Aim of the study
The prevalence of diabetes mellitus combined with depressive disorder (DD) is continuing to increase, yet it is currently under-recognized and its treatment remains inadequate. The present study aims to explore the underlying therapeutics and mechanisms of JTW on DD. Materials and
Conclusion
JTW could exert both hypoglycemic and antidepressant effects through activating the cAMP/PKA/CREB signaling pathway, its active component, Ber, could improve the damage to HT-22 cells induced by glucose combined with CORT via the activation of the cAMP/PKA/CREB pathway. Ber may be one of the effective components of the dual effects of JTW.
Methods
Chronic restraint stress was used on db/db mice to construct a mouse model of DD. The therapeutic effects of JTW were assessed by glucolipid metabolic indexes, behavioral tests, and depression-related neurotransmitter levels. The inflammatory status and cell apoptosis of different mice were investigated and the changes in the cAMP/PKA/CREB pathway were detected. Combining the
Results
JTW could improve the impaired glucose tolerance, lipid metabolism disorders, and depression-like symptoms in DD mice. Meanwhile, JTW could alleviate the inflammatory status, suppress the microglia activation, and improve hippocampal neuron apoptosis in DD mice. The dual effects of JTW might be associated with the activation of the cAMP/PKA/CREB pathway. Berberine (Ber) was identified for the in vitro experiment, it could reverse the apoptosis of HT-22 cells and up-regulate the depression-related neurotransmitter levels, and the effects of Ber were related to the activation of the cAMP/PKA/CREB pathway as well.