scholarly journals Hydrangea serrata (Thunb.) Ser. Extract Attenuate UVB-Induced Photoaging through MAPK/AP-1 Inactivation in Human Skin Fibroblasts and Hairless Mice

Nutrients ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 533 ◽  
Author(s):  
Hee-Soo Han ◽  
Ji-Sun Shin ◽  
Da-Bin Myung ◽  
Hye Ahn ◽  
Sun Lee ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Molecular Mechanisms ◽  
Mapk Signaling ◽  
Collagen Degradation ◽  
Hot Water ◽  
Mrna Levels ◽  
Skin Damage ◽  
Hairless Mice ◽  
Skin Photoaging ◽  
Mapk Signaling Pathways

Skin photoaging is mainly caused by exposure to ultraviolet (UV) light, which increases expressions of matrix metalloproteinases (MMPs) and destroys collagen fibers, consequently inducing wrinkle formation. Nutritional factors have received scientific attention for use as agents for normal skin functions. The aim of this study was to investigate the effect of hot water extracts from the leaves of Hydrangea serrata (Thunb.) Ser. (WHS) against ultraviolet B (UVB)-induced skin photoaging and to elucidate the underlying molecular mechanisms in human foreskin fibroblasts (Hs68) and HR-1 hairless mice. WHS recovered UVB-reduced cell viability and ameliorated oxidative stress by inhibiting intracellular reactive oxygen species (ROS) generation in Hs68 cells. WHS rescued UVB-induced collagen degradation by suppressing MMP expression, and reduced the mRNA levels of inflammatory cytokines. These anti-photoaging activities of WHS were associated with inhibition of the activator protein 1 (AP-1), signal transduction and activation of transcription 1 (STAT1), and mitogen-activated protein kinase (MAPK) signaling pathways. Oral administration of WHS effectively alleviated dorsal skin from wrinkle formation, epidermal thickening, collagen degradation, and skin dehydration in HR-1 hairless mice exposed to UVB. Notably, WHS suppressed UVB activation of the AP-1 and MAPK signaling pathways in dorsal mouse skin tissues. Taken together, our data indicate that WHS prevents UVB-induced skin damage due to collagen degradation and MMP activation via inactivation of MAPK/AP-1 signaling pathway.

Berberine inhibits lipopolysaccharide-induced expression of inflammatory cytokines by suppressing TLR4-mediated NF-ĸB and MAPK signaling pathways in rumen epithelial cells of Holstein calves

2019 ◽  
Vol 86 (2) ◽  
pp. 171-176 ◽  
Author(s):  
Chenxu Zhao ◽  
Yazhou Wang ◽  
Xue Yuan ◽  
Guoquan Sun ◽  
Bingyu Shen ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Signaling Pathways ◽  
Inflammatory Cytokines ◽  
Molecular Mechanisms ◽  
Mapk Signaling ◽  
Dependent Manner ◽  
Inflammatory Drug ◽  
Anti Inflammatory ◽  
Mapk Signaling Pathways ◽  
Rumen Epithelial Cells

AbstractSubacute ruminal acidosis (SARA) can increase the level of inflammation and induce rumenitis in dairy cows. Berberine (BBR) is the major active component of Rhizoma Coptidis, which is a type of Chinese anti-inflammatory drug for gastrointestinal diseases. The purpose of this study was to investigate the anti-inflammatory effects of BBR on lipopolysaccharide (LPS)-stimulated rumen epithelial cells (REC) and the underlying molecular mechanisms. REC were cultured and stimulated with LPS in the presence or absence of different concentrations of BBR. The results showed that cell viability was not affected by BBR. Moreover, BBR markedly decreased the concentrations and mRNA expression of pro-inflammatory cytokines, including tumor necrosis factor-α, interleukin-1β, and interleukin-6 in the LPS-treated REC in a dose-dependent manner. Importantly, Western blotting analysis showed that BBR significantly suppressed the protein expression of toll-like receptor 4 (TLR4) and myeloid differentiation primary response protein (MyD88) and the phosphorylation of nuclear factor-κB (NF-κB), inhibitory kappa B (IκBα), p38 mitogen-activated protein kinase (MAPK), and c-Jun N-terminal kinase (JNK) in LPS-treated REC. Furthermore, the results of immunocytofluorescence showed that BBR significantly inhibited the nuclear translocation of NF-κB p65 induced by LPS treatment. In conclusion, the protective effects of BBR on LPS-induced inflammatory responses in REC may be due to its ability to suppress the TLR4-mediated NF-κB and MAPK signaling pathways. These findings suggest that BBR can be used as an anti-inflammatory drug to treat inflammation induced by SARA.

scholarly journals Hypoxia Activates Notch4 via ERK/JNK/P38 MAPK Signaling Pathways to Promote Lung Adenocarcinoma Progression and Metastasis

2021 ◽  
Vol 9 ◽  
Author(s):  
Xiaochen Li ◽  
Xiaopei Cao ◽  
Hanqiu Zhao ◽  
Mingzhou Guo ◽  
Xiaoyu Fang ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Signaling Pathways ◽  
P38 Mapk ◽  
Molecular Mechanisms ◽  
Mapk Signaling ◽  
Binding Interaction ◽  
Lung Cancer Patients ◽  
Cell Progression ◽  
Mapk Signaling Pathways

Hypoxia contributes to the progression and metastasis of lung adenocarcinoma (LUAD). However, the specific underlying molecular mechanisms have not been fully elucidated. Here we report that Notch4 is upregulated in lung tissue from lung cancer patients. Functionally, Hypoxia activates the expressions of Delta-like 4 and Notch4, resulting in the excessive proliferation and migration of LUAD cells as well as apoptotic resistance. Notch4 silencing reduced ERK, JNK, and P38 activation. Meanwhile, Notch4 overexpression enhanced ERK, JNK, and P38 activation in LUAD cells. Furthermore, Notch4 exerted pro-proliferation, anti-apoptosis and pro-migration effects on LUAD cells that were partly reversed by the inhibitors of ERK, JNK, and p38. The binding interaction between Notch4 and ERK/JNK/P38 were confirmed by the co-immunoprecipitation assay. In vivo study revealed that Notch4 played a key role in the growth and metastasis of LUAD using two xenograft models. This study demonstrates that hypoxia activates Notch4-ERK/JNK/P38 MAPK signaling pathways to promote LUAD cell progression and metastasis.

scholarly journals Morin Induces Melanogenesis via Activation of MAPK Signaling Pathways in B16F10 Mouse Melanoma Cells

Molecules ◽  
2021 ◽  
Vol 26 (8) ◽  
pp. 2150
Author(s):  
SeoYeon Shin ◽  
JaeYeon Ko ◽  
MinJeong Kim ◽  
Nuri Song ◽  
KyungMok Park
Keyword(s):  
Protein Expression ◽  
Signaling Pathways ◽  
Molecular Mechanisms ◽  
Melanoma Cells ◽  
Mapk Signaling ◽  
Tyrosinase Activity ◽  
Melanin Biosynthesis ◽  
Mouse Melanoma ◽  
Melanin Contents ◽  
Mapk Signaling Pathways

Morin is a well-known flavonoid, and has been reported to have various properties, such as anti-cell death, antioxidant, and anti-inflammatory properties. Although studies on the biochemical and biological actions of morin have been reported, the melanin biosynthesis effects and molecular mechanisms are unknown. In this study, we first found that morin has the effect of enhancing melanin biosynthesis in B16F10 mouse melanoma cells, and analyzed the molecular mechanism. In this study, we examined the effects of morin on the melanin contents and tyrosinase activity, as well as the protein expression levels of the melanogenic enzymes TRP-1, TRP-2, and microphtalmia-associated transcription factor (MITF) in B16F10 mouse melanoma cells. Morin showed no cytotoxicity in the concentration range of 5–100 μM, and significantly increased the intracellular tyrosinase activity and melanin contents. In mechanism analysis, morin increased the protein expression of TRP-1, TRP-2, and MITF associated with melanogenesis. Furthermore, morin increased phosphorylated ERK and p38 at the early time, and decreased phosphorylated ERK after 12 h. The results suggest that morin enhances melanin synthesis through the MAPK signaling pathways in B16F10 mouse melanoma cells.

scholarly journals Activation of protein synthesis, regeneration, and MAPK signaling pathways following repeated bouts of eccentric cycling

2019 ◽  
Vol 317 (6) ◽  
pp. E1131-E1139 ◽  
Author(s):  
Denisse Valladares-Ide ◽  
Luis Peñailillo ◽  
Nicolás Collao ◽  
Hugo Marambio ◽  
Louise Deldicque ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Mrna Expression ◽  
Signaling Pathways ◽  
Muscle Damage ◽  
Vastus Lateralis ◽  
Mammalian Target Of Rapamycin ◽  
Ring Finger ◽  
Mapk Signaling ◽  
Mrna Levels ◽  
Mapk Signaling Pathways

