scholarly journals Eckol Inhibits Particulate Matter 2.5-Induced Skin Keratinocyte Damage via MAPK Signaling Pathway

Marine Drugs ◽  
2019 ◽  
Vol 17 (8) ◽  
pp. 444 ◽  
Author(s):  
Ao Xuan Zhen ◽  
Yu Jae Hyun ◽  
Mei Jing Piao ◽  
Pincha Devage Sameera Madushan Fernando ◽  
Kyoung Ah Kang ◽  
...  

Toxicity of particulate matter (PM) towards the epidermis has been well established in many epidemiological studies. It is manifested in cancer, aging, and skin damage. In this study, we aimed to show the mechanism underlying the protective effects of eckol, a phlorotannin isolated from brown seaweed, on human HaCaT keratinocytes against PM2.5-induced cell damage. First, to elucidate the underlying mechanism of toxicity of PM2.5, we checked the reactive oxygen species (ROS) level, which contributed significantly to cell damage. Experimental data indicate that excessive ROS caused damage to lipids, proteins, and DNA and induced mitochondrial dysfunction. Furthermore, eckol (30 μM) decreased ROS generation, ensuring the stability of molecules, and maintaining a steady mitochondrial state. The western blot analysis showed that PM2.5 promoted apoptosis-related protein levels and activated MAPK signaling pathway, whereas eckol protected cells from apoptosis by inhibiting MAPK signaling pathway. This was further reinforced by detailed investigations using MAPK inhibitors. Thus, our results demonstrated that inhibition of PM2.5-induced cell apoptosis by eckol was through MAPK signaling pathway. In conclusion, eckol could protect skin HaCaT cells from PM2.5-induced apoptosis via inhibiting ROS generation.

2020 ◽  
Author(s):  
Jing-Shuai Wu ◽  
Qin-Yu Meng ◽  
Xiao-Hui Shi ◽  
Zhen-Kun Zhang ◽  
Hua-Shi Guan ◽  
...  

Abstract Background: Neuroinflammatory processes are critical in the development and progression of Alzheimer's disease (AD). The potent anti-neuroinflammatory inhibitors are expected as the candidates to treat AD. Cryptotanshinone (1), a major bioactive constituent in the traditional Chinese medicinal herb Dan-Shen Salvia miltiorrhiza Bunge, has been reported to possess remarkable pharmacological activities, especially anti-oxidation and anti-inflammation. Methods: Cryptotanshinone (1) was biotransformed with the fungus Cunninghamella elegans AS3.2028 to improve its bioactivities and physicochemical properties. The structures of transformed products were elucidated by comprehensive spectroscopic analysis including HRESIMS, NMR and ECD data. Their anti-neuroinflammatory activities were assessed by ELISA, transcriptome analysis, western blot, and immunofluorescence methods. Results: Three oxygenated products (2–4) at C-3 of cryptotanshinone (1) were obtained, among them 2 was a new compound. All of the biotransformed products (2–4) were found to inhibit significantly lipopolysaccharide-induced nitric oxide production in BV2 microglia cells with the IC50 values of 0.16‒1.16 μM, approximately 2‒20 folds stronger than the substrate (1). These biotransformed products also displayed remarkably improved inhibitory effects on the production of inflammatory cytokines (IL-1β, IL-6, TNF-α, COX-2 and iNOS) in BV-2 cells via targeting TLR4 compared to substrate (1). The underlying mechanism of 2 was elucidated by comparative transcriptome analysis, which suggested that it reduced neuroinflammatory mainly through mitogen-activated protein kinase (MAPK) signaling pathway. Western blotting results revealed that 2 downregulated LPS-induced phosphorylation of JNK, ERK, and p38 in MAPK signaling pathway. Conclusion: The biotransformed products of cryptotanshinone exhibit potent anti-neuroinflammatory activities. These findings provide a basal material for the discovery of candidates in treating AD.


2020 ◽  
Vol 11 (9) ◽  
pp. 8133-8140
Author(s):  
Yalei Cui ◽  
Boshuai Liu ◽  
Xiao Sun ◽  
Zidan Li ◽  
Yanyan Chen ◽  
...  

Alfalfa saponins defend against oxidative stress by enhancing the antioxidant system and further inhibit cell apoptosis by activating the MAPK signaling pathway.


Author(s):  
Yu-Yan Zhao ◽  
Lin-Hui Chen ◽  
Liang Huang ◽  
Yong-Zhen Li ◽  
Chen Yang ◽  
...  

Cardiovascular and related metabolic diseases are significant global health challenges. Glucagon-like peptide 1 (GLP-1) is a brain-gut peptide secreted by ileal endocrine that is now an established drug target in type 2 diabetes (T2DM). GLP-1 targeting agents have been shown not only to treat T2DM, but also to exert cardiovascular protective effects through regulating multiple signaling pathways. The mitogen-activated protein kinase (MAPK) pathway, a common signal transduction pathway for transmitting extracellular signals to downstream effector molecules, is involved in regulating diverse cell physiological processes, including cell proliferation, differentiation, stress, inflammation, functional synchronization, transformation and apoptosis. The purpose of this review is to highlight the relationship between GLP-1 and cardiovascular disease (CVD), and discuss how GLP-1 exerts cardiovascular protective effects through MAPK signaling pathway. This review also discusses the future challenges in fully characterizing and evaluating the CVD protective effects of GLP-1 receptor agonists (GLP-1RA) at the cellular and molecular level. A better understanding of MAPK signaling pathway that are disregulated in CVD may aid in the design and development of promising GLP-1RA.


2016 ◽  
Vol 11 (12) ◽  
pp. 1934578X1601101 ◽  
Author(s):  
Pornngarm Limtrakul ◽  
Supachai Yodkeeree ◽  
Wanisa Punfa ◽  
Jatupol Srisomboon

Red rice has demonstrated several biological properties including anti-oxidant and anti-inflammation properties. However, the anti-photoaging activity has not yet been investigated. The aim of this study relates to the photo-protective effects of red rice extract (RRE) on UVB-induced skin aging. RRE was prepared and the active compounds and anti-oxidant activity were determined. The cytotoxicity of fibroblasts and secretions of IL-6 and IL-8 were evaluated. The effects of RRE on collagen and hyaluronic acid (HA) synthesis from fibroblasts were evaluated. Then, the collagenase and MMP-2 activity was determined. The effect of RRE on UV-induced MMP-1, nuclear factor kappa B (NF-κB), activator protein-1 (AP-1) and phosphorylation of MAPK protein expression was determined by western blot analysis. The RRE exerted a free radical scavenging property. RRE significantly increased collagen and HA synthesis in UVB-irradiated human fibroblasts. Moreover, RRE significantly inhibited UVB induced MMP-1 expression, MMP-2 and collagenase activity. Upon UVB irradiation, mitogen activated protein kinases (MAPKs) is activated and this pathway stimulates the expression of interleukin-6 and-8 (IL-6 and-8). Our results show that RRE decreases UVB-induced IL-6 and -8 production and the phosphorylation of c-Jun NH2-terminal kinase (JNK) and the p38 MAPK signaling process. In addition, RRE reduced UVB-induced activation of NF-κB and AP-1. RRE could suppress UV-induced inflammation and skin aging via the inhibition of the MAPK signaling pathway leading to the decrease of NF-κB and AP-1 activation resulting in a decrease in ECM degradation and an increase in ECM synthesis.


2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Yadi Wang ◽  
Yang Zhang ◽  
Bo Sun ◽  
Qing Tong ◽  
Liqun Ren

We investigated the potential protective effect of rutinum (RUT) against pirarubicin- (THP-) induced cardiotoxicity. THP was used to induce toxicity in rat H9c2 cardiomyoblasts. Positive control cells were pretreated with a cardioprotective agent dexrazoxane (DZR) prior to treatment with THP. Some of the cells were preincubated with RUT and a p38 mitogen-activated protein kinase (MAPK) inhibitor, SB203580, both individually and in combination, prior to THP exposure. At a dose range of 30–70 μM, RUT significantly prevented THP-induced reduction in cell viability; the best cardioprotective effect was observed at a dose of 50 μM. Administration of RUT and SB203580, both individually as well as in combination, suppressed the elevation of intracellular ROS, inhibited cell apoptosis, and reversed the THP-induced upregulation of TGF-β1, p-p38 MAPK, cleaved Caspase-9, Caspase-7, and Caspase-3. A synergistic effect was observed on coadministration of RUT and SB203580. RUT protected against THP-induced cardiotoxicity by inhibition of ROS generation and suppression of cell apoptosis. The cardioprotective effect of RUT appears to be associated with the modulation of the TGF-β1-p38 MAPK signaling pathway.


Aging ◽  
2021 ◽  
Vol 13 (18) ◽  
pp. 22556-22570
Author(s):  
Dong Cheng ◽  
Wencheng Tu ◽  
Libo Chen ◽  
Haoren Wang ◽  
Qinfu Wang ◽  
...  

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