scholarly journals Salix tetrasperma Roxb. Extract Alleviates Neuropathic Pain in Rats via Modulation of the NF-κB/TNF-α/NOX/iNOS Pathway

Antioxidants ◽  
2019 ◽  
Vol 8 (10) ◽  
pp. 482 ◽  
Author(s):  
Sobeh ◽  
Mahmoud ◽  
Rezq ◽  
Alsemeh ◽  
Sabry ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Sciatic Nerve ◽  
Brain Stem ◽  
Antioxidant Activities ◽  
Enzyme Linked Immunosorbent Assay ◽  
Dependent Manner ◽  
P53 Expression ◽  
Tnf Α ◽  
Cox 2

Patients with neuropathic pain experience chronic painful tingling, burning, and prickling sensations accompanied with hyperalgesia and/or allodynia. In this study, 38 secondary metabolites of a methanol extract from Salix tetrasperma flowers were identified by liquid chromatography-mass spectrometry (HPLC-MS/MS). The extract showed substantial anti-inflammatory, central and peripheral anti-nociceptive, antipyretic, and antioxidant activities in vitro and in different animal models. In the chronic constriction injury (CCI) rat model, the extract was able to attenuate and significantly relieve hyperalgesia and allodynia responses in a dose dependent manner and restore the myelin sheath integrity and Schwann cells average number in the sciatic nerve. The enzyme-linked immunosorbent assay (ELISA) showed that the extract significantly reduced the expression of various pro-inflammatory biomarkers including nuclear factor kabba B (NF-κB), tumor necrosis factor alpha (TNF-α), prostaglandin E2 (PGE2), 5-lipoxygenase (5-LOX), cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), and the oxidative stress biomarker NADPH oxidase 1 (NOX1), in brain stem and sciatic nerve tissues. These findings were supported by in vitro enzyme inhibition assays (COX-1, COX-2 and 5-LOX). Moreover, the extract significantly reduced p53 expression in the brain stem tissue. These findings support the use of S. tetrasperma in folk medicine to alleviate pain. It could be a promising natural product for further clinical investigations to treat inflammation, nociceptive pain and chronic neuropathic pain.

scholarly journals Bakuchiol Suppresses Inflammatory Responses Via the Downregulation of the p38 MAPK/ERK Signaling Pathway

2019 ◽  
Vol 20 (14) ◽  
pp. 3574 ◽  
Author(s):  
Hye-Sun Lim ◽  
Yu Jin Kim ◽  
Bu-Yeo Kim ◽  
Soo-Jin Jeong
Keyword(s):  
Mrna Expression ◽  
P38 Mapk ◽  
Inflammatory Responses ◽  
Mitogen Activated Protein Kinase ◽  
Enzyme Linked Immunosorbent Assay ◽  
Mice Model ◽  
Tnf Α ◽  
Cox 2

The purpose of the present study was to evaluate the effects of bakuchiol on the inflammatory response and to identify the molecular mechanism of the inflammatory effects in a lipopolysaccharide (LPS)-stimulated BV-2 mouse microglial cell line and mice model. The production of prostaglandin E2 (PGE2), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) was measured by enzyme-linked immunosorbent assay. The mRNA expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), TNF-α, and IL-6 was measured using reverse transcription–polymerase chain reaction analysis. Mitogen-activated protein kinase (MAPK) phosphorylation was determined by western blot analysis. In vitro experiments, bakuchiol significantly suppressed the production of PGE2 and IL-6 in LPS-stimulated BV-2 cells, without causing cytotoxicity. In parallel, bakuchiol significantly inhibited the LPS-stimulated expression of iNOS, COX-2, and IL-6 in BV-2 cells. However, bakuchiol had no effect on the LPS-stimulated production and mRNA expression of TNF-α or on LPS-stimulated c-Jun NH2-terminal kinase phosphorylation. In contrast, p38 MAPK and extracellular signal-regulated kinase (ERK) phosphorylation were inhibited by bakuchiol. In vivo experiments, Bakuchiol reduced microglial activation in the hippocampus and cortex tissue of LPS-injected mice. Bakuchiol significantly suppressed LPS-injected production of TNF-α and IL-6 in serum. These results indicate that the anti-neuroinflammatory effects of bakuchiol in activated microglia are mainly regulated by the inhibition of the p38 MAPK and ERK pathways. We suggest that bakuchiol may be beneficial for various neuroinflammatory diseases.

scholarly journals Protocatechuic acid as an inhibitor of the JNK/CXCL1/CXCR2 pathway relieves neuropathic pain in CCI rats

2021 ◽  
Author(s):  
Hong-xia Chang ◽  
Yue-feng Zhao
Keyword(s):  
Neuropathic Pain ◽  
Sciatic Nerve ◽  
Satellite Cells ◽  
Protocatechuic Acid ◽  
Thermal Hyperalgesia ◽  
Tnf Α ◽  
Chemokine Ligand ◽  
New Perspective

Emerging evidence has shown that protocatechuic acid (PCA) has antioxidant and anti-inflammatory effects. Evidence suggests that PCA can alleviate the injury of sciatic nerve, while the mechanism of its therapeutic effect on neuralgia remains unknown.         Chromium bowel ligation was used in vivo to establish a chronic constriction injury (CCI) rat model to induce sciatic nerve pain. Subsequently, two doses of PCA were used to treat CCI rats. In vitro, 10 ng/mL TNF-α was used to stimulate glial satellite cells derived from the dorsal root ganglia (DRG) L4-L6 of the sciatic nerve to simulate sciatic nerve pain. PCA relieved mechanical allodynia and thermal hyperalgesia in CCI rats. CCK-8 assay revealed that PCA inhibited the proliferation of glial satellite cells induced by TNF-α. Moreover, ELISA demonstrated that PCA could improve the inflammatory response of rats caused by CCI and cells induced by TNF-α. Next, RT-qPCR and Western blot assays showed that PCA blocked the c-Jun N-terminal kinase/the chemokine ligand 1/CXC chemokine receptor 2 (JNK/CXCL1/CXCR2) pathway by inhibiting CXCL1 levels in cells induced by TNF-α and DRG in CCI rats. In conclusion, PCA can alleviate neuropathic pain in CCI rats and improve oxidative stress by inhibiting the JNK/CXCL1/CXCR2 signaling pathway. Thus, these findings provide a new perspective for the treatment of neuropathic pain caused by CCI.

scholarly journals Higher Follicular Fluid Progesterone Down-regulated HPGD and COX2 in Granulosa Cells via Suppressing NF-кB Signaling in Endometriosis

2021 ◽  
Author(s):  
Jing-Yi Li ◽  
Jian-Peng Chen ◽  
Yu-Li Qian ◽  
Jun-Yan Ma ◽  
Fei-Da Ni ◽  
...  
Keyword(s):  
Granulosa Cells ◽  
Follicular Fluid ◽  
Chromatin Immunoprecipitation ◽  
Cell Model ◽  
Enzyme Linked Immunosorbent Assay ◽  
Dependent Manner ◽  
Serum Progesterone ◽  
Vitro Fertilization ◽  
Cox 2

