Potential of Ganoderma applanatum Extract as Anticancer and Immunomodulator in Diethylnitrosamine-induced Colon Cancer

Abstract

Ganoderma applanatum extract (GAE) exhibits numerous biological activities, particularly anticancer and immunomodulatory activities. This study aimed to examine the effect of GAE on colonic goblet cells, Lieberkuhn crypts, CD4+ and CD8+ cells in mice spleen. Mice were randomly divided into four groups (n = 6): normal control (KN) group given only distilled water, negative control (K-) group administered 100 mg/kg BW diethylnitrosamine (DEN), positive control (K+) group administered 100 mg/kg BW DEN + 10 mg/kg BW doxorubicin, and extract treatment (P) group administered 100 mg/kg BW DEN + 150 mg/kg BW GAE. Colon histology was assessed using haematoxylin and eosin staining. CD4+ and CD8+ percentages were determined by flow cytometry. Molecular docking of selected bioactive compounds of GAE with CD4+ (PDB ID: 1CDJ) and CD8+ (PDB ID: 1CD8) was performed using PyMol v1.74 and PyRx 0.8 software, with visualization using BIOVIA Discovery Studio 2019 and molecular dynamics via CABS-flex webserver. GAE significantly increased the number of goblet cells and Lieberkuhn crypt height in mice colon, with values of 28.00 ± 4.05 and 29.24 ± 4.61 µm, respectively. GAE improved colon histology and enhanced immunomodulation by increasing CD4+ and CD8+ cells in mice spleen, with values of 21.98 ± 3.03%, and 8.34 ± 0.86%, respectively. Molecular docking indicated lucidenic B had the highest binding affinity against CD4+ cells, while β-glucan had the highest binding affinity against CD8+ cells. Molecular dynamics confirmed complex stability (Root mean square fluctuation (RMSF) < 3 Å), suggesting stable ligand-receptor interactions in the plasma.