Journal: ACS Omega

Article Title: Receptor-Selective Modulation of Cannabinoid Signaling by Cardamonin: Integrating Molecular Dynamics, Free Energy Calculations, and Behavioral Validation

doi: 10.1021/acsomega.5c10026

Figure Lengend Snippet: Schematic overview of the study design combining computational and behavioral approaches. Cardamonin, a chalcone derivative, was evaluated for its interaction with cannabinoid receptors CB1 and CB2 using molecular dynamics simulations and MM/PBSA analyses. Parallel in vivo behavioral assaysVon Frey and Hargreaves testswere conducted in mice to assess mechanical and thermal antinociception, respectively.

Article Snippet: Cardamonin (MedChemExpress LLC, USA) and selective cannabinoid receptor 1 (CB1) antagonists SR141716 (MedChemExpress LLC, USA) and selective cannabinoid receptor 2 (CB2) antagonist SR144528 (MedChemExpress LLC, USA) were dissolved in dimethyl sulfoxide [DMSO], Tween 20 and diluted with saline at a ratio of 5:5:90 for intraperitoneal (i.p.) administration.

Techniques: In Vivo

Journal: ACS Omega

Article Title: Receptor-Selective Modulation of Cannabinoid Signaling by Cardamonin: Integrating Molecular Dynamics, Free Energy Calculations, and Behavioral Validation

doi: 10.1021/acsomega.5c10026

Figure Lengend Snippet: Docking poses of cardamonin with CB1 (A) and CB2 (B) receptors. (A) Cardamonin binds to CB1 with −8.7 kcal/mol, forming hydrogen bonds (SER 505 , ILE 267 ), hydrophobic contacts (PHE 170 , VAL 196 , LEU 193 , PHE 200 ), and a π-cation interaction (HIS 178 ). (B) In CB2 (−8.0 kcal/mol), cardamonin engages in hydrophobic interactions and a π-stacking (PHE117). Interaction types: hydrogen bonds (blue), hydrophobic (gray dashed), π-cation (orange dashed), π-stacking (green dashed).

Article Snippet: Cardamonin (MedChemExpress LLC, USA) and selective cannabinoid receptor 1 (CB1) antagonists SR141716 (MedChemExpress LLC, USA) and selective cannabinoid receptor 2 (CB2) antagonist SR144528 (MedChemExpress LLC, USA) were dissolved in dimethyl sulfoxide [DMSO], Tween 20 and diluted with saline at a ratio of 5:5:90 for intraperitoneal (i.p.) administration.

Techniques:

Journal: ACS Omega

Article Title: Receptor-Selective Modulation of Cannabinoid Signaling by Cardamonin: Integrating Molecular Dynamics, Free Energy Calculations, and Behavioral Validation

doi: 10.1021/acsomega.5c10026

Figure Lengend Snippet: Hydrogen bond interaction snapshots between cardamonin and cannabinoid receptors CB1 (A) and CB2 (B) at selected time points from molecular dynamics simulations. Each frame corresponds to a representative structure at 100, 250, 500, and 750 ns. Hydrogen bonds are depicted as red dashed lines with annotated distances (Å). In CB1, dynamic repositioning of the ligand allows alternating interactions with residues such as HSD 178 , ILE 267 , PHE 189 , ASP 184 , SER 173 , and LEU 193 . In contrast, the CB2 complex demonstrates a more consistent hydrogen bonding profile, particularly with SER 285 and GLY 284 . These interactions reflect the temporal stability and flexibility of ligand–receptor engagement during the simulation trajectory.

Article Snippet: Cardamonin (MedChemExpress LLC, USA) and selective cannabinoid receptor 1 (CB1) antagonists SR141716 (MedChemExpress LLC, USA) and selective cannabinoid receptor 2 (CB2) antagonist SR144528 (MedChemExpress LLC, USA) were dissolved in dimethyl sulfoxide [DMSO], Tween 20 and diluted with saline at a ratio of 5:5:90 for intraperitoneal (i.p.) administration.

Techniques:

Journal: ACS Omega

Article Title: Receptor-Selective Modulation of Cannabinoid Signaling by Cardamonin: Integrating Molecular Dynamics, Free Energy Calculations, and Behavioral Validation

doi: 10.1021/acsomega.5c10026

Figure Lengend Snippet: Principal Component Analysis (PCA) of CB1 and CB2 receptor complexes. (A) PCA projection of CB1 control (black) and cardamonin-bound complex (red) onto the first two principal components. Cardamonin binding induces broader conformational sampling. (B) PCA projection of CB2 control (black) and cardamonin-bound complex (red), showing overlapping conformational space and reduced ligand impact.

Article Snippet: Cardamonin (MedChemExpress LLC, USA) and selective cannabinoid receptor 1 (CB1) antagonists SR141716 (MedChemExpress LLC, USA) and selective cannabinoid receptor 2 (CB2) antagonist SR144528 (MedChemExpress LLC, USA) were dissolved in dimethyl sulfoxide [DMSO], Tween 20 and diluted with saline at a ratio of 5:5:90 for intraperitoneal (i.p.) administration.

Techniques: Control, Binding Assay, Sampling

Journal: ACS Omega

Article Title: Receptor-Selective Modulation of Cannabinoid Signaling by Cardamonin: Integrating Molecular Dynamics, Free Energy Calculations, and Behavioral Validation

doi: 10.1021/acsomega.5c10026

Figure Lengend Snippet: (A) Mechanical paw withdrawal threshold (mean ± SEM) in the Von Frey test. SHM and CDM groups displayed high thresholds (normal sensitivity), while VHC, CB1 – , and CB2 – groups exhibited mechanical allodynia. Co-treatment with cardamonin (CDM+CB1 – and CDM+CB2 – ) partially restored pain thresholds. (B) Thermal paw withdrawal latency (mean ± SEM) in the Hargreaves test. SHM group showed normal latency. CB1 – , CB2 – , and VHC groups exhibited thermal hyperalgesia. Cardamonin (CDM) increased latency significantly, and cotreatment with CB1 – or CB2 – partially restored thermal sensitivity.

Article Snippet: Cardamonin (MedChemExpress LLC, USA) and selective cannabinoid receptor 1 (CB1) antagonists SR141716 (MedChemExpress LLC, USA) and selective cannabinoid receptor 2 (CB2) antagonist SR144528 (MedChemExpress LLC, USA) were dissolved in dimethyl sulfoxide [DMSO], Tween 20 and diluted with saline at a ratio of 5:5:90 for intraperitoneal (i.p.) administration.

Techniques: