Pharmacokinetics and Protective Effects of Tartary Buckwheat Flour Extracts against Ethanol-Induced Liver Injury in Rats

The grains of Tartary buckwheat (Fagopyrum esculentum) are traditionally consumed on a daily basis and are used in the preparation of diverse processed foods owing to the high concentration of rutin, an antioxidant compound. However, rutin is highly concentrated in hull and bran, but not in edible flour fractions. Rutin-enriched TB flour extracts (TBFEs) were obtained by hydrothermal treatment (autoclaving, boiling, or steaming) and their pharmacokinetic profiles were evaluated following a single-dose oral administration in rats. The antioxidant and protective activities of the extracts against alcoholic liver disease (ALD) were investigated after repetitive oral administration of TBFEs for 28 days prior to ethanol ingestion. The results demonstrated that rutin-enriched TBFEs had better oral absorption and was retained longer in the bloodstream than native TBFE or standard rutin. The activities of antioxidant enzymes and intracellular antioxidant levels increased in ALD rats following TBFE treatments, especially following the administration of rutin-enriched TBFEs. The antioxidant activity of TBFEs consequently contributed toward protecting the liver against injury caused by repetitive ethanol administration, as confirmed by analyzing relative liver weight, liver injury markers, lipid peroxidation, and calcium permeability. These results suggest the promising potential of TBFEs as antioxidant-enriched functional foods for human health.

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Resina Draconis Reduces Acute Liver Injury and Promotes Liver Regeneration after 2/3 Partial Hepatectomy in Mice

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2020/2305784 ◽

2020 ◽

Vol 2020 ◽

pp. 1-10

Author(s):

Zhi-yong He ◽

Kai-han Lou ◽

Jia-hui Zhao ◽

Ming Zhang ◽

Lan-chun Zhang ◽

...

Keyword(s):

Liver Injury ◽

Liver Regeneration ◽

Partial Hepatectomy ◽

Acute Liver Injury ◽

Liver Weight ◽

Nuclear Antigen ◽

Protective Effects ◽

Weight Restoration ◽

Resina Draconis ◽

Proliferating Cell

Aim. To investigate the protective effects and possible mechanisms of action of resina draconis (RD) on acute liver injury and liver regeneration after 2/3 partial hepatectomy (PH) in mice. Methods. 2/3 PH was used to induce acute liver injury. Mice were divided into three groups: sham, vehicle + 2/3 PH, and RD + 2/3 PH. Resina draconis was administered intragastrically after 2/3 PH into the RD + 2/3 PH group, and the same volume of vehicle (1% sodium carboxymethyl cellulose) was injected into the vehicle + 2/3 PH group and sham group mice. The index of liver to body weight (ILBW) and proliferating cell nuclear antigen (PCNA) were assayed to evaluate liver regeneration. Blood and liver tissues were collected for serological and western blotting analysis. Results. Resina draconis protected against 2/3 PH-induced acute severe liver injury and promoted liver regeneration as shown by significantly increased ILBW compared with that of controls. 2/3 PH increased serum AST and ALT levels, which were significantly decreased by RD treatment, while 2/3 PH decreased serum TP and ALB, which were increased by RD treatment. In the RD + 2/3 PH group, PCNA expression was significantly increased compared with the 2/3 PH group. Further, hepatocyte growth factor (HGF), TNFα, and EGFR levels were increased in the RD group at postoperative days 2 and 4 compared with the those in the 2/3 PH group. Conclusion. Our results suggest that RD ameliorates acute hepatic injury and promotes liver cell proliferation, liver weight restoration, and liver function after 2/3 PH, probably via HGF, TNFα, and EGFR signaling.

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Protective effects of tartary buckwheat flavonoids on high TMAO diet-induced vascular dysfunction and liver injury in mice

Food & Function ◽

10.1039/c5fo00581g ◽

2015 ◽

Vol 6 (10) ◽

pp. 3359-3372 ◽

Cited By ~ 25

Author(s):

Yuanyuan Hu ◽

Yan Zhao ◽

Li Yuan ◽

Xingbin Yang

Keyword(s):

Liver Injury ◽

Vascular Dysfunction ◽

Tartary Buckwheat ◽

Protective Effects ◽

Vascular Changes ◽

Hepatoprotective Effects ◽

Flavonoid Fraction

This study was performed to investigate the liver and vascular changes in high trimethylamine-N-oxide (TMAO) diet-fed mice, and the possible vasoprotective and hepatoprotective effects of purified tartary buckwheat flavonoid fraction (TBF).

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Hepatoprotective effects of chamazulene against alcohol-induced liver damage by alleviation of oxidative stress in rat models

Open Life Sciences ◽

10.1515/biol-2020-0026 ◽

2020 ◽

Vol 15 (1) ◽

pp. 251-258

Author(s):

Xu Wang ◽

Ke Dong ◽

Yujing Ma ◽

Qizhi Jin ◽

Shujun Yin ◽

...

Keyword(s):

Oxidative Stress ◽

Liver Injury ◽

Serum Alkaline Phosphatase ◽

Positive Control ◽

Ethanol Administration ◽

Control Group ◽

Protective Effects ◽

Alcoholic Liver Injury ◽

Rat Models ◽

Hepatoprotective Effects

AbstractLiver injury and disease caused by alcohol is a common complication to human health worldwide. Chamazulene is a natural proazulene with antioxidant and anti-inflammatory properties. This study aims to investigate the hepatoprotective effects of chamazulene against ethanol-induced liver injury in rat models. Adult Wistar rats were orally treated with 50% v/v ethanol (8–12 mL/kg body weight [b.w.]) for 6 weeks to induce alcoholic liver injury. Chamazulene was administered orally to rats 1 h prior to ethanol administration at the doses of 25 and 50 mg/kg b.w. for 6 weeks. Silymarin, a commercial drug for hepatoprotection, was orally administered (50 mg/kg b.w.) for the positive control group. Chamazulene significantly reduced (p < 0.05) the levels of serum alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, and malondialdehyde, whereas the levels of antioxidant enzymes (glutathione peroxidase, catalase, and superoxide dismutase) and reduced glutathione were significantly restored (p < 0.05) in contrast to the ethanol model group. The levels of pro-inflammatory cytokines (tumour necrosis factor-α and interleukin-6) were suppressed by chamazulene (p < 0.05) with relevance to ethanol-induced liver injury. Histopathological alterations were convincing in the chamazulene-treated groups, which showed protective effects against alcoholic liver injury. Chamazulene has a significant hepatoprotective effect against ethanol-induced liver injury through alleviation of oxidative stress and prevention of inflammation.

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Fat-1 Transgenic Mice With Augmented n3-Polyunsaturated Fatty Acids Are Protected From Liver Injury Caused by Acute-On-Chronic Ethanol Administration

Frontiers in Pharmacology ◽

10.3389/fphar.2021.711590 ◽

2021 ◽

Vol 12 ◽

Author(s):

Jeffrey Warner ◽

Josiah Hardesty ◽

Ying Song ◽

Rui Sun ◽

Zhongbin Deng ◽

...

Keyword(s):

