scholarly journals Penthorum chinense Pursh alleviates ethanol-induced hepatic oxidative impairment in zebrafish via AMPK / p62 / Nrf2 / mTOR pathway

2021 ◽  
Author(s):  
xingtao zhao ◽  
mengting zhou ◽  
ying deng ◽  
chaocheng guo ◽  
li liao ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
High Performance ◽  
Blood Stasis ◽  
Mtor Signaling ◽  
Transgenic Zebrafish ◽  
Related Factor ◽  
Sequestosome 1 ◽  
Penthorum Chinense Pursh ◽  
Dose Dependent Decrease ◽  
Penthorum Chinense

Abstract Ethnopharmacological relevance: In China, Penthorum chinense Pursh (PCP) is renowned for its effectiveness in “promoting blood circulation” and “removing blood stasis”. It can “relieve the liver” and its application in the field of liver protection, including viral hepatitis, alcoholic liver, liver fibrosis, has been known for hundreds of years.Aim of the study: Oxidative stress is widely believed to exert a key role in the pathophysiology of alcoholic liver disease (ALD). Therefore, antioxidant therapy reflects a reasonable strategy for the prevention and treatment of ALD. Hence, this study aimed to elucidate the mechanism of PCP in ethanol-induced liver injury.Methods: Treatment of liver-specific transgenic zebrafish larvae (lfabp: EGFP) at three days post-fertilization (3 dpf) with different concentrations of PCP (100, 50, 25 μg / mL) for 48 h was followed by soaking in 350 mmol / L ethanol for 32 h. Liver function and fat accumulation were identified by phenotypic indicators and biochemical kits. The related proteins and gene expression were further estimated by western blotting and quantitative reverse transcriptase-polymerase chain reaction (RT-qPCR). Finally, high performance liquid chromatography (HPLC) was adopted to analyze the chemical composition of PCP extract.Results: Firstly, PCP mediated alleviation of ethanol-induced steatosis and reduction of aspartate aminotransferase (AST), alanine transaminase (ALT), total cholesterol (TC) and triglyceride (TG) related indexes were evident. Dose-dependent decrease of intracellular reactive oxygen species (ROS) production, the activity of malondialdehyde (MDA) and increased the activity of glutathione (GSH), Superoxide dismutase (SOD) and catalase (CAT) in zebrafish substantiated the role of PCP in relieving oxidative stress. Furthermore, PCP induced downregulation of sequestosome 1 (p62 / SQSTM1, p62), Atg13 and Beclin 1 expression promoted autophagy. Meanwhile, PCP contributed to the hepatoprotective function by downregulating the expression of kelch-like ECH-associated protein 1 (Keap1) and upregulating the expression of nucleus factor-E2-related factor 2 (Nrf2), which activated cytoprotective related gene HO-1. Moreover, HPLC of PCP extract confirmed the presence of various polyphenols with potential antioxidant effects. Finally, PCP appeared to promote the activated protein kinase (AMPK) / p62 / Nrf2 / mTOR signaling pathways, which were related to oxidative stress and autophagy in zebrafish.Conclusion: This study claimed that by activating the AMPK / p62 / Nrf2 / mTOR signaling pathway, PCP could attenuate ethanol-induced liver injury in zebrafish.

The hepatoprotective effect of aqueous extracts of Penthorum chinense Pursh against acute alcohol-induced liver injury is associated with ameliorating hepatic steatosis and reducing oxidative stress

2015 ◽  
Vol 6 (5) ◽  
pp. 1510-1517 ◽  
Author(s):  
Yi-Wei Cao ◽  
Yun Jiang ◽  
Da-Yong Zhang ◽  
Xiao-Jing Zhang ◽  
Yuan-Jia Hu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Liver Injury ◽  
Hepatic Steatosis ◽  
Folk Medicine ◽  
Hepatoprotective Effect ◽  
Aqueous Extracts ◽  
Health Food ◽  
Penthorum Chinense Pursh ◽  
Penthorum Chinense

Aqueous extracts ofPenthorum chinensePursh, a health food and folk medicine, protects against acute alcohol-induced liver injury.

scholarly journals Exposure to Salinity and Light Spectra Regulates Glucosinolates, Phenolics, and Antioxidant Capacity of Brassica carinata L. Microgreens

Antioxidants ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1183
Author(s):  
Sylvia Maina ◽  
Da Hye Ryu ◽  
Jwa Yeong Cho ◽  
Da Seul Jung ◽  
Jai-Eok Park ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
High Performance ◽  
Antioxidant Activities ◽  
Light Exposure ◽  
Brassica Carinata ◽  
Bioactive Metabolites ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Light Emitting ◽  
Flight Mass Spectrometry

The effect of salt treatment on Brassica carinata (BC) microgreens grown under different light wavelengths on glucosinolates (GLs) and phenolic compounds were evaluated. Quantifiable GLs were identified using ultra-high performance-quadrupole time of flight mass spectrometry. Extracts’ ability to activate antioxidant enzymes (superoxide dismutase (SOD) and catalase (CAT)) was evaluated on human colorectal carcinoma cells (HCT116). Furthermore, BC compounds’ ability to activate expression of nuclear transcription factor-erythroid 2 related factor (Nrf2) and heme-oxygenase-1 (HO-1) proteins was examined using specific antibodies on HCT116 cells. Sinigrin (SIN) was the abundant GLs of the six compounds identified and its content together with total aliphatic GLs increased in saline conditions. Fluorescent (FL) and blue plus red (B1R1) lights were identified as stable cultivation conditions for microgreens, promoting biomass and glucobrassicin contents, whereas other identified individual and total indole GLs behaved differently in saline and non-saline environments. Blue light-emitting diodes and FL light in saline treatments mostly enhanced SIN, phenolics and antioxidant activities. The increased SOD and CAT activities render the BC microgreens suitable for lowering oxidative stress. Additionally, activation of Nrf2, and HO-1 protein expression by the GLs rich extracts, demonstrate their potential to treat and prevent oxidative stress and inflammatory disorders. Therefore, effective salt treatments and light exposure to BC microgreens present an opportunity for targeted regulation of growth and accumulation of bioactive metabolites.

scholarly journals Kaposi's Sarcoma-Associated Herpesvirus Induces Nrf2 Activation in Latently Infected Endothelial Cells through SQSTM1 Phosphorylation and Interaction with Polyubiquitinated Keap1

2014 ◽  
Vol 89 (4) ◽  
pp. 2268-2286 ◽  
Author(s):  
Olsi Gjyshi ◽  
Stephanie Flaherty ◽  
Mohanan Valiya Veettil ◽  
Karen E. Johnson ◽  
Bala Chandran ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Endothelial Cells ◽  
De Novo ◽  
Related Factor ◽  
Antioxidant Genes ◽  
Kshv Infection ◽  
Sequestosome 1 ◽  
Nrf2 Activation ◽  
Latently Infected ◽  
Stress Signals

ABSTRACTNuclear factor erythroid 2-related factor 2 (Nrf2), the cellular master regulator of the antioxidant response, dissociates from its inhibitor Keap1 when activated by stress signals and participates in the pathogenesis of viral infections and tumorigenesis. Early duringde novoinfection of endothelial cells, KSHV induces Nrf2 through an intricate mechanism involving reactive oxygen species (ROS) and prostaglandin E2 (PGE2). When we investigated the Nrf2 activity during latent KSHV infection, we observed increased nuclear serine-40-phosphorylated Nrf2 in human KS lesions compared to that in healthy tissues. Using KSHV long-term-infected endothelial cells (LTC) as a cellular model for KS, we demonstrated that KSHV infection induces Nrf2 constitutively by extending its half-life, increasing its phosphorylation by protein kinase Cζ (PKCζ) via the infection-induced cyclooxygenase-2 (COX-2)/PGE2 axis and inducing its nuclear localization. Nrf2 knockdown in LTC decreased expression of antioxidant genes and genes involved in KS pathogenesis such as the NAD(P)H quinone oxidase 1 (NQO1), gamma glutamylcysteine synthase heavy unit (γGCSH), the cysteine transporter (xCT), interleukin 6 (IL-6), and vascular endothelial growth factor A (VEGF-A) genes. Nrf2 activation was independent of oxidative stress but dependent on the autophagic protein sequestosome-1 (SQSTM1; p62). SQSTM1 levels were elevated in LTC, a consequence of protein accumulation due to decreased autophagy and Nrf2-mediated transcriptional activation. SQSTM1 was phosphorylated on serine-351 and -403, while Keap1 was polyubiquitinated with lysine-63–ubiquitin chains, modifications known to increase their mutual affinity and interaction, leading to Keap1 degradation and Nrf2 activation. The latent KSHV protein Fas-associated death domain-like interleukin-1β-converting enzyme-inhibitory protein (vFLIP) increased SQSTM1 expression and activated Nrf2. Collectively, these results demonstrate that KSHV induces SQSTM1 to constitutively activate Nrf2, which is involved in the regulation of genes participating in KSHV oncogenesis.IMPORTANCEThe transcription factor Nrf2 is activated by stress signals, including viral infection, and responds by activating the transcription of cytoprotective genes. Recently, Nrf2 has been implicated in oncogenesis and was shown to be activated duringde novoKSHV infection of endothelial cells through ROS-dependent pathways. The present study was undertaken to determine the mechanism of Nrf2 activation during prolonged latent infection of endothelial cells, using an endothelial cell line latently infected with KSHV. We show that Nrf2 activation was elevated in KSHV latently infected endothelial cells independently of oxidative stress but dependent on the autophagic protein sequestosome-1 (SQSTM1), which was involved in the degradation of the Nrf2 inhibitor Keap1. Furthermore, our results indicated that the KSHV latent protein vFLIP participates in Nrf2 activation. This study suggests that KSHV hijacks the host's autophagic protein SQSTM1 to induce Nrf2 activation, thereby manipulating the infected host gene regulation to promote KS pathogenesis.

scholarly journals Antiphotoaging and Antimelanogenic Effects of Penthorum chinense Pursh Ethanol Extract due to Antioxidant- and Autophagy-Inducing Properties

2019 ◽  
Vol 2019 ◽  
pp. 1-14 ◽  
Author(s):  
Deok Jeong ◽  
Jongsung Lee ◽  
Sang Hee Park ◽  
You Ah Kim ◽  
Byoung Jun Park ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Ethanol Extract ◽  
Infectious Hepatitis ◽  
Uvb Irradiation ◽  
Protein Levels ◽  
B16f10 Cells ◽  
Penthorum Chinense Pursh ◽  
Cox 2 ◽  
Penthorum Chinense ◽  
Melanin Contents

Ethnopharmacological Relevance. Penthorum chinense Pursh (Penthoraceae) is a traditional herbal plant that has been used in China for the treatment of jaundice, cholecystitis, edema, and infectious hepatitis. In addition, the Korea Medicinal Plant Dictionary states that Penthorum chinense Pursh can be used to treat contusions and skin bruises by improving blood flow. Recent studies have shown that Penthorum chinense Pursh ethanol extract (Pc-EE) exhibits strong antioxidant effects. In this study, we examined the effects of Pc-EE on UVB-induced or H2O2-induced oxidative stress, as well as its antimelanogenic properties. Cell viability, matrix metalloproteinase (MMP) expression, cyclooxygenease-2 (COX-2), and interleukin-6 (IL-6) expression and moisturizing factors were investigated in keratinocytes. Collagen synthesis induction was measured in HEK293T cells. For melanogenesis, the effects of Pc-EE on melanin content and tyrosinase activity were measured. Additionally, the antimelanogenic- and autophagy-inducing activities of Pc-EE were examined using immunoblotting and confocal microscopy. Pc-EE protected HaCaT cells against death from UVB irradiation- or H2O2-induced oxidative stress. Pc-EE increased the promoter activity of the type 1 procollagen gene Col1A1 and decreased the expression of MMPs, COX-2, IL-6, and hyaluronidase induced by UVB irradiation- or H2O2-induced oxidative stress. Pc-EE showed a strong antioxidant effect in the DPPH assay. In α-melanocyte-stimulating hormone- (α-MSH-) stimulated B16F10 cells, Pc-EE reduced melanin production, decreased tyrosinase expression and microphthalmia-associated transcription factor (MITF) protein levels, and decreased the phosphorylation levels of p38 and JNK. In HEK293T cells, Pc-EE promoted the expression of GFP-LC3B. In B16F10 cells, the LC3B and melanin contents were reduced by Pc-EE and were restored by the autophagy inhibitor 3-methyladenine (3-MA). These results suggest that Pc-EE can be used as a skin protection agent due to its antiapoptotic, antiaging, anti-inflammatory, and antimelanogenic properties.

scholarly journals Bioactivity Evaluation of Pinocembrin Derivatives From Penthorum chinense Pursh Stems

2019 ◽  
Vol 14 (9) ◽  
pp. 1934578X1987589
Author(s):  
Qinchao Ding ◽  
Zhuo Jin ◽  
Jiahui Dong ◽  
Zhaolei Wang ◽  
Kai Jiang ◽  
...  
Keyword(s):  
High Performance ◽  
Radical Scavenging ◽  
Lactobacillus Rhamnosus ◽  
Ionization Mass ◽  
Dependent Manner ◽  
Penthorum Chinense Pursh ◽  
Molecular Masses ◽  
High Concentrations ◽  
Penthorum Chinense

The extract of Penthorum chinense Pursh (PCP), a well-known Miao herb medicine, has been used as a key component for a Chinese patented drug to treat several kinds of liver-related diseases. In this work, 3 pinocembrin derivatives, S1, S2, and S3, were isolated from PCP stems and identified with high-performance liquid chromatography and electrospray ionization mass spectrometer. The molecular masses of S1, S2, and S3 were identical to Pinocembrin-7-O-[4″,6″-hexahydroxydiphenoyl (HHDP)]-β-D-glucose, Pinocembrin-7-O-[3″-O-galloyl-4″,6″-(s)-HHDP)-β-D-glucose, and Thonningianin A, respectively. Their free radical scavenging capability was evaluated with the 2,2-diphenyl-1-picrylhydrazyl assay. The half-maximal effective concentrations of S1, S2, and S3 were 26.75, 9.06, and 5.50 μg/mL, respectively. In vitro AML-12 assays demonstrated that S1 (5-20 μg/mL), S2 (10-40 μg/mL), and S3 (10-40 μg/mL) not only protected cells from H2O2-induced oxidation and alcohol-induced cell damages, but also reduced oleic acid (OA)-induced triglyceride accumulations in a dose-dependent manner. However, the 3 compounds potently exhibited similar cytotoxicity effect at high concentrations. The half-maximal inhibitory concentrations of S1, S2, and S3 to AML-12 cells were 74.19, 85.86, and 80.43 μg/mL. In addition, the 3 compounds also showed antibacterial activity on Escherichia coli, Staphylococcus aureus, Enterococcus faecalis, Lactobacillus rhamnosus, and Bacillus subtilis.

scholarly journals The Keap1-Nrf2 System: A Mediator between Oxidative Stress and Aging

2021 ◽  
Vol 2021 ◽  
pp. 1-16
Author(s):  
Chao Yu ◽  
Jian-Hui Xiao
Keyword(s):  
Oxidative Stress ◽  
Protein Kinase ◽  
Molecular Mechanisms ◽  
Glycogen Synthase ◽  
Mammalian Target Of Rapamycin ◽  
Direct Interaction ◽  
Mitogen Activated Protein Kinase ◽  
Related Factor ◽  
Sequestosome 1 ◽  
Molecular Damage

Oxidative stress, a term that describes the imbalance between oxidants and antioxidants, leads to the disruption of redox signals and causes molecular damage. Increased oxidative stress from diverse sources has been implicated in most senescence-related diseases and in aging itself. The Kelch-like ECH-associated protein 1- (Keap1-) nuclear factor-erythroid 2-related factor 2 (Nrf2) system can be used to monitor oxidative stress; Keap1-Nrf2 is closely associated with aging and controls the transcription of multiple antioxidant enzymes. Simultaneously, Keap1-Nrf2 signaling is also modulated by a more complex regulatory network, including phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt), protein kinase C, and mitogen-activated protein kinase. This review presents more information on aging-related molecular mechanisms involving Keap1-Nrf2. Furthermore, we highlight several major signals involved in Nrf2 unbinding from Keap1, including cysteine modification of Keap1 and phosphorylation of Nrf2, PI3K/Akt/glycogen synthase kinase 3β, sequestosome 1, Bach1, and c-Myc. Additionally, we discuss the direct interaction between Keap1-Nrf2 and the mammalian target of rapamycin pathway. In summary, we focus on recent progress in research on the Keap1-Nrf2 system involving oxidative stress and aging, providing an empirical basis for the development of antiaging drugs.

Bio-assay guided identification of hepatoprotective polyphenols from Penthorum chinense Pursh on t-BHP induced oxidative stress injured L02 cells

2016 ◽  
Vol 7 (4) ◽  
pp. 2074-2083 ◽  
Author(s):  
Anqi Wang ◽  
Shengpeng Wang ◽  
Yun Jiang ◽  
Meiwan Chen ◽  
Yitao Wang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Active Fraction ◽  
Penthorum Chinense Pursh ◽  
Penthorum Chinense ◽  
L02 Cells ◽  
Bio Assay

This study identified an active fraction and quercetin as chemical principles for the traditional hepatoprotective herb Penthorum chinense.

scholarly journals Penthorum Chinense Pursh Protects Liver From Alcohol-induced Steatosis in Zebrafish by Mechanisms Including Inhibition of Oxidative Stress and Increase in Autophagy

2020 ◽  
Author(s):  
Xingtao Zhao ◽  
Mengting Zhou ◽  
Ying Deng ◽  
Chaocheng Guo ◽  
Li Liao ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Fatty Acids ◽  
Lipid Metabolism ◽  
Mrna Level ◽  
Protection Mechanism ◽  
Ameliorative Effect ◽  
Penthorum Chinense Pursh ◽  
Penthorum Chinense ◽  
Related Proteins ◽  
Regulate Lipid Metabolism

Abstract BackgroundAs an ATP-gated ion channel, P2X7 receptor (P2X7R) affects lipid metabolism by activating the dangerous molecule ATP derived from liver cells caused by alcohol. Penthorum chinense Pursh (PCP), known as “shenxiancao”, plays a significant role in treating liver disease among Miao people. We first investigated whether liver protection mechanism of PCP mediated by P2X7R. MethodsFirst, treatment of zebrafish transgenic (fabp10: EGFP) larvae with different concentrations of PCP after 48 h at 3 dpf, then soaked in 350 mmol/L ethanol for 32 h. Subsequently the ameliorative effect of PCP in zebrafish with alcoholic hepatosteatosis was studied. In addition, gene expression related to lipid metabolism, oxidative stress, and autophagy was detected from the mRNA level by RT-qPCR and related proteins were measured by Western blot. Then, larvae were stimulated with ATP alone to explore whether PCP was the target of P2X7R.ResultsPCP significantly improved liver function and lipid deposition in zebrafish with alcoholic hepatosteatosis, and regulated the expression of SREBP1, CHREBP and FAS by elevating LKB1 and AMPK, thereby inhibiting the synthesis of fatty acids. Also, SIRT1 was suppressed in the model group, while PCP upregulated the expression. Inecreased expression of PPARα, decreased PPARγ, and CPT1 then promoted the oxidation of fatty acids. PCP dose-dependently decreased intracellular ROS production in zebrafish, then reduced MDA activity elevation and increased GSH, CAT and SOD levels. The specific mechanism may be realized by up-regulating the antioxidant pathway of Keap1/Nrf2 and down-regulating the autophagy pathway of PI3K/Akt/mTOR to regulate lipid metabolism. After ATP stimulation, P2X7R is further activated, which in turn regulated Keap1/Nrf2 and mTOR/PI3K/Akt mRNA expression, while PCP reversed these changes.ConclusionsPCP may be a target of P2X7R involvement in the regulation of this mechanism through up-regulation of the antioxidant pathway of Keap1/Nrf2 and down-regulation of the autophagic pathway of mTOR/ PI3K/Akt to regulate lipid metabolism, suggesting that blocking P2X7R is an emerging strategy for the therapy of ALD.

Protective Effect of Swertiamarin on Myocardial Injury Through Activation of Nrf2/HO-1 Pathway in Heart Failure Model of Rats

2020 ◽  
Vol 18 (3) ◽  
pp. 260-265
Author(s):  
Xu Lin ◽  
Zheng Xiaojun ◽  
Lv Heng ◽  
Mo Yipeng ◽  
Tong Hong
Keyword(s):  
Oxidative Stress ◽  
Heart Failure ◽  
Ejection Fraction ◽  
Protective Effect ◽  
Infarct Size ◽  
Rat Model ◽  
Left Ventricular ◽  
Related Factor ◽  
Nuclear Factor ◽  
Internal Dimension

The purpose of this study was to evaluate the protective effect of swertiamarin on heart failure. To this end, a rat model of heart failure was established via left coronary artery ligation. Infarct size of heart tissues was determined using triphenyl tetrazolium chloride staining. Echocardiography was performed to evaluate cardiac function by the determination of ejection fraction, left ventricular internal dimension in diastole and left ventricular internal dimension in systole. The effect of swertiamarin on oxidative stress was evaluated via enzyme-linked immunosorbent assay. The mechanism was evaluated using western blot. Administration of swertiamarin reduced the infarct size of heart tissues in rat models with heart failure. Moreover, swertiamarin treatment ameliorated the cardiac function, increased ejection fraction and fractional shortening, decreased left ventricular internal dimension in diastole and left ventricular internal dimension in systole. Swertiamarin improved oxidative stress with reduced malondialdehyde, while increased superoxide dismutase, glutathione, and GSH peroxidase. Furthermore, nuclear-factor erythroid 2-related factor 2, heme oxygenase and NAD(P)H dehydrogenase (quinone 1) were elevated by swertiamarin treatment in heart tissues of rat model with heart failure. Swertiamarin alleviated heart failure through suppression of oxidative stress response via nuclear-factor erythroid 2-related factor 2/heme oxygenase-1 pathway providing a novel therapeutic strategy for heart failure.

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