Hepatoprotective activity of iridoids, seco-iridoids and analog glycosides from Gentianaceae on HepG2 cells via CYP3A4 induction and mitochondrial pathway

Liver disease or liver cancer is the sixth most common cancer and the third leading cause of cancer mortality in the world. Hepatitis viral infection, food additives, alcohol, fungal toxins (aflatoxins), toxic industrial chemicals, air and water pollutants are the major risk factors of liver cancer. Moreover, due to high tolerance of liver, HCC is seldom detected at an early stage and once detected treatment faces a poor prognosis in most cases.Fumaria indica possesses hepatoprotective activity as evidenced by the significant and dose dependent restoring the activities of entire liver cancer marker enzymes, diminution in tumor incidence, decrease in lipid peroxidation (LPO) and increase in the level of antioxidant enzymes (GSH, CAT, SOD, GPx and GST) through scavenging of free radicals, or by enhancing the activity of antioxidant, which then detoxify free radicals. These factors protect cells from ROS damage in NDEA and CCl4-induced hepatocarcinogenesis. Histopathological observations of liver tissues too correlated with the biochemical observations. Thus, present investigation suggested that the Fumaria indica would exert a chemoprotective effect by reversing the oxidant-antioxidant imbalance during hepatocarcinogenesis induced by NDEA and CCl4. Besides Fumaria indicais very much effective in preventing NDEA-induced multistage hepatocarcinogenesis possibly through antioxidant and antigenotoxic nature, which was confirmed by various liver injury and biochemical tumour markers enzymes. The hepatoprotective activity of a Fumaria indicaof 50 % ethanolic extract was studied using rats. The animals received a single intraperitoneal injection of N-nitrosodiethylamine 200mg/kg body wt followed by subcutaneous injection of CCl4 in a dose of 3 ml/kg body wt. Fumaria indica extract dose dependently and significantly the increase in serum hepatic enzyme levels after NDEAand CCl4 treatment compared to the toxin control group. The results of this study confirmed the antioxidant and hepatoprotective activity of the Fumaria indicaextract against carbon tetrachlorideand N-nitrosodiethylamine induced hepatotoxicity in rats. In addition to this, studies on molecular aspect of hepatoprotective therapy will give mechanistic information in hepatoprotective therapy and also critical balance should be there between the animal model and clinical research. The hepatoprotective properties of Fumaria indicashould provide useful information in the possible application in hepatic liver disease.

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The protective effects of carvacrol and thymol against paracetamol–induced toxicity on human hepatocellular carcinoma cell lines (HepG2)

Human & Experimental Toxicology ◽

10.1177/0960327115627688 ◽

2016 ◽

Vol 35 (12) ◽

pp. 1252-1263 ◽

Cited By ~ 23

Author(s):

SS Palabiyik ◽

E Karakus ◽

Z Halici ◽

E Cadirci ◽

Y Bayir ◽

...

Keyword(s):

Oxidative Stress ◽

Inflammatory Cytokines ◽

Hepg2 Cells ◽

Folk Medicine ◽

Hepatoprotective Activity ◽

High Dose ◽

Protective Effects ◽

And Oxidative Stress ◽

Pro Inflammatory Cytokines

Acetaminophen (APAP) overdose could induce liver damage and lead to acute liver failure. The treatment of APAP overdoses could be improved by new therapeutic strategies. Thymus spp., which has many beneficial effects and has been used in folk medicine, is one such potential strategy. In the present study, the hepatoprotective activity of the main constituents of Thymus spp., carvacrol and thymol, were evaluated in light of APAP-induced hepatotoxicity. We hoped to understand the hepatoprotective mechanism of these agents on the antioxidant system and pro-inflammatory cytokines in vitro. Dose-dependent effects of thymol and carvacrol (25, 50, and 100 µM) were tested on cultured HepG2 cells. N-Acetylcysteine (NAC) was tested as positive control. We showed that APAP inhibited HepG2 cell growth by inducing inflammation and oxidative stress. Incubating APAP-exposed HepG2 cells with carvacrol and thymol for 24 h ameliorated this inflammation and oxidative stress. We also evaluated alanine transaminase and lactate dehydrogenase levels of HepG2 cells. We found that thymol and carvacrol protected against APAP-induced toxicity in HepG2 cells by increasing antioxidant activity and reducing pro-inflammatory cytokines, such as tumor necrosis factor α and interleukin 1β. Taking together high-dose thymol and carvacrol treatment has an effect close to NAC treatment in APAP toxicity, but thymol has better treatment effect than carvacrol.

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Treatment with dibenzoxanthenes inhibits proliferation and induces apoptosis of HepG2 cells via the intrinsic mitochondrial pathway

RSC Advances ◽

10.1039/c6ra13901a ◽

2016 ◽

Vol 6 (76) ◽

pp. 72703-72714 ◽

Cited By ~ 4

Author(s):

Yong Chen ◽

Hui-Hui Yang ◽

Xiu-Zhen Wang ◽

Hua-Can Song

Keyword(s):

Biological Activity ◽

Hepg2 Cells ◽

Mitochondrial Pathway

Dibenzoxanthenes were reported to possess antitumor biological activity.

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Repression of Acetaminophen-Induced Hepatotoxicity in HepG2 Cells by Polyphenolic Compounds from Lauridia tetragona (L.f.) R.H. Archer

Molecules ◽

10.3390/molecules24112118 ◽

2019 ◽

Vol 24 (11) ◽

pp. 2118 ◽

Cited By ~ 3

Author(s):

Samuel Odeyemi ◽

John Dewar

Keyword(s):

Hepg2 Cells ◽

Antioxidant Properties ◽

Reducing Power ◽

Underlying Mechanism ◽

Hepatoprotective Activity ◽

Polyphenolic Compounds ◽

Hepatocellular Injury ◽

Liver Glutathione ◽

Total Antioxidant ◽

A Cell

Lauridia tetragona (L.f) R.H. Archer is routinely used in traditional medicine; however, its hepatoprotective property is yet to be scientifically proven. To this effect, the hepatoprotective activity of the polyphenolic-rich fractions (PPRFs) was investigated against acetaminophen (APAP) injured HepG2 cells. The ability of the PPRF to scavenge free radicals was tested against 2,2-diphenyl-1-picrylhydrazyl (DPPH), and [2,2′-azino-bis (3-ethylbenzothiazoline-6-sulfonicacid)] (ABTS). The ferric ion reducing power (FRAP) was also evaluated as a cell-free antioxidant assay. The hepatoprotective activity was then investigated by observing the effect of PPRFs against APAP-induced reduction in cell viability of HepG2 cells. The concentrations of alanine aminotransferase (AST), aspartate aminotransferase (ALT) and lactate dehydrogenase (LDH) released into the medium were evaluated while the underlying mechanism was further explored through western blot analysis. Thereafter, the isolated PPRFs were identified using UHPLC-QToF-MS. All six fractions of the PPRFs isolated showed significant antioxidant properties that were evident by the effective scavenging of DPPH, ABTS, and higher FRAP. The results indicated that PPRF pretreatments ameliorated APAP-induced hepatocellular injury by significantly inhibiting the leakage of AST, ALT, and LDH into the medium. The most active fractions for hepatoprotection were PPRF4 and PPRF6 with IC50 of 50.243 ± 8.03 and 154.59 ± 1.9 μg/mL, respectively. PPRFs markedly increased activities of liver superoxide dismutase, total antioxidant capacity, and liver glutathione concentration. Both PPRF4 and PPRF6 significantly increased the expression of Nrf2 and translocation. The LC-MS analysis revealed the presence of a wide variety of polyphenolics such as coumarin, ferulic acid, and caffeine among the dominant constituents. In conclusion, this study demonstrates that the isolated PPRFs have potential hepatoprotective activity that may be due to the increased expression of antioxidative genes dependent on Nrf2.

