nrf2 antagonist ml385  (MedChemExpress)

Journal: Chinese medicine

Article Title: The effect and mechanism of Germacrone in ameliorating alcoholic fatty liver by inhibiting Nrf2/Rbp4.

doi: 10.1186/s13020-025-01132-y

Figure Lengend Snippet: Fig. 5 Germacrone inhibits Nrf2-dependent Rbp4 expression in the ALD model. A, B The protein expression levels of Rbp4 in the ALD model treated with Germacrone and Brusatol (n = 3). C Correlation analysis of liver TG content and Rbp4 expression. D Rbp4 mRNA expression in HepG2 cells in the Control group, Model group, Brusatol group, and Germacrone group was analyzed by RT-qPCR (n = 6). E, F Western blot was used to detect the expression level of Rbp4 protein under different conditions (n = 3). Compared with the model group, *P < 0.05, **P < 0.01, ***P < 0.001

Article Snippet: After 3 days of adaptive feeding, C57BL/6 male mice were randomly divided into the following 4 groups with 6 mice in each group: (1) Control group: Mice were fed the Lieber–DeCarli standard liquid diet for 35 consecutive days without any other intervention. (2) Model group: mice were fed a liquid diet with low alcohol concentration for the first 6 days as a transition and then changed to the Lieber–DeCarli alcoholic liquid diet with 5% alcohol concentration from the 7 th day for 28 days without drug intervention. (3) Germacrone group: The feed was treated the same as the model group, and Germacrone (molecular formula: C15H22O, purity > 98%, Yuanye, Shanghai, China, 10 mg/kg) [7, 24] was given daily intragastric administration from day 8 for 21 days. (4) Brusatol group: the feed treatment was the same as the model group, and the Nrf2 antagonist Brusatol (Purity: 99.96%, Selleck, S7956, Shanghai, China, 2 mg/kg) [25] was intraperitoneally injected every other day from the 8 th day for 21 days.

Techniques: Expressing, Control, Quantitative RT-PCR, Western Blot

Journal: Chinese medicine

Article Title: The effect and mechanism of Germacrone in ameliorating alcoholic fatty liver by inhibiting Nrf2/Rbp4.

doi: 10.1186/s13020-025-01132-y

Figure Lengend Snippet: Fig. 7 Nrf2 binds to the Rbp4 promoter region and regulates its transcriptional activity. A ChIP-seq analysis shows Nrf2 binding sites in the Rbp4 promoter region. B Schematic diagram of predicted ARE sequences in the Rbp4 promoter region (− 2000 ~ + 200). C ChIP-qPCR results showing Nrf2 binding to the Rbp4 promoter region at 90 ~ 185 bp (n = 3). D ChIP-qPCR results showing significant Nrf2 binding at the Rbp4 promoter region − 1534 ~ − 1473 bp (n = 3). E ChIP-qPCR results showing significant Nrf2 binding at the Rbp4 promoter region − 1534 ~ − 1473 bp between the normal group and the ALD model group (n = 6). F ChIP-qPCR results showing significant Nrf2 binding at the Rbp4 promoter region 90 ~ 185 bp between the normal group and the ALD model group (n = 6). C, D Compared with the Control group, *P < 0.05, **P < 0.01, ***P < 0.001. E, F Compared with the Control-IP group, *P < 0.05, **P < 0.01, ***P < 0.001. Compared with the Model-Ig group, SP < 0.05, SSP < 0.01, SSSP < 0.001

Article Snippet: After 3 days of adaptive feeding, C57BL/6 male mice were randomly divided into the following 4 groups with 6 mice in each group: (1) Control group: Mice were fed the Lieber–DeCarli standard liquid diet for 35 consecutive days without any other intervention. (2) Model group: mice were fed a liquid diet with low alcohol concentration for the first 6 days as a transition and then changed to the Lieber–DeCarli alcoholic liquid diet with 5% alcohol concentration from the 7 th day for 28 days without drug intervention. (3) Germacrone group: The feed was treated the same as the model group, and Germacrone (molecular formula: C15H22O, purity > 98%, Yuanye, Shanghai, China, 10 mg/kg) [7, 24] was given daily intragastric administration from day 8 for 21 days. (4) Brusatol group: the feed treatment was the same as the model group, and the Nrf2 antagonist Brusatol (Purity: 99.96%, Selleck, S7956, Shanghai, China, 2 mg/kg) [25] was intraperitoneally injected every other day from the 8 th day for 21 days.