Abstract Background: Luteinized unruptured follicular follicle syndrome (LUFS) is a special type of ovulatory dysfunction and a common cause of infertility. It is estimated that its prevalence is 13% ~ 73% in endometriosis patients. Increasing evidences prove that LUFS is one of the reasons for endometriosis-related infertility. Any alteration in FF components and GCs in endometriosis may influence the developing oocyte and ovulation. This study aimed to explore the effect of local elevated progesterone in follicular fluid (FF) on ovulation in endometriosis patients.Methods: A Prospective study with matched pairs design was conducted at a reproductive medicine center between July 2017 and January 2018 in patients undergoing in vitro fertilization (IVF) or intracytoplasmic sperm injection treatment (ICSI), while granulosa tumor-like cell line KGN (Bena culture collection, China) was used as in vitro cell model. Alterations in follicular and peritoneal fluid (PF) components identified with metabolomics analyses; Differentially expressed genes in GCs identified with transcriptome analysis; Polymerase chain reaction (PCR), western blot, enzyme-linked immunosorbent assay (ELISA) and immunofluorescence were used to determine the expression of progesterone, NF-кB related genes, HPGD and COX-2; NF-кB binding identified with chromatin immunoprecipitation (ChIP).Results: Patients with endometriosis exhibited a significantly higher basal serum progesterone level, higher serum level of progesterone on trigger day and higher progesterone expression level in FF and PF. GCs from endometriosis patients revealed decreased expression of HPGD, COX-2 and suppressed NF-кB signaling, as manifested by decreased expressions of IL1R1 and IRAK3. Similarly, progesterone treatment in vitro down-regulated HPGD and COX2 expression and suppressed NF-кB signaling in KGN cells in a dose dependent manner, as manifested by decreased expressions of IL1R1, IRAK3, reduced pIкBα/IкBα ratio and nucleus translocation of p65. TNF-α, by contrast, increased expression of IL1R1, IRAK3, pIкBα, p65 and HPGD in KGN cells. Furthermore, one potential p65 binding site was identified in the promoter region of HPGD by chromatin immunoprecipitation.Conclusion: Endometriosis showed repression of NF-кB pathways and down-regulation of HPGD and COX2, which play important roles in the process of ovulation by participating in the metabolism of prostaglandin E2 (PGE2), in granulosa cells (GCs) due to elevated progesterone in FF.

scholarly journals The Acidic Fraction of Isatidis Radix Regulates Inflammatory Response in LPS-Stimulated RAW264.7 Macrophages through MAPKs and NF-κB Pathway

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Zhenyu Fan ◽  
Liangliang Cai ◽  
Yage Wang ◽  
Qiuyan Zhu ◽  
Shengnan Wang ◽  
...  
Keyword(s):  
Sore Throat ◽  
Mechanism Of Action ◽  
Inflammatory Activity ◽  
Enzyme Linked Immunosorbent Assay ◽  
Dependent Manner ◽  
Raw264.7 Macrophages ◽  
Tnf Α ◽  
Acidic Fraction ◽  
Cox 2 ◽  
Anti Inflammatory

Isatidis Radix, the dried root of Isatidis indigotica Fort, is a traditional heat-clearing and detoxicating herb, which has the antiviral and anti-inflammatory activity and immune regulation. It has been widely used to treat cold, fever, sore throat, mumps, and tonsillitis in clinics. A previous study demonstrated that the acidic fraction of Isatidis Radix (RIAF) had strong anti-inflammatory activity, but the mechanism of action was not well elucidated. Lipopolysaccharide- (LPS-) induced RAW264.7 cells were employed to observe the anti-inflammatory activity of RIAF. The level of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), nitric oxide (NO), prostaglandin E2 (PGE2), and interleukin-6 (IL-6) was determined by enzyme-linked immunosorbent assay kits. Western blot was performed to quantify the expression of extracellular signal-regulated kinase (ERK) 1/2, c-jun NH2-termianl kinase (JNK), p38, inducible NO synthetase (iNOS), cyclooxygenase (COX)-2, andnuclear factor-κB (NF-κB). Immunofluorescence assay and electrophoretic mobility shift assay (EMSA) were used to quantify the translocation and the binding-DNA activity of NF-κB. RIAF could inhibit the secretion of inflammatory cytokines (PGE2, IL-6, IL-1β, and NO, other than TNF-α) in a dose-dependent manner. Further investigation showed that the expression of iNOS and COX-2 induced by LPS were downregulated by treatment with RIAF. Meanwhile, data from the signal pathway exhibited that RIAF significantly suppressed the phosphorylation of ERK1/2, JNK, and p38 and reduced the translocation of NF-κB from the cytoplasm to nucleus, as well as the binding-DNA activity. The anti-inflammatory mechanism of action of RIAF was to reduce inflammation-associated gene expression (iNOS, COX-2, IL-1β, IL-6) by regulating the phosphorylation of the mitogen-activated protein kinases (MAPK) pathway and interventing the activation of the NF-κB pathway, which partly illustrated the basis of treatment of Isatidis Radix on cold, fever, sore throat, mumps, and tonsillitis in clinics.