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Hepatoprotective Activity of BV-7310, a Proprietary Herbal Formulation of Phyllanthus niruri, Tephrosia purpurea, Boerhavia diffusa, and Andrographis paniculata, in Alcohol-Induced HepG2 Cells and Alcohol plus a Haloalkane, CCl4, Induced Liver Damage in Rats

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2020/6428906 ◽

2020 ◽

Vol 2020 ◽

pp. 1-9

Author(s):

Debendranath Dey ◽

Sunetra Chaskar ◽

Narendra Bhatt ◽

Deepa Chitre

Keyword(s):

Body Weight ◽

Liver Damage ◽

Hepg2 Cells ◽

Liver Toxicity ◽

Hepatoprotective Activity ◽

Andrographis Paniculata ◽

Phyllanthus Niruri ◽

In Vivo Models ◽

Tephrosia Purpurea ◽

Boerhavia Diffusa

Excessive alcohol consumption is a worldwide threat with severe morbidity and mortality. Other than abstinence, there is still no FDA-approved drug for alcoholic liver disease (ALD). Liver is the primary site of ethanol metabolism and hence gets the most damage from excessive drinking. It triggers multiple signalling events including inflammation, leading to an array of hepatic lesions like steatosis, hepatitis, fibrosis, and cirrhosis. Similarly, when medications or xenobiotic compounds are ingested orally, the liver gets the highest exposure of those metabolites, which in turn can cause severe liver toxicity. BV-7310 is a standardized mixture of four Ayurvedic plants, namely, Phyllanthus niruri, Tephrosia purpurea, Boerhavia diffusa, and Andrographis paniculata. In different systems of traditional medicine, each of these plants has been known to have use in gastrointestinal disorders. We wanted to assess the combined effect of these plant extracts on alcohol-induced liver damage. First, we investigated the hepatoprotective activity of BV-7310 against alcohol-induced toxicity in human liver HepG2 cells. Ethanol treatment (120 mM for 48 hours) significantly showed toxicity (around 42%) in these cells, and coincubation with BV-7310 prevented ethanol-induced cell death in a dose-dependent manner. Interestingly, the formulation BV-7310 showed synergistic activity than any individual extract tested in this assay. BV-7310 also showed potent antioxidant activity in 2,2-diphenyl-1-picryl-hydrazyl (DPPH) assay. Next, we induced hepatitis in Sprague–Dawley (SD) rats using repeated alcohol (40%) dosing, and carbon tetrachloride (CCl4) 24 hours before termination. Both oral doses of BV-7310 (250 and 500 mg/kg body weight) protected the alcohol-induced body weight loss and significantly improved the elevated levels of liver enzymes compared to the vehicle treated group. Thus, BV-7310 prevents alcohol-induced toxicity in both in-vitro and in-vivo models and could be beneficial for the treatment of ALD or other conditions, which may cause liver toxicity.

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Characterization of cell-death pathways in Punta Toro virus-induced hepatocyte injury

Journal of General Virology ◽

10.1099/vir.0.2008/001644-0 ◽

2008 ◽

Vol 89 (9) ◽

pp. 2175-2181 ◽

Cited By ~ 3

Author(s):

Fangling Xu ◽

Xiaodong Liang ◽

Robert B. Tesh ◽

Shu-Yuan Xiao

Keyword(s):

Cell Death ◽

Hepg2 Cells ◽

Antigen Expression ◽

Mitochondrial Pathway ◽

Cellular Viability ◽

Tnf Receptor ◽

Extrinsic Pathway ◽

Punta Toro Virus

Punta Toro virus (PTV; genus Phlebovirus, family Bunyaviridae) causes apoptosis of hepatocytes in vivo in experimentally infected hamsters and in vitro in cultured HepG2 cells. Screening for expression of apoptosis-related genes has shown alterations in the genes for tumour necrosis factor-α (TNF-α) and the TNF receptor family. This study examined the roles of the TNF receptor-related extrinsic pathway and the Bcl-2 family-associated mitochondrial pathway in PTV-induced cell death. The effects of caspase inhibitors (caspIs) and TNF on cellular viability, virus replication, and morphological and biochemical changes in apoptosis were examined in HepG2 cells at different time points after infection with PTV (Adames strain). The results showed that caspIs dampened the virus-induced reduction in cellular viability, partially suppressed and delayed viral titres and antigen expression, and partially decreased the expression of apoptotic genes, caspase activities and DNA fragmentation. TNF treatment further decreased cellular viability after PTV infection and increased the level of apoptosis, whilst caspIs partially inhibited these effects. These findings indicate that TNF, caspase-8 and caspase-9 contribute to PTV-induced hepatocytic apoptosis and that additional mediators are probably also involved in this process. These mediators from different pathways correlated with one another and may be interlinked.

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Ethanol Extract ofDianthus chinensisL. Induces Apoptosis in Human Hepatocellular Carcinoma HepG2 CellsIn Vitro

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2012/573527 ◽

2012 ◽

Vol 2012 ◽

pp. 1-8 ◽

Cited By ~ 7

Author(s):

Kyoung Jin Nho ◽

Jin Mi Chun ◽

Ho Kyoung Kim

Keyword(s):

Hepatocellular Carcinoma ◽

Hepg2 Cells ◽

Chromatin Condensation ◽

Ethanol Extract ◽

Mitochondrial Pathway ◽

Carcinoma Cells ◽

Dependent Manner ◽

Caspase Inhibitor ◽

Caspase Activation ◽

Apoptotic Effects

Dianthus chinensisL. is used to treat various diseases including cancer; however, the molecular mechanism by which the ethanol extract ofDianthus chinensisL. (EDCL) induces apoptosis is unknown. In this study, the apoptotic effects of EDCL were investigated in human HepG2 hepatocellular carcinoma cells. Treatment with EDCL significantly inhibited cell growth in a concentration- and time-dependent manner by inducing apoptosis. This induction was associated with chromatin condensation, activation of caspases, and cleavage of poly (ADP-ribose) polymerase protein. However, apoptosis induced by EDCL was attenuated by caspase inhibitor, indicating an important role for caspases in EDCL responses. Furthermore, EDCL did not alter the expression of bax in HepG2 cells but did selectively downregulate the expression of bcl-2 and bcl-xl, resulting in an increase in the ratio of bax:bcl-2 and bax:bcl-xl. These results support a mechanism whereby EDCL induces apoptosis through the mitochondrial pathway and caspase activation in HepG2 cells.

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EFEKTIVITAS PENGGUNAAN EKSTRAK ANTOSIANIN TANAMAN BUNGA KEMBANG SEPATU UNTUK MENDETEKSI BORAKS PADA BAKSO

Jurnal Delima Harapan ◽

10.31935/delima.v8i2.126 ◽

2021 ◽

Vol 8 (2) ◽

pp. 21-25

Author(s):

Rio Purnama

Keyword(s):

Food Safety ◽

Human Body ◽

Food Additives ◽

Flower Extract ◽

Conducting Research ◽

Lack Of Knowledge

One of the causes of food safety problems in Indonesia is the lack of knowledge, responsibility and supervision by producers, consumers and the authorities. This results in cheating by irresponsible food producers, adding ingredients that can harm the human body. There are several ways to detect or detect the presence of hazardous food additives, one of which is using indicators made from natural ingredients added with several other ingredients that can detect hazardous food additives, one of which is borax. After conducting research on the effectiveness of hibiscus flower anthocyanin extract as an indicator of borax detection in meatballs, it was found that hibiscus flower extract can be used as an indicator for borax detection, seen from the change in the color of hibiscus flower extract which at first is brownish orange (purplish. ) After being absorbed with meatballs containing borax, the hibiscus flower extract changes its color to dark brown red, this is due to the pelagornidin antasianin compounds reacting with borax compounds.

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A little more on the classification and brief description of food additives

10.33920/igt-01-2105-07 ◽

2021 ◽

pp. 382-386

Author(s):

А.М. Agapkin

Keyword(s):

Human Body ◽

Food Additives ◽

General Classification ◽

Individual Features ◽

The Individual

A general classification and a brief description of food additives are presented. The consequences of their use for a human vary depending on the individual features of the organism, the amount of the substance used and the additive itself. Preservatives are considered the most harmful to the human body, since most of them have carcinogenic properties.

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