Efficacy of Polymethoxylated Flavonoids from Citrus depressa Extract on Alcohol-induced Liver Injury in Mice

Lee, Eun Young; Kim, Se Ho; Chang, Sukkum Ngullie; Lee, Jin-Hyung; Hwang, Buyng Su; Woo, Je‐Tae; Kang, Sun Chul; Lee, Jintae; Park, Jae Gyu

doi:10.1007/s12257-019-0310-4

Cited by 15 publications

(7 citation statements)

References 35 publications

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“…The supernatant was collected after centrifugation. Serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were measured using the previously described method [ 43 ] employing a chemistry analyzer (Mindary, WA, USA). Biochemical parameters were repeated three times.…”

Section: Methodsmentioning

confidence: 99%

5-O-Demethylnobiletin Alleviates CCl4-Induced Acute Liver Injury by Equilibrating ROS-Mediated Apoptosis and Autophagy Induction

Chang

Kim

Dey

et al. 2021

IJMS

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Polymethoxyflavanoids (PMFs) have exhibited a vast array of therapeutic biological properties. 5-O-Demethylnobiletin (5-DN) is one such PMF having anti-inflammatory activity, yet its role in hepatoprotection has not been studied before. Results from in vitro study revealed that 5-DN did not exert a high level of cytotoxicity on HepG2 cells at 40 μM, and it was able to rescue HepG2 cell death induced by carbon tetrachloride (CCl4). Subsequently, we investigated acute liver injury on BALB/c mice induced by CCl4 through the intraperitoneal injection of 1 mL/kg CCl4 and co-administration of 5-DN at (1 and 2 mg/kg) by oral gavage for 15 days. The results illustrated that treatment with 5-DN attenuated CCl4-induced elevated serum aminotransferase (AST)/alanine aminotransferase (ALT) ratio and significantly ameliorated severe hepatic damage such as inflammation and fibrosis evidenced through lesser aberrations in the liver histology of 5-DN dose groups. Additionally, 5-DN efficiently counteracted and equilibrated the production of ROS accelerated by CCl4 and dramatically downregulated the expression of CYP2E1 vitally involved in converting CCl4 to toxic free radicals and also enhanced the antioxidant enzymes. 5-DN treatment also inhibited cell proliferation and inflammatory pathway abnormally regulated by CCl4 treatment. Furthermore, the apoptotic response induced by CCl4 treatment was remarkably reduced by enhanced Bcl-2 expression and noticeable reduction in Bax, Bid, cleaved caspase 3, caspase 9, and apaf-1 expression. 5-DN treatment also induced the conversion of LC3 and promoted the autophagic flux. Conclusively, 5-DN exhibited hepatoprotective effects in vitro and in vivo and prevented liver fibrosis induced by CCl4.

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Section: Methodsmentioning

confidence: 99%

5-O-Demethylnobiletin Alleviates CCl4-Induced Acute Liver Injury by Equilibrating ROS-Mediated Apoptosis and Autophagy Induction

Chang

Kim

Dey

et al. 2021

IJMS

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“…Many other fruits such as apricot [ 162 ], guava [ 163 ], pomegranate [ 148 ], lemon [ 164 ], Citrus depressa [ 165 ], noni fruit [ 166 ], Opuntia ficus indica [ 167 ], jujube [ 168 ], and persimmon [ 147 ] were also reported to mitigate ALD. These findings confirm that daily intake of fruits may be an effective strategy for alleviating ALD.…”

Section: Multicomponent Food Plant Extracts Against Aldmentioning

confidence: 99%

Protective Mechanism of Edible Food Plants against Alcoholic Liver Disease with Special Mention to Polyphenolic Compounds

et al. 2021

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Alcoholic liver disease (ALD) is one type of liver disease, causing a global healthcare problem and mortality. The liver undergoes tissue damage by chronic alcohol consumption because it is the main site for metabolism of ethanol. Chronic alcohol exposure progresses from alcoholic fatty liver (AFL) to alcoholic steatohepatitis (ASH), which further lead to fibrosis, cirrhosis, and even hepatocellular cancer. Therapeutic interventions to combat ALD are very limited such as use of corticosteroids. However, these therapeutic drugs are not effective for long-term usage. Therefore, additional effective and safe therapies to cope with ALD are urgently needed. Previous studies confirmed that edible food plants and their bioactive compounds exert a protective effect against ALD. In this review article, we summarized the hepatoprotective potential of edible food plants and their bioactive compounds. The underlying mechanism for the prevention of ALD by edible food plants was as follows: anti-oxidation, anti-inflammation, lipid regulation, inhibition of apoptosis, gut microbiota composition modulation, and anti-fibrosis.

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“…For extraction of the whole cellular protein, the cells were lysed by the addition of RIPA buffer (1:100 dilutions with protease and phosphatase inhibitor) followed by incubation on ice for 30 min [ 49 ]. Later, the mixture was centrifuged at 12,000 rpm at 4 °C for 15 min.…”

Section: Methodsmentioning

confidence: 99%

Decursinol Angelate Arrest Melanoma Cell Proliferation by Initiating Cell Death and Tumor Shrinkage via Induction of Apoptosis

Chang

Khan

Kim

et al. 2021

IJMS

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Melanoma is known to aggressively metastasize and is one of the prominent causes of skin cancer mortality. This study was designed to assess the molecular mechanism of decursinol angelate (DA) against murine melanoma cell line (B16F10 cells). Treatment of DA resulted in growth inhibition and cell cycle arrest at G0/G1 (p < 0.001) phase, evaluated through immunoblotting. Moreover, autophagy-related proteins such as ATG-5 (p < 0.0001), ATG-7 (p < 0.0001), beclin-1 (p < 0.0001) and transition of LC3-I to LC3-II (p < 0.0001) were markedly decreased, indicating autophagosome inhibition. Additionally, DA treatment triggered apoptotic events which were corroborated by the occurrence of distorted nuclei, elevated reactive oxygen species (ROS) levels and reduction in the mitochondrial membrane potential. Subsequently, there was an increase in the expression of pro-apoptotic protein Bax in a dose-dependent manner, with the corresponding downregulation of Bcl-2 expression and cytochrome C expression following 24 h DA treatment in A375.SM and B16F10 cells. We substantiated our results for apoptotic occurrence through flow cytometry in B16F10 cells. Furthermore, we treated B16F10 cells with N-acetyl-L-cysteine (NAC). NAC treatment upregulated ATG-5 (p < 0.0001), beclin-1 (p < 0.0001) and LC3-I to LC3-II (p < 0.0001) conversion, which was inhibited in the DA treatment group. We also noticed a systematic upregulation of important markers for progression of G1 cell phase such as CDK-2 (p < 0.029), CDK-4 (p < 0.036), cyclin D1 (p < 0.0003) and cyclin E (p < 0.020) upon NAC treatment. In addition, we also observed a significant fold reduction (p < 0.05) in ROS fluorescent intensity and the expression of Bax (p < 0.0001), cytochrome C (p < 0.0001), cleaved caspase-9 (p > 0.010) and cleaved caspase-3 (p < 0.0001). NAC treatment was able to ameliorate DA-induced apoptosis and cell cycle arrest to support our finding. Our in vivo xenograft model also revealed similar findings, such as downregulation of CDK-2 (p < 0.0001) and CDK-4 (p < 0.0142) and upregulation of Bax (p < 0.0001), cytochrome C (p < 0.0001), cleaved caspase 3 (p < 0.0001) and cleaved caspase 9 (p < 0.0001). In summary, our study revealed that DA is an effective treatment against B16F10 melanoma cells and xenograft mice model.

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Efficacy of Polymethoxylated Flavonoids from Citrus depressa Extract on Alcohol-induced Liver Injury in Mice

Cited by 15 publications

References 35 publications

5-O-Demethylnobiletin Alleviates CCl4-Induced Acute Liver Injury by Equilibrating ROS-Mediated Apoptosis and Autophagy Induction

5-O-Demethylnobiletin Alleviates CCl4-Induced Acute Liver Injury by Equilibrating ROS-Mediated Apoptosis and Autophagy Induction

Protective Mechanism of Edible Food Plants against Alcoholic Liver Disease with Special Mention to Polyphenolic Compounds

Decursinol Angelate Arrest Melanoma Cell Proliferation by Initiating Cell Death and Tumor Shrinkage via Induction of Apoptosis

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