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12031a h89 mce cat  (MedChemExpress)


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    Structured Review

    MedChemExpress 12031a h89 mce cat
    12031a H89 Mce Cat, supplied by MedChemExpress, used in various techniques. Bioz Stars score: 97/100, based on 226 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
    https://www.bioz.com/product/h+89/H-89/pm42585016-166-130-132
    Average 97 stars, based on 226 article reviews
    12031a h89 mce cat - by Bioz Stars, 2026-09
    97/100 stars

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    Related Articles

    Inhibition:

    Article Title: CaRPOOL: a pooled calcium‑recording CRISPR screening platform identifies CCR7 as a modulator of cellular osmomechanosensing
    Article Snippet: .. For adenylyl cyclase or protein kinase A inhibition, cells were seeded and incubated overnight, then treated with SQ22536 (100 μM; MCE, HY‐100396) or H‐89 (10 μM; MCE, HY‐15979) for 2 h prior to experiments. .. For adenylyl cyclase activation, cells were treated with forskolin (20 μM; SelleckChem, S2449) for 5 s immediately before stimulation.

    Incubation:

    Article Title: CaRPOOL: a pooled calcium‑recording CRISPR screening platform identifies CCR7 as a modulator of cellular osmomechanosensing
    Article Snippet: .. For adenylyl cyclase or protein kinase A inhibition, cells were seeded and incubated overnight, then treated with SQ22536 (100 μM; MCE, HY‐100396) or H‐89 (10 μM; MCE, HY‐15979) for 2 h prior to experiments. .. For adenylyl cyclase activation, cells were treated with forskolin (20 μM; SelleckChem, S2449) for 5 s immediately before stimulation.

    Control:

    Article Title: Activation of the TGR5/cAMP/PKA/CREB axis in cholangiocytes mediates epithelial-mesenchymal transition and fibrosis in hepatolithiasis
    Article Snippet: When cell confluence reached approximately 70–80%, cells were treated with 500 μM taurodeoxycholic acid (TDCA; Sigma, Cat# T4009) for 24 h to establish a bile acid-induced biliary fibrosis model. Each condition was tested in triplicate, and the entire experiment was independently repeated twice to ensure reproducibility and data reliability. .. Based on the TDCA-induced cholangiocyte fibrosis cell model, additional pharmacological intervention groups were established as follows (3 technical replicates per group; each experiment was independently repeated twice): Control group (Control): no TDCA induction and no drug treatment; Model group (Model): treated with 500 μM TDCA for 24 h; Forskolin treatment group (Model + Forskolin): cells were co-treated with 500 μM TDCA and 50 μM forskolin (HY-15371, MCE) for 24 h [ ]; H-89 treatment group (Model + H-89): cells were co-treated with 500 μM TDCA and 100 μM H-89 (HY-15979, MCE) for 24 h [ ]; Combined treatment group (Model + Forskolin + H-89): cells were co-treated with 500 μM TDCA, 50 μM forskolin, and 100 μM H-89 for 24 h; TGR5 inhibitor combination group (Model + SBI-115 + Forskolin): cells were co-treated with 500 μM TDCA, 10 μM SBI-115 (TGR5 inhibitor), and 50 μM forskolin for 24 h. ..

    Article Title: Activation of the TGR5/cAMP/PKA/CREB axis in cholangiocytes mediates epithelial-mesenchymal transition and fibrosis in hepatolithiasis.
    Article Snippet: When cell 244 confluence reached approximately 70-80%, cells were treated with 500 μM taurodeoxycholic acid 245 (TDCA; Sigma, Cat# T4009) for 24 hours to establish a bile acid-induced biliary fibrosis model. 246 Each condition was tested in triplicate, and the entire experiment was independently repeated twice 247 to ensure reproducibility and data reliability. .. 248 249 AR TIC LE IN PR ES S H-89 and forskolin treatment 250 Based on the TDCA-induced cholangiocyte fibrosis cell model, additional pharmacological 251 intervention groups were established as follows (3 technical replicates per group; each experiment 252 was independently repeated twice):Control group (Control): no TDCA induction and no drug 253 treatment; Model group (Model): treated with 500 μM TDCA for 24 h; Forskolin treatment group 254 (Model + Forskolin): cells were co-treated with 500 μM TDCA and 50 μM forskolin (HY-15371, 255 MCE) for 24 h [19]; H-89 treatment group (Model + H-89): cells were co-treated with 500 μM 256 TDCA and 100 μM H-89 (HY-15979, MCE) for 24 h [20]; Combined treatment group (Model + 257 Forskolin + H-89): cells were co-treated with 500 μM TDCA, 50 μM forskolin, and 100 μM H-89 258 for 24 h; TGR5 inhibitor combination group (Model + SBI-115 + Forskolin): cells were co-treated 259 with 500 μM TDCA, 10 μM SBI-115 (TGR5 inhibitor), and 50 μM forskolin for 24 h. 260 261 CCK-8 Assay 262 HIBECs were digested and seeded into 96-well plates at a density of 1 × 104 cells per well, with 263 three technical replicates per group. .. After incubation at 37°C with 5% CO2 for 4-6 hours to allow 264 adherence, cells were treated with various concentrations of the following compounds: TDCA 265 (Sigma, Cat# T4009; 250, 500, 1000 μM), TGR5 agonist hyodeoxycholic acid (HDCA; 266 MedChemExpress, Cat# HY-113554; 50, 100, 200 μM), and TGR5 inhibitor SBI-115 (Sigma, Cat# 267 SML1790; 5, 10, 20 μM).

    Injection:

    Article Title: Therapeutic effects of alprostadil on CCl 4 -induced hepatic fibrosis in rats and investigation of its molecular mechanisms.
    Article Snippet: Extended author information available on the last page of the article Abstract Hepatic fibrosis (HF) is driven by hepatic stellate cell (HSC) activation.. Although cyclic adenosine monophosphate (cAMP) is a key antifibrotic signal, whether pharmacological cAMP elevation acts through protein kinase A (PKA) or exchange protein directly activated by cAMP 1 (EPAC1) remains unclear.. Alprostadil (PGE1) elevates intracellular cAMP, but its antifibrotic mechanism is undefined.

    CCK-8 Assay:

    Article Title: Therapeutic effects of alprostadil on CCl 4 -induced hepatic fibrosis in rats and investigation of its molecular mechanisms.
    Article Snippet: Extended author information available on the last page of the article Abstract Hepatic fibrosis (HF) is driven by hepatic stellate cell (HSC) activation.. Although cyclic adenosine monophosphate (cAMP) is a key antifibrotic signal, whether pharmacological cAMP elevation acts through protein kinase A (PKA) or exchange protein directly activated by cAMP 1 (EPAC1) remains unclear.. Alprostadil (PGE1) elevates intracellular cAMP, but its antifibrotic mechanism is undefined.

    Article Title: Activation of the TGR5/cAMP/PKA/CREB axis in cholangiocytes mediates epithelial-mesenchymal transition and fibrosis in hepatolithiasis.
    Article Snippet: When cell 244 confluence reached approximately 70-80%, cells were treated with 500 μM taurodeoxycholic acid 245 (TDCA; Sigma, Cat# T4009) for 24 hours to establish a bile acid-induced biliary fibrosis model. 246 Each condition was tested in triplicate, and the entire experiment was independently repeated twice 247 to ensure reproducibility and data reliability. .. 248 249 AR TIC LE IN PR ES S H-89 and forskolin treatment 250 Based on the TDCA-induced cholangiocyte fibrosis cell model, additional pharmacological 251 intervention groups were established as follows (3 technical replicates per group; each experiment 252 was independently repeated twice):Control group (Control): no TDCA induction and no drug 253 treatment; Model group (Model): treated with 500 μM TDCA for 24 h; Forskolin treatment group 254 (Model + Forskolin): cells were co-treated with 500 μM TDCA and 50 μM forskolin (HY-15371, 255 MCE) for 24 h [19]; H-89 treatment group (Model + H-89): cells were co-treated with 500 μM 256 TDCA and 100 μM H-89 (HY-15979, MCE) for 24 h [20]; Combined treatment group (Model + 257 Forskolin + H-89): cells were co-treated with 500 μM TDCA, 50 μM forskolin, and 100 μM H-89 258 for 24 h; TGR5 inhibitor combination group (Model + SBI-115 + Forskolin): cells were co-treated 259 with 500 μM TDCA, 10 μM SBI-115 (TGR5 inhibitor), and 50 μM forskolin for 24 h. 260 261 CCK-8 Assay 262 HIBECs were digested and seeded into 96-well plates at a density of 1 × 104 cells per well, with 263 three technical replicates per group. .. After incubation at 37°C with 5% CO2 for 4-6 hours to allow 264 adherence, cells were treated with various concentrations of the following compounds: TDCA 265 (Sigma, Cat# T4009; 250, 500, 1000 μM), TGR5 agonist hyodeoxycholic acid (HDCA; 266 MedChemExpress, Cat# HY-113554; 50, 100, 200 μM), and TGR5 inhibitor SBI-115 (Sigma, Cat# 267 SML1790; 5, 10, 20 μM).

    Reverse Transcription:

    Article Title: Therapeutic effects of alprostadil on CCl 4 -induced hepatic fibrosis in rats and investigation of its molecular mechanisms.
    Article Snippet: Extended author information available on the last page of the article Abstract Hepatic fibrosis (HF) is driven by hepatic stellate cell (HSC) activation.. Although cyclic adenosine monophosphate (cAMP) is a key antifibrotic signal, whether pharmacological cAMP elevation acts through protein kinase A (PKA) or exchange protein directly activated by cAMP 1 (EPAC1) remains unclear.. Alprostadil (PGE1) elevates intracellular cAMP, but its antifibrotic mechanism is undefined.

