## 3 Results and Discussion
### Molecular Docking Analyses  
In a prior study, we employed GC-MS to identify the alkaloid compositions in chloroform, methanol, and water alkaloid extracts. These components were identified as isoquinoline alkaloids, specifically allocryptope (the primary alkaloid), tetrahydropalmatine, and tetrahydroroberberine N-oxide (also known as trans-cannadine-N-oxide) [12]. With this knowledge, we performed molecular docking studies to examine the potential interactions of these alkaloids from the different extracts with specific target proteins, namely GCLC, HO-1, KEAP1, NRF2, and NQO1. The results of these molecular docking analyses are presented in Table 3. The Vina score is an empirical scoring method that takes into account a range of factors, including Gaussian steric interaction terms, a repulsion term, hydrophobic and hydrogen-bond interactions, and an entropy term related to the count of rotatable bonds [103]. The Gibbs binding energy between a ligand and its target protein becomes more favorable as the Vina score becomes more negative, indicating a stronger binding potential. Contact residues and bonds indicate the amino acids and structural connections between ligands and their target proteins. Hydrogen bond interactions are depicted with teal dotted lines, electrostatic interactions with yellow dotted lines, and hydrophobic interactions with grey dotted lines [50]. According to our docking results, allocryptope displayed the binding affinity in the order of NQO1 > NRF2 > KEAP1 = HO-1 > GCLC. For tetrahydroropalmatine, the binding preference was NQO1 > NRF2 > KEAP1 > GCLC > HO-1. The binding pattern for tetrahydroroberberine N-oxide (trans-cannadine-N-oxide) was NQO1 > GCLC > KEAP1 > NRF2 > HO-1. These findings suggest that the alkaloids exhibit strong binding potentials with the target proteins and may exert effects via interactions with these proteins. It is also noteworthy that the influence of the alkaloid extracts on the expression levels of the GCLC, HO-1, NRF2, NQO1, and KEAP1 genes mirrors the binding potential of the ligands (allocryptope, tetrahydroropalmatine, and tetrahydroroberberine N-oxide) to these target proteins. As of now, there is no existing research documenting the binding affinity between these specific ligands and target proteins. \begin{table}
\begin{tabular}{c c c c c c} \hline \hline
**Ligand** & & & & & \\ \hline Target Protein & GCLC & HO-1 & KEAP1 & NRF2 & NQO1 \\ \hline Vina Score & \(-7.9\) & \(-8.0\) & \(-8.0\) & \(-8.1\) & \(-9.7\) \\ (kkal/mol) & & & & & & \\ \hline \hline \end{tabular}
\begin{tabular}{c c c c c}  & Chain A: AN215 & & & Chain X: ALA366 & Chain A: TYR334 & SER16 PRO102 \\  & CHE252 TRP314 & Chain A: LYS18 & GLY367 CVS368 & PHE335 ARG336 & LEU103 GLN104 \\  & ASN155 SER18 & CHA A: LYS18 & VAL369 VAL418 & TYR572 HIS75 & TRP105 PHE106 \\  & ASN155 SER18 & THR21 LVS22 HIS25 & VAL420 VAL465 & THR58P HE577 & TRP147 TH148 \\  & GLY319 LVS359 & THR26 GLU29 & ALA466 VAL467 & Chain B: TYR334 & GLY149 GLY150 \\  & SER360 TYR362 & TYR134 TH1835 & VAL512 CYS513 & ARG336 GLN337 & TYR155 HIS161 \\  & SER363 SER364 & LEU138 GLY139 & VAL514 ILE559 & ASN382 SER383 & Chain N: ILE50 \\  & TRP514 MET517 & SER142 PHE207 & THF860 VAL604 & PRO384 & PHE65 GLN66 \\  & LYS518 HHS521 & VAL606 ALA607 & Chain C: GLY76 & TYR67 PRO68 \\  & & VAL608 & GLY81 GLU82 & GLU117 YYR126 \\  & & & & & \\ \hline \hline \end{tabular}
\end{table} 
Table 3: Molecular docking results of ligands and target proteins. Isoquinoline alkaloids in alkaloid extracts appear to inhibit the activity of KEAP1, the inhibitory protein responsible for suppressing NRF2. The order of action of alkaloids on KEAP is tetrahydropropalmatine > allocryptopine > tetrahydroberberine N-oxide (Trans-cannadine-N-oxide). By preventing the binding between NRF2 and KEAP1, our isoquinoline alkaloids in alkaloid extracts permit the activation of NRF2. The order of