Fatty Acids ◽

Liver Disease ◽

Liver Injury ◽

Polyunsaturated Fatty Acids ◽

Dietary Fatty Acids ◽

Ethanol Administration ◽

Protective Effects ◽

Hepatic Expression ◽

N3 Polyunsaturated Fatty Acids ◽

Pai 1

Alcohol-associated liver disease (ALD) is the leading cause of liver disease worldwide, and alcohol-associated hepatitis (AH), a severe form of ALD, is a major contributor to the mortality and morbidity due to ALD. Many factors modulate susceptibility to ALD development and progression, including nutritional factors such as dietary fatty acids. Recent work from our group and others showed that modulation of dietary or endogenous levels of n6-and n3-polyunsaturated fatty acids (PUFAs) can exacerbate or attenuate experimental ALD, respectively. In the current study, we interrogated the effects of endogenous n3-PUFA enrichment in a mouse model which recapitulates features of early human AH using transgenic fat-1 mice which endogenously convert n6-PUFAs to n3-PUFAs. Male wild type (WT) and fat-1 littermates were provided an ethanol (EtOH, 5% v/v)-containing liquid diet for 10 days, then administered a binge of EtOH (5 g/kg) by oral gavage on the 11th day, 9 h prior to sacrifice. In WT mice, EtOH treatment resulted in liver injury as determined by significantly elevated plasma ALT levels, whereas in fat-1 mice, EtOH caused no increase in this biomarker. Compared to their pair-fed controls, a significant EtOH-mediated increase in liver neutrophil infiltration was observed also in WT, but not fat-1 mice. The hepatic expression of several cytokines and chemokines, including Pai-1, was significantly lower in fat-1 vs WT EtOH-challenged mice. Cultured bone marrow-derived macrophages isolated from fat-1 mice expressed less Pai-1 and Cxcl2 (a canonical neutrophil chemoattractant) mRNA compared to WT when stimulated with lipopolysaccharide. Further, we observed decreased pro-inflammatory M1 liver tissue-resident macrophages (Kupffer cells, KCs), as well as increased liver T regulatory cells in fat-1 vs WT EtOH-fed mice. Taken together, our data demonstrated protective effects of endogenous n3-PUFA enrichment on liver injury caused by an acute-on-chronic EtOH exposure, a paradigm which recapitulates human AH, suggesting that n3-PUFAs may be a viable nutritional adjuvant therapy for this disease.

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Thioacetamide-induced liver injury: protective role of genistein

Canadian Journal of Physiology and Pharmacology ◽

10.1139/cjpp-2014-0192 ◽

2014 ◽

Vol 92 (11) ◽

pp. 965-973 ◽

Cited By ~ 16

Author(s):

Dalia O. Saleh ◽

Gehad A. Raheem Abdel Jaleel ◽

Sally A. El-Awdan ◽

Fatma Oraby ◽

Manal Badawi

Keyword(s):

Liver Injury ◽

Body Mass ◽

Antioxidant Properties ◽

Elevated Serum ◽

Serum Levels ◽

Daily Basis ◽

Protective Role ◽

Protective Effects ◽

Necrosis Factor Alpha ◽

Stress Markers

This study aimed to investigate the possible protective effects of genistein (GEN), a phytoestrogen, on the liver injury induced in rats by thioacetamide (TTA; 200.0 mg·(kg body mass)–1; administered 3 times a week by intraperitoneal injection). GEN (0.5, 1.0, or 2.0 mg·(kg body mass)–1; by subcutaneous injection) was concurrently administered on a daily basis for 8 weeks, and its effects were evaluated 24 h after the administration of the last dose. The results from this study revealed that TTA-induced liver injury was associated with massive changes in the serum levels of liver biomarkers, oxidative stress markers, and liver inflammatory cytokines. Treatment of TAA-induced liver injury in rats with GEN decreased the elevated serum levels of aspartate aminotransferase, alanine aminotransferase, and total and direct bilirubin, and increased the serum level of albumin. GEN also restored the liver levels of malondialdehyde and reduced glutathione, as well as tumor necrosis factor-alpha, interleukin-6, and their modulator nuclear factor kappa-light-chain-enhancer of activated B cells. From our results, it can be concluded that GEN attenuates the liver injury-induced in rats with TAA, and this hepatoprotective role is attributed to its anti-inflammatory and antioxidant properties.

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Protective effects of fucoidan against ethanol-induced liver injury through maintaining mitochondria function and mitophagy balance in rats.

Food & Function ◽

10.1039/d0fo03220d ◽

2021 ◽

Author(s):

Huichao Zhao ◽

Shuang Liu ◽

Hui Zhao ◽

Meilan Xue ◽

Huaqi Zhang ◽

...

Keyword(s):

Liver Disease ◽

Liver Injury ◽

Alcoholic Liver Disease ◽

Therapeutic Strategy ◽

Hepatic Lesion ◽

Protective Effects ◽

Regulatory Effects

For alcoholic liver disease (ALD), mitophagy was reported as a promising therapeutic strategy to alleviate the hepatic lesion elicited by ethanol. This study was to investigate the regulatory effects of...

