Effects of Gomisin A on the Promotor Action and Serum Bile Acid Concentration in Hepatocarcinogenesis Induced by 3'-Methyl-4-dimethylamino-azobenzene.

Miyamoto, Ken‐ichi; Hiramatsu, Kazuyoshi; Ohtaki, Yumiko; Kanitani, Masanao; Nomura, Masatoshi; Aburada, Masaki

doi:10.1248/bpb.18.1443

Cited by 9 publications

(5 citation statements)

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“…To date, evaluation of the effects of lignans on bile acids has only been conducted in animal models, mainly in the context of cholestasis [ 42 , 43 , 44 , 45 , 46 ] or hepatocarcinogenesis [ 47 , 48 ]. In vitro, ENL has been shown to inhibit cholesterol 7α hydroxylase (CYP7A1) activity, the enzyme involved in catalyzing the rate-limiting step in the conversion of cholesterol to primary bile acids, [ 49 ].…”

Section: Discussionmentioning

confidence: 99%

Effect of a Flaxseed Lignan Intervention on Circulating Bile Acids in a Placebo-Controlled Randomized, Crossover Trial

et al. 2020

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Plant lignans and their microbial metabolites, e.g., enterolactone (ENL), may affect bile acid (BA) metabolism through interaction with hepatic receptors. We evaluated the effects of a flaxseed lignan extract (50 mg/day secoisolariciresinol diglucoside) compared to a placebo for 60 days each on plasma BA concentrations in 46 healthy men and women (20–45 years) using samples from a completed randomized, crossover intervention. Twenty BA species were measured in fasting plasma using LC-MS. ENL was measured in 24-h urines by GC-MS. We tested for (a) effects of the intervention on BA concentrations overall and stratified by ENL excretion; and (b) cross-sectional associations between plasma BA and ENL. We also explored the overlap in bacterial metabolism at the genus level and conducted in vitro anaerobic incubations of stool with lignan substrate to identify genes that are enriched in response to lignan metabolism. There were no intervention effects, overall or stratified by ENL at FDR < 0.05. In the cross-sectional analysis, irrespective of treatment, five secondary BAs were associated with ENL excretion (FDR < 0.05). In vitro analyses showed positive associations between ENL production and bacterial gene expression of the bile acid-inducible gene cluster and hydroxysteroid dehydrogenases. These data suggest overlap in community bacterial metabolism of secondary BA and ENL.

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Section: Discussionmentioning

confidence: 99%

Effect of a Flaxseed Lignan Intervention on Circulating Bile Acids in a Placebo-Controlled Randomized, Crossover Trial

et al. 2020

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“…However, its role in the suppression of HCC tumorigenesis remains unclear. GM analogues such as Gomisin A and Gomisin N have been found to exhibit inhibitory effects on proliferation and carcinogenesis of HCC, − but the effects of these gomisins on miRNAs expression and their molecular targets remain unclear. Here, we found that GM modulates TRBP-mediated miRNA biogenesis and exhibits potent anti-hepatoma effects by reconstituting tumor-related proteins and signaling pathways in vitro and in vivo .…”

Section: Introductionmentioning

confidence: 99%

Identification of a Novel TAR RNA-Binding Protein 2 Modulator with Potential Therapeutic Activity against Hepatocellular Carcinoma

Zhou

et al. 2021

J. Med. Chem.

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Imbalance miRNAs contribute to tumor formation; therefore, the development of small-molecule compounds that regulate miRNA biogenesis is an important strategy in oncotherapy. Here, (−)-Gomisin M1 (GM) was found to modulate miRNA biogenesis to inhibit the proliferation, migration, and invasion of hepatocellular carcinoma (HCC) cells. GM modulated expression profiles of miRNA and protein in HCC cells and suppressed tumor growth in a mouse model. Mechanistically, GM affected miRNA maturation by targeting TAR RNA-binding protein 2 (TRBP), with an efficacy higher than that of enoxacin, and promoted the binding of TRBP with Dicer. Structural simplification and a preliminary structure−activity relationship study via the synthesis of 20 GM derivatives showed that compound 9 exhibited more potent inhibitory activity in HCC cell proliferation and affinity for TRBP than did GM. These results suggest that TRBP may be a novel potential therapeutic target in HCC and compound 9 may be a potential drug candidate for the treatment of HCC.

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“…Furthermore, gomisin A was shown to be tightly correlated with hepatocarcinogenesis. Finally, oral administration of gomisin A significantly inhibited the increase in serum bile acids (deoxycholic acid), occurrence of preneoplastic lesions, and the number of GST-P-positive loci in the liver (15)(16)(17). Although hepatic and renal disease induced by CCl 4 has been studied extensively, the mechanism by which these organs are protected against damage has not been widely investigated.…”

Section: Introductionmentioning

confidence: 99%

Protective effects of gomisin A isolated from Schisandra chinensis against CCl4-induced hepatic and renal injury

Hwang

Kim

Lee

et al. 2013

International Journal of Molecular Medicine

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The aim of the present study was to investigate the protective effects of gomisin A, a lignan compound isolated from Schisandra chinensis, against liver and kidney damage induced by CCl(4) exposure. We assessed alterations in organ weights, levels of serum biochemical indicators, and activation of the caspase-3 and MAPK signaling pathways and carried out histological analysis of liver and kidney tissue in rats pretreated with gomisin A for four days. In the gomisin A/CCl(4)-treated group, only the liver experienced a significant increase in weight, whereas the other organs did not undergo any changes. Five biochemical indicators in serum indicated that liver and kidney toxicity dramatically decreased upon gomisin A pretreatment, although the decrease in ratios varied. Upon histological analysis, the gomisin A/CCl(4)-treated group showed less hepatocellular necrosis, a poorly dilated central vein in the liver section, decreased diameter of the glomerulus, a lower number of capillaries, and a convoluted tubule in the kidney section. Furthermore, the formation of active caspase-3 was inhibited by gomisin A pretreatment in the gomisin A/CCl(4)-treated group, whereas the expression level of Bax protein was slightly increased. Western blot analysis revealed that there were differences between the liver and kidney in terms of activation of the MAPK signaling pathway. In the liver, gomisin A pretreatment increased phosphorylation of three members of the MAPK pathway when compared to that in the vehicle pretreatment group. However, in the kidney, only the phosphorylation level of p38 was elevated upon gomisin A pretreatment, whereas levels of the other two members were decreased. These results suggest that gomisin A induces marked protective effects against hepatic and renal injury induced by CCl(4) exposure through differential regulation of the MAPK signal transduction pathway.

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Effects of Gomisin A on the Promotor Action and Serum Bile Acid Concentration in Hepatocarcinogenesis Induced by 3'-Methyl-4-dimethylamino-azobenzene.

Cited by 9 publications

References 0 publications

Effect of a Flaxseed Lignan Intervention on Circulating Bile Acids in a Placebo-Controlled Randomized, Crossover Trial

Effect of a Flaxseed Lignan Intervention on Circulating Bile Acids in a Placebo-Controlled Randomized, Crossover Trial

Identification of a Novel TAR RNA-Binding Protein 2 Modulator with Potential Therapeutic Activity against Hepatocellular Carcinoma

Protective effects of gomisin A isolated from Schisandra chinensis against CCl4-induced hepatic and renal injury

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