Evidence Details for
PMID Title Journal Year Abstract
34630618 Electroacupuncture Synergistically Inhibits Proinflammatory Cytokine Production and Improves Cognitive Function in Rats with Cognitive Impairment due to Hepatic Encephalopathy through p38MAPK/STAT3 and TLR4/NF-kappaB Signaling Pathways. Evid Based Complement Alternat Med. 2021 Oct 1;2021:7992688. doi: 10.1155/2021/7992688. eCollection 2021. 2021 OBJECTIVE: To investigate the effect of electroacupuncture (EA) on cognitive dysfunction in rats with hepatic encephalopathy and its underlying mechanism. METHODS: Fifty Wistar rats were randomly divided into a normal group (n = 10) and model group (n = 40). Rat models of hepatic encephalopathy were established by administration of carbon tetrachloride and thioacetamide for a total of 12 weeks. At the 9th week after modeling, rats with cognitive impairment in the model group were identified by conducting the Morris water maze test, which were then randomly divided into a control group (CCl(4)) and treatment groups including EA group (CCl(4) + EA), lactulose group (CCl(4) + Lac), and EA plus lactulose group (CCl(4) + CM), with 9 rats in each group. At the end of the 9th week, rats in CCl(4) + Lac and CCl(4) + CM groups had lactulose gavage at a dose of 10 mL/kg body weight, while normal control and CCl(4) groups had gavage with the same volume of normal saline once a day for 21 days until the end of the experiment. Rats in CCl(4) + EA and CCl(4) + CM groups underwent acupuncture at Baihui (GV[DU]20), Shenting (GV[DU]24), and Zusanli (ST36) acupoints, among which EA at Baihui and Shenting acupoints were given once daily for 30 min lasting for 21 consecutive days. The effect of the treatment was measured by the Morris water maze test for learning and memory ability and magnetic resonance spectroscopy (MRS) for neuronal metabolism in the hippocampus of rats with hepatic encephalopathy. Pathological change in the rat hippocampus was observed by HE staining, while serum ammonia and liver function markers were detected. Western blot and real-time fluorescent quantitative PCR were used to detect the expressions of specific genes and proteins in the brain tissue. RESULTS: Compared with those in the control group, rats undergoing EA had significantly shortened escape latency and increased number of platform crossing. H&E staining confirmed that EA improved brain tissue necrosis and ameliorated nuclear pyknosis in rats with hepatic encephalopathy. Significantly decreased levels of serum ammonia, alanine aminotransferase (ALT), aspartate transaminase (AST), total bilirubin (TBil), and total bile acid (TBA) were observed in rats undergoing EA, as well as improved levels of total protein (TP) and albumin (ALB). In addition, EA inhibited the brain expressions of TNF-alpha, IL-1beta, IL-6, iNOS, TLR4, MyD88, NF-kappaB, p38MAPK, phosphorylated (p)-p38MAPK, STAT3, and p-STAT3 genes, as well as protein expressions of TNF-alpha, IL-6, TLR4, MyD88, NF-kappaB, p38MAPK, p-p38MAPK, STAT3, and p-STAT3. MRS showed increased Glx/Cr and decreased NAA/Cr, Cho/Cr and mI/Cr in the control group, and EA significantly reversed such changes in Glx/Cr and mI/Cr values. CONCLUSION: EA ameliorated the production of excessive proinflammatory cytokines in the hippocampus of rats with cognitive dysfunction secondary to hepatic encephalopathy, which also gave rise to subsequent changes such as reduced blood ammonia level, brain-protective activated astrocytes, and lower degree of brain tissue injury. The p38MAPK/STAT3 and TLR4/MyD88/NF-kappaB signaling pathways may be involved. EA can also improve the metabolism of NAA and Cho in the rat hippocampus and thereby improve learning and memory abilities."

