Ginsenoside Rb1 prevents osteoporosis via the AHR/PRELP/NF-κB signaling axis

Area of Science:

• Pharmacology and Molecular Biology
• Bone Biology and Osteoporosis Research

Background:

• Ginsenoside Rb1 (GRb1) shows promise in treating aging-related diseases, particularly osteoporosis (OP).
• Recent research highlights GRb1's potential as an anti-osteoporosis agent.
• The precise mechanism of GRb1's action in improving OP requires further elucidation.

Purpose of the Study:

• To identify the molecular mechanism by which GRb1 exerts its anti-osteoporosis effects.
• To investigate the role of the aryl hydrocarbon receptor (AHR) and proline/arginine-rich end leucine-rich repeat protein (PRELP) in GRb1's action.
• To explore the relationship between AHR, PRELP, and the nuclear factor-kappa B (NF-κB) pathway in the context of osteoporosis.

Main Methods:

• Construction of a dexamethasone (DEX)-induced rat model of osteoporosis for GRb1 treatment evaluation.
• In silico screening of GRb1 action targets followed by in vitro functional validation.
• Luciferase and chromatin immunoprecipitation assays to confirm the interaction between AHR and PRELP.
• Assessment of osteogenic differentiation markers, mineralization, and calcium nodule formation in isolated osteoblasts.

Main Results:

• GRb1 treatment enhanced osteoblast differentiation, linked to aryl hydrocarbon receptor (AHR) upregulation.
• AHR directly promoted proline/arginine-rich end leucine-rich repeat protein (PRELP) transcription by binding to its promoter region, leading to PRELP upregulation.
• PRELP was found to inhibit the nuclear factor-kappa B (NF-κB) pathway activation, thereby mediating AHR's pro-osteogenic effects.
• GRb1 effectively ameliorated osteoporosis in DEX-induced rats through the identified AHR/PRELP/NF-κB signaling axis.

Conclusions:

• Ginsenoside Rb1 (GRb1) demonstrates potential as an effective agent for preventing osteoporosis progression.
• The study reveals a novel molecular mechanism involving the AHR/PRELP/NF-κB axis in GRb1's anti-osteoporosis effects.
• These findings offer a theoretical basis for developing GRb1-based therapeutic strategies for osteoporosis.