Salidroside, A Natural Antioxidant, Improves β-Cell Survival and Function via Activating AMPK Pathway

Area of Science:

• Endocrinology and Metabolism
• Cell Biology
• Pharmacology

Background:

• Oxidative stress exacerbates type 2 diabetes mellitus (T2DM) progression and leads to pancreatic beta-cell failure.
• Salidroside, a natural antioxidant from Rhodiola rosea, has potential therapeutic properties.
• Understanding salidroside's protective mechanisms on beta cells in diabetes is crucial.

Purpose of the Study:

• To evaluate the protective effects of salidroside against diabetes-associated oxidative stress in pancreatic beta cells.
• To elucidate the underlying molecular mechanisms of salidroside's action on beta cell survival and function.

Main Methods:

• In vivo studies using diabetic db/db mice and high-fat diet-induced diabetic mice.
• In vitro studies using Min6 cells and isolated cultured mouse islets.
• Assessment of oxidative stress markers, beta cell mass, replication, mitochondrial function, and key signaling pathways (NOX2, JNK, caspase 3, FOXO1, PDX1, AMPK, AKT).

Main Results:

• Salidroside ameliorated hyperglycemia, reduced oxidative stress, and increased beta-cell mass and replication in diabetic mice.
• In vitro, salidroside suppressed reactive oxygen species, restored mitochondrial membrane potential, and inhibited apoptosis by modulating NOX2 and JNK-caspase 3 pathways.
• Salidroside activated the AMPK-AKT pathway, leading to FOXO1 inhibition and PDX1 nuclear localization, thereby reversing beta-cell dysfunction. These effects were dependent on AMPK activation.

Conclusions:

• Salidroside demonstrates significant beneficial metabolic effects and protects pancreatic beta cells from diabetes-induced failure.
• The protective action of salidroside on beta cells is mediated through AMPK activation, highlighting a novel therapeutic role.
• Rhodiola rosea, containing salidroside, shows potential as a dietary supplement for managing type 2 diabetes.