A Novel Compound, “FA-1” Isolated from Prunus mume, Protects Human Bronchial Epithelial Cells and Keratinocytes from Cigarette Smoke Extract-Induced Damage

Jang, Andrew J.; Lee, Ji Hyeok; Yotsu‐Yamashita, Mari; Park, Joodong; Kye, Steve; Benza, Raymond L.; Passineau, Michael J.; Jeon, You Jin; Nyunoya, Toru

doi:10.1038/s41598-018-29701-2

Cited by 14 publications

(9 citation statements)

References 38 publications

(48 reference statements)

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“…It is noteworthy that the antioxidant mixture of ascorbic acid (250 μΜ) with rutin (50 μΜ), which was used as reference, did not show any protection on keratinocytes (Figure 4), although the same concentrations as those described in literature were used (38)(39)(40). Moreover, known antioxidants such as resveratrol, and a furaldehyde isolated from the extract of the Japanese apricot which decrease lipid peroxidation derived aldehydes and N-acetyl cysteine which attenuated the damage provided by CS have been shown to partially protect skin cells from the oxidative effects of CS (36,41,42). However, the antioxidant-protective effect of Pinus halepensis bark extract seems to be even superior, since it is an agent able to absolutely inhibit oxidative stress or enhance viability even after the serious oxidative stress induced by CS-conditioned media (Figures 2-6).…”

Section: Discussionmentioning

confidence: 88%

Protective Effects of Pinus halepensis Bark Extract and Nicotine on Cigarette Smoke-induced Oxidative Stress in Keratinocytes

Pavlou

Antoniadou

Peraki

et al. 2020

In Vivo

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Background/Aim: Cigarette smoke (CS) is a major environmental health threat. The oxidative stress induced by CS on keratinocytes and the possible protective effect of nicotine, its receptor inhibitors, and Pinus halepensis bark extract in relation to known antioxidants were investigated. Materials and Methods: Primary mouse keratinocytes were exposed to cigarette smoke in the presence and absence of Pinus halepensis bark extract (1 μg/ml), rutin (50 μΜ) and ascorbic acid (250 μΜ), nicotine (1 μM) with or without mecamylamine (5 μM) and α-bungarotoxin (0.1 μΜ). Keratinocyte viability and oxidative stress were evaluated by MTT and fluorescence assays. Results: Pinus halepensis bark extract decreased the oxidative stress and increased the viability of keratinocytes, and moreover, these effects were more pronounced compared to the mixture of rutin and Lascorbic acid. Nicotine significantly enhanced the viability potentiation of the beneficial effect induced by Pinus halepensis bark extract. Mecamylamine and α-bungarotoxin showed no specific effect. Conclusion: Pinus halepensis bark extract in combination with nicotine may successfully reverse skin damage induced by cigarette smoke. Cigarette smoke (CS) is a global problem of our society and according to the World Health Organization "the tobacco epidemic is one of the biggest public health threats the world has ever faced, killing more than 8 million people a year" (1). The Lancet Commission on pollution and health characterized CS as more dangerous than AIDS, tuberculosis, and malaria (2). CS is associated with cardiovascular diseases, higher risk of skin diseases, such as squamous cell carcinoma and atopic dermatitis, and is connected with decreased wound healing rate (3-7). The skin is the most important target for the harmful effect of CS pollution. Both solid and gas products of CS contain aniline, N-nitrosodimethylamine, benzopyrenes, acrolein, formaldehyde, N-nitrosopyrrolidine that are considered to be toxic, causing serious oxidative damage (8). CS produces reactive oxygen and nitrogen species oxidizing important biomolecules such as DNA, proteins and lipids leading to tissue injury which is translated to enhanced inflammatory phenomena (9-14). One of the main constituents of CS is nicotine; it is an agonist of acetylcholine and acts on the epidermis via the keratinocyte nicotinic acetylcholine receptors (nAChRs) (15). nAChRs are large (290 kDa) pentameric transmembrane complexes, which are ligand-gated ion channels (LGICs) permeable to Na, K and Ca ions (16, 17). Nicotine activity is doubtful as it has been shown to exert both toxic and beneficial effects; it has been reported as neurotoxic and neuroprotectant (18), toxic to muscles and lung epithelium (19, 20), beneficial in colitis (21), while its potential activity on mitochondria apparently requires further investigation (22). Concerning inflammatory and wound healing processes, the effect of nicotine is considered rather negative, while topical nAchR antagonists have been shown to improve these negativ...