Evidence Sentence: Significantly decreased levels of serum ammonia, alanine aminotransferase (ALT), aspartate transaminase (AST), total bilirubin (TBil), and total bile acid (TBA) were observed in rats undergoing EA, as well as improved levels of total protein (TP) and albumin (ALB).
Evidence Sentence: Alanine aminotransferase (ALT), aspartate transaminase (AST), albumin (ALB), total protein (TP), albumin (ALB), and total bilirubin (TBil) are commonly used indicators for liver function.
Evidence Sentence: Compared with normal control, serum levels of TBil, ALT, AST, and TBA in the CCl4 group were significantly increased (P < 0.001), and the levels of TP and ALB were significantly decreased (P < 0.05).
Evidence Sentence: Meanwhile, compared with the CCl4 group, the levels of TBil, ALT, AST, and TBA in CCl4+EA, CCl4+Lac, and CCl4+CM groups were significantly decreased (P < 0.05) and the TP level was significantly increased (P < 0.05), whereas the ALB level in the CCl4 + CM group was significantly increased (P < 0.05).
Evidence Sentence: Significantly decreased levels of serum ammonia, alanine aminotransferase (ALT), aspartate transaminase (AST), total bilirubin (TBil), and total bile acid (TBA) were observed in rats undergoing EA, as well as improved levels of total protein (TP) and albumin (ALB).
Evidence Sentence: Alanine aminotransferase (ALT), aspartate transaminase (AST), albumin (ALB), total protein (TP), albumin (ALB), and total bilirubin (TBil) are commonly used indicators for liver function.
Evidence Sentence: Significantly decreased levels of serum ammonia, alanine aminotransferase (ALT), aspartate transaminase (AST), total bilirubin (TBil), and total bile acid (TBA) were observed in rats undergoing EA, as well as improved levels of total protein (TP) and albumin (ALB).
Evidence Sentence: Alanine aminotransferase (ALT), aspartate transaminase (AST), albumin (ALB), total protein (TP), albumin (ALB), and total bilirubin (TBil) are commonly used indicators for liver function.
Evidence Sentence: Compared with normal control, serum levels of TBil, ALT, AST, and TBA in the CCl4 group were significantly increased (P < 0.001), and the levels of TP and ALB were significantly decreased (P < 0.05).
Evidence Sentence: Meanwhile, compared with the CCl4 group, the levels of TBil, ALT, AST, and TBA in CCl4+EA, CCl4+Lac, and CCl4+CM groups were significantly decreased (P < 0.05) and the TP level was significantly increased (P < 0.05), whereas the ALB level in the CCl4 + CM group was significantly increased (P < 0.05).
Evidence Sentence: Compared with the CCl4 group, AST levels in both CCl4 + EA and CCl4 + CM groups were significantly decreased (P < 0.05), while TBil and ALT levels in the CCl4 + CM group were significantly decreased (P < 0.05) (Figures 2(a)-2(f)).
Evidence Sentence: In addition, EA inhibited the brain expressions of TNF-alpha, IL-1beta, IL-6, iNOS, TLR4, MyD88, NF-kappaB, p38MAPK, phosphorylated (p)-p38MAPK, STAT3, and p-STAT3 genes, as well as protein expressions of TNF-alpha, IL-6, TLR4, MyD88, NF-kappaB, p38MAPK, p-p38MAPK, STAT3, and p-STAT3.
Evidence Sentence: In this study, mRNA and protein expressions of TNF-alpha, IL-1beta, and IL-6 in brain tissues of rats in the CCl4 group were significantly upregulated compared with the normal control group (P < 0.01); Meanwhile, compared with the CCl4 group, the mRNA and protein expressions of TNF-alpha, IL-1beta, and IL-6 in brain tissues of rats in each treatment group were significantly downregulated (P < 0.05), especially those in CCl4 + EA and CCl4 + CM groups (P < 0.05) (Figures 5(a)-5(c), 6(a), 6(b), 7(a)).