Nickel-refining dust regulates the expression of inflammatory factors in NIH/3T3 cells

2019 ◽  
Vol 35 (3) ◽  
pp. 239-247 ◽  
Author(s):  
Runan Qin ◽  
Yue Wang ◽  
Shengyuan Wang ◽  
Bing Xia ◽  
Rui Xin ◽  
...  
Keyword(s):  
Inflammatory Factors ◽  
Dependent Manner ◽  
3T3 Cells ◽  
Related Factors ◽  
Experimental Conditions ◽  
Tnf Α ◽  
Cox 2 ◽  
Nih 3T3 ◽  
Nih 3T3 Cells

Nickel (Ni) is a metal known to be a human carcinogen that occupational workers can be exposed to during the process of Ni refining. We investigated the molecular mechanism of inflammation that is induced by Ni-refining dust in a factory, using concentrations of 0, 25, 50, and 100 µg/mL for 24 h and 48 h, in vitro. Quantitative real-time polymerase chain reactions (qRT-PCR), Western blot analysis, and enzyme-linked immunosorbent assays (ELISA) were used to detect the transcriptional expression levels of nuclear factor-κB (NF-κB), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2). Results showed that Ni-refining dust decreased the secretion of IL-6 under the experimental conditions. In contrast, Ni-refining dust activated NF-κB expression and stimulated the secretion of TNF-α, IL-1β, iNOS, and COX-2 in a dose- and time-dependent manner. To summarize, we demonstrated that exposure to Ni-refining dust can induce the expression of NF-κB in NIH/3T3 cells and the secretion of inflammation related factors. This provides a new basis for further study of the inflammatory effects of Ni-refining dust.

scholarly journals Dihydromyricetin attenuates inflammation through TLR4/NF-kappaB pathway

Open Medicine ◽  
2019 ◽  
Vol 14 (1) ◽  
pp. 719-725 ◽  
Author(s):  
Nianshui Jing ◽  
Xinnan Li
Keyword(s):  
Primary Response ◽  
Enzyme Linked Immunosorbent Assay ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Tnf Α ◽  
Cox 2 ◽  
Nf Kappab ◽  
Factor Α ◽  
Oxide Synthase

AbstractMicroglia plays a complex role in neuroinflammation, which has been implicated in neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease. This study aims to explore the effect and mechanism of Dihydromyricetin (DHM) on lipopolysaccharide (LPS)-induced inflammation in microglial BV-2 cells. Cell viability was measured by 3-[4,5-dimethylthiazol-2-yl]2,5-diphenyltetrazolium bromide (MTT) assay. The pro-inflammatory mediators and cytokines including interleukin (IL)-6, IL-1β, and tumor necrosis factor-α (TNF-α); inducible nitric oxide synthase (iNOS); and cyclooxygenase 2 (COX-2) were measured by enzyme-linked immunosorbent assay (ELISA) and/or quantitative real-time PCR (qRT-PCR). The expression of p-p65, p-IκBα, toll-like receptor 4 (TLR4), and myeloid differentiation primary response 88 (MyD88) were analyzed by western blot. The present study showed that DHM treatment alleviated LPS-induced viability reduction, suppressed the mRNA levels of IL-6, IL‐1β and TNF-α, inhibited the mRNA and protein expression of iNOS and COX-2, and attenuated the activation of NF-кB and TLR4 signaling in a concentration-dependent manner. In conclusion, DHM exerts an anti-inflammatory effect on LPS-induced BV-2 microglial cells, possibly through TRL4/NF-κB signaling pathway.

scholarly journals Dezocine attenuates neuropathic pain by inhibiting ERK1/2 signaling in rats

2019 ◽  
Author(s):  
Chan Shen ◽  
Shi Sheng ◽  
Ling Yu ◽  
Naixing Xin
Keyword(s):  
Neuropathic Pain ◽  
Quantitative Polymerase Chain Reaction ◽  
Mammalian Target Of Rapamycin ◽  
Life Quality ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Expression Levels ◽  
Withdrawal Threshold ◽  
Tnf Α ◽  
Cox 2

