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

Author(s):  
Xingtao Zhao ◽  
Mengting Zhou ◽  
Ying Deng ◽  
Chaocheng Guo ◽  
Li Liao ◽  
...  

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.

2018 ◽  
Vol 50 (4) ◽  
pp. 1216-1229 ◽  
Author(s):  
Chia-Hui Chen ◽  
Song-Kun Shyue ◽  
Chiao-Po Hsu ◽  
Tzong-Shyuan Lee

Background/Aims: Olanzapine, an atypical antipsychotic drug, has therapeutic effects for schizophrenia. However, clinical reports indicate that patients taking atypical antipsychotic drugs are at high risk of metabolic syndrome with unclear mechanisms. We investigated the effect of olanzapine on atherosclerosis and the mechanisms in apolipoprotein E-null (apoE-/-) mice. Methods: ApoE-/- mice were used as in vivo models. Western blot analysis was used to evaluate protein expression. Conventional assay kits were applied to assess the levels of cholesterol, triglycerides, free cholesterol, cholesteryl ester, fatty acids, glycerol, and cytokines. Results: Daily treatment with olanzapine (3 mg/kg body weight) for four weeks increased mean arterial blood pressure and the whitening of brown adipose tissue in mice. In addition, olanzapine impaired aortic cholesterol homeostasis and exacerbated hyperlipidemia and aortic inflammation, which accelerated atherosclerosis in mice. Moreover, lipid accumulation in liver, particularly total cholesterol, free cholesterol, fatty acids, and glycerol, was increased with olanzapine treatment in apoE-/- mice by upregulating the expression of de novo lipid synthesis-related proteins and downregulating that of cholesterol clearance- or very low-density lipoprotein secretion-related proteins. Conclusion: Olanzapine may exacerbate atherosclerosis by deregulating hepatic lipid metabolism and worsening hyperlipidemia and aortic inflammation.


2022 ◽  
Vol 12 (1) ◽  
Author(s):  
Saad Mohamed Asseri ◽  
Nehal M. Elsherbiny ◽  
Mohamed El-Sherbiny ◽  
Iman O. Sherif ◽  
Alsamman M. Alsamman ◽  
...  

AbstractThe burden of diabetes mellitus (DM) and associated complications is increasing worldwide, affecting many organ functionalities including submandibular glands (SMG). The present study aims to investigate the potential ameliorative effect of glycyrrhizic acid (GA) on diabetes-induced SMG damage. Experimental evaluation of GA treatment was conducted on a rat model of type I diabetes. Animals were assigned to three groups; control, diabetic and GA treated diabetic groups. After 8 weeks, the SMG was processed for assessment of oxidative stress markers, autophagy related proteins; LC3, Beclin-1 and P62, vascular regulator ET-1, aquaporins (AQPs 1.4 and 5), SIRT1 protein expressions in addition to LC3 and AQP5 mRNA expressions. Also, parenchymal structures of the SMG were examined. GA alleviated the diabetes-induced SMG damage via restoring the SMG levels of oxidative stress markers and ET-1 almost near to the normal levels most probably via regulation of SIRT1, AQPs and accordingly LC-3, P62 and Beclin-1levels. GA could be a promising candidate for the treatment of diabetes-induced SMG damage via regulating oxidative stress, autophagy and angiogenesis.


2017 ◽  
Vol 95 (4) ◽  
pp. 431-444 ◽  
Author(s):  
Anusha Ratneswaran ◽  
Margaret Man-Ger Sun ◽  
Holly Dupuis ◽  
Cynthia Sawyez ◽  
Nica Borradaile ◽  
...  

2015 ◽  
Vol 6 (5) ◽  
pp. 1510-1517 ◽  
Author(s):  
Yi-Wei Cao ◽  
Yun Jiang ◽  
Da-Yong Zhang ◽  
Xiao-Jing Zhang ◽  
Yuan-Jia Hu ◽  
...  

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


2009 ◽  
Vol 10 (1) ◽  
pp. 53-63 ◽  
Author(s):  
Lorraine M. Sordillo ◽  
G. A. Contreras ◽  
Stacey L. Aitken

AbstractDairy cattle are susceptible to increased incidence and severity of disease during the periparturient period. Increased health disorders have been associated with alterations in bovine immune mechanisms. Many different aspects of the bovine immune system change during the periparturient period, but uncontrolled inflammation is a dominant factor in several economically important disorders such as metritis and mastitis. In human medicine, the metabolic syndrome is known to trigger several key events that can initiate and promote uncontrolled systemic inflammation. Altered lipid metabolism, increased circulating concentrations of non-esterified fatty acids and oxidative stress are significant contributing factors to systemic inflammation and the development of inflammatory-based diseases in humans. Dairy cows undergo similar metabolic adaptations during the onset of lactation, and it was postulated that some of these physiological events may negatively impact the magnitude and duration of inflammation. This review will discuss how certain types of fatty acids may promote uncontrolled inflammation either directly or through metabolism into potent lipid mediators. The relationship of increased lipid metabolism and oxidative stress to inflammatory dysfunction will be reviewed as well. Understanding more about the underlying cause of periparturient health disorders may facilitate the design of nutritional regimens that will meet the energy requirements of cows during early lactation and reduce the susceptibility to disease as a function of compromised inflammatory responses.


2014 ◽  
Vol 2014 ◽  
pp. 1-18 ◽  
Author(s):  
Waseem Hassan ◽  
Gao Rongyin ◽  
Abdelkader Daoud ◽  
Lin Ding ◽  
Lulu Wang ◽  
...  

Oxidative stress interferes with hepatic lipid metabolism at various levels ranging from benign lipid storage to so-called second hit of inflammation activation. Isoquercitrin (IQ) is widely present flavonoid but its effects on hepatic lipid metabolism remain unknown. We used free fatty acids (FFA) induced lipid overload and oxidative stress model in two types of liver cells and measured cell viability, intracellular lipids, and reactive oxygen species (ROS) within hepatocytes. In addition, Intracellular triglycerides (TG), superoxide dismutase (SOD), and malondialdehyde (MDA) were examined. A novelin vitromodel was used to evaluate correlation between lipid lowering and antioxidative activities. Furthermore, 34 major cytokines and corresponding ROS levels were analyzed in FFA/LPS induced coculture model between hepatocytes and Kupffer cells. At molecular level AMPK pathway was elucidated. We showed that IQ attenuated FFA induced lipid overload and ROS within hepatocytes. Further, IQ reversed FFA induced increase in intracellular TG SOD and MDA. It was shown that antioxidative activity of IQ correlates with its lipid lowering potentials. IQ reversed major proinflammatory cytokines and oxidative stress in FFA/LPS induced coculture model. Finally, AMPK pathway was found responsible for metabolic benefits at molecular level. IQ strikingly manifests antioxidative and related lipid lowering activities in hepatocytes.


2019 ◽  
Vol 2019 ◽  
pp. 1-14 ◽  
Author(s):  
Deok Jeong ◽  
Jongsung Lee ◽  
Sang Hee Park ◽  
You Ah Kim ◽  
Byoung Jun Park ◽  
...  

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.


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