Computational Screening Of Cistanche-Derived Lignan Compounds As Natural 5 -Reductase Inhibitors For The Potential Treatment Of Benign Prostatic Hyperplasia (BPH)

 

1. Homology Modeling and Model Optimization of 5 -Reductase

Cistanche-derived herbal compounds5 -reductase (5-AR), a homology model of the 5-AR type II isoform (primarily expressed in the prostate) was constructed.

3CMF

16.1%

39.4%

.

Out of 10 generated models, the one with the lowest PDF Total Energy (1696.06)DOPE Score (-26914.41) was selected for further refinement. Initial evaluation did , prompting structural optimization.

molecular dynamics-based energy minimization

Verify3D Score: 89.76 (↑ from 73.87)

: 96.85% residues in allowed regions

: 82.43 (>80 threshold)

using the LibDock algorithm.

 

 

 

2. Molecular Docking Results: Binding Affinity to 5-AR

as a reference (LibDock Score: 80.15), 12 compounds from .

Olivil-9-O- -D-glucopyranoside

(–)-Secoisolariciresinol-9-O- -D-glucopyranoside

9-Acetyl-glucopyranoside

5-Methoxy-secoisolariciresinol

Cyclo-olivil-O- -D-glucopyranoside

(–)-Secoisolariciresinol

Quercetin-3-O- -D-glucoside

9,9'-Diacetyl-glucopyranoside

🧬 were the dominant compound type among the top 12, suggesting that are the key bioactives for 5-AR inhibition.

3. ADMET Evaluation of Cistanche Compounds

3.1 Solubility at 25℃

A key determinant for oral bioavailability.

All compounds except compound (4) demonstrated .

3.2 Intestinal Absorption

Compounds (3), (5), (7), and (12) showed , indicating favorable oral delivery.

3.3 Hepatotoxicity

Compound (5), (7), and (9) showed potential to reduce adverse reactions (ADRs).

3.4 CYP450 2D6 Inhibition

Only compound (4) was predicted to inhibit CYP2D6, suggesting possible drug-drug interaction risk.

3.5 Blood-Brain Barrier (BBB) Penetration

Compounds (5) and (7) can potentially cross the BBB, which may influence CNS-related side effects or benefits.

3.6 Plasma Protein Binding

High plasma protein binding observed in compound (4) and (5); others remained largely in free form.

4. Discussion

natural inhibitors of 5-AR, and structural features suitable for further development.

(–)-Secoisolariciresinolbest overall drug-likeness, although it showed mild hepatotoxicity. This suggests a need for (e.g., prodrug design or structural modification) before clinical application.

💡
multi-target pharmacological properties of Cistanche lignans - including anti-inflammatory, androgen-regulating effects - make them ideal candidates for herbal-based BPH therapies.

🌿

to steroidal 5-AR inhibitors like finasteride.

molecular docking + ADMET profiling.

 

🔧

In vitro and in vivo validation (e.g., DHT-induced BPH model)

 

5-AR 3D model (PDB format)

High-resolution compound structures (SDF/MOL)