Abstract Background Neuropathic pain severely impacts patients’ life quality. Dezocine can be used for the treatment of pain. The present study intended to explore the effects of dezocine in chronic constriction injury (CCI) induced neuropathic pain as well as the possible responsible molecules in rats. Methods There were 3 subgroups, ie, control group, CCI group and dezocine+CCI group. The values of paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) in rats were determined by a dynamic plantar esthesiometer. The ipsilateral lumbar spinal cords in rats were extracted for the detection of protein levels of phosphorylated-mammalian target of rapamycin (p-mTOR) and p-extracellular signal-regulated kinase 1/2 (p-ERK1/2) by western blot analysis; and the mRNA and protein expression levels of interleukin (IL)-6, tumor necrosis factor (TNF)-α, and cyclooxygenase-2 (COX-2) by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and enzyme-linked immunosorbent assay (ELISA), respectively. Results In comparison with control group, there were lower values of PWT and PWL in CCI group, which were partially reversed by dezocine. In addition, compared to control group, the expression levels of p-mTOR, p-ERK1/2, IL-6, TNF-α and COX-2 were upregulated by CCI, which were attenuated by dezocine. Conclusions In conclusion, the analgesic effect of dezocine on CCI induced neuropathic pain might be correlated with inhibiting of the p-mTOR and p-ERK1/2 signaling pathway.

scholarly journals Kirenol inhibits TNF-α-induced proliferation and migration of HaCaT cells by regulating NF-κB pathway

2021 ◽  
Vol 13 (4) ◽  
pp. 44-53
Author(s):  
Jin Li ◽  
Fang Ren ◽  
Wenliang Yan ◽  
Hong Sang
Keyword(s):  
Cell Migration ◽  
Cell Viability ◽  
Signaling Pathway ◽  
Inflammatory Cytokines ◽  
Cell Counting ◽  
Enzyme Linked Immunosorbent Assay ◽  
Dependent Manner ◽  
Hacat Cells ◽  
Tnf Α

Psoriasis is a common chronic, inflammatory skin disease possessing properties of inflammatory cell infiltration and excessive proliferation of keratinocytes, the occurrence and development of which remain fully elucidated. Therefore, the study was designed to determine the effects of kirenol (50, 100 and 200 μg/mL) on Cultured Human Keratinocytes (cells) (HaCaT) in vitro and reveal its molecular mechanism. The in vitro psoriasis model was established utilizing tumor necrosis factor-α (TNF-α)-stimulated HaCaT cells. Kirenol, a diterpenoid compound, was applied at different concentrations (50, 100 and 200 μg/mL) to HaCaT cells for 24 h. The Cell Counting Kit-8 (CCK-8) and thymidine monobromodeoxyuridine (BrdU) assays were used to assess cell viability and proliferation, followed by assessment of cell migration by Transwell assay. Subsequently, inflammatory cytokines were measured by enzyme-linked immunosorbent assay (ELISA), and Western blot assay was used to evaluate expres-sions of p65, p-p65, IκBα and p-IκBα. Activities of superoxide dismutase (SOD), catalase (CAT), glutathione (GSH) and malondialdehyde (MDA) contents were measured spectrophotometrically. The results demonstrated that TNF-α induced a significant increase in cell viability and inflammatory cytokines, including expressions of Interleukin (IL)-6, IL-8, IL-22 and IL-1β in HaCaT cells, which was dose-dependently inhibited by kirenol. Similarly, TNF-α-induced cell migration was also suppressed by kirenol treatment. Furthermore, TNF-α stimuli induced the upregulation of phosphorylation levels of p65 and IκBα as well as p-p65–p65 and p-IκBα–IκBα ratios, whereas kirenol significantly suppressed the activation of cellular nuclear factor-kappa B (NF-κB) signaling pathway. In addition, kirenol significantly decreased the level of MDA but increased the levels of SOD, CAT and GSH in a dose-dependent manner. These results proposed that kirenol could inhibit the proliferation, migration, expression of inflammatory factors, and oxidative stress in HaCaT cells via suppressing NF-κB signaling pathway.