The aim of this study was to examine the activation of skeletal muscle signaling pathways related to protein synthesis and the gene expression of regeneration/degradation markers following repeated bouts of eccentric cycling. Nine untrained men (25.4 ± 1.9 yr) performed two 30-min eccentric cycling bouts (ECC1, ECC2) at 85% of maximal concentric workload, separated by 2 wk. Muscle biopsies were taken from the vastus lateralis before and 2 h after each bout. Indirect markers of muscle damage were assessed before and 24–48 h after exercise. Changes in the Akt/mammalian target of rapamycin (mTOR)/rbosomal protein S6 kinase 1 (S6K1)/ribosomal protein S6 (rpS6) and MAPK signaling pathways were measured by Western blot and changes in mRNA expression of IL-6 and IL-1β, and myogenic regulatory factors (MRFs) were measured by real-time PCR. ECC1 induced greater increases in indirect markers of muscle damage compared with ECC2. Phosphorylation of S6K1 and rpS6 increased after both exercise bouts ( P < 0.05), whereas phosphorylation of mTOR increased after ECC2 only ( P = 0.03). Atrogin-1 mRNA expression decreased after ECC1 and ECC2 ( P < 0.05) without changes in muscle RING-finger protein-1 mRNA. Basal mRNA levels of myoblast determination protein-1 (MyoD), MRF4, and myogenin were higher 2 wk after ECC1 ( P < 0.05). MRF4 mRNA increased after ECC1 and ECC2 ( P < 0.05), whereas MyoD mRNA expression increased only after ECC1 ( P = 0.03). Phosphorylation of JNK and p38 MAPK increased after both exercise bouts ( P < 0.05), similar to IL-6 and IL-1β mRNA expression. All together, these results suggest that differential regulation of the mTOR pathway and MRF expression could mediate the repeated bout effect observed between an initial and secondary bout of eccentric exercise.

scholarly journals Frutescone O from Baeckea frutescens Blocked TLR4-Mediated Myd88/NF-κB and MAPK Signaling Pathways in LPS Induced RAW264.7 Macrophages

2021 ◽  
Vol 12 ◽  
Author(s):  
Xiaobing Lin ◽  
Junhan Zhang ◽  
Decai Fan ◽  
Jiqin Hou ◽  
Hao Wang ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Molecular Mechanisms ◽  
Mapk Signaling ◽  
Raw264.7 Cells ◽  
Raw264.7 Macrophages ◽  
Anti Inflammatory ◽  
Baeckea Frutescens ◽  
Myd88 Signaling ◽  
Myeloid Differentiation Factor ◽  
Mapk Signaling Pathways

Frutescone O was isolated from the aerial parts of Baeckea frutescens L., which was commonly used as a folk medicinal material for treating anti-inflammatory disease in South East Asia. This study aimed to investigate the anti-inflammatory activity and related signaling cascade of Frutescone O (Fru) in LPS induced RAW264.7 cells. The anti-inflammation activity of Frutescone O was determined according to the inhibitory effects on the secretion of nitric oxide (NO), expression of inducible NO synthase, and pro-inflammatory cytokines. The regulation of Myeloid differentiation factor 88 (Myd88), inhibition of NF-κB, and MAPK pathways were further investigated for molecular mechanisms. Fru significantly decreased the expression of iNOS and the production of NO in LPS-stimulated RAW264.7 cells. It also dose-dependently suppressed LPS induced expression of IL-1β, IL-6, and TNF-α. Furthermore, Fru remarkably inhibited the upregulation of NF-κB (p50) expression in the nucleus and the phosphorylation ratio of p38, JNK, ERK, and Myd88 signaling protein. The molecular docking and cellular thermal shift assay (CETSA) results indicated that Fru participated in a robust and stable interaction with the active site of TLR4-MD2. Thus, Fru suppressed the LPS induced inflammation in RAW264.7 cells by blocking the TLR4 mediated signal transduction through the NF-κB and MAPK signaling pathways and inhibiting the Myd88 and iNOS expression.

scholarly journals Computational and In Vitro Analysis of Plumbagin’s Molecular Mechanism for the Treatment of Hepatocellular Carcinoma

2021 ◽  
Vol 12 ◽  
Author(s):  
Yanfei Wei ◽  
Yuning Lin ◽  
Wanjun Chen ◽  
Shasha Liu ◽  
Lijie Jin ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Signaling Pathways ◽  
Molecular Mechanisms ◽  
Mapk Signaling ◽  
Network Pharmacology ◽  
Therapeutic Effects ◽  
Anticancer Properties ◽  
Vitro Analysis ◽  
Mapk Signaling Pathways

Hepatocellular carcinoma (HCC) is the fifth most common malignant tumor and the second leading cause of cancer-related death in the world. Plumbagin (PL) is a small molecule naphthoquinone compound isolated from Plumbago zeylanica L. that has important anticancer properties, but its mechanism requires further investigation. In this study, we used a comprehensive network pharmacology approach to study the mechanism of action of PL for the treatment of HCC. The method includes the construction of multiple networks; moreover, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to identify biological processes and signaling pathways. Subsequently, in vitro experiments were performed to verify the predicted molecular mechanisms obtained from the network pharmacology-based analysis. Network pharmacological analysis showed that PL may exert anti-HCC effects by enhancing reactive oxygen species (ROS) production to generate oxidative stress and by regulating the PI3K/Akt and MAPK signaling pathways. In vitro experiments confirmed that PL mainly mediates the production of ROS, regulates the PI3K/Akt and MAPK signaling pathways to promote apoptosis and autophagy, and shows significant therapeutic effects on HCC. In conclusion, our work proposes a comprehensive systems pharmacology approach to explore the potential mechanism of PL for the treatment of HCC.