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Protective Effect of Pyrus ussuriensis Maxim. Extract against Ethanol-Induced Gastritis in Rats

Antioxidants ◽

10.3390/antiox10030439 ◽

2021 ◽

Vol 10 (3) ◽

pp. 439

Author(s):

Naila Boby ◽

Muhammad Aleem Abbas ◽

Eon-Bee Lee ◽

Zi-Eum Im ◽

Walter H. Hsu ◽

...

Keyword(s):

Therapeutic Option ◽

Adenosine Monophosphate ◽

Ethanol Ingestion ◽

Dependent Manner ◽

Protective Effects ◽

Gastric Mucosal Lesions ◽

Cellular Degeneration ◽

Mucosal Lesions ◽

Pyrus Ussuriensis Maxim

Pyrus ussuriensis Maxim (Korean pear) has been used for hundreds of years as a traditional herbal medicine for asthma, cough, and atopic dermatitis in Korea and China. Although it was originally shown to possess anti-inflammatory, antioxidant, and antiatopic properties, its gastroprotective effects have not been investigated. In the present study, we evaluated the protective effects of Pyrus ussuriensis Maxim extract (PUE) against ethanol-induced gastritis in rats. The bioactive compound profile of PUE was determined by gas chromatography mass spectroscopy (GC-MS) and high-performance liquid chromatography (HPLC). The gastroprotection of PUE at different doses (250 and 500 mg/kg body weight) prior to ethanol ingestion was evaluated using an in vivo gastritis rat model. Several endpoints were evaluated, including gastric mucosal lesions, cellular degeneration, intracellular damage, and immunohistochemical localization of leucocyte common antigen. The gastric mucosal injury and ulcer score were determined by evaluating the inflamed gastric mucosa and by histological examination. To identify the mechanisms of gastroprotection by PUE, antisecretory action and plasma prostaglandin E2 (PGE2), gastric mucosal cyclic adenosine monophosphate (cAMP), and histamine levels were measured. PUE exhibited significant antioxidant effects with IC50 values of 56.18 and 22.49 µg/mL for 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2′- azino-di-(3-ethylbenzothiazoline)-6-sulfonic acid (ABTS) inhibition (%), respectively. In addition, GC/MS and HPLC analyses revealed several bioactive compounds of PUE. Pretreatment with PUE significantly (P < 0.05) decreased the ulcer index by preventing gastric mucosal lesions, erosion, and cellular degeneration. An immunohistochemical analysis revealed that PUE markedly attenuated leucocyte infiltration in a dose-dependent manner. The enhancement of PGE2 levels and attenuation of cAMP levels along with the inhibition of histamine release following PUE pretreatment was associated with the cytoprotective and healing effects of PUE. In contrast, the downregulation of the H+/K+ ATPase pathway as well as muscarinic receptor (M3R) and histamine receptor (H2R) inhibition was also involved in the gastroprotective effects of PUE; however, the expression of cholecystokinin-2 receptors (CCK2R) was unchanged. Finally, no signs of toxicity were observed following PUE treatment. Based on our results, we conclude that PUE represents an effective therapeutic option to reduce the risk of gastritis and warrants further study.

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Lemon Balm and Dandelion Leaf Extracts Synergistically Protect against Carbon Tetrachloride-Induced Acute Liver Injury in Mice

Applied Sciences ◽

10.3390/app11010390 ◽

2021 ◽

Vol 11 (1) ◽

pp. 390

Author(s):

Beom-Rak Choi ◽

Il-Je Cho ◽

Su-Jin Jung ◽

Jae-Kwang Kim ◽

Dae-Geon Lee ◽

...

