Identifying Chinese Medicine Components Using UHPLC Techniques

• Researchers at the First Hospital of Hunan University of Chinese Medicine characterized 102 chemical components of Xiaoyao Pill (XYP) using UHPLC-Q-TOF-MS/MS, identifying 10 prototype components and 16 metabolites that can be absorbed in the brain after oral administration.
• Through network pharmacology and molecular docking, the study identified 420 common targets shared between XYP compounds and depression, with TP53, EGFR, PTGS2, ESR1, and PPARG being core targets. These are mainly involved in the PI3K-Akt and MAPK signaling pathways, which are linked to apoptosis and inflammatory response.
• While the study provides experimental evidence for the antidepressant activity of XYP and its potential targets, it acknowledges the need for more research into the precise molecular mechanisms of active compounds to fully understand their antidepressant effects.

Researchers from the First Hospital of Hunan University of Chinese Medicine in Changsha, China studied the components of the Xiaoyao Pill (XYP), a type of traditional Chinese medicine, that has proven effective in treating depression. Their findings were published in the Journal of Chromatography B (1).

Depression is a psychological disorder with high disability and mortality rates. Various factors can contribute to depression, such as genetics, hormonal imbalances, and environmental stress; over time, physical symptoms can manifest. Affecting people all over the world, according to the World Health Organization (WHO), depression is one of the most prevalent mental health disorders in China (2). The WHO estimates that 54 million people in China suffer from depression. As part of combatting the condition, that country has made efforts to provide more people with diagnosis and care.

Common treatment strategies for depression include psychotherapy, pharmacotherapy, and antidepressants; however, these medications can have significant side effects. Recent research has looked into antidepressant traditional Chinese medicines (TCM), with one well-known TCM for depression being the XYP. According to TCM theory, some of the main syndromes of depression are liver stagnation and spleen deficiency syndrome; in different studies, XYP was found to treat both of those conditions (3).

While XYP has been found to be effective in treating depression, there is a lack of research on the XYP components that get absorbed in the brain. The United States Food and Drug Administration (FDA) does not regulate supplements the way prescription drugs are regulated (4). Furthermore, there is a lack of network pharmacology studies that specifically focus on depression. In this study, the scientists aimed to reveal the antidepressant active ingredients and related molecular mechanisms of XYP. First, ultrahigh-performance liquid chromatography-quadrupole time-of-flight–tandem mass spectrometry (UHPLC-Q-TOF-MS/MS) was used to characterize XYP components and simultaneously identify components in brain tissue and cerebrospinal fluid (CSF) after oral administration of XYP, respectively. Following this, network pharmacology and molecular docking were performed to predict the targets and pathways of these components.

In total, 102 chemical components, 10 prototype components, and 16 metabolites absorbed in the brain were identified in XYP. Network pharmacology analysis showed the compounds sharing 420 common targets with depression. TP53, EGFR, PTGS2, ESR1, PPARG, and other 68 targets were considered core targets, mainly enriched in PI3K-Akt and MAPK signaling pathways. Further analysis revealed associated apoptosis and inflammatory response. Molecular docking revealed that paeoniflorin, liquiritin, and atractylenolide III were found to have the highest binding energy to TP53, ESR1 and PPARG, which can affect signaling pathways to regulate inflammatory responses and cell apoptosis.

This study was shown to provide experimental evidence for elucidating XYP response compounds and the formation of quality control. That said, the scientists only analyzed the active components in XYP, overlooking the active components potentially playing an antidepressant effect molecular mechanism. They intend to address this in future research efforts.

References

(1) Zhou, S.; Wang, Y.; Xie, M.; et al. Uncovering the Antidepressant Active Ingredients and Related Molecular Mechanisms of Xiaoyao Pill Using Integrated Pharmacological Strategy. J. Chromatogr. B 2025, 1255, 124502. DOI: 10.1016/j.jchromb.2025.124502

(2) Mental Health in China. World Health Organization 2025. https://www.who.int/china/health-topics/mental-health (accessed 2025-5-30)

(3) Xue, Z.; Huang, Z.; Cheng, S-L.; Wang, X-H.; Zhou, X.; Ma, Q-Y.; Chen, J-X. Efficacy and Safety of Xiaoyao Pills for Mild to Moderate Depression: Study Protocol for a Randomized Controlled Trial. Trials 2022, 23 (10). DOI: 10.1186/s13063-021-05909-y

(4) Lubeck, B. What is Xiao Yao San? Verywell Health 2024. https://www.verywellhealth.com/xiao-yao-wan-88943 (accessed 2025-6-2)

(Source: chromatographyonline.com)