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Background and Purpose: Kaempferol-3-O-sophoroside (PCS-1) is the main component in Crocus sativus (Saffron), a herb with mood-enhancing properties. AMP-activated protein kinase (AMPK) is a potential therapeutic target for depression. This study explores the antidepressive-like properties of PCS-1 and its AMPK activation to confirm AMPK as a target for antidepression., Experimental Approach: Corticosterone (CORT)-induced PC12 cell injury served as an in vitro model to evaluate the neuroprotective effect of PCS-1. Neuro-2a cells and primary neurons were utilized to evaluate the synaptogenesis role of PCS-1. CORT-induced mouse depression model and chronic unpredictable mild stress (CUMS) model were used to assess the antidepressive-like properties of PCS-1 through behavioural tests, magnetic resonance imaging, and biochemical index measurements. Western blot and immunofluorescence assays were used to study the mechanisms of PCS-1. Cellular thermal shift assay was used to confirm the binding target., Key Results: PCS-1 (12.5-50 μM) ameliorated CORT-induced PC12 cell damage, oxidative stress and inflammation. PCS-1 alone promoted an increase in synapses in Neuro-2a cells and primary neurons. Oral administration of PCS-1 (10 and 20 mg·kg -1 ) ameliorated weight loss, dyskinesia, and hippocampal volume reduction induced by CORT and CUMS. PCS-1 bound to AMPK to improve the expression of brain-derived neurotrophic factor (BDNF) and induce autophagy., Conclusion and Implications: PCS-1 binds to AMPK to promote BDNF production and autophagy enhancement, ultimately achieving antidepressant effects. This study provides support for the clinical application of saffron petals and provides further evidence for AMPK as a potential target for antidepression., (© 2023 British Pharmacological Society.)

Caloric restriction (CR) is effective in slowing aging and delaying aging-related diseases in many species, but the mechanism is complex and not fully elucidated. This study aimed to evaluate the beneficial effects of a caloric restriction diet on learning and memory, and further to elucidate the mechanisms. Thirty-six week-old male C57/BL mice were randomly divided into three groups: normal control (NC group), high-energy (HE group) and CR group. After 44weeks, the Morris water maze was used to examine learning and memory abilities. Western blotting and immunohistochemistry were used to detect changes in proteins involved in the adenosine monophosphate-activated protein kinase (AMPK) pathway in the mouse hippocampus. Compared with NC group, the swimming distance and escape latency were shorter in the CR group. The protein and mRNA expression of AMPK and glucose transporter type 4 (GLUT4) in the CR group were significantly higher than that in HE group. CR increased serum insulin-like growth factor, adiponectin and vaspin, decreased blood glucose and serum malondialdehyde, and improved insulin sensitivity. Our findings demonstrate that a CR diet may improve hippocampus-dependent spatial learning ability of C57/BL mice, accompanied with an increase in AMPK and GLUT4 expression, which indicates AMPK pathway was associated with the neuroprotective effect of CR in mice., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Aim: Adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) is known as a mammalian cell energy sensor, which could regulate cellular energy metabolism via sensing the alterations of energy balance, such as oversupply or lack of glucose and fatty acid. Recent studies have suggested that AMPK could also regulate many other biological processes, including cell cycling, inflammation, protein synthesis, and so on. In this study, AMPK signaling in high-glucose-induced dysfunction of mesangial cells (MCs) was investigated., Methods: Established rat glomerular MCs were treated under normal glucose (5.6 mM glucose) or high-glucose conditions (30 mM glucose). mRNA levels of AMPK subunits were detected by reverse transcriptase-polymerase chain reaction. Expressions of AMPKα, phosphorylated AMPKα (p-AMPKα), phosphorylated acetyl-CoA carboxylase (p-ACC), and collagen IV were measured by Western blot., Results: Under high-glucose conditions, AMPKα protein expression and mRNA levels were significantly decreased. High-glucose treatment also induced a notable decrease in p-AMPKα and p-ACC expression. AMPKα activation by 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside (AICAR) effectively ameliorated high-glucose-induced dysfunction of MCs, including cell proliferation, cell-cycle progression, and collagen IV production., Conclusion: High glucose impaired AMPKα in its expression and activity; AICAR significantly ameliorated high-glucose-induced proliferation of MCs and collagen IV production, indicating a role of AMPKα in high-glucose-induced dysfunction of MCs.