Depression is a stress-related disorder that seriously threatens people's physical and mental health. Xiaoyaosan is a classical traditional Chinese medicine formula, which has been used to treat mental depression since ancient times. More and more notice has been given to the relationship between the occurrence of necroptosis and the pathogenesis of mental disorders. The purpose of present study is to explore the potential mechanism of Xiaoyaosan for the treatment of depression using network pharmacology and experimental research, and identify the potential targets of necroptosis underlying the antidepressant mechanism of Xiaoyaosan. The mice model of depression was induced by chronic unpredictable mild stress (CUMS) for 6 weeks. Adult C57BL/6 mice were randomly divided into five groups, including control group, chronic unpredictable mild stress group, Xiaoyaosan treatment group, necrostatin-1 (Nec-1) group and solvent group. Drug intervention performed from 4 to 6 week of modeling. The mice in Xiaoyaosan treatment group received Xiaoyaosan by intragastric administration (0.254 g/kg/d), and mice in CUMS group received 0.5 ml physiological saline. Meanwhile, the mice in Nec-1 group were injected intraperitoneally (i.p.) with Nec-1 (10 mg/kg/d), and the equivalent volume of DMSO/PBS (8.3%) was injected into solvent group mice. The behavior tests such as sucrose preference test, forced swimming test and novelty-suppressed feeding test were measured to evaluate depressive-like behaviors of model mice. Then, the active ingredients in Xiaoyaosan and the related targets of depression and necroptosis were compiled through appropriate databases, while the "botanical drugs-active ingredients-target genes" network was constructed by network pharmacology analysis. The expressions of RIPK1, RIPK3, MLKL, -MLKL were detected as critical target genes of necroptosis and the potential therapeutic target compounds of Xiaoyaosan. Furthermore, the levels of neuroinflammation and microglial activation of hippocampus were measured by detecting the expressions of IL-1β, Lipocalin-2 and IBA1, and the hematoxylin and eosin (H&E) stained was used to observe the morphology in hippocampus sections. After 6-weeks of modeling, the behavioral data showed that mice in CUMS group and solvent group had obvious depressive-like behaviors, and the medication of Xiaoyaosan or Nec-1 could improve these behavioral changes. A total of 96 active ingredients in Xiaoyaosan which could regulate the 23 key target genes were selected from databases. Xiaoyaosan could alleviate the core target genes in necroptosis and improve the hippocampal function and neuroinflammation in depressed mice. The activation of necroptosis existed in the hippocampus of CUMS-induced mice, which was closely related to the pathogenesis of depression. The antidepressant mechanism of Xiaoyaosan included the regulation of multiple targets in necroptosis. It also suggested that necroptosis could be a new potential target for the treatment of depression.
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http://dx.doi.org/10.3389/fphar.2021.773562 | DOI Listing |
J Ethnopharmacol
December 2024
School of Chinese Medicine, Beijing University of Chinese Medicine, Beijing, 100029, PR China; Guangzhou Key Laboratory of Formula-Pattern of Traditional Chinese Medicine, Formula-Pattern Research Center, School of Traditional Chinese Medicine, Jinan University, Guangzhou, 510632, PR China. Electronic address:
Ethnopharmacological Relevance: Xiaoyaosan, a classic Chinese herbal formula, exhibits promising antidepressant effects. However, its specific antidepressant mechanisms remain incompletely understood. Previous studies have highlighted the significant role of DNA methylation in the pathogenesis of major depressive disorder (MDD).
View Article and Find Full Text PDFPhytomedicine
December 2024
College of Korean Medicine, Daejeon University, Daejeon, 34520, Republic of Korea; Institute of Bioscience & Integrative Medicine, Daejeon University, Daejeon, 34520, Republic of Korea. Electronic address:
Background: Soyo-san (Xiaoyao-san; SYS), a traditional herbal medicine formula, has been used for treating mood disorders, especially depression and anxiety. Modified SYS (mSYS) is formulated by adding or removing herbs to SYS, and is mainly used in cases of mood disorders with comorbid diseases such as diabetes, digestive disorders, and anorexia. However, there has been no detailed comparative analysis of the differences in efficacy and underlying neurological mechanisms between SYS and mSYS.
View Article and Find Full Text PDFHeliyon
October 2024
Faculty of Psychology, Southwest University, Chongqing, China.
Objective: Depression is a mental disorder characterized by persistent feelings of sadness, decreased interest or pleasure in activities and reduced energy. As a highly prevalent disorder, it seriously endangers the psychosocial functioning of patients. Many scholars have conducted clinical studies on the treatment of depression using different herbal remedies, but there are no studies that integrate these remedies to explore the general medication rule.
View Article and Find Full Text PDFFront Psychiatry
September 2024
Guangzhou Key Laboratory of Formula-pattern Research Center, School of Traditional Chinese Medicine, Jinan University, Guangzhou, China.
Front Pharmacol
August 2024
Department of Chinese Medicine, The First Affiliated Hospital of Bengbu Medical University, Bengbu, Anhui, China.
Introduction: Xiaoyaosan (XYS), a traditional Chinese formula, not only has good antitumor effects but also attenuates distress, anorexia, and quality of life (QoL) by regulating neurology, the microbiota, immunology, and oxidative stress. This study aimed to assess the effect of XYS on QoL, psychological pressure, and spiritual well-being in breast cancer patients undergoing adjuvant chemotherapy.
Methods: This prospective cohort study enrolled 176 postoperative breast cancer patients who received adjuvant chemotherapy combined with (n = 81) or without (n = 95) XYS for comparison.
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