Gigantol ameliorates CCl4-induced liver injury via preventing activation of JNK/cPLA2/12-LOX inflammatory pathway

Xue, Yaru; Deng, Qiangqiang; Zhang, Qingli; Ma, Zhenghua; Chen, Binfan; Yu, Xiaolu; Peng, Huige; Yao, Sheng; Liu, Jia; Yang, Yong; Pan, Guoyu

doi:10.1038/s41598-020-79400-0

Cited by 25 publications

(14 citation statements)

References 37 publications

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“…and Bulbophyllum leopardium with reference to antifibrotic activity in vitro [ 30 ], while marylaurencinol-A ( 4 ) was isolated from Cymbidium Great Flower “Marylaurencin” with antimicrobial activities [ 11 ]. Gigantol ( 7 ) and tristin ( 8 ) have mainly been referred to as isolated metabolites from Dendrobium sp., with gigantol displaying a wide range of bioactivities, including anti-oxidant, anti-mutagen, anti-platelet aggregation, anti-spasmodic and anti-ageing effects [ 41 , 42 ]. Furthermore, in the chemical category of 1,4-phenanthrenequinones, 5-hydroxy-2-methoxy-1,4-phenanthrenequinone ( 5 ) and ephemeranthoquinone-B ( 6 ) were isolated from Cymbidium sp., with 5-hydroxy-2-methoxy-1,4-phenanthrenequinone showing cytotoxic activity against human cell lung cancer (NCI-H187) cell line [ 21 ] and ephemeranthoquinone-B showing antimicrobial and antioxidant activities in vitro [ 18 ].…”

Section: Resultsmentioning

confidence: 99%

Phytochemical Analysis and Dermo-Cosmetic Evaluation of Cymbidium sp. (Orchidaceae) Cultivation By-Products

et al. 2021

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Cymbidium is one of the most popular genera in Orchidaceae family, commercialized either as loose flowers or as potted plants in floriculture worldwide. The non-marketable parts are typically discarded (e.g., unsuitable flowers, leaves, pseudobulbs, roots), generating an enormous quantity of unutilized biomass. The above by-products were studied through phytochemical analysis and investigated for their dermo-cosmetic potential. The initial antioxidant, anti-tyrosinase, anti-elastase, and anti-collagenase assays of the total extracts indicated that the pseudobulb and root ethyl acetate extracts were the most potent. Those extracts were then submitted to chromatographic separation leading to the isolation of 16 secondary metabolites (four phenanthrenes, three 1,4-phenanthrenquinones, three dibenzyls, two phenolic acid derivatives, two sterols, one dehydrodiconiferyl alcohol derivative, and one simple phenolic compound), including 6-hydroxy-5,7-dimethoxy-1,4-phenanthrenequinone (cymbisamoquinone), which was identified as a new natural product. In parallel, 48 metabolites were identified by UPLC-HRMS analysis of the extracts. The biological evaluation of the isolated compounds revealed that gigantol and tristin present important anti-tyrosinase activity, while bulbophyllanthrin, 3-hydroxy-2,4,7-trimethoxy-phenanthrene, marylaurencinol A, 5-hydroxy-2-methoxy-1,4-phenanthrenequinone, and ephemeranthroquinone B show dose-dependent anti-collagenase activity. In contrast to isolated metabolites, which may act selectively on specific enzymes, the initial total extracts exhibited inhibitory activity against tyrosinase, elastase, and collagenase enzymes, thus showing better prospects for use in dermo-cosmetic formulations.

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Section: Resultsmentioning

confidence: 99%

Phytochemical Analysis and Dermo-Cosmetic Evaluation of Cymbidium sp. (Orchidaceae) Cultivation By-Products

et al. 2021

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“…This would suggest that baicalein mediated inhibition of CCl 4 -induced ferroptosis is partly dependent on the inhibition of ALOX12 activity. Previous studies also showed that inhibition of ALOX12 gene expression also contributed to inhibition of inflammatory response [ 71 ]. Whether the inhibition of ALOX12 gene expression contributes significantly to the inhibitory effect of baicalein on CCl 4 –induced inflammatory still requires further investigation.…”

Section: Discussionmentioning

confidence: 95%

Inhibition of Oxidative Stress and ALOX12 and NF-κB Pathways Contribute to the Protective Effect of Baicalein on Carbon Tetrachloride-Induced Acute Liver Injury