Evidence Sentence: In addition, EA inhibited the brain expressions of TNF-alpha, IL-1beta, IL-6, iNOS, TLR4, MyD88, NF-kappaB, p38MAPK, phosphorylated (p)-p38MAPK, STAT3, and p-STAT3 genes, as well as protein expressions of TNF-alpha, IL-6, TLR4, MyD88, NF-kappaB, p38MAPK, p-p38MAPK, STAT3, and p-STAT3.
Evidence Sentence: EA Effectively Ameliorated Inflammation in HE Rats by Inhibiting Inflammatory Factors Such as TNF-alpha, IL-6, and IL-1beta
Evidence Sentence: In this study, mRNA and protein expressions of TNF-alpha, IL-1beta, and IL-6 in brain tissues of rats in the CCl4 group were significantly upregulated compared with the normal control group (P < 0.01); Meanwhile, compared with the CCl4 group, the mRNA and protein expressions of TNF-alpha, IL-1beta, and IL-6 in brain tissues of rats in each treatment group were significantly downregulated (P < 0.05), especially those in CCl4 + EA and CCl4 + CM groups (P < 0.05) (Figures 5(a)-5(c), 6(a), 6(b), 7(a)).
Evidence Sentence: In addition, EA inhibited the brain expressions of TNF-alpha, IL-1beta, IL-6, iNOS, TLR4, MyD88, NF-kappaB, p38MAPK, phosphorylated (p)-p38MAPK, STAT3, and p-STAT3 genes, as well as protein expressions of TNF-alpha, IL-6, TLR4, MyD88, NF-kappaB, p38MAPK, p-p38MAPK, STAT3, and p-STAT3.
Evidence Sentence: Elevated blood ammonia can stimulate iNOS expression, promote NO production, increase cerebral blood flow, and result in astrocyte edema.
Evidence Sentence: Rats in the CCl4 group had significantly increased expression of iNOS mRNA (vs normal group, P < 0.01).
Evidence Sentence: Meanwhile, rats in each treatment group had downregulated expression of iNOS mRNA in brain tissues (vs CCl4 group, P < 0.05); among which, rats in CCl4 + EA and CCl4 + CM groups had significantly decreased iNOS mRNA compared with the CCl4 + Lac group (P < 0.05) (Figure 5(d)).
Evidence Sentence: In addition, EA inhibited the brain expressions of TNF-alpha, IL-1beta, IL-6, iNOS, TLR4, MyD88, NF-kappaB, p38MAPK, phosphorylated (p)-p38MAPK, STAT3, and p-STAT3 genes, as well as protein expressions of TNF-alpha, IL-6, TLR4, MyD88, NF-kappaB, p38MAPK, p-p38MAPK, STAT3, and p-STAT3.
Evidence Sentence: Our results showed that compared with normal control, the mRNA and protein expressions of TLR4, MyD88, and NF-kappaB in rat brains in the CCl4 group were significantly increased (all P < 0.001), while expressions of those in the brain of HE rats were significantly decreased (all P < 0.05).
Evidence Sentence: Moreover, mRNA and protein expressions of TLR4, MyD88, and NF-kappaB in the CCl4 + CM group were significantly decreased compared with the CCl4+Lac group (P < 0.05) (Figures 5(e)-5(g), 6(c)-6(e), Figure 7(b)).
Evidence Sentence: In addition, EA inhibited the brain expressions of TNF-alpha, IL-1beta, IL-6, iNOS, TLR4, MyD88, NF-kappaB, p38MAPK, phosphorylated (p)-p38MAPK, STAT3, and p-STAT3 genes, as well as protein expressions of TNF-alpha, IL-6, TLR4, MyD88, NF-kappaB, p38MAPK, p-p38MAPK, STAT3, and p-STAT3.
Evidence Sentence: Our results showed that compared with normal control, the mRNA and protein expressions of TLR4, MyD88, and NF-kappaB in rat brains in the CCl4 group were significantly increased (all P < 0.001), while expressions of those in the brain of HE rats were significantly decreased (all P < 0.05).
Evidence Sentence: Moreover, mRNA and protein expressions of TLR4, MyD88, and NF-kappaB in the CCl4 + CM group were significantly decreased compared with the CCl4+Lac group (P < 0.05) (Figures 5(e)-5(g), 6(c)-6(e), Figure 7(b)).
Evidence Sentence: The p38MAPK/STAT3 and TLR4/MyD88/NF-kappaB signaling pathways may be involved.
Evidence Sentence: The p38MAPK/STAT3 and TLR4/MyD88/NF-kappaB signaling pathways may be involved.
Evidence Sentence: Electroacupuncture Synergistically Inhibits Proinflammatory Cytokine Production and Improves Cognitive Function in Rats with Cognitive Impairment due to Hepatic Encephalopathy through p38MAPK/STAT3 and TLR4/NF-kappaB Signaling Pathways
Evidence Sentence: EA Inhibited the p38MAPK/STAT3 Signaling Pathway and Thereby Reduced the Inflammatory Response
Evidence Sentence: In summary, EA downregulated the expressions of p38MAPK-STAT3 mRNA and related proteins by activating the p38MAPK-STAT3 signaling pathway and thereby modulated the inflammatory response in rats with HE.
Evidence Sentence: In addition, EA inhibited the brain expressions of TNF-alpha, IL-1beta, IL-6, iNOS, TLR4, MyD88, NF-kappaB, p38MAPK, phosphorylated (p)-p38MAPK, STAT3, and p-STAT3 genes, as well as protein expressions of TNF-alpha, IL-6, TLR4, MyD88, NF-kappaB, p38MAPK, p-p38MAPK, STAT3, and p-STAT3.
Evidence Sentence: STAT3 is considered one of the possible substrates of MAPK, which is the common pathway of intracellular signal transmission among different inflammatory cells and various inflammatory mediators and is involved in various biological reactions such as immune response and cell proliferation, differentiation, migration, and apoptosis.
Evidence Sentence: In this study, after 3 weeks of acupuncture treatment, the mRNA and protein expressions of p38MAPK, p-p38MAPK, STAT3, and p-STAT3 in brain tissues of rats in the CCl4 group were significantly increased compared with those in the normal control group (P < 0.001), indicating that MAPK and STAT3 signaling pathways could have simultaneously been activated under the inflammatory response in HE.
Evidence Sentence: Compared with the CCl4 group, the mRNA and protein expressions of p38MAPK, p-p38MAPK, STAT3, and p-STAT3 in brain tissues of HE rats in all treatment groups were significantly decreased (P < 0.05).
Evidence Sentence: Compared with the CCl4 + Lac group, expressions of p38MAPK, p-p38MAPK, STAT3, and p-STAT3 in the CCl4 + CM group were significantly downregulated (P < 0.05).
Evidence Sentence: In addition, EA inhibited the brain expressions of TNF-alpha, IL-1beta, IL-6, iNOS, TLR4, MyD88, NF-kappaB, p38MAPK, phosphorylated (p)-p38MAPK, STAT3, and p-STAT3 genes, as well as protein expressions of TNF-alpha, IL-6, TLR4, MyD88, NF-kappaB, p38MAPK, p-p38MAPK, STAT3, and p-STAT3.
Evidence Sentence: Our results showed that compared with normal control, the mRNA and protein expressions of TLR4, MyD88, and NF-kappaB in rat brains in the CCl4 group were significantly increased (all P < 0.001), while expressions of those in the brain of HE rats were significantly decreased (all P < 0.05).
Evidence Sentence: Moreover, mRNA and protein expressions of TLR4, MyD88, and NF-kappaB in the CCl4 + CM group were significantly decreased compared with the CCl4+Lac group (P < 0.05) (Figures 5(e)-5(g), 6(c)-6(e), Figure 7(b)).
Evidence Sentence: EA Activated TLR4/MyD88/NF-kappaB Signaling Pathway
Evidence Sentence: The TLR4/MyD88/NF-kappaB signaling pathway was widely distributed in various tissues and cells of the body, which can mediate the expression of inflammatory factors in cells.
Evidence Sentence: Our results suggest that EA may alleviate brain injury in rats with HE by regulating the TLR4/MyD88/NF-kappaB signaling pathway.
Evidence Sentence: EA Activated TLR4/MyD88/NF-kappaB Signaling Pathway
Evidence Sentence: The TLR4/MyD88/NF-kappaB signaling pathway was widely distributed in various tissues and cells of the body, which can mediate the expression of inflammatory factors in cells.
Evidence Sentence: Our results suggest that EA may alleviate brain injury in rats with HE by regulating the TLR4/MyD88/NF-kappaB signaling pathway.
Evidence Sentence: EA Activated TLR4/MyD88/NF-kappaB Signaling Pathway
Evidence Sentence: The TLR4/MyD88/NF-kappaB signaling pathway was widely distributed in various tissues and cells of the body, which can mediate the expression of inflammatory factors in cells.
Evidence Sentence: Our results suggest that EA may alleviate brain injury in rats with HE by regulating the TLR4/MyD88/NF-kappaB signaling pathway.
Evidence Sentence: The p38MAPK/STAT3 and TLR4/MyD88/NF-kappaB signaling pathways may be involved.
Evidence Sentence: The p38MAPK/STAT3 and TLR4/MyD88/NF-kappaB signaling pathways may be involved.
Evidence Sentence: Intervention of various targets in the TLR4/MyD88/NF-kappaB signaling transduction pathway has been found to reduce the inflammatory response of tissue to brain injury.
Evidence Sentence: Intervention of various targets in the TLR4/MyD88/NF-kappaB signaling transduction pathway has been found to reduce the inflammatory response of tissue to brain injury.
Evidence Sentence: Intervention of various targets in the TLR4/MyD88/NF-kappaB signaling transduction pathway has been found to reduce the inflammatory response of tissue to brain injury.
Evidence Sentence: Electroacupuncture Synergistically Inhibits Proinflammatory Cytokine Production and Improves Cognitive Function in Rats with Cognitive Impairment due to Hepatic Encephalopathy through p38MAPK/STAT3 and TLR4/NF-kappaB Signaling Pathways
Evidence Sentence: Electroacupuncture Synergistically Inhibits Proinflammatory Cytokine Production and Improves Cognitive Function in Rats with Cognitive Impairment due to Hepatic Encephalopathy through p38MAPK/STAT3 and TLR4/NF-kappaB Signaling Pathways
Evidence Sentence: In addition, EA inhibited the brain expressions of TNF-alpha, IL-1beta, IL-6, iNOS, TLR4, MyD88, NF-kappaB, p38MAPK, phosphorylated (p)-p38MAPK, STAT3, and p-STAT3 genes, as well as protein expressions of TNF-alpha, IL-6, TLR4, MyD88, NF-kappaB, p38MAPK, p-p38MAPK, STAT3, and p-STAT3.
Evidence Sentence: EA Effectively Ameliorated Inflammation in HE Rats by Inhibiting Inflammatory Factors Such as TNF-alpha, IL-6, and IL-1beta
Evidence Sentence: In this study, mRNA and protein expressions of TNF-alpha, IL-1beta, and IL-6 in brain tissues of rats in the CCl4 group were significantly upregulated compared with the normal control group (P < 0.01); Meanwhile, compared with the CCl4 group, the mRNA and protein expressions of TNF-alpha, IL-1beta, and IL-6 in brain tissues of rats in each treatment group were significantly downregulated (P < 0.05), especially those in CCl4 + EA and CCl4 + CM groups (P < 0.05) (Figures 5(a)-5(c), 6(a), 6(b), 7(a)).