INTERNATIONAL JOURNAL OF MASS SPECTROMETRY
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2018
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IF 1.826
Ning-Ning Zhao,Yu-Fei Sun,Li Zong,Shu Liu,Feng-Rui Song,Zhi-Qiang Liu,Shu-Ying Liu
Disorder of lipid metabolism is closely related to the incidence of Alzheimer's disease (AD). Regulation of lipid disorder is one of the important mechanisms of drug therapy for AD. In this study, serum lipidomics study based on an online liquid extraction surface analysis coupled to direct infusion mass spectrometry (Online-LESA-direct infusion MS) was established and applied to assess the efficacy of Ding-Zhi-Xiao-Wan (DZXW) for treating AD in rats by regulating lipid metabolism disorders. Dried serum spot (DSS) samples of 10 health control (HG), 10 AD, 10 DZXW, and 10 donepezil rats were directly detected by Online-LESA-direct infusion MS without prior treatments. And the acquired data was analyzed by multivariate statistical analyses such as PCA and PLS-DA to identify potential lipid biomarkers in serum. By this method, 15 compounds were screened and identified, belonging to phosphatidylcholines (PCs), sphingomyelins (SMs) and lysophosphatides (LPCs), which were considered as potential lipid biomarkers with AD mechanisms. Among them, the levels of PCs and SMs were markedly declined, and the levels of LPCs were increased in the AD group. Moreover, compared with administrating donepezil, the observed PCs and SMs were more up-regulation to normal levels with the treatment of DZXW in AD rats, which indicated that DZXW can play a better role in the treatment of AD by regulating lipid metabolism. And the results of the study also showed that the Online-LESA-direct infusion MS on DSS analytical strategy has a potential to become a high-throughput analysis method for large-scale clinical diagnostics analysis.
研究领域:
神经科学
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药理学
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代谢组学
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产品关联
DOI
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2024
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IF 4.8
Zhangjie Wu,Ying Yin,Ruiyi Liu,Xianhui Li,Yan Sun,Suk-yu Yau,Lei Wu,Yan Liu,Miroslav Adzic,Hailou Zhang,Gang Chen
Ethnopharmacological relevance Jiawei-Xiaoyao Pill (JWX), a classic formula in traditional Chinese medicine, is derived from Xiaoyao Pill by adding significant amounts of Gardeniae Fructus (GF) and Moutan Cortex (MC). It is frequently used for the treatment of depression. JWX has been demonstrated to uniquely elicit rapid antidepressant-like effects within the prescribed dosage range. To date, GF has been shown to have rapid antidepressant-like effects, but a much higher dose is required than its proportion in JWX. It is assumed that the synergism of GF with a minimum number of other herbs in JWX serves as a refined formula that exerts these rapid antidepressant-like effects. Identification of a refined formula is important for prioritizing the herbs and ingredients to optimize the quality control of JWX. However, such a refined formula for JWX has not been identified yet Aim of the study Here we aimed to identify a refined formula derived from JWX for optimized rapid antidepressant-like effects. Since the neuroinflammation mechanism involving in depression treatment has not been previously investigated for JWX, we tested the mechanism for both JWX and the refined formula Materials and methods Individual herbs (MC ; ASR, Angelica Sinensis Radix; Bupleuri Radix; Paeonia Radix Alba ) that show antidepressant-like responses were mixed with GF at the proportional dosage in JWX to identify the refined formula. Rapid antidepressant-like effects were assessed by using NSF (Novelty Suppressed Feeding Test) and other behavioral tests following a single administration. The identified formula was further tested using a lipopolysaccharide (LPS)-induced depressive model, and the molecular signaling mechanisms were investigated using western blot analysis, immunofluorescence, and pharmacological inhibition of mTOR signaling. Scopolamine (Scop) is used as a positive control for induction of rapid antidepressant effects Results A combination of GF, MC and ASR (GMA) at their dosages proportional to JWX induced behavioral signs of rapid antidepressant-like responses in both normal and LPS-treated mice, with the antidepressant-like effects sustained for 5 d. Similar to JWX or Scop, GMA rapidly reduced the neuroinflammation signaling of Iba-1-NF-кB, enhanced neuroplasticity signaling of CaMKII-mTOR-BDNF, and attenuated the upregulated expressions of the NMDAR sub-units GluN1 and GluN2B in the hippocampus of LPS-treated mice. GMA, JWX and Scop rapidly restored the number of BDNF-positive cells reduced by LPS treatment, in the CA3 region of the hippocampus. Furthermore, rapamycin, a selective inhibitor of mTOR, blunted the rapid antidepressant-like effects and hippocampal BDNF signaling upregulation by GMA Conclusion GMA may serve as a refined formula from JWX, capable of inducing rapid antidepressant-like effects. In LPS-induced depression model, the effects of GMA were mediated via rapidly alleviating neuroinflammation and enhancing neuroplasticity
研究领域:
药理学
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神经科学
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中医
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行为科学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2023
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IF 5.4
Zheng-Wei Zhang,Pei Han,Jie Fu,Hang Yu,Hui Xu,Jia-Chun Hu,Jin-Yue Lu,Xin-Yu Yang,Hao-Jian Zhang,Meng-Meng Bu,Jian-Dong Jiang,Yan Wang
Ethnopharmacological relevance Traditional Chinese medicines (TCMs) are often prepared in oral dosage forms, making TCMs interact with gut microbiota after oral administration, which could affect the therapeutic effect of TCM. Xiaoyao Pills (XYPs) are a commonly used TCM in China to treat depression. The biological underpinnings, however, are still in its infancy due to its complex chemical composition. Aim of the study The study aims to explore XYPs’ underlying antidepressant mechanism from both in vivo and in vitro. Materials and methods XYPs were composed of 8 herbs, including the root of Bupleurum chinense DC. , the root of Angelica sinensis (Oliv.) Diels, the root of Paeonia lactiflora Pall., the sclerotia of Poria cocos (Schw.) Wolf, the rhizome of Glycyrrhiza uralensis Fisch., the leaves of Mentha haplocalyx Briq., the rhizome of Atractylis lancea var. chinensis (Bunge) Kitam., and the rhizome of Zingiber officinale Roscoe, in a ratio of 5:5:5:5:4:1:5:5. The chronic unpredictable mild stress (CUMS) rat models were established. After that, the sucrose preference test (SPT) was carried out to evaluate if the rats were depressed. After 28 days of treatment, the forced swimming test and SPT were carried out to evaluate the antidepressant efficacy of XYPs. The feces, brain and plasma were taken out for 16SrRNA gene sequencing analysis, untargeted metabolomics and gut microbiota transformation analysis. Results The results revealed multiple pathways affected by XYPs. Among them, the hydrolysis of fatty acids amide in brain decreased most significant via XYPs treatment. Moreover, the XYPs' metabolites which mainly derived from gut microbiota (benzoic acid, liquiritigenin , glycyrrhetinic acid and saikogenin D) were found in plasma and brain of CUMS rats and could inhibit the levels of FAAH in brain, which contributed to XYPs’ antidepressant effect. Conclusions The potential antidepressant mechanism of XYPs by untargeted metabolomics combined with gut microbiota-transformation analysis was revealed, which further support the theory of gut-brain axis and provide valuable evidence of the drug discovery .
研究领域:
药理学
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神经科学
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微生物学
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中医药
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）