    Real-time Polymerase Chain Reaction:

    Article Title: Therapeutic effects of alprostadil on CCl 4 -induced hepatic fibrosis in rats and investigation of its molecular mechanisms.
    Article Snippet: Extended author information available on the last page of the article Abstract Hepatic fibrosis (HF) is driven by hepatic stellate cell (HSC) activation.. Although cyclic adenosine monophosphate (cAMP) is a key antifibrotic signal, whether pharmacological cAMP elevation acts through protein kinase A (PKA) or exchange protein directly activated by cAMP 1 (EPAC1) remains unclear.. Alprostadil (PGE1) elevates intracellular cAMP, but its antifibrotic mechanism is undefined.

    Lysis:

    Article Title: Therapeutic effects of alprostadil on CCl 4 -induced hepatic fibrosis in rats and investigation of its molecular mechanisms.
    Article Snippet: Extended author information available on the last page of the article Abstract Hepatic fibrosis (HF) is driven by hepatic stellate cell (HSC) activation.. Although cyclic adenosine monophosphate (cAMP) is a key antifibrotic signal, whether pharmacological cAMP elevation acts through protein kinase A (PKA) or exchange protein directly activated by cAMP 1 (EPAC1) remains unclear.. Alprostadil (PGE1) elevates intracellular cAMP, but its antifibrotic mechanism is undefined.

    Protease Inhibitor:

    Article Title: Therapeutic effects of alprostadil on CCl 4 -induced hepatic fibrosis in rats and investigation of its molecular mechanisms.
    Article Snippet: Extended author information available on the last page of the article Abstract Hepatic fibrosis (HF) is driven by hepatic stellate cell (HSC) activation.. Although cyclic adenosine monophosphate (cAMP) is a key antifibrotic signal, whether pharmacological cAMP elevation acts through protein kinase A (PKA) or exchange protein directly activated by cAMP 1 (EPAC1) remains unclear.. Alprostadil (PGE1) elevates intracellular cAMP, but its antifibrotic mechanism is undefined.

    Bicinchoninic Acid Protein Assay:

    Article Title: Therapeutic effects of alprostadil on CCl 4 -induced hepatic fibrosis in rats and investigation of its molecular mechanisms.
    Article Snippet: Extended author information available on the last page of the article Abstract Hepatic fibrosis (HF) is driven by hepatic stellate cell (HSC) activation.. Although cyclic adenosine monophosphate (cAMP) is a key antifibrotic signal, whether pharmacological cAMP elevation acts through protein kinase A (PKA) or exchange protein directly activated by cAMP 1 (EPAC1) remains unclear.. Alprostadil (PGE1) elevates intracellular cAMP, but its antifibrotic mechanism is undefined.

    SDS Page:

    Article Title: Therapeutic effects of alprostadil on CCl 4 -induced hepatic fibrosis in rats and investigation of its molecular mechanisms.
    Article Snippet: Extended author information available on the last page of the article Abstract Hepatic fibrosis (HF) is driven by hepatic stellate cell (HSC) activation.. Although cyclic adenosine monophosphate (cAMP) is a key antifibrotic signal, whether pharmacological cAMP elevation acts through protein kinase A (PKA) or exchange protein directly activated by cAMP 1 (EPAC1) remains unclear.. Alprostadil (PGE1) elevates intracellular cAMP, but its antifibrotic mechanism is undefined.

    Immunoprecipitation:

    Article Title: Therapeutic effects of alprostadil on CCl 4 -induced hepatic fibrosis in rats and investigation of its molecular mechanisms.
    Article Snippet: Extended author information available on the last page of the article Abstract Hepatic fibrosis (HF) is driven by hepatic stellate cell (HSC) activation.. Although cyclic adenosine monophosphate (cAMP) is a key antifibrotic signal, whether pharmacological cAMP elevation acts through protein kinase A (PKA) or exchange protein directly activated by cAMP 1 (EPAC1) remains unclear.. Alprostadil (PGE1) elevates intracellular cAMP, but its antifibrotic mechanism is undefined.

    Magnetic Beads:

    Article Title: Therapeutic effects of alprostadil on CCl 4 -induced hepatic fibrosis in rats and investigation of its molecular mechanisms.
    Article Snippet: Extended author information available on the last page of the article Abstract Hepatic fibrosis (HF) is driven by hepatic stellate cell (HSC) activation.. Although cyclic adenosine monophosphate (cAMP) is a key antifibrotic signal, whether pharmacological cAMP elevation acts through protein kinase A (PKA) or exchange protein directly activated by cAMP 1 (EPAC1) remains unclear.. Alprostadil (PGE1) elevates intracellular cAMP, but its antifibrotic mechanism is undefined.

    Enzyme-linked Immunosorbent Assay:

    Article Title: Therapeutic effects of alprostadil on CCl 4 -induced hepatic fibrosis in rats and investigation of its molecular mechanisms.
    Article Snippet: Extended author information available on the last page of the article Abstract Hepatic fibrosis (HF) is driven by hepatic stellate cell (HSC) activation.. Although cyclic adenosine monophosphate (cAMP) is a key antifibrotic signal, whether pharmacological cAMP elevation acts through protein kinase A (PKA) or exchange protein directly activated by cAMP 1 (EPAC1) remains unclear.. Alprostadil (PGE1) elevates intracellular cAMP, but its antifibrotic mechanism is undefined.

