scholarly journals Huanglian Jiedu Decoction Exerts Antipyretic Effect by Inhibiting MAPK Signaling Pathway

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Xing Li ◽  
Shizhang Wei ◽  
Xiao Ma ◽  
Haotian Li ◽  
Manyi Jing ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Western Blotting ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Network Pharmacology ◽  
Potential Mechanism ◽  
Model Group ◽  
Rat Serum ◽  
Antipyretic Effect ◽  
Tnf Α

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.

Xenobiotic-induced TNF-α expression and apoptosis through the p38 MAPK signaling pathway

2005 ◽  
Vol 155 (2) ◽  
pp. 227-238 ◽  
Author(s):  
Daniel E. Frigo ◽  
Katinka A. Vigh ◽  
Amanda P. Struckhoff ◽  
Steven Elliott ◽  
Barbara S. Beckman ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
P38 Mapk ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Tnf Α

scholarly journals Tetrahydropalmatinee alleviates diabetic neuropathic pain by inhibiting the inflammation via p38-MAPK signaling pathway in microglia

2021 ◽  
Author(s):  
Lianzhi Cheng ◽  
Junlong Ma ◽  
Aijuan Jiang ◽  
Kai Cheng ◽  
Fanjing Wang ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Neuropathic Pain ◽  
Signaling Pathway ◽  
P38 Mapk ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Inflammatory Factors ◽  
Specific Marker ◽  
Diabetic Neuropathic Pain ◽  
Tnf Α

Abstract Object: Exploring the effect of Tetrahydropalmatine (THP) on diabetic neuropathic pain (DNP) and its possible mechanism. Methods: The type 2 diabetic (T2DM) rat models were prepared by high-fat and high-sugar feeding combined with a single small-dose intraperitoneal injection of streptozotocin (STZ). When the mechanical withdrawal threshold (MWT) and the thermal withdrawal latency (TWL) of T2DM model rats decreased to less than 85% which were judged as DNP-bearing rats. After treatment with or without THP, the protein expression of hypertonic glycerol reactive kinase (p38), phosphorylated hypertonic glycerol-responsive kinase (p-p38) and OX42 (a specific marker of microglia) were detected by Western Blot and and the mRNA content of p38 and OX42 were detected by qRT-PCR. The expression of pro-inflammatory factors IL-1β, IL-6, TNF-α, as well as chemotactic factors and their receptors including CXCL1, CXCR2, CCL2 and CCR2 in spinal tissues were detected by ELISA. Serum FINS and GSP content were also detected by ELISA. Double-label immunofluorescence were used to observe the expression of OX42 and p-p38 in the spinal dorsal horn. Results: Results showed that THP inhibited microglial activation of spinal in DNP rats. And after THP intervention, the MWT and TWL of DNP rats decreased, the expression of p38, p-p38 and OX42 in the spinal cord tissues of rats was significantly reduced while the mRNA of p38 and OX42 also reduced. The expression of IL-1β, IL-6, TNF-α, CXCL1, CXCR2, CCL2 and CCR2 in the spinal cord tissues of rats was significantly reduced (P < 0.01). At the same time, THP significantly proved FINS, but did not affect FBG and GSP in DNP rats. Conclusions: THP significantly alleviates pain symptoms in DNP rats, and this effect may be achieved by inhibiting the inflammatory response caused by the activation of microglia mediated by the p38-MAPK signaling pathway.

scholarly journals EphB4/ TNFR2/Erk/MAPK signaling pathway comprises a signaling axis to mediate the positive effect of TNF-α on osteogenic differentiation

2019 ◽  
Author(s):  
Yu Zhang ◽  
Chengzhe Yang ◽  
Shaohua Ge ◽  
Limei Wang ◽  
Jin Zhang ◽  
...  
Keyword(s):  
Osteogenic Differentiation ◽  
Signaling Pathway ◽  
Mapk Signaling ◽  
Precursor Cells ◽  
Mapk Signaling Pathway ◽  
Erk Mapk ◽  
Low Concentrations ◽  
Tnf Α ◽  
Signaling Axis ◽  
Positive Effect

