1. Academic Validation
  2. Puerarin alleviates depressive-like behaviors in high-fat diet-induced diabetic mice via modulating hippocampal GLP-1R/BDNF/TrkB signaling

Puerarin alleviates depressive-like behaviors in high-fat diet-induced diabetic mice via modulating hippocampal GLP-1R/BDNF/TrkB signaling

  • Nutr Neurosci. 2022 Aug 30;1-14. doi: 10.1080/1028415X.2022.2112439.
Yumin Liu 1 Ziqi Hu 1 Jing Wang 1 2 Yanjun Liao 1 Luan Shu 1 2
Affiliations

Affiliations

  • 1 Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, People's Republic of China.
  • 2 Key Laboratory of New Drug Delivery System of Chinese Materia Medica, Jiangsu Province Academy of Chinese Medicine, Nanjing, People's Republic of China.
Abstract

Objective: Depression is one of the most common complications in patients with diabetes. Our previous study demonstrated puerarin, a dietary isoflavone, improved glucose homeostasis and β-cell regeneration in high-fat diet (HFD)-induced diabetic mice. Here, we aim to evaluate the potential effect of puerarin on diabetes-induced depression.

Methods: The co-occurrence of diabetes and depression with related biochemical alterations were confirmed in HFD mice and db/db mice, respectively using behavioral analysis, ELISA and western blotting assay. Furthermore, impacts of puerarin on depression-related symptoms and pathological changes were investigated in HFD mice.

Results: The results showed that puerarin effectively alleviated the depression-like behaviors of HFD mice, down-regulated serum levels of corticosterone and IL-1β, while up-regulated the content of 5-hydroxytryptamine. Simultaneously, puerarin increased the number of hippocampal neurons in HFD mice, and suppressed the Apoptosis of neurons to protect the hippocampal neuroplasticity. GLP-1R expression in hippocampus of HFD mice was enhanced by puerarin, which subsequently activated AMPK, CREB and BDNF/TrkB signaling to improve neuroplasticity. Importantly, our data indicated that puerarin had an advantage over fluoxetine or metformin in treating diabetes-induced depression.

Conclusion: Taken together, puerarin exerts anti-depressant-like effects on HFD diabetic mice, specifically by improving hippocampal neuroplasticity via GLP-1R/BDNF/TrkB signaling. Puerarin as a dietary supplement might be a potential candidate in intervention of diabetes with comorbid depression.

Keywords

5-HT; 5-hydroxytryptamine; AMP-activated protein kinase; AMPK; BDNF; CORT; CREB; Depression; ERK; GLP-1R; HFD; T2DM; TrkB; brain-derived neurotrophic factor; cAMP-response element binding protein; corticosterone; diabetes; extracellular regulated protein kinases; glucagon-like peptide 1 receptor; high-fat diet; hippocampus; neuroplasticity; puerarin; type 2 diabetes; tyrosine kinase receptor B.

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