Techniques: Activity Assay, ChIP-sequencing, Binding Assay, ChIP-qPCR, Control

Journal: Chinese medicine

Article Title: The effect and mechanism of Germacrone in ameliorating alcoholic fatty liver by inhibiting Nrf2/Rbp4.

doi: 10.1186/s13020-025-01132-y

Figure Lengend Snippet: Fig. 8 Mechanism of Germacrone in the Treatment of Alcohol-Induced Liver Disease (ALD). Under alcohol exposure, reactive oxygen species (ROS) and foreign electrophilic reagents inhibit the ubiquitination of Nrf2, leading to its nuclear translocation. In the nucleus, Nrf2 binds to antioxidant response elements (AREs), promoting the transcription of downstream target genes, including Rbp4 (lipid transport protein), HO-1, and Gsta1 (oxidative stress-regulated proteins). This process accelerates lipid transport, lipid accumulation, and oxidative damage in hepatocytes, which contributes to the progression of ALD (left panel). In contrast, Germacrone (Germacrone), the active component of Jia-Ga-Song-Tang (JGST), effectively inhibits Nrf2 activation and nuclear translocation, thereby down-regulating the expression of Rbp4, HO-1, and Gsta1. This reduces lipid accumulation and oxidative stress, protecting hepatocytes and improving liver health (right panel)

Article Snippet: After 3 days of adaptive feeding, C57BL/6 male mice were randomly divided into the following 4 groups with 6 mice in each group: (1) Control group: Mice were fed the Lieber–DeCarli standard liquid diet for 35 consecutive days without any other intervention. (2) Model group: mice were fed a liquid diet with low alcohol concentration for the first 6 days as a transition and then changed to the Lieber–DeCarli alcoholic liquid diet with 5% alcohol concentration from the 7 th day for 28 days without drug intervention. (3) Germacrone group: The feed was treated the same as the model group, and Germacrone (molecular formula: C15H22O, purity > 98%, Yuanye, Shanghai, China, 10 mg/kg) [7, 24] was given daily intragastric administration from day 8 for 21 days. (4) Brusatol group: the feed treatment was the same as the model group, and the Nrf2 antagonist Brusatol (Purity: 99.96%, Selleck, S7956, Shanghai, China, 2 mg/kg) [25] was intraperitoneally injected every other day from the 8 th day for 21 days.

Techniques: Ubiquitin Proteomics, Translocation Assay, Activation Assay, Expressing

Journal: Antioxidants

Article Title: Melatonin Nuclear Receptors Mediate Green-and-Blue-Monochromatic-Light-Combinations-Inhibited B Lymphocyte Apoptosis in the Bursa of Chickens via Reducing Oxidative Stress and Nfκb Expression

doi: 10.3390/antiox11040748

Figure Lengend Snippet: Nrf2 ( A ), HO-1 ( B ), p-iκb ( C ), p-p65 ( D ) protein level in bursa at P42. The results of each group were expressed as the mean ± standard error. Differences between seven light treatment groups were evaluated by one-way ANOVA, and values with no common letters differ significantly ( p < 0.05).

Article Snippet: In addition, bursal B lymphocytes of the G→B group were prepared with either RORα antagonist (SR3335, 5 μM, MCE, Weehawken, NJ, USA), RORα agonist (SR1078, 10 μM, MCE, Weehawken, NJ, USA), RORγ antagonist (GSK2981278, 1 μM, MCE, Weehawken, NJ, USA), Nrf2 antagonist (ML385, 5 μM, MCE, Weehawken, NJ, USA), Nfκb antagonist (BAY, 1 μM, MCE, Weehawken, NJ, USA) for 30 min before the addition of LPS and melatonin.