Abstract Low concentrations of tumor necrosis factor-alpha and its receptor TNFR2 are both reported to promote osteogenic differentiation of osteoblast precursor cells. Moreover, low concentrations of TNF-α up-regulate the expression of EphB4. However, the molecular mechanisms underlying TNF-α-induced osteogenic differentiation and the roles of TNFR2 and EphB4 have not been fully elucidated. This study showed that with increase in ALP activity, mRNA and protein expression of Runx2, BSP and EphB4, TNFR2 expression was significantly promoted under 0.5 ng/ml TNF-α stimulation in osteoblast precursor cells MC3T3-E1. After TNFR2 was inhibited by gene knockdown with lentivirus-mediated shRNA interference or by a neutralizing antibody against TNFR2, the pro-osteogenic effect of TNF-α was partly reversed, but up-regulation of EphB4 by TNF-α kept unchanged. With EphB4 forward signaling suppressed by a potent inhibitor of EphB4 auto-phosphorylation, NVP-BHG712, TNF-α-enhanced expressions of TNFR2, BSP and Runx2 were significantly decreased. Further investigation into the signaling pathways revealed that TNF-α significantly augmented expression of p-JNK, p-Erk and p-p38, however, only p-Erk expression was significantly inhibited in TNFR2-knockdown cells. In addition, the Erk pathway inhibitor, U0126 (10μM), significantly inhibited the protein levels of Runx2 and BSP when compared with cells treated with TNF-α only. In conclusion, the EphB4, TNFR2 and Erk/MAPK signaling pathway comprise a signaling axis to mediate the positive effect of TNF-α on osteogenic differentiation.

scholarly journals Network Pharmacology Study Reveals the Mechanism of Astragali Radix in Treatment of Diabetic Nephropathy

2020 ◽  
Author(s):  
Chongmei Tian ◽  
Jing-bai Chen ◽  
Xiang Chen ◽  
Dao-zong Xia
Keyword(s):  
Diabetic Nephropathy ◽  
Signaling Pathway ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Network Pharmacology ◽  
Signal Pathways ◽  
Therapeutic Effects ◽  
Disease Network ◽  
Astragali Radix ◽  
Target Disease

Abstract Background Diabetic nephropathy (DN), a unique complication of diabetes, could contribute to an increase in mortality. In this study, we predicted and proved the molecular pharmacological mechanism concerning the protective effects of Astragali Radix on DN. Methods The same potential target genes from Astragali Radix and DN were analyzed and constructed the protein interaction network. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment-related major targets and signal pathways were performed. The drug-ingredients-target-disease network was visually built using Cytoscape 3.6.1. The beneficial pharmacological activities of quercetin from Astragali Radix were confirmed by CCK-8 assay, determination of antioxidant parameters and Western blotting analysis. Results There are 12 bioactive components from Astragali Radix and 56 same targets between Astragali Radix and DN. The GO analysis results showed that the biological processes mainly included protein homodimerization activity. KEGG analysis indicate that the screened targets were most closely linked to the mitogen-activated protein kinase (MAPK) signaling pathway. The drug-ingredients-target-disease network results revealed that the therapeutic effects of Astragali Radix mainly included oxidative stress, inflammatory reaction and apoptosis. During the verification process, quercetin from Astragali Radix could attenuate cytotoxicity, enhance catalase (CAT) and superoxide dismutase (SOD) activities and suppress MAPK signaling pathway. Conclusions In the current study, network pharmacology with experimental analysis predicted and proved the therapeutic function of Astragali Radix by improving antioxidant capacity and suppressing MAPK signaling pathway, these investigations could provide a new perspective for further exploration of Astragali Radix on DN treatment.

Rho-kinase mediates TNF-α-induced MCP-1 expression via p38 MAPK signaling pathway in mesangial cells

2010 ◽  
Vol 402 (4) ◽  
pp. 725-730 ◽  
Author(s):  
Keiichiro Matoba ◽  
Daiji Kawanami ◽  
Sho Ishizawa ◽  
Yasushi Kanazawa ◽  
Tamotsu Yokota ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
P38 Mapk ◽  
Mesangial Cells ◽  
Rho Kinase ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Tnf Α

scholarly journals A network pharmacology analysis on drug-like compounds from Ganoderma lucidum for alleviation of Atherosclerosis

