scholarly journals Acupuncture at Back-Shu and Front-Mu Acupoints Prevents Gastric Ulcer by Regulating the TLR4/MyD88/NF-κB Signaling Pathway

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Li Li ◽  
Hao Zang ◽  
Yang Jiang ◽  
Yue Zhang ◽  
Shuangshuang Mu ◽  
...  

Purpose. To assess the preventive effects of acupuncture at back-shu and front-mu acupoints on rats with restraint water-immersion stress (RWIS)-induced gastric ulcer. Methods. Thirty-six rats were randomly divided into four groups for 10 days of treatment as follows: the normal group received no treatment; the model group received RWIS-induced gastric ulcer; the omeprazole group was administered omeprazole orally every 2 days; and the electroacupuncture group received electroacupuncture at the RN12 and BL21 acupoints every 2 days. After 10 days of treatment, except for the normal group, all rats were induced with gastric ulcer by RWIS for 3 h. The ulcer index (UI), ulcer inhibition rate, and histopathological score were calculated. We determined the levels of tumor necrosis factor (TNF)-α and interleukin (IL)-6 in serum, and the activities of myeloperoxidase (MPO), malondialdehyde (MDA), superoxide dismutase (SOD), nitric oxide (NO), and glutathione peroxidase (GSH-Px) in serum and gastric tissues. Protein expression of MyD88, nuclear factor (NF)-κB (p65), and toll-like receptor (TLR) 4 was quantified in gastric tissues. Results. The electroacupuncture and omeprazole groups were equivalent in terms of UI, ulcer inhibition rate, and histopathological score. The serum levels of TNF-α and IL-6 were significantly lower in the electroacupuncture group compared with the omeprazole group ( P  < 0.05). Compared with the model group, there were significant changes in the levels of NO, MPO, GSH-Px, and MDA in all other groups, while the expression of TLR4, MyD88, and NF-κB p65 in gastric tissue decreased significantly in the electroacupuncture group. The expression of TLR4 was substantially lower in the electroacupuncture group compared with the omeprazole group. Conclusion. Acupuncture at back-shu and front-mu acupoints played a role in preventing gastric ulcer by inhibiting extracellular signals, stimulating kinases in serum and gastric tissues, and activating the inhibition of the TLR4 signaling pathway.


Medicines ◽  
2018 ◽  
Vol 5 (3) ◽  
pp. 106 ◽  
Author(s):  
Yuanjun Deng ◽  
Kairui Tang ◽  
Runsen Chen ◽  
Yajie Liu ◽  
Huan Nie ◽  
...  

Background: In traditional Chinese medicine, the Shugan-Jianpi recipe is often used in the treatment of nonalcoholic fatty liver disease (NAFLD). This study aimed to explore the mechanism of the Shugan-Jianpi recipe in relation to rats with NAFLD induced by a high-fat diet. Methods: Rats were randomly divided into eight groups: normal group (NG), model group (MG), low-dose Chaihu–Shugan–San group (L-CG), high-dose Chaihu–Shugan–San group (H-CG), low-dose Shenling–Baizhu–San group (L-SG), high-dose Shenling–Baizhu–San group (H-SG), low dose of integrated-recipes group (L-IG), and high dose of integrated-recipes group (H-IG). After 26 weeks, a lipid profile, aspartate, and alanine aminotransferases in serum were detected. The serum levels of inflammatory factors including interleukin (IL)-1β, IL-6, and tumor necrosis factor-alpha (TNF-α) were analyzed using the enzyme linked immunosorbent assay (ELISA) method. Hepatic pathological changes were observed with hematoxylin-eosin (HE) and oil red O staining. The expression of the p38 mitogen-activated protein kinases (MAPK)/nuclear factor-κB (NF-κB) pathway was detected by quantitative real-time PCR and Western blotting. Results: A pathological section revealed that NAFLD rats have been successfully reproduced. Compared with the model group, each treatment group had different degrees of improvement. The Shugan-Jianpi recipe can inhibit the serum levels of IL-1β, IL-6, and TNF-α in NAFLD rats. The expression of mRNA and a protein related to the p38 MAPK/NF-κB signaling pathway were markedly decreased as a result of the Shugan-Jianpi recipe. Conclusions: The Shugan-Jianpi recipe could attenuate NAFLD progression, and its mechanism may be related to the suppression of the p38 MAPK/NF-κB signaling pathway in hepatocytes.



2019 ◽  
Vol 17 ◽  
pp. 205873921985285
Author(s):  
Li Xiong ◽  
Guobo Xie ◽  
Binhua Luo ◽  
Zhiliang Mei

This study aims to evaluate the effect of Shenfu Qiangxin on TGF-β/Smads signaling pathway-related molecules in myocardial tissue of rats with heart failure. Five rats were selected as sham-operated group, while another 15 rats with heart failure were divided into three groups, including model group, losartan group, and Shenfu Qiangxin group. Rats in losartan group were given losartan intragastric intervention, the rats in Shenfu Qiangxin group were given Shenfu Qiangxin mixture intervention, while rats in another two groups were given equal volume of sterile saline intervention. During the treatment, the levels of B-type brain natriuretic peptide (BNP), lactate dehydrogenase (LDH), free fatty acids (FFA), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and TGF-β/Smads signaling pathway were measured in rats. Compared with model group, the expression of ejection fraction (EF), left ventricular ejection fraction (LVSP), TGF-β 1, Smad2, and Smad3 significantly decreased in sham-operated group, losartan group, and Shenfu Qiangxin group, while left ventricular end-diastolic volume (LVEDV), left ventricular end-diastolic diameter (LVDd), left ventricular end-diastolic pressure (LVEDP), BNP, LDH, FFA, TNF-α, and IL-6 levels increased ( P < 0.05). Compared with sham-operated group, the expression of EF, LVSP, TGF-beta 1, Smad2, and Smad3 dramatically decreased in losartan group, Shenfu Qiangxin group, but LVEDV, LVDd, LVEDP, BNP, LDH, FFA, TNF-α, and IL-6 levels increased ( P < 0.05). Compared with losartan group, the expression of EF, LVSP, TGF-beta 1, Smad2, and Smad3 upregulated in Shenfu Qiangxin group, while LVEDV, LVDd, LVEDP, BNP, LDH, FFA, TNF-α, and IL-6 levels downregulated ( P < 0.05). Consequently, Shenfu Qiangxin could effectively improve the heart function of rats with heart failure, and play an anti-heart failure role by regulating the expression of related molecules of TGF-β/Smads signaling pathway.



2016 ◽  
Vol 40 (3-4) ◽  
pp. 527-537 ◽  
Author(s):  
Jian-Ying Luo ◽  
Dan Fu ◽  
Ya-Qin Wu ◽  
Ying Gao

Background/Aims: The present study aimed to investigate the effects of the JAK2/STAT3/SOSC1 signaling pathway on the secretion function of vascular endothelial cells (VECs) in a rat model of pregnancy-induced hypertension (PIH). Methods: A PIH rat model was established. Forty-eight pregnant Sprague-Dawley female rats were selected and assigned into four groups: the normal group (normal non-pregnant rats), the non-PIH group (pregnant rats without PIH), the PIH group (pregnant rats with PIH) and the AG490 group (pregnant rats with PIH treated with AG490). Systolic blood pressure (SBP) and urinary protein (UP) were measured. The expressions of JAK2/STAT3/SOSC1 signaling pathway-related proteins in placenta tissues were detect by Western blotting. Radioimmunoassay was applied to detect serum levels of nitric oxide (NO), super oxide dismutase (SOD), placental growth factor (PGF), thromboxane B2 (TXB2) and endothelin (ET). Enzyme-linked immunosorbent assay (ELISA) was used to determine serum levels of interleukin-6 (IL-6), interleukin-10 (IL-10) and tumor necrosis factor-α (TNF-α). Results: Compared with the normal and non-PIH groups, the PIH and AG490 groups had higher SBP and UP levels at 17th and 25th day of pregnancy. The expressions of p/t-JAK2, p/t-STAT3 and SOSC1 in the PIH and AG490 groups were higher than those in the non-PIH group, while the expressions of p/t-JAK2, p/t-STAT3 and SOSC1 in the AG490 group were lower than those in the PIH group. Compared with the non-PIH group, serum levels of ET, TXB2, IL-6 and TNF-α were increased in the PIH and AG490 groups, while serum levels of NO, SOD, 6-keto-PGF1a and IL-10 levels were reduced. Furthermore, the AG490 had lower serum levels of ET, TXB2, IL-6 and TNF-α and higher serum levels of NO, SOD, 6-keto-PGF1a and IL-10 than those in the PIH group. Conclusion: Our study provides evidence that inhibition of the JAK2/STAT3/SOSC1 signaling pathway could improve the secretion function of VECs in PIH rats.



2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Xing Li ◽  
Shizhang Wei ◽  
Xiao Ma ◽  
Haotian Li ◽  
Manyi Jing ◽  
...  

Aim. The aim of this study was to explore the antipyretic effect and potential mechanism of Huanglian Jiedu Decoction (HLJDD) on LPS-induced fever in rats. Materials and Methods. The fever rat model was established by LPS. Anal temperature of rats was measured every 1 hour after modeling. TNF-α, IL-6, PGE2, and cAMP in rat serum or hypothalamus tissue were detected by ELISA kit. In order to explore the potential active ingredients and mechanism of antipyretic effect of HLJDD, we predicted the underlying antipyretic mechanism by using network pharmacology and then verified its mechanism by Western Blotting. Results. The results showed that HLJDD can alleviate LPS-induced fever in rats. The expression levels of TNF-α, IL-6, PGE2, and cAMP in the treatment group were significantly lower than those in the model group. Western Blotting results showed that the protein expression of p-ERK, p-JNK, and p-P38 was significantly inhibited. Conclusion. The findings suggest that HLJDD has a good antipyretic effect on LPS-induced fever in rats, which may be closely related to the inhibition of MAPK signaling pathway.



2020 ◽  
Author(s):  
Yao Liu ◽  
Jinqiang Zhu ◽  
Xiaohong Jin ◽  
Meiping Dong ◽  
Junfen Zheng

Abstract Background: This study aimed to explore the effect of miR-146b-3p on acute respiratory distress syndrome in septic mice by regulating PI3K/AKT signaling pathway. Methods: Seventy C57BL/6 mice were divided into normal group ( n = 10) and modeling group ( n = 60, mice for constructing septic mice models with acute respiratory distress syndrome). Model mice were subdivided into model group (without any treatment), negative control (NC) mimic group (injection with miRNA NC), miR-146b-3p mimic group (injection with miR-146b-3p mimic), si-NC group (injection with PI3Kγ siRNA NC), si-PI3Kγ group (injection with PI3Kγ interference sequence), and miR-146b-3p mimic + oe-PI3Kγ group (injection with miR-146b-3p mimic + PI3Kγ overexpression plasmid). Dual-luciferase reporter assay was conducted to determine the target relationship between miR-146b-3p and PI3Kγ. Wet weight/dry weight (W/D) ratio of the left lung was measured. Hematoxylin and eosin stain was used to detect the pathological change of mouse lung. ELISA was employed to measure serum interleukin (IL) -1β and IL-18 levels. miR-146b-3p and PI3Kγ expressions were detected by qRT-PCR. PI3Kγ, AKT, NLRP3, apoptosis-associated speck-like protein caspase recruitment domain (ASC) and Caspase-1 protein expressions were detected by Western blotting. Results: miR-146b-3p negatively regulated PI3Kγ. The lung tissues in other groups compared with normal group had down-regulated miR-146b-3p, up-regulated PI3Kγ, p-AKT, ASC, NLRP3 and Caspase-1 proteins, higher W/D ratio, and more serum IL-1β and IL-18 (all P < 0.05). All indicators in miR-146b-3p mimic group and si-PI3Kγ group were significantly improved as compared to model group (all P < 0.05). Up-regulated PI3Kγ, p-AKT, ASC, NLRP3 and Caspase-1 proteins and higher W/D ratio and IL-1β and IL-18 levels in serum existed in miR-146b-3p mimic + oe-PI3Kγ group compared with miR-146b-3p mimic group (all P < 0.05). Conclusions: Up-regulation of miR-146b-3p can restrain PI3K/AKT signaling pathway, thereby improving acute respiratory distress syndrome in septic mice.