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Section: Discussionmentioning

confidence: 88%

Protective Effects of Pinus halepensis Bark Extract and Nicotine on Cigarette Smoke-induced Oxidative Stress in Keratinocytes

Pavlou

Antoniadou

Peraki

et al. 2020

In Vivo

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“…β(1,6)-branched oligosaccharides, as the products of MGAT5B, are well-known predictors of poor prognosis and decreased survival time in human cancers (32), which is consistent with our findings. In addition, ALDH3A1 has previously been correlated with cigarette smoke in airway epithelial cells (33). The correlation between these two metabolic genes and immune editing in the TME suggests that they should be the focus of further research.…”

Section: Discussionmentioning

confidence: 93%

Identification and validation of a metabolism-related model and associated with tumor-infiltrating lymphocytes in p53 mutant lung adenocarcinoma patients

Zheng¹,

Sun²,

Zhou³

et al. 2021

Ann Transl Med

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Background:The immunosuppressive tumor microenvironment produced by cancer cells is a key mechanisms of cancer immune escape. In this study, we investigated the relationship between the metabolic patterns and tumor immune environment in the TME of lung adenocarcinoma (LUAD) with the p53 mutation. Methods:The clinical data of 495 LUAD patients was obtained from The Cancer Genome Atlas as transcriptomic and somatic mutation data. Using differential analysis, survival analysis, and a LASSO regression model based on metabolic unigenes from KEGG pathways, a tumor metabolic model was constructed to predict the prognosis of LUAD patients. Subsequently, nomogram, receiver operating characteristic, and decision curve analyses were conducted to assess the predictive ability of the model. In addition, the ESTIMATE and CIBERSORT algorithms were used to detect tumor purity and estimate the fractions of 22 immune cell types in each patient, respectively. We found a correlation between the composition of immune cells and the tumor metabolic model. The results were validated using an independent GSE72094 dataset with 442 patients, as well as an immunohistochemistry assay, RT-qPCR, and western blot. Results:The tumor metabolic model reassigned the risk score of every patient, and a tumor metabolic risk score (TMRS) was generated to show the predictive ability for patient prognoses (hazard ratio =0.39; 95% confidence interval: 0.18-0.85). Using a combination of TMRS and clinical features, a nomogram was produced with a predictive accuracy of 0.72. Further analysis showed that CD4 memory resting T cells and M1 macrophages may by correlated with the TMRS, which corresponded to immunoediting in p53 mutant patients. Additionally, the similar expression of ALDH3A1 and MGAT5B were also verified by wetlab experiments.Conclusions: Based on the identified tumor metabolism-immune landscape, we were able to predict a metabolism risk score for patient prognosis and identify a correlation with two types of infiltrating lymphocytes in the TME of p53-mutated LUAD. This landscape provides insights that will help identify the molecular mechanisms of immune-editing tumor metabolism.

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“…Compounds derived from P. mume seeds also protected granulose cells from H 2 O 2 -induced apoptosis and promoted estradiol secretion (Kono et al, 2014). In a recent study, Jang et al (2018) found that a new compound isolated from P. mume increased the concentrations of aldehyde dehydrogenase (ALDH) and Werner's syndrome protein (WRN) in a dose-dependent manner and protected human bronchial epithelial cells and human epidermal keratinocytes from cigarette smoke-induced oxidative damage and DNA damage.…”

Section: Anti-inflammatory and Antioxidant Activitiesmentioning

confidence: 99%

Comprehensive Review of Phytochemical Constituents, Pharmacological Properties, and Clinical Applications of Prunus mume

Gong

Tang

Song³

et al. 2021

Front. Pharmacol.

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Prunus mume is one of the most ancient medicinal herbs and health foods commonly used in Asian countries. It is widely used as a constituent of many medicinal preparations and as a food ingredient for its beneficial health effects. In this review, we retrieved reports from PubMed, embase, Scopus, and SciFinder databases, to collect extensive scientific evidence on the phytochemical constituents, pharmacological properties, and clinical applications of Prunus mume. The literature review revealed that approximately 192 compounds have been isolated from different parts of the plant, and their molecular structures have been identified. The pharmacological properties of the plant, including anti-diabetic, liver-protective, antitumor, antimicrobial, antioxidant, and anti-inflammatory activities, as well as their underlying mechanisms, have been clarified by in vitro and in vivo studies. Clinical studies, although very limited, have been highlighted in this review to provide a reference for further exploration on therapeutic applications of the plant.

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A Novel Compound, “FA-1” Isolated from Prunus mume, Protects Human Bronchial Epithelial Cells and Keratinocytes from Cigarette Smoke Extract-Induced Damage

Cited by 14 publications

References 38 publications

Protective Effects of Pinus halepensis Bark Extract and Nicotine on Cigarette Smoke-induced Oxidative Stress in Keratinocytes

Protective Effects of Pinus halepensis Bark Extract and Nicotine on Cigarette Smoke-induced Oxidative Stress in Keratinocytes

Identification and validation of a metabolism-related model and associated with tumor-infiltrating lymphocytes in p53 mutant lung adenocarcinoma patients

Comprehensive Review of Phytochemical Constituents, Pharmacological Properties, and Clinical Applications of Prunus mume

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