Astragalus polysaccharide protects mouse cornea from type 1 diabetes and activates AMPK-dependent autophagy

Astragalus polysaccharide (APS) has various pharmacological effects including anti-oxidative stress and regulating blood glucose. However, the protective effects of APS on corneal nerve in type 1 diabetes (T1DM) have not been fully demonstrated. This study aims to explore the protective effects of APS on T1DM corneal neuropathy. T1DM mice were established using streptozotocin and were given APS (100, 200, and 400 mg/kg) by gavage. Additionally, primary mouse trigeminal ganglion neurons were collected to expose to 25 mmol/L high glucose (HG) and APS (50, 100, and 200 μg/mL) for 48 h. An adenosine 5'-monophosphate-activated protein kinase (AMPK) inhibitor (10 μM, Compound C, CC) was used to block the AMPK signaling pathway. Measurement of oxidative stress and Reactive Oxygen Species (ROS), corneal sensitivity, corneal epithelial wound healing, immunofluorescence and Western blotting assays were performed. APS decreased blood glucose and levels of malondialdehyde (MDA) and ROS in T1DM mice, while APS increased weight, levels of superoxide dismutase (SOD), glutathione (GSH), corneal sensitivity and corneal neural length, along with enhancing corneal epithelial wound healing ability. APS promoted neuron growth and decreased ROS levels in TG neurons exposing HG. Notably, APS increased relative levels of p-AMPK, microtubule-Associated Protein 1 Light Chain 3 (LC3)-II and Autophagy related 4B cysteine peptidase (Atg4b), while decreased p-mechanistic target of rapamycin kinase (mTOR). CC partially antagonized the beneficial effects of APS on TG neurons and activation of AMPK-dependent Autophagy. This study clarified the protective effects of APS on corneal nerve function in T1DM, and one key mechanism was AMPK-dependent Autophagy.

AMPK; Astragalus polysaccharide; Autophagy; Corneal neuropathy; Type 1 diabetes.