Syringa oblata Lindl extract alleviated corticosterone-induced depression via the cAMP/PKA-CREB-BDNF pathway

Syringa oblata Lindl (ZDX) is a plant in the Oleaceae family that is the primary ingredient in the classic Tibetan medicine AKARU sinensis. The plant's stem is used as a medicine, and Tibetan doctors often use it as a sedative, a use with a history of nearly 100 years. Tibetan medicine mainly uses lilac to treat headache, forgetfulness, insomnia, irritability and other symptoms. Depression is a chronic mental disorder characterized by low mood, cognitive impairments, and physical discomfort, and it has become a significant public health issue. Given the limitations of existing treatments, interest in alternative therapies, including herbal medicines, is increasing.

To elucidate the mechanism of ZDX extract in the treatment of depression.

A depression-like mouse model was established via the subcutaneous injection of corticosterone (CORT) into the groin, and a model of PC12 cell injury was established via CORT treatment. The antidepressant effect of the ZDX extract was subsequently evaluated via weight measurements, the sucrose preference test (SPT), the forced swimming test (FST), the open field test(OFT), the tail suspension test (TST), HE staining, Nissl staining and ELISA. Moreover, immunofluorescence staining, qRT‒PCR and Western blotting were used to determine whether ZDX extract can regulate the cAMP/PKA-CREB-BDNF pathway to prevent depression and neuronal apoptosis.

ZDX extract significantly improved depression-like behaviours; inhibited decreases in the protein levels of cAMP, PKA, CREB and BDNF; and increased proliferative activity in the hippocampus and cortex. In addition, in vitro, ZDX extract attenuated CORT-induced injury and apoptosis in hippocampal neurons and inhibited CORT-induced decreases in the mRNA expression levels of cAMP, PKA, CREB and BDNF.

These findings suggest that ZDX extract has potential as a novel antidepressant therapeutic agent, offering a complementary approach to current treatments by targeting multiple pathways involved in the pathogenesis of depression. Further research is warranted to explore the clinical applications of ZDX extract in the treatment of depression.