Zhuang medicine Shuanglu Tongnao Compound Recipe treats stroke by affecting the intestinal flora regulated by the TLR4/NF-κB signaling pathway

Abstract

Background: The standardized treatment of ischemic stroke (IS) with Shuanglu Tongnao Compound Recipe (SLTNCR) combined with Western medicine has improved the life quality and neurological function of patients and achieved a satisfactory clinical effect. However, the underlying mechanisms of SLTNCR in the treatment of IS remain unclear.Methods: A rat model of IS was prepared using Longa's wire bolus method. SLTNCR was administered by gavage with following doses: low dose, 7.16 g•kg −1 ; middle dose, 14.33 g•kg −1 ; high dose, 28.66 g•kg −1 .The expressions of toll-like receptor 4 (TLR4), tumor necrosis factor (TNF-α), interleukin-1β (IL-1β), IL-6, nuclear factor-κB (NF-κB), etc., brain neuron damage, small intestine structure, and the structure of intestinal flora of rats in the high, medium, and low dose SLTNCR groups as well as the Injury + Clostridium butyricum and Injury + Edaravone groups were detected by 16SrRNA gene sequencing, western blot, hematoxylin-eosin (HE) staining, enzyme-linked immunosorbent assay (ELISA), and polymerase chain reaction (PCR).Results: SLTNCR significantly reduced the brain water content, decreased the cerebral infarct size, and improved the neurological deficits, neuronal damage, small bowel tissue damage, and expression of inflammatory factors [B-cell CLL/lymphoma 2 (Bcl-2), BCL2 associated agonist of cell death (Bad), cleavedcaspase-3] in brain tissue. SLTNCR administration significantly inhibited expressions of TLR4, NF-κB, and inhibitor of nuclear factor kappa B (IκB), and decreased phosphorylation levels of NF-κB and IκB in the small intestinal tissues of IS rats. Moreover, SLTNCR also significantly upregulated the expression of intestinal barrier function-related molecules [zona occludens 1 (ZO-1), occludin, claudin-5] and regulated the expression of colonic TLR4, TNF-α, IL-6, and IL-1β. SLTNCR can improve the symptoms of IS rats by improving brain and small intestinal function, particularly by regulating the TLR4/NF-κB signaling pathway, apoptotic proteins, and inflammatory factors in brain tissue. Gut microbiota analysis helped to identify the pharmacological mechanisms underlying the effects of SLTNCR on intestinal bacterial diversity and flora structure in IS rats.Conclusions: SLTNCR can alleviate symptoms of IS and the potential mechanism of its effect is to protect brain tissue by suppressing inflammation. SLTNCR can also alter the structure and diversity of the bacterial community in IS.

Role of gut microbiota in ischemic stroke: A narrative review of human and animal studies

“…We identified 140 articles, of which 32 articles were deemed irrelevant to our research topic, nine were reviews, two were letters to the editor, one was an editorial, one was a perspective piece, one was a comment, one was a duplicate publication, and one was an un‐peer‐reviewed preprint; these were excluded by two authors who independently assessed the articles. Ultimately, 92 studies, 5–96 including 38 human studies and 54 animal studies, were selected as being highly relevant to our research topic. The flowchart of the article selection process is depicted in Figure 1.…”

The Interplay between Medical Plants and Gut Microbiota in Cancer

“…A diet rich in vegetables has several benefits in terms of health promotion and is linked to a reduction in systemic and local intestinal inflammation. For example, resveratrol is a substance contained in peanuts, grapes, berries, and red wine, in plants after fungal infection, exposure to ultra-violet (UV) radiation, and mechanical injury, and acts by inhibiting NF-KB and consenting Bcl-2 to exert its proapoptotic effect [20,28,55,[100][101][102][103][104][105][106][107][108][109]. During inflammatory processes, immune cells produce interleukin 6 (IL-6) which ties to the soluble IL-6 receptor or the membrane IL-6 receptor and forms a complex that interacts with glycoprotein 130 and determines an upregulation of the transcription factor signal transducer and activator of transcription 3 (STAT-3).…”