Qingyangshen, or Root of Auricledleaf Swallowwort, a traditional ethnic medicinal plant long used in Southwest China's Yunnan Province. Photo: Scrrenshot from website

A Chinese research team has identified a new potential target to develop antidepressant drug from Qingyangshen, or Root of Auricledleaf Swallowwort, a traditional ethnic medicinal plant long used in Southwest China's Yunnan Province, according to Kunming University of Science and Technology, Science and Technology Daily reported Sunday.

The team, led by professors Xu Tianrui and Xiang Cheng from the university's School of Life Science and Technology, found that Qingyangshen glycosides, the plant's core active compound, can alleviate depression-related behaviors by simultaneously suppressing inflammation, reducing oxidative damage and stabilizing neurotransmitters in the brain.

The findings were published in the international journal Phytomedicine.  

Depression has become a widespread mental health disorder globally, while existing clinical drugs fail to provide effective treatment for more than 30 percent of patients, according to the researchers. Previous studies have established a strong link between chronic inflammation and depression, but existing anti-inflammatory drugs have limited targeting capabilities, underscoring the need for new therapeutic targets and lead compounds.

Qingyangshen, a plant of the Cynanchum genus in the Apocynaceae family, has long been used as a traditional medicine by ethnic groups including the Naxi, Yi and Bai peoples in Yunnan, mainly for treating neurological conditions such as epilepsy and neurasthenia. 

The researchers systematically examined the pharmacological effects of Qingyangshen extract and its core active compound, Qingyangshen glycosides. Tests using mouse, zebrafish and fruit fly models repeatedly showed that the compound significantly improved depression-related behaviors induced by inflammation, according to the report.

To identify the compound's target, the team developed a dual-discrimination model for four subtypes of prostaglandin E2 receptors and combined it with AI-powered machine learning. The researchers screened hundreds of G protein-coupled receptors and identified the prostaglandin E2 subtype 4 receptor as the direct target of Qingyangshen glycosides.

Multiple molecular experiments confirmed that the compound binds directly to the receptor and acts as an inhibitory ligand. Further experiments involving animals with the receptor knocked out in the hippocampus showed that the antidepressant effects of Qingyangshen glycosides disappeared completely when the receptor was absent, providing the first in-vivo evidence that the receptor is essential for the compound's therapeutic effects.

An illustration of the research. Photo: Screenshot from the website

The study establishes the prostaglandin E2 subtype 4 receptor as a potential new target for antidepressant drug development and points to a new approach to treating depression through inflammatory pathways. It also identifies Qingyangshen glycosides as a potential lead compound for developing highly targeted anti-inflammatory antidepressants, creating a research chain from ethnic medicinal plants and active compounds to drug targets and new drug development.

Global Times