Techniques:

Journal: Antioxidants

Article Title: Melatonin Nuclear Receptors Mediate Green-and-Blue-Monochromatic-Light-Combinations-Inhibited B Lymphocyte Apoptosis in the Bursa of Chickens via Reducing Oxidative Stress and Nfκb Expression

doi: 10.3390/antiox11040748

Figure Lengend Snippet: Effects of RORα antagonists, RORα agonist, RORγ antagonist, Nrf2 antagonists and p65 antagonists on Caspase-3 protein ( A , B ), Bcl-2 protein ( C ), Bax protein ( D ), ROS level ( E ) of bursal B-lymphocyte in response to LPS in the G→B group. SR3335 is a RORα antagonist; SR1078 is a RORα agonist; GSK1981278 is a RORγ antagonist; ML385 is an NRF2 antagonist; BAY is a p65 antagonist. Differences between seven light treatment groups were evaluated by one-way ANOVA, and values with no common letters differ significantly ( p < 0.05).

Article Snippet: In addition, bursal B lymphocytes of the G→B group were prepared with either RORα antagonist (SR3335, 5 μM, MCE, Weehawken, NJ, USA), RORα agonist (SR1078, 10 μM, MCE, Weehawken, NJ, USA), RORγ antagonist (GSK2981278, 1 μM, MCE, Weehawken, NJ, USA), Nrf2 antagonist (ML385, 5 μM, MCE, Weehawken, NJ, USA), Nfκb antagonist (BAY, 1 μM, MCE, Weehawken, NJ, USA) for 30 min before the addition of LPS and melatonin.

Techniques:

Journal: Antioxidants

Article Title: Melatonin Nuclear Receptors Mediate Green-and-Blue-Monochromatic-Light-Combinations-Inhibited B Lymphocyte Apoptosis in the Bursa of Chickens via Reducing Oxidative Stress and Nfκb Expression

doi: 10.3390/antiox11040748

Figure Lengend Snippet: Effects of RORα antagonists, RORα agonist, RORγ antagonist, Nrf2 antagonists and p65 antagonists on Nrf2 ( A ), HO-1 ( B ), p-iκb ( C ), p-p65 ( D ) protein level of bursal B-lymphocyte in response to LPS in the G→B group. SR3335 is a RORα antagonist; SR1078 is a RORα agonist; GSK1981278 is a RORγ antagonist; ML385 is an NRF2 antagonist; BAY is a p65 antagonist. Differences between seven light treatment groups were evaluated by one-way ANOVA, and values with no common letters differ significantly ( p < 0.05).

Article Snippet: In addition, bursal B lymphocytes of the G→B group were prepared with either RORα antagonist (SR3335, 5 μM, MCE, Weehawken, NJ, USA), RORα agonist (SR1078, 10 μM, MCE, Weehawken, NJ, USA), RORγ antagonist (GSK2981278, 1 μM, MCE, Weehawken, NJ, USA), Nrf2 antagonist (ML385, 5 μM, MCE, Weehawken, NJ, USA), Nfκb antagonist (BAY, 1 μM, MCE, Weehawken, NJ, USA) for 30 min before the addition of LPS and melatonin.

Techniques:

Journal: Antioxidants

Article Title: Melatonin Nuclear Receptors Mediate Green-and-Blue-Monochromatic-Light-Combinations-Inhibited B Lymphocyte Apoptosis in the Bursa of Chickens via Reducing Oxidative Stress and Nfκb Expression

doi: 10.3390/antiox11040748

Figure Lengend Snippet: Effects of RORα antagonists, RORα agonist, RORγ antagonist, Nrf2 antagonists and p65 antagonists on pro-inflammatory cytokine TNF-α ( A ), IFN-γ ( B ), IL-6 ( C ), anti-inflammatory cytokine IL-10 ( D ) level of bursal B-lymphocyte in response to LPS in the G→B group. SR3335 is a RORα antagonist; SR1078 is a RORα agonist; GSK1981278 is a RORγ antagonist; ML385 is an NRF2 antagonist; BAY is a p65 antagonist. Differences between seven light treatment groups were evaluated by one-way ANOVA, and values with no common letters differ significantly ( p < 0.05).

Article Snippet: In addition, bursal B lymphocytes of the G→B group were prepared with either RORα antagonist (SR3335, 5 μM, MCE, Weehawken, NJ, USA), RORα agonist (SR1078, 10 μM, MCE, Weehawken, NJ, USA), RORγ antagonist (GSK2981278, 1 μM, MCE, Weehawken, NJ, USA), Nrf2 antagonist (ML385, 5 μM, MCE, Weehawken, NJ, USA), Nfκb antagonist (BAY, 1 μM, MCE, Weehawken, NJ, USA) for 30 min before the addition of LPS and melatonin.

Techniques: