Modulatory Effects of Silymarin on Benzo[a]pyrene-Induced Hepatotoxicity

Jee, Seung-Cheol; Kim, Min; Sung, Jung‐Suk

doi:10.3390/ijms21072369

Cited by 21 publications

(21 citation statements)

References 68 publications

(84 reference statements)

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“…Silymarin, a phytocomplex extracted from the medicinal plant Silybum marianum (“milk thistle”), is widely known for its hepatoprotective functions [ 140 ]. In addition, they have a protective effect against injuries to the brain [ 141 ], heart [ 142 ], and kidneys [ 143 ].…”

Section: Resultsmentioning

confidence: 99%

A Review of the Role of Flavonoids in Peptic Ulcer (2010–2020)

et al. 2020

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Peptic ulcers are characterized by erosions on the mucosa of the gastrointestinal tract that may reach the muscle layer. Their etiology is multifactorial and occurs when the balance between offensive and protective factors of the mucosa is disturbed. Peptic ulcers represent a global health problem, affecting millions of people worldwide and showing high rates of recurrence. Helicobacter pylori infection and the use of non-steroidal anti-inflammatory drugs (NSAIDs) are one of the most important predisposing factors for the development of peptic ulcers. Therefore, new approaches to complementary treatments are needed to prevent the development of ulcers and their recurrence. Natural products such as medicinal plants and their isolated compounds have been widely used in experimental models of peptic ulcers. Flavonoids are among the molecules of greatest interest in biological assays due to their anti-inflammatory and antioxidant properties. The present study is a literature review of flavonoids that have been reported to show peptic ulcer activity in experimental models. Studies published from January 2010 to January 2020 were selected from reference databases. This review refers to a collection of flavonoids with antiulcer activity in vivo and in vitro models.

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Section: Resultsmentioning

confidence: 99%

A Review of the Role of Flavonoids in Peptic Ulcer (2010–2020)

et al. 2020

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“…In gene knockout models, AhR knockout resulted in increased BPDE-DNA adduct formation compared with the wild type [ 46 ], and NRF2 knockout resulted in enhanced oxidative damage compared with the wild type [ 47 ]. Our previous study on the attenuation of B[a]P cytotoxicity by silymarin revealed that NRF2 knockdown increases BPDE-DNA adduct formation [ 48 ]. Therefore, we hypothesized that (1) quercetin and isorhamnetin increase the expression level of AhR and NRF2, or (2) quercetin and isorhamnetin increase the gene regulatory activity of AhR and NRF2.…”

Section: Discussionmentioning

confidence: 99%

Quercetin and Isorhamnetin Attenuate Benzo[a]pyrene-Induced Toxicity by Modulating Detoxification Enzymes through the AhR and NRF2 Signaling Pathways

et al. 2021

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Benzo[a]pyrene, classified as a Group 1 carcinogen, is metabolized to B[a]P-7,8-dihydrodiol-9,10-epoxide (BPDE), causing DNA mutations and eventually cancer. Quercetin is a dietary flavonoid abundant in fruits and vegetables. After quercetin intake, quercetin’s metabolites isorhamnetin and miquelianin are more highly concentrated than quercetin in the human plasma. In this study, we investigated the molecular mechanisms associated with the cytoprotective effect of quercetin and its metabolites against benzo[a]pyrene from a detoxification perspective. Quercetin and its metabolite isorhamnetin reduced benzo[a]pyrene-induced cytotoxicity, whereas the metabolite miquelianin did not mitigate benzo[a]pyrene-induced cytotoxicity. Moreover, quercetin and isorhamnetin reduced intracellular levels of BPDE-DNA adducts. The formation and elimination of BPDE is mediated by the xenobiotic detoxification process. Quercetin and isorhamnetin increased the gene and protein expression levels of phase I, II, and III enzymes involved in xenobiotic detoxification. Furthermore, quercetin and isorhamnetin induced the translocation of aryl hydrocarbon receptor (AhR) and nuclear factor erythroid 2-related factor 2 (NRF2), which regulate the expression level of phase enzymes. Our results suggest that quercetin and isorhamnetin promote the metabolism, detoxification, and elimination of B[a]P, thereby increasing anti-genotoxic effects and protecting against B[a]P-induced cytotoxicity.

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“…Cell viability assay was performed to evaluate the cytotoxicities of B[a]P and curcumin (Sigma-Aldrich Chemical, St. Louis, MO, USA) on HepG2 cells. The concentration (10 µM) of B[a]P was selected based on the evidence reported in our previous study which showed cytotoxicity of the B[a]P occurring in a dose-dependent manner on HepG2 cells [ 8 ]. HepG2 cells were seeded at a density of 1 × 10 4 cells/well in 96-well plates containing MEM with B[a]P (10 µM) or curcumin (0, 1, 5, 10, 20, or 40 µM) and cultured for 48 h. The cells were then incubated with EZ-CYTOX reagent (DOGEN, Seoul, Korea) for an additional 2 h. Cell absorbance at 450 nm was measured using a microplate reader (Tecan, Männedorf, Switzerland), and the cell viability with or without the treatment of B[a]P or curcumin was assessed.…”

Section: Methodsmentioning

confidence: 99%

“…Recent studies have focused on natural bioactive compounds that are derived from functional foods and attenuate chemical-induced toxicities [ 2 , 7 , 8 ]. Benzo[a]pyrene (B[a]P) is widely known as a chemical carcinogen of polycyclic aromatic hydrocarbon, listed as a group-1 carcinogen by the International Agency for Research on Cancer (IARC) [ 9 , 10 , 11 ].…”

Section: Introductionmentioning

confidence: 99%

Curcumin Suppresses the Lipid Accumulation and Oxidative Stress Induced by Benzo[a]pyrene Toxicity in HepG2 Cells

et al. 2021

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Benzo[a]pyrene (B[a]P) is a potentially hepatotoxic group-1 carcinogen taken up by the body through ingestion of daily foods. B[a]P is widely known to cause DNA and protein damages, which are closely related to cell transformation. Accordingly, studies on natural bioactive compounds that attenuate such chemical-induced toxicities have significant impacts on public health. This study aimed to uncover the mechanism of curcumin, the major curcuminoid in turmeric (Curcuma longa), in modulating the lipid accumulation and oxidative stress mediated by B[a]P cytotoxicity in HepG2 cells. Curcumin treatment reduced the B[a]P-induced lipid accumulation and reactive oxygen spicies (ROS) upregulation and recovered the cell viability. Cytochrome P450 family 1 subfamily A polypeptide 1 (CYP1A1) and Cytochrome P450 subfamily B polypeptide 1 (CYP1B1) downregulation resulting from decreased aryl hydrocarbon receptor (AhR) translocation into nuclei attenuated the effects of B[a]P-induced lipid accumulation and repressed cell viability, respectively. Moreover, the curcumin-induced reduction in ROS generation decreased the nuclear translocation of Nuclear factor erythroid-2-related factor 2 (Nrf2) and the expression of phase-II detoxifying enzymes. These results indicate that curcumin suppresses B[a]P-induced lipid accumulation and ROS generation which can potentially induce nonalcoholic fatty liver disease (NAFLD) and can shed a light on the detoxifying effect of curcumin.

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Modulatory Effects of Silymarin on Benzo[a]pyrene-Induced Hepatotoxicity

Cited by 21 publications

References 68 publications

A Review of the Role of Flavonoids in Peptic Ulcer (2010–2020)

A Review of the Role of Flavonoids in Peptic Ulcer (2010–2020)

Quercetin and Isorhamnetin Attenuate Benzo[a]pyrene-Induced Toxicity by Modulating Detoxification Enzymes through the AhR and NRF2 Signaling Pathways

Curcumin Suppresses the Lipid Accumulation and Oxidative Stress Induced by Benzo[a]pyrene Toxicity in HepG2 Cells

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