Dai

Wang

et al. 2021

Antioxidants

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This study investigates the protective effect of baicalein on carbon tetrachloride (CCl4)-induced acute liver injury and the underlying molecular mechanisms. Mice were orally administrated baicalein at 25 and 100 mg/kg/day for 7 consecutive days or ferrostatin-1 (Fer-1) at 10 mg/kg was i.p. injected in mice at 2 and 24 h prior to CCl4 injection or the vehicle. Our results showed that baicalein or Fer-1 supplementation significantly attenuated CCl4 exposure-induced elevations of serum alanine aminotransferase and aspartate aminotransferase, and malondialdehyde levels in the liver tissues and unregulated glutathione levels. Baicalein treatment inhibited the nuclear factor kappa-B (NF-κB) pathway, activated the erythroid 2-related factor 2 (Nrf2)/heme oxygenase 1 (HO-1) pathway in liver tissues, and markedly improved CCl4-induced apoptosis, inflammation and ferroptosis in liver tissues exposed with CCl4. In vitro, baicalein treatment improved CCl4 -induced decreases of cell viabilities and knockdown of Nrf2 and arachidonate 12-lipoxygenase (ALOX12) genes partly abolished the protective effect of baicalein on CCl4 -induced cytotoxicity in HepG2 cells. In conclusion, our results reveal that baicalein supplementation ameliorates CCl4-induced acute liver injury in mice by upregulating the antioxidant defense pathways and downregulating oxidative stress, apoptosis, inflammation and ferroptosis, which involved the activation of Nrf2 pathway and the inhibition of ALOX12 and NF-κB pathways.

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“…Conversely, the oxidative stress response of iRhom2-knockout mice did not increase after alcohol stimulation compared to the nonalcoholic treatment group. JNK activation is a key pathway leading to oxidative stress [ 50 , 51 , 52 , 53 ]. Moreover, iRhom2 has been previously proven to regulate JNK and induce the oxidative stress response to liver injuries [ 54 ].…”

Section: Discussionmentioning

confidence: 99%

Deficiency in Inactive Rhomboid Protein2 (iRhom2) Alleviates Alcoholic Liver Fibrosis by Suppressing Inflammation and Oxidative Stress

Liu

Kuang

Dai

et al. 2022

IJMS

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Chronic alcohol exposure can lead to liver pathology relating to inflammation and oxidative stress, which are two of the major factors in the incidence of liver fibrosis and even liver cancer. The underlying molecular mechanisms regarding hepatic lesions associated with alcohol are not fully understood. Considering that the recently identified iRhom2 is a key pathogenic mediator of inflammation, we performed in vitro and in vivo experiments to explore its regulatory role in alcohol-induced liver fibrosis. We found that iRhom2 knockout significantly inhibited alcohol-induced inflammatory responses in vitro, including elevated expressions of inflammatory cytokines (IL-1β, IL-6, IL-18, and TNF-α) and genes associated with inflammatory signaling pathways, such as TACE (tumor necrosis factor-alpha converting enzyme), TNFR1 (tumor necrosis factor receptor 1), and TNFR2, as well as the activation of NF-κB. The in vivo results confirmed that long-term alcohol exposure leads to hepatocyte damage and fibrous accumulation. In this pathological process, the expression of iRhom2 is promoted to activate the TACE/NF-κB signaling pathway, leading to inflammatory responses. Furthermore, the deletion of iRhom2 blocks the TACE/NF-κB signaling pathway and reduces liver damage and fibrosis caused by alcohol. Additionally, the activation of the JNK/Nrf2/HO-1 signaling pathway caused by alcohol exposure was also noted in vitro and in vivo. In the same way, knockout or deleting iRhom2 blocked the JNK/Nrf2/HO-1 signaling pathway to regulate the oxidative stress. Therefore, we contend that iRhom2 is a key regulator that promotes inflammatory responses and regulates oxidative stress in alcoholic liver fibrosis lesions. We posit that iRhom2 is potentially a new therapeutic target for alcoholic liver fibrosis.

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Gigantol ameliorates CCl4-induced liver injury via preventing activation of JNK/cPLA2/12-LOX inflammatory pathway

Cited by 25 publications

References 37 publications

Phytochemical Analysis and Dermo-Cosmetic Evaluation of Cymbidium sp. (Orchidaceae) Cultivation By-Products

Phytochemical Analysis and Dermo-Cosmetic Evaluation of Cymbidium sp. (Orchidaceae) Cultivation By-Products

Inhibition of Oxidative Stress and ALOX12 and NF-κB Pathways Contribute to the Protective Effect of Baicalein on Carbon Tetrachloride-Induced Acute Liver Injury

Deficiency in Inactive Rhomboid Protein2 (iRhom2) Alleviates Alcoholic Liver Fibrosis by Suppressing Inflammation and Oxidative Stress

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