Keyword(s):

Carbon Tetrachloride ◽

Liver Injury ◽

Acute Liver Injury ◽

Antioxidant Activities ◽

Body Weight Gain ◽

Histopathological Analysis ◽

Related Factor ◽

Mrna Levels ◽

Protective Effects ◽

Lemon Balm

Lemon balm and dandelion are commonly used medicinal herbs exhibiting numerous pharmacological activities that are beneficial for human health. In this study, we explored the protective effects of a 2:1 (w/w) mixture of lemon balm and dandelion extracts (MLD) on carbon tetrachloride (CCl4)-induced acute liver injury in mice. CCl4 (0.5 mL/kg; i.p.) injection inhibited body weight gain and increased relative liver weight. Pre-administration of MLD (50–200 mg/kg) for 7 days prevented these CCl4-mediated changes. In addition, histopathological analysis revealed that MLD synergistically alleviated CCl4-mediated hepatocyte degeneration and infiltration of inflammatory cells. MLD decreased serum aspartate aminotransferase and alanine transferase activities and reduced the number of liver cells that stained positive for cleaved caspase-3 and cleaved poly(ADP-ribose) polymerase, suggesting that MLD protects against CCl4-induced hepatic damage via the inhibition of apoptosis. Moreover, MLD attenuated CCl4-mediated lipid peroxidation and protein nitrosylation by restoring impaired hepatic nuclear factor erythroid 2-related factor 2 mRNA levels and its dependent antioxidant activities. Furthermore, MLD synergistically decreased mRNA and protein levels of tumor necrosis factor-α, interleukin-1β, and interleukin-6 in the liver. Together, these results suggest that MLD has potential for preventing acute liver injury by inhibiting apoptosis, oxidative stress, and inflammation.

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Lactobacillus acidophilus LA5 improves saturated fat-induced obesity mouse model through the enhanced intestinal Akkermansia muciniphila

Scientific Reports ◽

10.1038/s41598-021-85449-2 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Thunnicha Ondee ◽

Krit Pongpirul ◽

Peerapat Visitchanakun ◽

Wilasinee Saisorn ◽

Suthicha Kanacharoen ◽

...

Keyword(s):

Liver Injury ◽

Lactobacillus Acidophilus ◽

Hepg2 Cells ◽

Saturated Fat ◽

Liver Weight ◽

Gram Negative ◽

Fecal Microbiome ◽

Akkermansia Muciniphila ◽

Anti Inflammatory ◽

Inflammatory Molecules

AbstractObesity, a major healthcare problem worldwide, induces metabolic endotoxemia through the gut translocation of lipopolysaccharides (LPS), a major cell wall component of Gram-negative bacteria, causing a chronic inflammatory state. A combination of several probiotics including Lactobacillus acidophilus 5 (LA5), a potent lactic acid-producing bacterium, has previously been shown to attenuate obesity. However, data on the correlation between a single administration of LA5 versus microbiota alteration might be helpful for the probiotic adjustment. LA5 was administered daily together with a high-fat diet (HFD) for 8 weeks in mice. Furthermore, the condition media of LA5 was also tested in a hepatocyte cell-line (HepG2 cells). Accordingly, LA5 attenuated obesity in mice as demonstrated by weight reduction, regional fat accumulation, lipidemia, liver injury (liver weight, lipid compositions, and liver enzyme), gut permeability defect, endotoxemia, and serum cytokines. Unsurprisingly, LA5 improved these parameters and acidified fecal pH leads to the attenuation of fecal dysbiosis. The fecal microbiome analysis in obese mice with or without LA5 indicated; (i) decreased Bacteroidetes (Gram-negative anaerobes that predominate in non-healthy conditions), (ii) reduced total fecal Gram-negative bacterial burdens (the sources of gut LPS), (iii) enhanced Firmicutes (Gram-positive bacteria with potential benefits) and (iv) increased Verrucomycobia, especially Akkermansia muciniphila, a bacterium with the anti-obesity property. With LA5 administration, A. muciniphila in the colon were more than 2,000 folds higher than the regular diet mice as determined by 16S rRNA. Besides, LA5 produced anti-inflammatory molecules with a similar molecular weight to LPS that reduced cytokine production in LPS-activated HepG2 cells. In conclusion, LA5 attenuated obesity through (i) gut dysbiosis attenuation, partly through the promotion of A. muciniphila (probiotics with the difficulty in preparation processes), (ii) reduced endotoxemia, and (iii) possibly decreased liver injury by producing the anti-inflammatory molecules.

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