alisol b  (MedChemExpress)

Journal: CNS Neuroscience & Therapeutics

Article Title: ShenQi DiHuang Decoction (SQDHD) Ameliorates Neuroinflammation and Neuropsychiatric Manifestations in Pristane Induced Lupus Mice via Blocking JAK1‐STAT3 Pathway

doi: 10.1002/cns.70814

Figure Lengend Snippet: Analysis and identification of the primary active compounds of SQDHD against NPSLE. (A) CT network. Red denotes the five primary active compounds of SQDHD (Alisol B Acetate, Hederagenin, Ellagic acid, Wogonin, and Quercetin) with the highest degree values. Pink denotes the top 15 targets. Gray denotes compounds with lower degree values with their associated targets. (B) Heatmap of docking scores. Identification of the binding affinities between the five primary active compounds, Upadacitinib, and the nine targets enriched in the JAK–STAT pathway. (C) Representative images of docking complexes. The 3D structures of JAK1 in complex with the five primary active compounds and Upadacitinib at the same or proximal binding sites. (D) Representative western blot bands from CETSA. Quantitative analysis of JAK1. (E) Representative western blot bands from DARTS assay. Quantitative analysis of JAK1. Data are expressed as mean ± SEM ( n = 3 per group). Statistical analysis was conducted using One‐way ANOVA followed by Tukey's post hoc test. * p < 0.05 or ** p < 0.01.

Article Snippet: Subsequently, the cells were pretreated with serum‐free culture medium, SQDHD, Upadacitinib (1 μM), SQDHD + Colivelin (1 μM, MCE), Alisol B Acetate or Hederagenin for 2 h. After pretreatment, serum from either control or PIL mice was introduced, and the cells were harvested 24 h later.

Techniques: Binding Assay, Western Blot

Journal: CNS Neuroscience & Therapeutics

Article Title: ShenQi DiHuang Decoction (SQDHD) Ameliorates Neuroinflammation and Neuropsychiatric Manifestations in Pristane Induced Lupus Mice via Blocking JAK1‐STAT3 Pathway

doi: 10.1002/cns.70814

Figure Lengend Snippet: Effects and mechanisms of Alisol B Acetate or Hederagenin on bEnd.3 cells and primary endothelial cells induced by lupus serum. (A–D) Cell viability assessment. Quantitative analysis of varying concentrations of Alisol B Acetate or Hederagenin in both bEnd.3 cells and primary endothelial cells. (E–H) Representative western blot bands of JAK1, p‐JAK1, STAT3, and p‐STAT3 in bEnd.3 cells or primary endothelial cells treated with Alisol B Acetate or Hederagenin. Quantitative analysis of the ratios of p‐JAK1/JAK1 and p‐STAT3/STAT3. (I–L) Representative western blot bands of VCAM‐1 and P‐selectin in bEnd.3 cells or primary endothelial cells treated with Alisol B Acetate or Hederagenin. Data are expressed as mean ± SEM ( n = 3 per group). Statistical analysis was conducted using One‐way ANOVA followed by Tukey's post hoc test. Cell viability assessment: * p < 0.05 or ** p < 0.01 vs. 0 μM Alisol B Acetate or 0 μM Hederagenin. Western blot test: ## p < 0.01 vs. Ctrl serum group, * p < 0.05 or ** p < 0.01 vs. lupus serum group.

Article Snippet: Subsequently, the cells were pretreated with serum‐free culture medium, SQDHD, Upadacitinib (1 μM), SQDHD + Colivelin (1 μM, MCE), Alisol B Acetate or Hederagenin for 2 h. After pretreatment, serum from either control or PIL mice was introduced, and the cells were harvested 24 h later.

Techniques: Western Blot

Journal: Nutrients

Article Title: Alisol B Alleviates Hepatocyte Lipid Accumulation and Lipotoxicity via Regulating RARα-PPARγ-CD36 Cascade and Attenuates Non-Alcoholic Steatohepatitis in Mice