    AST Assay:

    Article Title: Therapeutic effects of alprostadil on CCl 4 -induced hepatic fibrosis in rats and investigation of its molecular mechanisms.
    Article Snippet: Extended author information available on the last page of the article Abstract Hepatic fibrosis (HF) is driven by hepatic stellate cell (HSC) activation.. Although cyclic adenosine monophosphate (cAMP) is a key antifibrotic signal, whether pharmacological cAMP elevation acts through protein kinase A (PKA) or exchange protein directly activated by cAMP 1 (EPAC1) remains unclear.. Alprostadil (PGE1) elevates intracellular cAMP, but its antifibrotic mechanism is undefined.

    Western Blot:

    Article Title: Therapeutic effects of alprostadil on CCl 4 -induced hepatic fibrosis in rats and investigation of its molecular mechanisms.
    Article Snippet: Extended author information available on the last page of the article Abstract Hepatic fibrosis (HF) is driven by hepatic stellate cell (HSC) activation.. Although cyclic adenosine monophosphate (cAMP) is a key antifibrotic signal, whether pharmacological cAMP elevation acts through protein kinase A (PKA) or exchange protein directly activated by cAMP 1 (EPAC1) remains unclear.. Alprostadil (PGE1) elevates intracellular cAMP, but its antifibrotic mechanism is undefined.

    other:

    Article Title: Propranolol alleviates cerebral infarction through the β2-AR-mediated ERK/NLRP3 pathway
    Article Snippet: H-89 , MCE , Cat# HY-15979A.



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    PKA inhibition by <t>H89</t> abolishes the neuroprotective and antidepressant effects of NDP-MSH. (A) Experimental timeline and grouping strategy. Mice were assigned to Vehicle, LPS, LPS + NDP-MSH(NDP), LPS + NDP-MSH + H89(LNH), or H89 groups. (B) Representative locomotor traces in the OFT. (C) Behavioral assessments. NDP-MSH significantly increased sucrose preference in LPS-treated mice, whereas H89 co-treatment abolished this effect in the SPT. (One-way ANOVA, F (4, 41) = 13.96, p < 0.0001, followed by Tukey’s multiple comparisons test. Vehicle vs. LPS: q (41) = 6.649, p < 0.001; Vehicle vs. LNH: q (41) = 6.804, p < 0.001; LPS vs. NDP: q (41) = 4.128, p < 0.05; NDP vs. LNH: q (41) = 4.237, p < 0.05). NDP-MSH restored total distance traveled reduced by LPS; H89 partly reversed this improvement in the OFT (One-way ANOVA, F (4, 41) = 29.92, p < 0.0001, followed by Tukey’s multiple comparisons test. Vehicle vs. LPS: q (41) = 13.07, p < 0.0001; Vehicle vs. NDP: q (41) = 7.823, p < 0.0001; Vehicle vs. LNH: q (41) = 11.660, p < 0.0001; LPS vs. NDP, q (41) = 5.225, p < 0.01). NDP-MSH partly restored central zone entries reduced by LPS; H89 partly reversed this improvement in the OFT (Kruskal-Wallis non-parametric test, H (4) = 30.23, p < 0.0001, followed by Dunn's multiple comparisons test. Vehicle vs. LPS: Z = 4.745, p < 0.0001; Vehicle vs. NDP: Z = 2.600, p = 0.093; Vehicle vs. LNH: Z = 3.924, p < 0.0001; H89 vs. LPS: Z = 3.615, p < 0.01) (Veh, n = 8; H89, n = 8; LPS, n = 10; NDP, n = 9; LNH, n = 11). (D) ELISA quantification of IL-1β levels in the PFC. NDP-MSH reversed LPS-induced IL-1β elevation, whereas H89 prevented this effect (One-way ANOVA, F (4, 25) = 18.02, p < 0.0001, followed by Tukey’s multiple comparisons test. Vehicle vs. LPS, q (25) = 9.990, p < 0.0001; Vehicle vs. LNH: q (25) = 6.190, p < 0.01; LPS vs. NDP, q (25) = 8.350, p < 0.0001; NDP vs. LNH, q (25) = 4.549, p < 0.05) (n = 6 mice per group). (E) Representative images of mPFC neuronal dendrites by Golgi-Cox staining. Scale bar = 20 μm. Column graphs illustrate the relative spine numbers. NDP-MSH significantly increased spine density reduced by LPS treatment, whereas co-treatment with the PKA inhibitor H89 abolished this restorative effect (One-way ANOVA, F (4, 20) = 36.61, p < 0.0001, followed by Tukey’s multiple comparisons test. Veh vs. LPS, q (20) = 13.07, p < 0.0001; Veh vs. NDP, q (20) = 6.820, p < 0.001; Veh vs. LNH, q (20) = 12.82, p < 0.0001; LPS vs. NDP, q (20) = 6.245, p < 0.01; NDP vs. LNH, q (20) = 5.995, p < 0.01) (n = 5 mice per group, with 4-6 sections per mouse; at least 10 dendritic segments were randomly selected and quantified per section). (F) Quantification of relative Iba-1 fluorescence intensity, NDP-MSH normalized LPS-evoked microglial activation; H89 co-treatment restored microglial density to LPS-like levels (One-way ANOVA, F (4, 10) = 19.57, p < 0.001, followed by Tukey’s multiple comparisons test. Veh vs. LPS, q (10) = 8.650, p < 0.001; Veh vs. LNH, q (10) = 8.412, p < 0.01; LPS vs. NDP, q (10) = 5.940, p < 0.05; NDP vs. LNH, q (10) = 5.702, p < 0.05) (n = 3 mice per group). (G) Representative immunofluorescence images of Iba-1 staining in the mPFC, Scale bar = 100 µm. Data are presented as mean ± SEM. *p < 0.05, **p < 0.01, ***p < 0.001. ****p < 0.0001. Source: BioRender.com .
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    MedChemExpress hy 15979a rapamycin sigma aldrich
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    97
    MedChemExpress h89
    Hesperetin and Naringenin increased cAMP level and [Ca 2+ ] i after glucose stimulation in murine L cells. (A,B) Intracellular cAMP levels from GLUTag cells in response to 10 μM Hesperetin (A) or 10 μM Naringenin (B) (n = 5). (C,D) GLP-1 secretion from GLUTag cells in response to 10 μM Hesperetin (C) or 10 μM Naringenin (D) with 10 μM <t>H89</t> or vehicle (n = 5). (E) The intracellular calcium concentration ([Ca 2+ ] i ) of GLUTag cells stimulated with 20 mM glucose plus vehicle or 10 μM Hesperetin was detected by using a Ca 2+ indicator, Fluo‐4 (n = 10). The change of fluorescence after stimulation was normalized to the basal fluorescence (ΔF/F 0 ) was measured by area under the curve (AUC). (F) GLP-1 secretion from GLUTag cells in response to 10 μM Hesperetin with 5 μM Nifedipine or vehicle (n = 5). (G) The intracellular calcium concentration ([Ca 2+ ] i ) of GLUTag cells stimulated with 20 mM glucose plus vehicle or 10 μM Naringenin was detected by using a Ca 2+ indicator, Fluo‐4 (n = 10). The change of fluorescence after stimulation was normalized to the basal fluorescence (ΔF/F 0 ). (H) GLP-1 secretion from GLUTag cells in response to 10 μM Naringenin with 5 μM Nifedipine or vehicle (n = 5). Black arrows indicated the initial time of glucose stimulation. ** p < 0.01, *** p < 0.001 by Mann-Whitney U-test, ns means not significant. Data are expressed as the mean ± SEM.
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    PKA inhibition by H89 abolishes the neuroprotective and antidepressant effects of NDP-MSH. (A) Experimental timeline and grouping strategy. Mice were assigned to Vehicle, LPS, LPS + NDP-MSH(NDP), LPS + NDP-MSH + H89(LNH), or H89 groups. (B) Representative locomotor traces in the OFT. (C) Behavioral assessments. NDP-MSH significantly increased sucrose preference in LPS-treated mice, whereas H89 co-treatment abolished this effect in the SPT. (One-way ANOVA, F (4, 41) = 13.96, p < 0.0001, followed by Tukey’s multiple comparisons test. Vehicle vs. LPS: q (41) = 6.649, p < 0.001; Vehicle vs. LNH: q (41) = 6.804, p < 0.001; LPS vs. NDP: q (41) = 4.128, p < 0.05; NDP vs. LNH: q (41) = 4.237, p < 0.05). NDP-MSH restored total distance traveled reduced by LPS; H89 partly reversed this improvement in the OFT (One-way ANOVA, F (4, 41) = 29.92, p < 0.0001, followed by Tukey’s multiple comparisons test. Vehicle vs. LPS: q (41) = 13.07, p < 0.0001; Vehicle vs. NDP: q (41) = 7.823, p < 0.0001; Vehicle vs. LNH: q (41) = 11.660, p < 0.0001; LPS vs. NDP, q (41) = 5.225, p < 0.01). NDP-MSH partly restored central zone entries reduced by LPS; H89 partly reversed this improvement in the OFT (Kruskal-Wallis non-parametric test, H (4) = 30.23, p < 0.0001, followed by Dunn's multiple comparisons test. Vehicle vs. LPS: Z = 4.745, p < 0.0001; Vehicle vs. NDP: Z = 2.600, p = 0.093; Vehicle vs. LNH: Z = 3.924, p < 0.0001; H89 vs. LPS: Z = 3.615, p < 0.01) (Veh, n = 8; H89, n = 8; LPS, n = 10; NDP, n = 9; LNH, n = 11). (D) ELISA quantification of IL-1β levels in the PFC. NDP-MSH reversed LPS-induced IL-1β elevation, whereas H89 prevented this effect (One-way ANOVA, F (4, 25) = 18.02, p < 0.0001, followed by Tukey’s multiple comparisons test. Vehicle vs. LPS, q (25) = 9.990, p < 0.0001; Vehicle vs. LNH: q (25) = 6.190, p < 0.01; LPS vs. NDP, q (25) = 8.350, p < 0.0001; NDP vs. LNH, q (25) = 4.549, p < 0.05) (n = 6 mice per group). (E) Representative images of mPFC neuronal dendrites by Golgi-Cox staining. Scale bar = 20 μm. Column graphs illustrate the relative spine numbers. NDP-MSH significantly increased spine density reduced by LPS treatment, whereas co-treatment with the PKA inhibitor H89 abolished this restorative effect (One-way ANOVA, F (4, 20) = 36.61, p < 0.0001, followed by Tukey’s multiple comparisons test. Veh vs. LPS, q (20) = 13.07, p < 0.0001; Veh vs. NDP, q (20) = 6.820, p < 0.001; Veh vs. LNH, q (20) = 12.82, p < 0.0001; LPS vs. NDP, q (20) = 6.245, p < 0.01; NDP vs. LNH, q (20) = 5.995, p < 0.01) (n = 5 mice per group, with 4-6 sections per mouse; at least 10 dendritic segments were randomly selected and quantified per section). (F) Quantification of relative Iba-1 fluorescence intensity, NDP-MSH normalized LPS-evoked microglial activation; H89 co-treatment restored microglial density to LPS-like levels (One-way ANOVA, F (4, 10) = 19.57, p < 0.001, followed by Tukey’s multiple comparisons test. Veh vs. LPS, q (10) = 8.650, p < 0.001; Veh vs. LNH, q (10) = 8.412, p < 0.01; LPS vs. NDP, q (10) = 5.940, p < 0.05; NDP vs. LNH, q (10) = 5.702, p < 0.05) (n = 3 mice per group). (G) Representative immunofluorescence images of Iba-1 staining in the mPFC, Scale bar = 100 µm. Data are presented as mean ± SEM. *p < 0.05, **p < 0.01, ***p < 0.001. ****p < 0.0001. Source: BioRender.com .

    Journal: Frontiers in Pharmacology

    Article Title: NDP-MSH rescues LPS-induced neuroinflammation, synaptic deficits, and depressive-like behaviors in mice: involvement of MC1R–cAMP/PKA signaling

    doi: 10.3389/fphar.2026.1895800

    Figure Lengend Snippet: PKA inhibition by H89 abolishes the neuroprotective and antidepressant effects of NDP-MSH. (A) Experimental timeline and grouping strategy. Mice were assigned to Vehicle, LPS, LPS + NDP-MSH(NDP), LPS + NDP-MSH + H89(LNH), or H89 groups. (B) Representative locomotor traces in the OFT. (C) Behavioral assessments. NDP-MSH significantly increased sucrose preference in LPS-treated mice, whereas H89 co-treatment abolished this effect in the SPT. (One-way ANOVA, F (4, 41) = 13.96, p < 0.0001, followed by Tukey’s multiple comparisons test. Vehicle vs. LPS: q (41) = 6.649, p < 0.001; Vehicle vs. LNH: q (41) = 6.804, p < 0.001; LPS vs. NDP: q (41) = 4.128, p < 0.05; NDP vs. LNH: q (41) = 4.237, p < 0.05). NDP-MSH restored total distance traveled reduced by LPS; H89 partly reversed this improvement in the OFT (One-way ANOVA, F (4, 41) = 29.92, p < 0.0001, followed by Tukey’s multiple comparisons test. Vehicle vs. LPS: q (41) = 13.07, p < 0.0001; Vehicle vs. NDP: q (41) = 7.823, p < 0.0001; Vehicle vs. LNH: q (41) = 11.660, p < 0.0001; LPS vs. NDP, q (41) = 5.225, p < 0.01). NDP-MSH partly restored central zone entries reduced by LPS; H89 partly reversed this improvement in the OFT (Kruskal-Wallis non-parametric test, H (4) = 30.23, p < 0.0001, followed by Dunn's multiple comparisons test. Vehicle vs. LPS: Z = 4.745, p < 0.0001; Vehicle vs. NDP: Z = 2.600, p = 0.093; Vehicle vs. LNH: Z = 3.924, p < 0.0001; H89 vs. LPS: Z = 3.615, p < 0.01) (Veh, n = 8; H89, n = 8; LPS, n = 10; NDP, n = 9; LNH, n = 11). (D) ELISA quantification of IL-1β levels in the PFC. NDP-MSH reversed LPS-induced IL-1β elevation, whereas H89 prevented this effect (One-way ANOVA, F (4, 25) = 18.02, p < 0.0001, followed by Tukey’s multiple comparisons test. Vehicle vs. LPS, q (25) = 9.990, p < 0.0001; Vehicle vs. LNH: q (25) = 6.190, p < 0.01; LPS vs. NDP, q (25) = 8.350, p < 0.0001; NDP vs. LNH, q (25) = 4.549, p < 0.05) (n = 6 mice per group). (E) Representative images of mPFC neuronal dendrites by Golgi-Cox staining. Scale bar = 20 μm. Column graphs illustrate the relative spine numbers. NDP-MSH significantly increased spine density reduced by LPS treatment, whereas co-treatment with the PKA inhibitor H89 abolished this restorative effect (One-way ANOVA, F (4, 20) = 36.61, p < 0.0001, followed by Tukey’s multiple comparisons test. Veh vs. LPS, q (20) = 13.07, p < 0.0001; Veh vs. NDP, q (20) = 6.820, p < 0.001; Veh vs. LNH, q (20) = 12.82, p < 0.0001; LPS vs. NDP, q (20) = 6.245, p < 0.01; NDP vs. LNH, q (20) = 5.995, p < 0.01) (n = 5 mice per group, with 4-6 sections per mouse; at least 10 dendritic segments were randomly selected and quantified per section). (F) Quantification of relative Iba-1 fluorescence intensity, NDP-MSH normalized LPS-evoked microglial activation; H89 co-treatment restored microglial density to LPS-like levels (One-way ANOVA, F (4, 10) = 19.57, p < 0.001, followed by Tukey’s multiple comparisons test. Veh vs. LPS, q (10) = 8.650, p < 0.001; Veh vs. LNH, q (10) = 8.412, p < 0.01; LPS vs. NDP, q (10) = 5.940, p < 0.05; NDP vs. LNH, q (10) = 5.702, p < 0.05) (n = 3 mice per group). (G) Representative immunofluorescence images of Iba-1 staining in the mPFC, Scale bar = 100 µm. Data are presented as mean ± SEM. *p < 0.05, **p < 0.01, ***p < 0.001. ****p < 0.0001. Source: BioRender.com .

