scholarly journals A Diterpenoid, 14-Deoxy-11, 12-Didehydroandrographolide, in Andrographis paniculata Reduces Steatohepatitis and Liver Injury in Mice Fed a High-Fat and High-Cholesterol Diet

Nutrients ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 523 ◽  
Author(s):  
Yun-Ta Liu ◽  
Haw-Wen Chen ◽  
Chong-Kuei Lii ◽  
Jia-Hua Jhuang ◽  
Chin-Shiu Huang ◽  
...  
Keyword(s):  
Liver Injury ◽  
Caspase 3 ◽  
Andrographis Paniculata ◽  
Receptor Protein ◽  
Heme Oxygenase 1 ◽  
Nuclear Factor ◽  
High Cholesterol ◽  
High Fat ◽  
Cholesterol Accumulation ◽  
Anti Inflammatory

14-Deoxy-11,12-didehydroandrographolide (deAND), a diterpenoid in Andrographis paniculata (Burm. f.) Nees, acts as a bioactive phytonutrient that can treat many diseases. To investigate the protective effects of deAND on reducing fatty liver disease, male mice were fed a high-fat and high-cholesterol (HFHC) diet without or with 0.05% and 0.1% deAND supplementation. Cholesterol accumulation, antioxidant, and anti-inflammatory activities in liver and liver injury were evaluated after deAND treatment. The results show that deAND treatment for seven weeks reduced plasma alanine aminotransferase activity and lowered hepatic cholesterol accumulation, tumor nuclear factor-α, and histological lesions. The 0.1% deAND treatment reduced HFHC diet-induced apoptosis by lowering the caspase 3/pro-caspase 3 ratio. After 11 weeks of deAND treatment, increased NOD-like receptor protein 3 (NLRP3), capase-1, and interleukin-1β protein levels in liver were suppressed by deAND treatment. In addition, nuclear factor erythroid 2-related factor 2 (Nrf2) mRNA expression, heme oxygenase-1 protein expression, and the activities of glutathione peroxidase and glutathione reductase were increased in mice fed the HFHC diet. However, those activities of antioxidant enzymes or proteins were also upregulated by 0.1% deAND treatment. Furthermore, deAND treatment tended to lower hepatic lipid peroxides. Finally, deAND treatment reversed the depletion of hepatic glutamate level induced by the HFHC diet. These results indicate that deAND may ameliorate HFHC diet-induced steatohepatitis and liver injury by increasing antioxidant and anti-inflammatory activities.

scholarly journals Dendrobium officinale Flower Extraction Mitigates Alcohol-Induced Liver Injury in Mice: Role of Antisteatosis, Antioxidative, and Anti-Inflammatory

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Yu-Lin Wu ◽  
Si-Han Huang ◽  
Chun-Mei He ◽  
Bo Qiu ◽  
Jing-Jing Liu ◽  
...  
Keyword(s):  
Liver Injury ◽  
Protective Effect ◽  
Serum Levels ◽  
Dendrobium Officinale ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Nuclear Factor ◽  
Quinone Oxidoreductase ◽  
Inflammatory Infiltration ◽  
Anti Inflammatory

The study aimed to evaluate the protective effect of Dendrobium officinale flower extraction (DOFE) on alcohol-induced liver injury and its probable mechanisms in mice. The chemical composition of DOFE was performed via UPLC/MS. Male Kunming mice were used to establish alcohol-induced liver injury models by oral gavage of 56% alcohol. Results showed that DOFE dramatically attenuated the increased serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total cholesterol (TC), and triacylglycerol (TG). Meanwhile, hematoxylin and eosin and Oil Red O staining showed that DOFE attenuated degeneration, inflammatory infiltration, and lipid droplet accumulation. DOFE was also found to suppress the activity of malonaldehyde (MDA) and enhanced the level of glutathione (GSH) and the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) in the liver. The protection of DOFE against oxidative stress was associated with the downregulation of hepatic cytochrome P450 2E1 (CYP2E1) and upregulation of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and NAD(P)H quinone oxidoreductase l (NQO1). Additionally, DOFE suppressed inflammation via downregulating Toll-like receptor-4 (TLR-4) and nuclear factor kappa-B P65 (NF-κB P65). Thus, DOFE exhibited a significant protective effect against alcohol-induced liver injury through its antisteatosis, antioxidative, and anti-inflammatory effect.

Freshwater clam extract reduces liver injury by lowering cholesterol accumulation, improving dysregulated cholesterol synthesis and alleviating inflammation in high-fat, high-cholesterol and cholic acid diet-induced steatohepatitis in mice

2018 ◽  
Vol 9 (9) ◽  
pp. 4876-4887 ◽  
Author(s):  
Hsien-Tsung Yao ◽  
Pei-Feng Lee ◽  
Chong-Kuei Lii ◽  
Yun-Ta Liu ◽  
Szu-Han Chen
Keyword(s):  
Liver Injury ◽  
Cholic Acid ◽  
Cholesterol Synthesis ◽  
Corbicula Fluminea ◽  
High Cholesterol ◽  
High Fat ◽  
Cholesterol Accumulation ◽  
Freshwater Clam ◽  
Acid Diet ◽  
Protective Food

Freshwater clam (Corbicula fluminea) is a traditional liver-protective food in Asia.

scholarly journals Allopurinol ameliorates liver injury in type 1 diabetic rats through activating Nrf2

2021 ◽  
Vol 35 ◽  
pp. 205873842110314
Author(s):  
Fei Zeng ◽  
Jierong Luo ◽  
Hong Han ◽  
Wenjie Xie ◽  
Lingzhi Wang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Liver Injury ◽  
Caspase 3 ◽  
Serum Levels ◽  
Diabetic Rats ◽  
Heme Oxygenase 1 ◽  
Liver Protein ◽  
Lipid Peroxidation Product ◽  
Protein Expressions

Hyperglycemia-induced oxidative stress plays important roles in the development of non-alcoholic fatty liver disease (NAFLD), which is a common complication in diabetic patients. The Nrf2-Keap1 pathway is important for cell antioxidant protection, while its role in exogenous antioxidant mediated protection against NAFLD is unclear. We thus, postulated that antioxidant treatment with allopurinol (ALP) may attenuate diabetic liver injury and explored the underlying mechanisms. Control (C) and streptozotocin (STZ)-induced diabetes rats (D) were untreated or treated with ALP for 4 weeks starting at 1 week after diabetes induction. Serum levels of alanine aminotransferase (ALT) and aspartate transaminase (AST), production of lipid peroxidation product malondialdehyde (MDA), and serum superoxide dismutase (SOD) were detected. Liver protein expressions of cleaved-caspase 3, IL-1β, nuclear factor-erythroid-2-related factor-2 (Nrf2), heme oxygenase-1 (HO-1), P62, Kelch-like ECH-associated protein 1 (Keap1), and LC3 were analyzed. In vitro, cultured rat normal hepatocytes BRL-3A were grouped to normal glucose (5.5 mM, NG) or high glucose (25 mM, HG) and treated with or without allopurinol (100 µM) for 48 h. Rats in the D group demonstrated liver injury evidenced as increased serum levels of ALT and AST. Diabetes increased apoptotic cell death, enhanced liver protein expressions of cleaved-caspase 3 and IL-1β with concomitantly increased production of MDA while serum SOD content was significantly reduced (all P < 0.05 vs C). In the meantime, protein levels of Nrf2, HO-1, and P62 were reduced while Keap1 and LC3 were increased in the untreated D group as compared to control ( P < 0.05 vs C). And all the above alterations were significantly attenuated by ALP. Similar to our findings obtained from in vivo study, we got the same results in in vitro experiments. It is concluded that ALP activates the Nrf2/p62 pathway to ameliorate oxidative stress and liver injury in diabetic rats.

Estrogen deficiency worsens steatohepatitis in mice fed high-fat and high-cholesterol diet

2011 ◽  
Vol 301 (6) ◽  
pp. G1031-G1043 ◽  
Author(s):  
Yoshihiro Kamada ◽  
Shinichi Kiso ◽  
Yuichi Yoshida ◽  
Norihiro Chatani ◽  
Takashi Kizu ◽  
...  
Keyword(s):  
Risk Factor ◽  
Liver Injury ◽  
Postmenopausal Women ◽  
Serum Cholesterol ◽  
Estrogen Deficiency ◽  
Macrophage Infiltration ◽  
High Cholesterol ◽  
High Fat ◽  
Gene Expressions ◽  
Cholesterol Levels

Recent studies indicate an accelerated progression of nonalcoholic steatohepatitis (NASH) in postmenopausal women. Hypercholesterolemia, an important risk factor for NASH progression, is often observed after menopause. This study examined the effects of estrogen on NASH in ovariectomized (OVX) mice fed a high-fat and high-cholesterol (HFHC) diet. To investigate the effects of estrogen deficiency, OVX mice and sham-operated (SO) mice were fed normal chow or HFHC diet for 6 wk. Next, to investigate the effects of exogenous estrogen replenishment, OVX mice fed with HFHC diet were treated with implanted hormone release pellets (containing 17β-estradiol or placebo vehicle) for 6 wk. OVX mice on the HFHC diet showed enhanced liver injury with increased liver macrophage infiltration and elevated serum cholesterol levels compared with SO-HFHC mice. Hepatocyte monocyte chemoattractant protein-1 (MCP1) protein expression in OVX-HFHC mice was also enhanced compared with SO-HFHC mice. In addition, hepatic inflammatory gene expressions, including monocytes chemokine (C-C motif) receptor 2 (CCR2), were significantly elevated in OVX-HFHC mice. Estrogen treatment improved serum cholesterol levels, liver injury, macrophage infiltration, and inflammatory gene expressions in OVX-HFHC mice. Moreover, the elevated expression of liver CCR2 and MCP1 were decreased by estrogen treatment in OVX-HFHC mice, whereas low-density lipoprotein dose dependently enhanced CCR2 expression in THP1 monocytes. Our study demonstrated that estrogen deficiency accelerated NASH progression in OVX mice fed HFHC diet and that this effect was improved by estrogen therapy. Hypercholesterolemia in postmenopausal women would be a potential risk factor for NASH progression.

scholarly journals Role of nuclear factor-κ B and heme oxygenase-1 in the mechanism of action of an anti-inflammatory chalcone derivative in RAW 264.7 cells

2004 ◽  
Vol 142 (7) ◽  
pp. 1191-1199 ◽  
Author(s):  
María José Alcaraz ◽  
Ana María Vicente ◽  
Amparo Araico ◽  
José N Dominguez ◽  
María Carmen Terencio ◽  
...  
Keyword(s):  
Heme Oxygenase ◽  
Mechanism Of Action ◽  
Raw 264.7 Cells ◽  
Heme Oxygenase 1 ◽  
Raw 264.7 ◽  
Nuclear Factor ◽  
Chalcone Derivative ◽  
Anti Inflammatory ◽  
Nuclear Factor Κ B

Cpt1a promoted ROS-induced oxidative stress and inflammation in liver injury via the Nrf2/HO-1 and NLRP3 inflammasome signaling pathway

2020 ◽  
Author(s):  
Xigang Luo ◽  
Dapeng Sun ◽  
Yinxiang Wang ◽  
Fengxiang Zhang ◽  
Yi Wang
Keyword(s):  
Oxidative Stress ◽  
Liver Injury ◽  
Signaling Pathway ◽  
Nlrp3 Inflammasome ◽  
Receptor Protein ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Over Expression ◽  
Vitro Model

Various liver diseases caused by liver damage seriously affect people’s health. The purpose of this study was to clarify that the effects and mechanism of Carnitine palmitoyltransferase 1 (Cpt1a) on oxidative stress and inflammation in liver injury. It was found that the expression of Cpt1a mRNA was up-regulated in model mice of liver injury. So, over-expression of Cpt1a increased reactive oxygen species (ROS) production and malondialdehyde (MDA) levels, and reduced superoxide dismutase (SOD), glutathione (GSH) and glutathione peroxidase (GSH-px) levels in vitro model of liver injury. It was also shown that over-expression of Cpt1a suppressed the Nuclear factor-erythroid-2-related factor 2 (Nrf2)/ heme oxygenase-1 (HO-1) signaling pathway. In summary, these data indicate that Cpt1a promotes ROS-induced oxidative stress in liver injury via the Nrf2/HO-1 and nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome signaling pathway.

scholarly journals Anti-Inflammatory Effects of Lasia spinosa Leaf Extract in Lipopolysaccharide-Induced RAW 264.7 Macrophages

2020 ◽  
Vol 21 (10) ◽  
pp. 3439 ◽  
Author(s):  
Thanh Q. C. Nguyen ◽  
Tran Duy Binh ◽  
Tuan L. A. Pham ◽  
Yen D. H. Nguyen ◽  
Dai Thi Xuan Trang ◽  
...  
Keyword(s):  
Leaf Extract ◽  
Inflammatory Diseases ◽  
Raw 264.7 Cells ◽  
Inflammatory Factors ◽  
Heme Oxygenase 1 ◽  
Raw 264.7 ◽  
Related Factor ◽  
Nuclear Factor ◽  
Raw 264.7 Macrophages ◽  
Anti Inflammatory

Lasia spinosa (L.) Thwaites was used as a traditional medicine to treat many inflammatory diseases for centuries. However, its effects on the inflammatory response are not yet characterized. In this study, we investigated the anti-inflammatory activities of L. spinosa leaf extract in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages. We found that ethanol extracts of L. spinosa leaves showed anti-oxidant activity due to the presence of high levels of polyphenolic compounds. Treatment with the leaf extract significantly repressed the production of inflammatory mediators such as nitric oxide and reactive oxygen species and the expression of pro-inflammatory cytokines in the LPS-stimulated RAW 264.7 cells. Moreover, L. spinosa leaf extract treatment prevented activation of the nuclear factor-kappa B pathway by inhibiting nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha (IκBα) degradation. Furthermore, the mitogen-activated kinase and phosphoinositide-3-kinase/protein kinase B (PI3K/Akt) pathways were suppressed upon treatment with the leaf extract. In addition to suppressing inflammatory factors, the extract also activated the nuclear factor erythroid 2-related factor 2/heme-oxygenase-1 pathway. We propose that L. spinosa leaf extract has the potential as an effective therapeutic agent for alleviating oxidative stress and excessive inflammation.

Epimedium koreanum Ameliorates Oxidative Stress-Mediated Liver Injury by Activating Nuclear Factor Erythroid 2-Related Factor 2

2018 ◽  
Vol 46 (02) ◽  
pp. 469-488 ◽  
Author(s):  
Ji Yun Jung ◽  
Sang Mi Park ◽  
Hae Li Ko ◽  
Jong Rok Lee ◽  
Chung A Park ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Liver Injury ◽  
Hepg2 Cells ◽  
Liver Diseases ◽  
Caspase 3 ◽  
Glutathione Depletion ◽  
Related Factor ◽  
Nuclear Factor ◽  
Nrf2 Activation ◽  
Anti Oxidant