2021 ◽  
Author(s):  
Ki Kwang Oh ◽  
Md. Adnan ◽  
Dong Ha Cho
Keyword(s):  
Signaling Pathways ◽  
Signaling Pathway ◽  
Ganoderma Lucidum ◽  
Mapk Signaling ◽  
Mendelian Inheritance ◽  
Chronic Inflammatory Disease ◽  
Mapk Signaling Pathway ◽  
Venn Diagram ◽  
Network Pharmacology ◽  
Overlapping Genes

Abstract Background: Ganoderma lucidum (GL) is known as a potent alleviator against chronic inflammatory disease like atherosclerosis (AS), but its critical bioactive compounds and their mechanisms against AS have not been unveiled. This research aimed to identify the key compounds(s) and mechanism(s) of GL against AS through network pharmacology.Methods: The compounds from GL were identified by gas chromatography-mass spectrum (GC-MS), and SwissADME screened their physicochemical properties. Then, the gene(s) associated with the screened compound(s) or AS related genes were identified by public databases, and we selected the overlapping genes using a Venn diagram. The networks between overlapping genes and compounds were visualized, constructed, and analyzed by RStudio. Finally, we performed molecular docking test (MDT) to identify key gene(s), compound(s) on AutoDockVina.Results: A total of 35 compounds in GL was detected via GC-MS, and 34 compounds (accepted by the Lipinski's rule) were selected as drug-like compounds (DLCs). A total of 34 compounds were connected to the number of 785 genes and 2,606 AS-related genes were identified by DisGeNET and Online Mendelian Inheritance in Man (OMIM). The final 98 overlapping genes were extracted between the compounds-genes network and AS-related genes. On Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, the number of 27 signaling pathways were sorted out, and a hub signaling pathway (MAPK signaling pathway), a core gene (PRKCA), and a key compound (Benzamide, 4-acetyl-N-(2,6-dimethylphenyl)) were selected among the 27 signaling pathways via MDT. Conclusion: Overall, we found that the identified 3 DLCs from GL have potent anti-inflammatory efficacy, improving AS by inactivating the MAPK signaling pathway.

scholarly journals Network Pharmacology Study and Experimental Confirmation Revealing the Ameliorative Effects of Decursin on Chemotherapy-Induced Alopecia

2021 ◽  
Vol 14 (11) ◽  
pp. 1150
Author(s):  
Mi Hye Kim ◽  
Sang Jun Park ◽  
Woong Mo Yang
Keyword(s):  
Signaling Pathway ◽  
Mapk Signaling ◽  
Hair Follicles ◽  
Functional Enrichment ◽  
Network Pharmacology ◽  
Chemical Stimulus ◽  
Dorsal Skin ◽  
Response To Chemotherapy ◽  
Tnf Α ◽  
Protein Expressions

Decursin, a pyranocoumarin compound from the root of Angelica gigas Nakai as a main constituent, has been reported to have various biological activities, including anti-inflammatory, anticancer, and antioxidant effects. This study aimed to predict and confirm the pharmacological relevance of Decursin on chemotherapy-induced alopecia (CIA) with the underlying molecular mechanisms. Decursin-targeted genes were compared with the gene set of alopecia and investigated through functional enrichment analysis. CIA was induced in C57BL/6J mice by injection of cyclophosphamide, and 1, 10, and 100 μM of Decursin were topically treated to depilated dorsal skin. KGF+ expression was detected in the dorsal skin tissues. Based on the predicted results, caspase, PIK3/AKT, and MAPKs protein expressions by Decursin were analyzed in the TNF-α-induced keratinocytes. The Decursin network had 60.20% overlapped genes with the network of alopecia. Biological processes, such as cellular response to chemical stimulus, apoptosis, PI3K-AKT signaling pathway, and MAPK signaling pathway, were derived from the Decursin network. In the Decursin-treated skin, there was morphological hair growth and histological restoration of hair follicles in the CIA mice. The KGF+ fluorescence and protein expressions were significantly increased by Decursin treatment. In addition, caspase-3, -7, and -8 expressions, induced by TNF-α, were dose-dependently decreased along with the inhibition of PI3K, AKT, ERK, and p38 expressions in Decursin-treated keratinocytes. These findings indicated that Decursin would be a potent therapeutic option for hair loss, in response to chemotherapy.

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