2020 ◽  
Vol 40 (6) ◽  
Author(s):  
Chunyan Li ◽  
Tingfeng Han ◽  
Run Li ◽  
Liming Fu ◽  
Lei Yue

Abstract To explore the regulation mechanism of miR-26a-5p and connective tissue growth factor (CTGF) in lipopolysaccharide (LPS)-induced alveolar macrophages, which is a severe pneumonia cell model. MH-S cells were grouped into Normal group, Model group, negative control (NC) group, miR-26a-5p mimic group, oe-CTGF group, miR-26a-5p mimic + oe-CTGF group. The expression level of miR-26a-5p, CTGF and Toll-like receptor (TLR) signaling related molecules (TLR2, TLR4 and nuclear factor-κB p65) were detected by qRT-PCR and WB, respectively. The cell viability and apoptosis rate were detected by methyl thiazolyl tetrazolium (MTT) and flow cytometry, respectively. Compared with the Normal group, the expression level of miR-26a-5p was significantly decreased, while CTGF protein level was significantly increased in the Model group. Compared with the Model group, MH-S cells with miR-26a-5p overexpression showed enhanced cell viability, decreased apoptosis rate, declined expression level of TLR signaling related molecules and reduced level of tumor necrosis factor-α (TNF-α), interleukin (IL) 6 (IL-6) and IL-1β, while those with CTGF overexpression had an opposite phenotype. In conclusion, miR-26a-5p can inhibit the expression of CTGF and mediate TLR signaling pathway to inhibit the cell apoptosis and reduce the expression of proinflammatory cytokines in alveolar macrophages which is a cell model of severe pneumonia.



2018 ◽  
Vol 16 ◽  
pp. 205873921879453
Author(s):  
Haisheng Hu ◽  
Haiyan Jin ◽  
Longli Yu ◽  
Shiping Qu

The purpose of this study was to explore the role and possible mechanism of inhibiting extracellular signal-regulated kinase (ERK) pathway on rheumatoid arthritis synovial hyperplasia and angiogenesis. Thirty six Sprague–Dawley rats were randomly assigned into normal group, model group, and intervention group, 12 rats in each group. The measures of enzyme-linked immunosorbent assay (ELISA), RT-PCR, Western blot, and HE immunohistochemical staining were used to examine specific indicators in this study. The levels of interleukin 1β (IL-1β), tumor necrosis factor α (TNF-α), and angiopoietin-1 (Ang-1) in the serum of model group were significantly increased ( P < 0.05) compared to the normal groups. In contrast with the model group rats, the levels of IL-1β, TNF-α, and Ang-1 in the intervention group were all significantly decreased ( P < 0.05). In addition, the mRNA expression of IL-1β, TNF-α, vascular endothelial growth factor (VEGF), and Ang-1 in the synovial tissue of the model group was distinctly higher than those in the normal group ( P < 0.05). Simultaneously, the levels of cytokines in the intervention group were obviously decreased compared to the model group ( P < 0.05). The expression of phosphorylated state of ERK1/2 (p-ERK1/2), p-JNK, and p-38 in model group rats were significantly higher than those in normal group ( P < 0.05), while the expression of p-ERK1/2 in intervention group rats was evidently decreased compared to model groups ( P < 0.05). Finally, the arthritis index and arthritis volume in intervention group were decreased obviously ( P < 0.05). Inhibition of ERK pathway could suppress the levels of inflammatory cytokines in synovial tissue and also inhibit the proliferation of synovial tissue, and reduce angiogenesis and pannus formation in synovial membrane.



2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Jue Zhou ◽  
Zhi-Ming Ding ◽  
Paul J. Hardiman