scholarly journals Ethyl Acetate Extract of Asclepias curassavica Induced Apoptosis in Human Cancer Cells via Activating p38 and JNK MAPK Signaling Pathways

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Xi Zheng ◽  
Ying Xu ◽  
Bei Liu ◽  
Yan Qi ◽  
Ying Zhang ◽  
...  
Keyword(s):  
Ethyl Acetate ◽  
Signaling Pathways ◽  
Antitumor Effect ◽  
Molecular Mechanisms ◽  
Ethyl Acetate Extract ◽  
Mapk Signaling ◽  
Asclepias Curassavica ◽  
Induced Apoptosis ◽  
Mapk Signaling Pathways

Background. Asclepias curassavica L. (Asclepiadaceae), as a traditional medicinal plant, is used as treatment for tumors in traditional Chinese and Indian medical practice. However, its underlying molecular mechanisms remain largely unresolved. The current study investigated its antitumor activity and the underlying molecular mechanisms. Method. Cell viability was detected by a real-time cell analysis system and MTT assay. Antitumor effect of ethyl acetate extract of Asclepias curassavica (EAAC) on NIC-H1975 tumors in vivo was assessed in BALB/c-nu/nu mouse. Apoptosis was measured using Hoechst33342 staining and Annexin V/PI-staining. Apoptosis-related proteins and MAPK signaling pathways were analyzed based on Western blot assay. Results. EAAC exhibited the highest cytotoxic activity in vitro than other polar parts. Meanwhile, EAAC could inhibit sensitive cell line NIC-H1975 proliferation in a concentration-dependent and time-dependent manner. Furthermore, EAAC had a significant inhibitory effect on NIC-H1975 tumor growth in BALB/c-nu/nu mouse. NIC-H1975 cells showed obvious apoptosis characteristics after EAAC treatment. Fas, caspase family members caspase 3, caspase 9, and caspase 8 showed dose-dependent induction by EAAC treatment, with increasing PARP cleavage. Additionally, EAAC significantly downregulated antiapoptotic proteins Bcl-2, XIAP, survivin, and Mcl-1 and upregulated proapoptosis proteins Bak, Bax, as well as activation of p38 and JNK MAPK signaling pathways. Moreover, inhibiting p38 and JNK MAPK by pharmacological inhibitors abrogated EAAC-induced apoptosis. Conclusion. Our data indicated that EAAC exerted potent antitumor effect both in vitro and in vivo by triggering the apoptotic pathway.

scholarly journals CgSTE11 mediates cross tolerance to multiple environmental stressors in Candida glabrata

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Mian Huang ◽  
Jibran Khan ◽  
Manpreet Kaur ◽  
Julian Daniel Torres Vanega ◽  
Orlando Andres Aguilar Patiño ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Candida Glabrata ◽  
Molecular Mechanisms ◽  
Mapk Signaling ◽  
Environmental Stressors ◽  
Mitogen Activated Protein Kinase ◽  
Cross Tolerance ◽  
Adaptive Laboratory Evolution ◽  
Candida Spp ◽  
Mapk Signaling Pathways

AbstractCandida glabrata is a human commensal and an opportunistic human fungal pathogen. It is more closely related to the model yeast Saccharomyces cerevisiae than other Candida spp. Compared with S. cerevisiae, C. glabrata exhibits higher innate tolerance to various environmental stressors, including hyperthermal stress. Here we investigate the molecular mechanisms of C. glabrata adaptation to heat stress via adaptive laboratory evolution. We show that all parallel evolved populations readily adapt to hyperthermal challenge (from 47 °C to 50 °C) and exhibit convergence in evolved phenotypes with extensive cross-tolerance to various other environmental stressors such as oxidants, acids, and alcohols. Genome resequencing identified fixation of mutations in CgSTE11 in all parallel evolved populations. The CgSTE11 homolog in S. cerevisiae plays crucial roles in various mitogen-activated protein kinase (MAPK) signaling pathways, but its role is less understood in C. glabrata. Subsequent verification confirmed that CgSTE11 is important in hyperthermal tolerance and the observed extensive cross-tolerance to other environmental stressors. These results support the hypothesis that CgSTE11 mediates cross-talks between MAPK signaling pathways in C. glabrata in response to environmental challenges.

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