An Integrated Pharmacology-Based Analysis for Antidepressant Mechanism of Chinese Herbal Formula Xiao-Yao-San

Yuan, Naijun; Gong, Lian; Tang, Kairui; He, Liangliang; Hao, Wenzhi; Li, Xiaojuan; Ma, Qingyu; Chen, Jiaxu

doi:10.3389/fphar.2020.00284

Cited by 51 publications

(27 citation statements)

References 57 publications

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“…To explore whether XYS could suppress the lipid accumulation induced by CORT, we generated an ox-LDL and CORTinduced stress model in rat PMs following the treatment of XYS-containing serum. Our results showed that CORTinduced stress inhibited proliferation and increased lipid accumulation in PMs, which was similar to the results of previous studies (24,25). We also found that serum including XYS could dose-dependently increase proliferation, decrease lipid accumulation, and elevate TC level in CORT-induced PMs.…”

Section: Discussionsupporting

confidence: 91%

Xiaoyaosan (Tiaogan-Liqi therapy) protects peritoneal macrophages from corticosterone-induced stress by regulating the interaction between glucocorticoid receptor and ABCA1

Chen

Huang

et al. 2020

Ann Transl Med

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Background: Previous studies have reported that Xiaoyaosan (XYS), Tiaogan-Liqi therapy, has a protective function in depressive disorder, and can regulate body weight and corticosterone (CORT) level. However, little is known about the effect of XYS in treating atherosclerosis. This study aimed to explore the influence XYS on macrophage foam cell formation and related mechanism.Methods: Rat peritoneal macrophages (PMs) were separated and stimulated with CORT and oxidized low density lipoprotein (ox-LDL). The serum was obtained from rats treated with different doses of XYS and was added into the medium for macrophages. Then, the cell activity and lipid content of PMs were measured through Cell Counting Kit-8 (CCK-8) assay and oil red staining, respectively. The expressions of glucocorticoid receptor (GR), ATP binding cassette subfamily A member 1 (ABCA1), and heat shock protein 90 (HSP90) were detected. In addition, overexpression of GR and ABCA1 was performed and the effect on XYS treatment was subsequently assessed. Results:The CCK-8 assay showed the serum increased cell activity of CORT-induced stress PMs in a XYS dose-dependent manner. Oil red staining and enzyme-linked immunosorbent assay (ELISA) showed that the serum decreased lipids of PMs. In the XYS treated groups, HSP90 protein was decreased and protein levels of ABCA1 and GR were increased in cytoplasm, while GR protein in nucleus was decreased.Co-immunoprecipitation (Co-IP) assay indicated GR might interact with HSP90 and be involved with the function of XYS. Furthermore, overexpression of GR attenuated the protective function of XYS on CORTinduced stress in PMs, while overexpression of ABCA1 enhanced that.Conclusions: This study denoted that XYS could protect PMs from CORT-induced stress by regulating the interaction of GR and ABCA1, which might contribute to the treatment of atherosclerosis.

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Section: Discussionsupporting

confidence: 91%

Xiaoyaosan (Tiaogan-Liqi therapy) protects peritoneal macrophages from corticosterone-induced stress by regulating the interaction between glucocorticoid receptor and ABCA1

Chen

Huang

et al. 2020

Ann Transl Med

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“…The expression of P-Akt in the hippocampus of sodium arseniteexposed rats was significantly lower than that in the control group (Srivastava et al, 2018). Naijun Yuan et al also found that Xiaoyaosan could increase the P-AKT/AKT ratio in cortisolinduced PC-12 cells (Yuan et al, 2020). Decreased Akt activity and decreased extracellular regulatory kinase activity coexist in depression, and autopsy studies have demonstrated that the activity of the PI3K-Akt signaling pathway is decreased in suicidal patients with major depression (Karege et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

“…at a ratio of 5:5:5:5:5:5:4:1. Xiaoyaosan (batch number J2447) was provided by Jiuzhitang Co., Ltd. (Changsha, China) and was prepared as previously described (Yuan et al, 2020). One gram of fine powder of Xiaoyaosan was obtained from 2.10 g of raw herbs.…”

Section: Preparation Of Xiaoyaosanmentioning

confidence: 99%

Xiaoyaosan Alleviates Hippocampal Glutamate-Induced Toxicity in the CUMS Rats via NR2B and PI3K/Akt Signaling Pathway

Zhou

Liu

et al. 2021

Front. Pharmacol.