doi: 10.3390/nu14122411

Figure Lengend Snippet: Alisol B ameliorated NASH in a DIO+CCl 4 -induced murine model. ( A ) The chemical structure of Alisol B. The therapeutic effects of Alisol B (100 mg/kg, once daily, p.o.) were evaluated in DIO+CCl 4 -induced mice as described in the Materials and Methods. ( B ) Body weight and ( C ) average food intake were measured. ( D ) H&E staining (200× magnification) and Sirius Red staining (100× magnification) were performed. ( E ) NAS score, steatosis score, ballooning score, and inflammation score were quantified. ( F ) Liver TG, ( G ) serum ALT and ( H ) AST, ( I ) hepatic mRNA levels of inflammatory cytokines, ( J ) hepatic MDA, and ( K ) GSH levels were measured. ( L ) Percentage of collagen deposition was calculated. ( M ) Western blot analysis of hepatic α-SMA and Col-1a1 expression was conducted and quantified. Data are presented as the mean ± SD, n = 8. # p < 0.05, ## p < 0.01 compared with the normal control group; * p < 0.05, ** p < 0.01 compared with the DIO+CCl 4 group.

Article Snippet: Then, the mice were orally administered with Alisol B, obeticholic acid (OCA, purity > 98%, Cat#HY-12222, MedChemExpress, Monmouth Junction, NJ, USA), or vehicle (0.25% CMC-Na, w / v ) once daily, and intraperitoneally injected with CCl 4 (0.05 mL/kg, Aladdin, Shanghai, China) or vehicle (olive oil) twice weekly for further 5 weeks.

Techniques: Staining, Western Blot, Expressing, Control

Journal: Nutrients

Article Title: Alisol B Alleviates Hepatocyte Lipid Accumulation and Lipotoxicity via Regulating RARα-PPARγ-CD36 Cascade and Attenuates Non-Alcoholic Steatohepatitis in Mice

doi: 10.3390/nu14122411

Figure Lengend Snippet: Alisol B ameliorated NASH in a CDA diet-induced murine model. The therapeutic effects of Alisol B (100 mg/kg, once daily, p.o.) were evaluated in CDA diet-fed mice as described in the Materials and Methods. ( A ) Body weight and ( B ) average food intake were measured. ( C ) H&E staining (200× magnification) and Sirius Red staining (100× magnification) were performed. ( D ) NAS score, steatosis score, ballooning score, and inflammation score were quantified. ( E ) Serum AST and ( F ) ALT levels, ( G ) liver TG, and ( H ) hepatic mRNA levels of inflammatory cytokines were measured. ( I ) Percentage of collagen deposition was calculated. ( J ) Western blot analysis of hepatic α-SMA and Col-1a1 was conducted and quantified. Data are expressed as mean ± SD, n = 8. # p < 0.05, ## p < 0.01 compared with the normal control group; * p < 0.05, ** p < 0.01 compared with the CDA group.

Article Snippet: Then, the mice were orally administered with Alisol B, obeticholic acid (OCA, purity > 98%, Cat#HY-12222, MedChemExpress, Monmouth Junction, NJ, USA), or vehicle (0.25% CMC-Na, w / v ) once daily, and intraperitoneally injected with CCl 4 (0.05 mL/kg, Aladdin, Shanghai, China) or vehicle (olive oil) twice weekly for further 5 weeks.

Techniques: Staining, Western Blot, Control

Journal: Nutrients

Article Title: Alisol B Alleviates Hepatocyte Lipid Accumulation and Lipotoxicity via Regulating RARα-PPARγ-CD36 Cascade and Attenuates Non-Alcoholic Steatohepatitis in Mice

doi: 10.3390/nu14122411

Figure Lengend Snippet: Alisol B ameliorated cellular TG accumulation in primary hepatocytes by inhibiting FFA uptake in a CD36-dependent manner. Mouse primary hepatocytes were incubated with indicated concentration of Alisol B under PA (0.2 mM)-stimulated condition. ( A ) RT-PCR analysis and ( B ) Western blot analysis of CD36 expression, ( C ) BODIPY-C16 fluorescence (600× magnification), ( D ) cellular TG, and ( E ) Oil Red O staining (200× magnification) were conducted. ( F – H ) Primary hepatocytes were pretreated with CD36 siRNA for 24 h and then treated with Alisol B (10 μM) under PA-induced conditions. ( F ) CD36 mRNA level, ( G ) BODIPY-C16 fluorescence (600× magnification), and ( H ) cellular TG were examined. Data are expressed as mean ± SD, n = 5. # p < 0.05, ## p < 0.01 compared with the normal control group; * p < 0.05, ** p < 0.01 compared with the PA-induced group.

Article Snippet: Then, the mice were orally administered with Alisol B, obeticholic acid (OCA, purity > 98%, Cat#HY-12222, MedChemExpress, Monmouth Junction, NJ, USA), or vehicle (0.25% CMC-Na, w / v ) once daily, and intraperitoneally injected with CCl 4 (0.05 mL/kg, Aladdin, Shanghai, China) or vehicle (olive oil) twice weekly for further 5 weeks.

Techniques: Incubation, Concentration Assay, Reverse Transcription Polymerase Chain Reaction, Western Blot, Expressing, Fluorescence, Staining, Control

Journal: Nutrients

Article Title: Alisol B Alleviates Hepatocyte Lipid Accumulation and Lipotoxicity via Regulating RARα-PPARγ-CD36 Cascade and Attenuates Non-Alcoholic Steatohepatitis in Mice

doi: 10.3390/nu14122411

Figure Lengend Snippet: Alisol B inhibited oxidative stress and inflammation in primary hepatocytes in a CD36-dependent manner. Mouse primary hepatocytes were incubated with indicated concentration of Alisol B under PA (0.2 mM)-stimulated conditions. ( A ) Cellular ROS level; ( B ) the mRNA levels of IL-1β, IL-6, and TNF-α; and ( C ) JNK1/2 and NF-κB phosphorylation were detected. ( D – F ) Primary hepatocytes were pretreated with CD36 siRNA for 24 h and then treated with Alisol B (10 μM) under PA-induced conditions. ( D ) Cellular ROS; ( E ) the mRNA levels of IL-1β, IL-6, and TNF-α; and ( F ) JNK1/2 and NF-κB phosphorylation were detected. Data are expressed as mean ± SD, n = 5 for all of the groups, except for n = 6 in Figure ( F ). # p < 0.05 compared with the normal control group; * p < 0.05, ** p < 0.01 compared with the PA-induced group.

Article Snippet: Then, the mice were orally administered with Alisol B, obeticholic acid (OCA, purity > 98%, Cat#HY-12222, MedChemExpress, Monmouth Junction, NJ, USA), or vehicle (0.25% CMC-Na, w / v ) once daily, and intraperitoneally injected with CCl 4 (0.05 mL/kg, Aladdin, Shanghai, China) or vehicle (olive oil) twice weekly for further 5 weeks.

Techniques: Incubation, Concentration Assay, Phospho-proteomics, Control

Journal: Nutrients

Article Title: Alisol B Alleviates Hepatocyte Lipid Accumulation and Lipotoxicity via Regulating RARα-PPARγ-CD36 Cascade and Attenuates Non-Alcoholic Steatohepatitis in Mice

doi: 10.3390/nu14122411

Figure Lengend Snippet: Alisol B suppressed CD36 expression through downregulating PPARγ, and this effect was independent of FXR. ( A ) The mRNA expression of hepatic LXR, PXR, AHR, PPARγ, and their target genes were examined in DIO+CCl 4 -induced NASH mice. ( B ) The gene expression of PPARγ was measured in PA-induced primary hepatocytes treated with Alisol B. ( C ) Huh7 cells were transiently transfected and then treated with Alisol B (10 μM) in the presence of Rosiglitazone. The transactivation activity of PPARγ was detected in luciferase reporter assay. ( D – G ) Mouse primary hepatocytes were treated with Alisol B (10 μM) and Rosiglitazone (10 μM) under PA-stimulated conditions. ( D ) CD36 mRNA level, € BODIPY-C16 fluorescence (600× magnification), ( F ) cellular TG, and ( G ) cellular ROS were evaluated. ( H ) Huh7 cells were transiently transfected and then treated with Alisol B. The agonistic activity on FXR was detected in luciferase reporter assay. ( I ) The mRNA levels of FXR and CD36 in FXR knockdown hepatocytes treated with Alisol B (10 μM) were detected. ( J ) The mRNA level of CD36 in hepatocytes treated with Alisol B (10 μM) in the presence of Gugglusterone (10 μM) was detected. Data in ( A ) are expressed as mean ± SD, n = 8. * p < 0.05, ** p < 0.01 compared with DIO+CCl 4 group. Data in ( B – H ) are expressed as mean ± SD, n = 5. # p < 0.05, ## p < 0.01 compared with normal control group; * p < 0.05, ** p < 0.01 compared with the PA-induced group or Rosiglitazone-induced group. Data in (I,J) are expressed as mean ± SD, n = 5. ** p < 0.01 compared with the normal control group.

Article Snippet: Then, the mice were orally administered with Alisol B, obeticholic acid (OCA, purity > 98%, Cat#HY-12222, MedChemExpress, Monmouth Junction, NJ, USA), or vehicle (0.25% CMC-Na, w / v ) once daily, and intraperitoneally injected with CCl 4 (0.05 mL/kg, Aladdin, Shanghai, China) or vehicle (olive oil) twice weekly for further 5 weeks.

Techniques: Expressing, Gene Expression, Transfection, Activity Assay, Luciferase, Reporter Assay, Fluorescence, Knockdown, Control

Journal: Nutrients

Article Title: Alisol B Alleviates Hepatocyte Lipid Accumulation and Lipotoxicity via Regulating RARα-PPARγ-CD36 Cascade and Attenuates Non-Alcoholic Steatohepatitis in Mice

doi: 10.3390/nu14122411

Figure Lengend Snippet: Alisol B decreased CD36 expression and attenuated hepatocyte lipid accumulation and lipotoxicity via regulating RARα-HNF4α-PPARγ cascade. ( A ) HEK293 cells were transient transfected and then treated with Alisol B. The agonistic activity on RARα was detected in luciferase reporter assay. ( B ) The gene expression of RARα was detected. ( C ) The mRNA levels of RARα, HNF4α, PPARγ, and CD36 were measured in hepatocytes treated with Alisol B (10 μM). ( D – G ) Primary hepatocytes were transfected with RARα siRNA for 24 h and then treated with Alisol B (10 μM). ( D ) The mRNA levels of RARα, HNF4α, PPARγ, and CD36; ( E ) BODIPY-C16 fluorescence (600× magnification); ( F ) cellular TG; and ( G ) cellular ROS were detected. ( H – K ) Primary hepatocytes were overexpressed with RARα via transient plasmid transfection for 24 h. ( H ) The mRNA levels of RARα, HNF4α, PPARγ, and CD36; ( I ) BODIPY-C16 fluorescence (600× magnification); ( J ) cellular TG; and ( K ) cellular ROS were conducted. Data are expressed as mean ± SD, n = 5. In ( F , G , J , K ), ## p < 0.01 compared with normal control group; * p < 0.05, ** p < 0.01 compared with the PA-induced group. In the other figures, * p < 0.05, ** p < 0.01 compared with the normal control group.

Article Snippet: Then, the mice were orally administered with Alisol B, obeticholic acid (OCA, purity > 98%, Cat#HY-12222, MedChemExpress, Monmouth Junction, NJ, USA), or vehicle (0.25% CMC-Na, w / v ) once daily, and intraperitoneally injected with CCl 4 (0.05 mL/kg, Aladdin, Shanghai, China) or vehicle (olive oil) twice weekly for further 5 weeks.

Techniques: Expressing, Transfection, Activity Assay, Luciferase, Reporter Assay, Gene Expression, Fluorescence, Plasmid Preparation, Control

Journal: Nutrients

Article Title: Alisol B Alleviates Hepatocyte Lipid Accumulation and Lipotoxicity via Regulating RARα-PPARγ-CD36 Cascade and Attenuates Non-Alcoholic Steatohepatitis in Mice

doi: 10.3390/nu14122411

Figure Lengend Snippet: Alisol B regulated RARα-mediated transcriptional cascade and inhibited JNK/NF-κB signaling pathway in NASH mice. Hepatic mRNA levels of RARα, HNF4α, and PPARγ were examined in ( A ) DIO+CCl 4 -induced NASH mice and ( B ) CDA diet-induced NASH mice. JNK1/2 and NF-κB phosphorylation were detected in ( C ) DIO+CCl 4 -induced NASH mice and ( D ) CDA-diet-induced NASH mice. Data are expressed as mean ± SD, n = 8. # p < 0.05, ## p < 0.01 compared with the normal control group; * p < 0.05, ** p < 0.01 compared with the DIO+CCl 4 group or CDA group.

Article Snippet: Then, the mice were orally administered with Alisol B, obeticholic acid (OCA, purity > 98%, Cat#HY-12222, MedChemExpress, Monmouth Junction, NJ, USA), or vehicle (0.25% CMC-Na, w / v ) once daily, and intraperitoneally injected with CCl 4 (0.05 mL/kg, Aladdin, Shanghai, China) or vehicle (olive oil) twice weekly for further 5 weeks.

Techniques: Phospho-proteomics, Control