Physicochemical investigation and molecular docking analysis of Maha yogaraj Guggulu tablet and virtual screening of its major bioactive compound

Guggulsterone plays a significant role in cholesterol-lowering by inhibiting Farnesoid X Receptor. The present study aims to identify the isomers of Guggulsterone with high binding affinity and good binding interaction with targeted protein and positive control atorvastatin. The pharmacokinetic parameters of Guggulsterone isomers were estimated from P.K.C.S.M. online server, and molecular docking analysis was performed from Autodock V.® 4.2.6 Program. From the computer-aided drug designing, we have confirmed that guggulsterone isomers are inhibitors of the CYP3A4 enzyme and hepatotoxic. Guggulsterone isomer showed a stronger binding affinity when compared with atorvastatin. The docking score for Guggulsterone was -9.28 kcal/mol, E-Guggulsterone -9.56 kcal/mol, Z-Guggulsterone -9.79 kcal/mol, M-Guggulsterone -9.45 kcal/mol, and positive control atorvastatin -8.26 kcal/mol. The present study revealed that the isomers of Guggulsterone have high binding affinity and good binding interaction with targeted proteins.

 

Comments:

It seems like you're discussing a research study exploring the potential of Guggulsterone isomers as cholesterol-lowering agents through inhibiting the Farnesoid X Receptor (FXR). The study involved several computational methods, including estimating pharmacokinetic parameters through the PKCSM online server and performing molecular docking analysis using the Autodock V.® 4.2.6 Program. Here's a breakdown of the key findings:

1. **Objective**: To identify Guggulsterone isomers with high binding affinity and strong interactions with the targeted protein (FXR), comparing them with the positive control, atorvastatin.

2. **Results**:
   - **Binding Affinity**: The study found that Guggulsterone isomers (E-Guggulsterone, Z-Guggulsterone, and M-Guggulsterone) exhibited stronger binding affinities (ranging from -9.28 to -9.79 kcal/mol) compared to the positive control, atorvastatin (-8.26 kcal/mol).
   - **Target Interaction**: Guggulsterone isomers showed good binding interactions with the targeted protein (FXR), potentially suggesting their effectiveness in inhibiting FXR activity.

3. **CYP3A4 Inhibition and Hepatotoxicity**: Additionally, the computer-aided drug design indicated that Guggulsterone isomers act as inhibitors of the CYP3A4 enzyme and may possess hepatotoxic effects.

4. **Conclusion**: The study suggests that Guggulsterone isomers hold promise as potential FXR inhibitors for lowering cholesterol levels. However, their inhibition of CYP3A4 and potential hepatotoxicity should be considered and further investigated for safety and efficacy.

This research represents an initial computational analysis, and further experimental validation would be necessary to confirm these findings and evaluate the actual efficacy and safety of these Guggulsterone isomers as cholesterol-lowering agents.