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Purpose: It is revealed that Xiaoyaosan could reduce glutamate level in the hippocampus of depressed rats, whose metabolism leads to the pathophysiology of depression. However, the underlying mechanism remains unclear. This study aims to explore the effect of Xiaoyaosan on glutamate metabolism, and how to regulate the excitatory injury caused by glutamate.Methods: Rats were induced by chronic unpredictable mild stress, then divided into control, vehicle (distilled water), Xiaoyaosan, fluoxetine, vehicle (DMSO), Xiaoyaosan + Ly294002 and Ly294002 groups. Ly294002 was microinjected into the lateral ventricular catheterization at 5 mM. Xiaoyaosan (2.224 g/kg) and fluoxetine (2.0 mg/kg) were orally administered for three weeks. The open field test (OFT), forced swimming test (FST), and sucrose preference test (SPT) were used to assess depressive behavior. The glutamate and corticosterone (CORT) levels were detected by ELISA. Western blot, immunochemistry or immunofluorescence were used to detect the expressions of NR2B, MAP2, PI3K and P-AKT/Akt in the hippocampal CA1 region. The mRNA level of MAP2, NR2B and PI3K were detected by RT-qPCR.Results: Compared to the rats in control group, body weight and food intake of CUMS rats was decreased. CUMS rats also showed depression-like behavior as well as down regulate the NR2B and PI3K/Akt signaling pathway. Xiaoyaosan treatments could increase food intake and body weight as well as improved time spent in the central area, total distance traveled in the OFT. Xiaoyaosan could also decrease the immobility time as well as increase the sucrose preference in SPT. Moreover, xiaoyaosan decreased the level of glutamate in the hippocampal CA1 region and serum CORT in CUMS rats. Furthermore, xiaoyaosan improved the expression of MAP2 as well as increased the expression of NR2B, PI3K and the P-AKT/AKT ratio in the hippocampal CA1 region in the CUMS rats.Conclusion: Xiaoyaosan treatment can exert the antidepressant effect by rescuing hippocampal neurons loss induced by the glutamate-mediated excitotoxicity in CUMS rats. The underlying pathway maybe through NR2B and PI3K/Akt signaling pathways. These results may suggest the potential of Xiaoyaosan in preventing the development of depression.

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“…Systems pharmacology is an emerging systematic methodology that combines oral bioavailability screening, multiple drug targets prediction and validation, and network pharmacology, providing a holistic approach to explore the targets and mechanisms of TCM. In recent years, systems pharmacology has been widely used to reveal the potential mechanism of TCM formulas ( Liu et al, 2016 ; Yuan et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

Systems Pharmacology Approach and Experiment Evaluation Reveal Multidimensional Treatment Strategy of LiangXueJieDu Formula for Psoriasis

et al. 2021

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Clinical studies have demonstrated the anti-psoriatic effect of the LiangXueJieDu (LXJD) herbal formula. However, the systemic mechanism and the targets of the LXJD formula have not yet been elucidated. In the present study, a systems pharmacology approach, metabolomics, and experimental evaluation were employed. First, by systematic absorption-distribution-metabolism-excretion (ADME) analysis, 144 active compounds with satisfactory pharmacokinetic properties were identified from 12 herbs of LXJD formula using the TCMSP database. These active compounds could be linked to 125 target proteins involved in the pathological processes underlying psoriasis. Then, the networks constituting the active compounds, targets, and diseases were constructed to decipher the pharmacological actions of this formula, indicating its curative effects in psoriasis treatment and related complications. The psoriasis-related pathway comprising several regulatory modules demonstrated the synergistic mechanisms of LXJD formula. Furthermore, the therapeutic effect of LXJD formula was validated in a psoriasis-like mouse model. Consistent with the systems pharmacology analysis, LXJD formula ameliorated IMQ-induced psoriasis-like lesions in mice, inhibited keratinocyte proliferation, improved keratinocyte differentiation, and suppressed the infiltration of CD3+ T cells. Compared to the model group, LXJD formula treatment remarkably reduced the expression of inflammatory cytokines and factors, such as IL-1β, IL-6, TNF-α, Cox2, and inhibited the phosphorylation of p-P65, p-IқB, p-ERK, p-P38, p-PI3K, p-AKT, indicating that LXJD formula exerts its therapeutic effect by inhibiting the MAPK, PI3K/AKT, and NF-қB signaling pathways. The metabolic changes in the serum of psoriasis patients were evaluated by liquid chromatography coupled with orbitrap mass spectrometry (LC-MS). The LXJD formula improved two perturbed metabolic pathways of glycerophospholipid metabolism and steroid hormone biosynthesis. Overall, this study revealed the complicated anti-psoriatic mechanism of LXJD formula and also offered a reliable strategy to elucidate the complex therapeutic mechanism of this Chinese herbal formula in psoriasis from a holistic perspective.

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An Integrated Pharmacology-Based Analysis for Antidepressant Mechanism of Chinese Herbal Formula Xiao-Yao-San

Cited by 51 publications

References 57 publications

Xiaoyaosan (Tiaogan-Liqi therapy) protects peritoneal macrophages from corticosterone-induced stress by regulating the interaction between glucocorticoid receptor and ABCA1

Xiaoyaosan (Tiaogan-Liqi therapy) protects peritoneal macrophages from corticosterone-induced stress by regulating the interaction between glucocorticoid receptor and ABCA1

Xiaoyaosan Alleviates Hippocampal Glutamate-Induced Toxicity in the CUMS Rats via NR2B and PI3K/Akt Signaling Pathway

Systems Pharmacology Approach and Experiment Evaluation Reveal Multidimensional Treatment Strategy of LiangXueJieDu Formula for Psoriasis

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