scholarly journals Radiosensitization by CpG ODN7909 in an epidermoid laryngeal carcinoma Hep-2 cell line

2017 ◽  
Vol 45 (6) ◽  
pp. 2009-2022 ◽  
Author(s):  
Shu Wang ◽  
Xiaoqun Liu ◽  
Tiankui Qiao ◽  
Qi Zhang
Keyword(s):  
Cell Viability ◽  
Survival Curve ◽  
Cell Counting ◽  
Enzyme Linked Immunosorbent Assay ◽  
Cell Cycle Distribution ◽  
Dependent Manner ◽  
Western Blots ◽  
Apoptosis Rate ◽  
Tnf Α

Objective To evaluate the radiosensitivity effect of CpG oligodeoxyribonucleotide (ODN) 7909 on human epidermoid cancer strain-2 (Hep-2) cells in vitro and discuss the potential for improved radiotherapy treatment in patients with laryngeal squamous cell carcinoma. Methods Toll-like receptor ( TLR) 9 expression was assessed in Hep-2 cells using Western blots and reverse transcription polymerase chain reaction. Cell Counting Kit-8 was used to detect Hep-2 cell viability at 24 and 48 h following treatment with different CpG ODN7909 concentrations. Cellular colonization was evaluated using microscopy. Cell cycle distribution and apoptosis rate was determined with flow cytometry. Interleukin (IL)-12 and tumour necrosis factor (TNF)-α concentrations were detected by enzyme-linked immunosorbent assay. Results Hep-2 cells were found to express TLR9, and CpG ODN7909 treatment suppressed Hep-2 cell viability in a dose- and time-dependent manner. Cell survival curve analyses revealed a sensitivity enhancement ratio of the mean death dose of 1.225 for CpG ODN7909 plus irradiation versus irradiation alone. Furthermore, the population of Gap 2/mitotic-phase cells, apoptosis rate and secreted IL-12 and TNF-α levels were significantly increased in Hep-2 cells treated with CpG ODN7909 plus irradiation versus IR alone. Conclusion CpG ODN7909 enhanced the radiosensitivity of Hep-2 cells in vitro.

scholarly journals 1-Phenyl-6,7-dihydroxy-isochroman suppresses lipopolysaccharide-induced pro-inflammatory mediator production in human monocytes

2011 ◽  
Vol 106 (1) ◽  
pp. 33-36 ◽  
Author(s):  
Giuliana Trefiletti ◽  
Anna Rita Togna ◽  
Valentina Latina ◽  
Carolina Marra ◽  
Marcella Guiso ◽  
...  
Keyword(s):  
Olive Oil ◽  
Virgin Olive Oil ◽  
Extra Virgin Olive Oil ◽  
Dependent Manner ◽  
Human Monocytes ◽  
Beneficial Effects ◽  
Tnf Α ◽  
Cox 2 ◽  
Anti Inflammatory

Extra-virgin olive oil is an integral ingredient of the Mediterranean diet, and it has been suggested that its high consumption has beneficial effects on human health. Its protective effect, in particular against the development of CVD, has been related not only to the high content of oleic acid, but also to the antioxidant and anti-inflammatory properties of polyphenols. In order to verify the anti-inflammatory and anti-atherogenic properties of hydroxy-isochromans, a class of ortho-diphenols present in extra-virgin olive oil, we investigated the potential ability of 1-phenyl-6,7-dihydroxy-isochroman (L137) to modulate the production of key inflammatory mediators by human monocytes, by evaluating its in vitro effects on prostanoid (thromboxane A2 and PGE2) and cytokine (TNF-α) production. Its effect on the protein expression of the inducible form of cyclo-oxygenase-2 (COX-2), a pro-inflammatory enzyme responsible for elevated prostanoid levels, was also explored. The results showed that L137 significantly inhibited both prostanoid and TNF-α production in lipopolysaccharide-primed human monocytes in a dose-dependent manner, by inhibiting the COX activity of COX-2. We also demonstrated that the effects of the isochroman are mediated, at least partly, through the suppression of NF-κB activation leading to the down-regulation of the synthesis of COX-2.

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