further analyzed by transcriptome sequencing, and GO and KEGG enrichment analysis results showed that immune function was the main pathway enriched by differential genes after GCis formula intervention. More importantly, our results showed that GCis pretreatment had no significant effect on the mRNA expression of IL-1β, IL-6, and TNF-α in the brain. These results indicated that the GCis formula could enhance immunity after ICH. The intestinal barrier function was further investigated in the present study, considering the origin of the source of infection. Our results showed that the mRNA expressions of intestinal ZO-1, SIgA, and MUC2 were significantly increased, villi structure was intact, inflammatory cell infiltration was reduced, and goblet cell number was increased after GCis formula treatment. These results suggest that the GCis formula can enhance the intestinal mucosal immune barrier. This study provides a herb formula (GCis) that could enhance peripheral immunity and intestinal mucosal immune barrier to prevent pulmonary infection induced by ICH. It would be beneficial in the prevention of severe clinical infections.

Project description:BackgroundIntracerebral hemorrhage (ICH) is a devastating medical emergency with high mortality and severe neurological deficit. ICH-related poor outcomes are due to a combination of pathological processes that could be complicated by secondary insults. TWIK-related K+ channel 1 (TREK-1) is a two-pore-domain potassium channel that is highly expressed in the mammalian nervous system. Previous studies have shown that TREK-1 channels play important roles in various central nervous system diseases. However, its role in the secondary injuries after intracerebral hemorrhage remains unknown. In this study, we explored the function of TREK-1 in secondary blood-brain barrier injuries and neuroinflammation after intracerebral hemorrhage in mice.MethodsAdult male TREK-1-/- mice and WT mice were subjected to a collagenase-induced ICH model. Immunostaining, western blot, and enzyme-linked immunosorbent assay were used to assess inflammatory infiltration and neuronal death. Blood-brain barrier compromise was assessed using electron microscopy and Evans Blue dye injection on days 1 and 3 after intracerebral hemorrhage. Magnetic resonance imaging and behavioral assessments were conducted to evaluate the neurologic damage and recovery after intracerebral hemorrhage.ResultsGenetic deficiency of TREK-1 channel exacerbated blood-brain barrier impairment and promoted cerebral edema after intracerebral hemorrhage. Meanwhile, TREK-1 deficiency aggravated focal inflammatory featured by the increased recruitment of microglia and neutrophils, the enhanced secretion of proinflammatory factors interleukin-1 beta (IL-1β), tumor necrosis factor alpha (TNF-α), and cell adhesion molecules (CAMs). Furthermore, TREK-1 deficiency promoted neuronal injury and neurological impairment.ConclusionsThese results establish the first in vivo evidence for the protective role of TREK-1 in blood-brain barrier injury and neuroinflammation after intracerebral hemorrhage. TREK-1 may thereby be harnessed to a potential therapeutical target for the treatment of intracerebral hemorrhage.

Dataset Information

Liangxue Tongyu Prescription Alleviates Brain Damage in Acute Intracerebral Hemorrhage Rats by Regulating Intestinal Mucosal Barrier Function.

Background

Methods

Results

Conclusion

Publications

Liangxue Tongyu Prescription Alleviates Brain Damage in Acute Intracerebral Hemorrhage Rats by Regulating Intestinal Mucosal Barrier Function.

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