    Article Snippet: Treatment regimens were as follows: vehicle-treated mice received equivalent volumes of saline; the LPS group received lipopolysaccharide (LPS; 1 mg/kg; L2880, Sigma-Aldrich, United States); the LPS + NDP-MSH group received LPS (1 mg/kg) together with NDP-MSH (2 mg/kg; HY-N2466, MedChemExpress, United States); the LPS + NDP-MSH + H89 group received LPS (1 mg/kg), NDP-MSH (2 mg/kg), and the PKA inhibitor H89 (10 mg/kg; HY-15979A, MedChemExpress, United States); and the H89-alone group received H89 (10 mg/kg).

    Techniques: Inhibition, Enzyme-linked Immunosorbent Assay, Staining, Fluorescence, Activation Assay, Immunofluorescence

    NDP-MSH Normalizes LPS-induced Metabolic Reprogramming through cAMP/PKA Signaling. (A) Principal component analysis (PCA) score plot of untargeted metabolomic profiles from saline control (CTRL), LPS-treated (LPS), drug-treated (NDP), drug plus inhibitor-treated (LNH), inhibitor alone (H89), and quality control (QC) samples. Biological samples included n = 4 mice per treatment group (CTRL, LPS, NDP, LNH, and H89). QC samples (n = 3) were used for quality control and were excluded from statistical comparisons. (B) Bar plot showing the number of significantly altered metabolites (upregulated and downregulated) across pairwise comparisons (limma, FDR <0.2, |log 2 fold change| ≥ 0.15; QC samples excluded). (C) Scatter plot showing the correlation between LPS-induced metabolic changes (LPS vs. CTRL) and drug-induced changes (NDP vs. LPS). (D) Scatter plot showing the correlation between drug-induced changes (NDP vs. LPS) and inhibitor-on-drug effects (LNH vs. NDP). (E) Heatmap showing a selected subset of metabolites whose LPS-induced changes were reversed by NDP-MSH treatment and whose NDP-MSH-mediated reversal was blocked by H89. Relative metabolite intensities were Z-score normalized across group means. (F) KEGG pathway enrichment analysis of drug-responsive metabolites. Source: BioRender.com .

    Journal: Frontiers in Pharmacology

    Article Title: NDP-MSH rescues LPS-induced neuroinflammation, synaptic deficits, and depressive-like behaviors in mice: involvement of MC1R–cAMP/PKA signaling

    doi: 10.3389/fphar.2026.1895800

    Figure Lengend Snippet: NDP-MSH Normalizes LPS-induced Metabolic Reprogramming through cAMP/PKA Signaling. (A) Principal component analysis (PCA) score plot of untargeted metabolomic profiles from saline control (CTRL), LPS-treated (LPS), drug-treated (NDP), drug plus inhibitor-treated (LNH), inhibitor alone (H89), and quality control (QC) samples. Biological samples included n = 4 mice per treatment group (CTRL, LPS, NDP, LNH, and H89). QC samples (n = 3) were used for quality control and were excluded from statistical comparisons. (B) Bar plot showing the number of significantly altered metabolites (upregulated and downregulated) across pairwise comparisons (limma, FDR <0.2, |log 2 fold change| ≥ 0.15; QC samples excluded). (C) Scatter plot showing the correlation between LPS-induced metabolic changes (LPS vs. CTRL) and drug-induced changes (NDP vs. LPS). (D) Scatter plot showing the correlation between drug-induced changes (NDP vs. LPS) and inhibitor-on-drug effects (LNH vs. NDP). (E) Heatmap showing a selected subset of metabolites whose LPS-induced changes were reversed by NDP-MSH treatment and whose NDP-MSH-mediated reversal was blocked by H89. Relative metabolite intensities were Z-score normalized across group means. (F) KEGG pathway enrichment analysis of drug-responsive metabolites. Source: BioRender.com .

    Article Snippet: Treatment regimens were as follows: vehicle-treated mice received equivalent volumes of saline; the LPS group received lipopolysaccharide (LPS; 1 mg/kg; L2880, Sigma-Aldrich, United States); the LPS + NDP-MSH group received LPS (1 mg/kg) together with NDP-MSH (2 mg/kg; HY-N2466, MedChemExpress, United States); the LPS + NDP-MSH + H89 group received LPS (1 mg/kg), NDP-MSH (2 mg/kg), and the PKA inhibitor H89 (10 mg/kg; HY-15979A, MedChemExpress, United States); and the H89-alone group received H89 (10 mg/kg).

    Techniques: Metabolomic, Saline, Control

    Hesperetin and Naringenin increased cAMP level and [Ca 2+ ] i after glucose stimulation in murine L cells. (A,B) Intracellular cAMP levels from GLUTag cells in response to 10 μM Hesperetin (A) or 10 μM Naringenin (B) (n = 5). (C,D) GLP-1 secretion from GLUTag cells in response to 10 μM Hesperetin (C) or 10 μM Naringenin (D) with 10 μM H89 or vehicle (n = 5). (E) The intracellular calcium concentration ([Ca 2+ ] i ) of GLUTag cells stimulated with 20 mM glucose plus vehicle or 10 μM Hesperetin was detected by using a Ca 2+ indicator, Fluo‐4 (n = 10). The change of fluorescence after stimulation was normalized to the basal fluorescence (ΔF/F 0 ) was measured by area under the curve (AUC). (F) GLP-1 secretion from GLUTag cells in response to 10 μM Hesperetin with 5 μM Nifedipine or vehicle (n = 5). (G) The intracellular calcium concentration ([Ca 2+ ] i ) of GLUTag cells stimulated with 20 mM glucose plus vehicle or 10 μM Naringenin was detected by using a Ca 2+ indicator, Fluo‐4 (n = 10). The change of fluorescence after stimulation was normalized to the basal fluorescence (ΔF/F 0 ). (H) GLP-1 secretion from GLUTag cells in response to 10 μM Naringenin with 5 μM Nifedipine or vehicle (n = 5). Black arrows indicated the initial time of glucose stimulation. ** p < 0.01, *** p < 0.001 by Mann-Whitney U-test, ns means not significant. Data are expressed as the mean ± SEM.

    Journal: Frontiers in Pharmacology

    Article Title: Hesperetin and Naringenin promote glucagon-like peptide-1 secretion from L-cell through activation of TGR5 and alleviated type 2 diabetes

    doi: 10.3389/fphar.2026.1838267

    Figure Lengend Snippet: Hesperetin and Naringenin increased cAMP level and [Ca 2+ ] i after glucose stimulation in murine L cells. (A,B) Intracellular cAMP levels from GLUTag cells in response to 10 μM Hesperetin (A) or 10 μM Naringenin (B) (n = 5). (C,D) GLP-1 secretion from GLUTag cells in response to 10 μM Hesperetin (C) or 10 μM Naringenin (D) with 10 μM H89 or vehicle (n = 5). (E) The intracellular calcium concentration ([Ca 2+ ] i ) of GLUTag cells stimulated with 20 mM glucose plus vehicle or 10 μM Hesperetin was detected by using a Ca 2+ indicator, Fluo‐4 (n = 10). The change of fluorescence after stimulation was normalized to the basal fluorescence (ΔF/F 0 ) was measured by area under the curve (AUC). (F) GLP-1 secretion from GLUTag cells in response to 10 μM Hesperetin with 5 μM Nifedipine or vehicle (n = 5). (G) The intracellular calcium concentration ([Ca 2+ ] i ) of GLUTag cells stimulated with 20 mM glucose plus vehicle or 10 μM Naringenin was detected by using a Ca 2+ indicator, Fluo‐4 (n = 10). The change of fluorescence after stimulation was normalized to the basal fluorescence (ΔF/F 0 ). (H) GLP-1 secretion from GLUTag cells in response to 10 μM Naringenin with 5 μM Nifedipine or vehicle (n = 5). Black arrows indicated the initial time of glucose stimulation. ** p < 0.01, *** p < 0.001 by Mann-Whitney U-test, ns means not significant. Data are expressed as the mean ± SEM.

    Article Snippet: H89 (HY-15979), Nifedipine (HY-B0284), GW 4064 (HY-50108), INT777 (HY-15677), TAK-875 (HY-10480), GSK1292263 (HY-12066), TUG-891 (HY-100881) and Exendin-(9-39) amide (HY-P0264) were purchased from MedChemExpress (Shanghai, China).

    Techniques: Concentration Assay, Fluorescence, MANN-WHITNEY