Oxidative stress induced by reactive oxygen species is the main cause of various liver diseases. This study investigated the hepatoprotective effect of Epimedium koreanum Nakai water extract (EKE) against arachidonic acid (AA)[Formula: see text][Formula: see text][Formula: see text]iron-mediated cytotoxicity in HepG2 cells and carbon tetrachloride (CCl4-)-mediated acute liver injury in mice. Pretreatment with EKE (30 and 100[Formula: see text][Formula: see text]g/mL) significantly inhibited AA[Formula: see text][Formula: see text][Formula: see text]iron-mediated cytotoxicity in HepG2 cells by preventing changes in the expression of cleaved caspase-3 and poly(ADP-ribose) polymerase. EKE attenuated hydrogen peroxide production, glutathione depletion, and mitochondrial membrane dysfunction. EKE also increased the nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2), transactivated anti-oxidant response element harboring luciferase activity, and induced the expression of anti-oxidant genes. Furthermore, the cytoprotective effect of EKE against AA[Formula: see text][Formula: see text][Formula: see text]iron was blocked in Nrf2 knockout cells. Ultra-performance liquid chromatography analysis showed that EKE contained icariin, icaritin, and quercetin; icaritin and quercetin were both found to protect HepG2 cells from AA[Formula: see text][Formula: see text][Formula: see text]iron via Nrf2 activation. In a CCl4-induced mouse model of liver injury, pretreatment with EKE (300[Formula: see text]mg/kg) for four consecutive days ameliorated CCl4-mediated increases in serum aspartate aminotransferase activity, histological activity index, hepatic parenchyma degeneration, and inflammatory cell infiltration. EKE also decreased the number of nitrotyrosine-, 4-hydroxynonenal-, cleaved caspase-3-, and cleaved poly(ADP-ribose) polymerase-positive cells in hepatic tissues. These results suggest EKE is a promising candidate for the prevention or treatment of oxidative stress-related liver diseases via Nrf2 activation.

scholarly journals Antagonistic Efficacy of Luteolin against Lead Acetate Exposure-Associated with Hepatotoxicity is Mediated via Antioxidant, Anti-Inflammatory, and Anti-Apoptotic Activities

Antioxidants ◽  
2019 ◽  
Vol 9 (1) ◽  
pp. 10 ◽  
Author(s):  
Wafa A. AL-Megrin ◽  
Afrah F. Alkhuriji ◽  
Al Omar S. Yousef ◽  
Dina M. Metwally ◽  
Ola A. Habotta ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Lead Acetate ◽  
Interleukin 1 ◽  
Treated Group ◽  
Control Group ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Nuclear Factor ◽  
Toxic Heavy Metal ◽  
Anti Inflammatory

The abundant use of lead (Pb; toxic heavy metal) worldwide has increased occupational and ecosystem exposure, with subsequent negative health effects. The flavonoid luteolin (LUT) found in many natural foodstuffs possesses antioxidant and anti-inflammatory properties. Herein, we hypothesized that LUT could mitigate liver damage induced by exposure to lead acetate (PbAc). Male Wistar rats were allocated to four groups: control group received normal saline, LUT-treated group (50 mg/kg, oral, daily), PbAc-treated group (20 mg/kg, i.p., daily), and LUT+PbAc-treated group (received the aforementioned doses via the respective routes of administration); the rats were treated for 7 days. The results revealed that PbAc exposure significantly increased hepatic Pb residue and serum activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total bilirubin value. Oxidative reactions were observed in the liver tissue following PbAc intoxication, characterized by the depletion and downregulation of antioxidant proteins (glutathione, glutathione reductase, glutathione peroxidase, superoxide dismutase, catalase, nuclear factor erythroid 2-related factor 2, and heme oxygenase-1), and an increase in oxidants (malondialdehyde and nitric oxide). Additionally, PbAc increased the release and expression of the pro-inflammatory cytokines (tumor necrosis factor alpha and interleukin-1 beta), inducible nitric oxide synthase, and nuclear factor kappa B. Moreover, PbAc enhanced hepatocyte loss by increasing the expression of pro-apoptotic proteins (Bax and caspase-3) and downregulating the anti-apoptotic protein (Bcl-2). The changes in the aforementioned parameters were further confirmed by noticeable histopathological lesions. LUT supplementation significantly reversed all of the tested parameters in comparison with the PbAc-exposed group. In conclusion, our findings describe the potential mechanisms involved in the alleviation of PbAc-induced liver injury by luteolin via its potent anti-inflammatory, antioxidant, and anti-apoptotic properties.

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