The objective of this study is to identify the changes of metabolites in the rat endometriosis models treated with Gui-Zhi-Fu-Ling-capsules (GZFLC), a classic Chinese medicinal formula, and to explore the effects of GZFLC on the serum levels of transforming growth factor-β1 (TGF-β1) and the mRNA expression levels of vascular endothelial growth factor (VEGF) and glucose transporter 4 (GLUT-4) in the endometriotic tissues. Forty female Wistar rats were randomly divided into the sham-operation group (Normal group), Model group, Danazol group, and GZFLC group. The serum levels of TGF-β1 were measured using enzyme-linked immune-sorbent assay (ELISA). The mRNA expression levels of VEGF and GLUT-4 in the endometriotic tissue of the rat endometriosis models were measured using real-time quantitative PCR. The metabolites in urine were detected by 1H NMR method. Eight identified metabolites of the NMR resonance were involved in the glycolysis metabolism. Among the 8 metabolites, Lactate, Acetate, TMA, and Formate were downregulated with GZFLC. Citrate, TMAO, Taurine, and Hippurate were unregulated with GZFLC. The serum levels of TGF-β1 in the Danazol and GZFLC groups were significantly higher than those of Normal group and significantly lower than the Model group. GZFLC treatment significantly decreased the GLUT-4 and VEGF mRNA expression levels in the endometriotic tissues of the endometriosis rats (P < 0.05). GZFLC significantly decreased the GLUT-4 mRNA expression levels in rats of GZFLC group compared with Danazol group. It is through regulating the metabolites changes of glycolysis or gluconeogenesis that GZFLC significantly affected the expression levels of TGF-β1, GLUT-4, and VEGF of the model rats with endometriosis.



2012 ◽  
Vol 40 (03) ◽  
pp. 599-610 ◽  
Author(s):  
Cheng-Mu Hu ◽  
Qi Cao ◽  
Xiong-Wen Lv ◽  
Wen-Ming Cheng ◽  
Rong Li ◽  
...  

Alcoholic fatty liver (AFL) is a reversible condition, but it can potentiate the development of alcoholic hepatitis and even cirrhosis by increasing oxidant generation, which is one of the key pathogenic factors and could result in alcoholic liver disease (ALD). Total flavonoids from Litsea coreana (TFLC), an active component extracted from Litsea coreana leve, have been shown to have therapeutic effects on hyperlipidemia. The present study was to evaluate the protective effects of TFLC on alcoholic fatty liver (AFL) in rats, and investigate the potential mechanism. An AFL model in rats was established by intaking different doses of alcohol (concentration from 5% to 40%) over 12 weeks. Serum levels of TG, TC, LDL-C, HDL-C, TNF-α, insulin, and glucose were measured, histopathologic changes were determined, and expression of adipose differentiation-related protein (ADRP) in the liver were evaluated by Western blotting and immunohistochemistry, respectively. The results showed that treatment with TFLC resulted in decreased serum levels of TG, TC, LDL-C, TNF-α, glucose and insulin, as well as improved liver index. Morphological evaluation revealed rats in model group developed a severe steatosis, but the severities of liver steatosis were effectively ameliorated in TFLC (200 and 400 mg/kg) treated groups. Expression of hepatic ADRP were increased in model group, and suppressed in TFLC treated groups. These results suggest that TFLC had a protective effect on AFL rats; the mechanism may be involved in regulation serum lipid profiles via down-regulation of hepatic expression of ADRP in AFL rats.



2014 ◽  
Vol 2014 ◽  
pp. 1-17 ◽  
Author(s):  
Jie Li ◽  
Li Peng ◽  
Hong Du ◽  
Yangtian Wang ◽  
Bin Lu ◽  
...  

Objective. To investigate the effect of beraprost sodium (BPS) on diabetic cardiomyopathy and the underlying mechanism.Methods. A total of 40 Sprague Dawley rats were randomly divided into the normal control group (N=10) and the model group (N=30). The model group was fed a high-fat diet followed by a one-time dose of streptozotocin (STZ) to establish the diabetes mellitus model. After that, rats were randomly divided into two groups with or without BPS intervention. After 8 weeks, we explored the role of the p38 MAPK signaling pathway in inflammation, oxidative stress, cardiac morphology, and myocardial apoptosis.Results. Compared with control, the ratio of heart-weight to body-weight and the serum levels of SOD and GSH in the BPS group significantly increased, the expression of p38 MAPK, the serum levels of MDA, TGF-β1, TNF-α, HIF-1α, MMP-9, caspase-3, BNP, ANP, and heart Bax expression significantly decreased, and heart Bcl-2 expression significantly increased. H&E staining in diabetic rats showed the cardiac muscle fibers derangement, the widening gap, the pyknotic and fragmented nuclei, and more apoptosis.Conclusions. BPS effectively showed protective effects on diabetic myocardial cells, possibly through the inhibition of p38 MAPK signaling pathway.



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