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Comparative bioactivity evaluation and chemical profiling...
Glycyrrhiza uralensis is a popular medicinal plant worldwide. Its roots and rhizomes are used as the traditional Chinese medicine Gan-Cao. However, little is known on medicinal potential and chemistry of the other parts of the plant. In this work, the biological activities and chemical components of the roots, stems, leaves, and seeds of G. uralensis were investigated comparatively. The four parts exhibited different but noticeable biological activities. The chemicals in the four parts were globally characterized by liquid chromatography coupled with mass spectrometry (LC/MS) on a Thermo Vanquish UHPLC system connected to a Q-Exactive quadrupole Orbitrap mass spectrometer. By integrating molecular networking, compound spectral matching, MS2LDA-based substructure recognition, and reference standards comparison, a total of 1301 compounds were rapidly characterized. Three flavonoid C-glycosides were purified and their structures were identified by NMR spectroscopic analysis. Orthogonal partial least squares-discriminate analysis (OPLS-DA) further revealed 196 differential chemicals for the four parts. This work will promote the medicinal resource utilization of G. uralensis.
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2. Materials and methods
2.1. Chemicals and reagents
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1, 1-diphenyl-2-picrylhydrazyl (DPPH) and ascorbic acid were from DeSiTe Biological Technology Co., Ltd. (Chengdu, China).
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Astilbin ameliorates depressive-like behavior caused ...
Postnatal immune activation (PIA) can affect normal brain development and increase the risk of behavioral abnormalities in later life, including depressive-like behavior. Therefore, there is an urgent need to find safe and effective clinical medications for PIA. Recently, the protective effect of astilbin (ASB) in nervous system diseases has attracted much attention. However, the effect of ASB on neurodevelopmental diseases remains unclear. In this study, we used a lipopolysaccharide (LPS)-induced PIA mouse model and found that ASB specificall
improved PIA-induced depressive-like behavior but not anxiety-like behavior in adult mice. Astrocytes play an essential role in regulating neuroinflammation, and are the most abundant cell type in the brain. In the PIA model, we found that ASB selectively inhibited astrocyte activation but not microglial activation in the cortex
and hippocampus. Moreover, our results showed that ASB specifically upregulated the expression of menin protein in astrocytes and blocked the entry of P65 protein into the nucleus, thus inhibiting the secretion of IL-1β and TNF-α by astrocytes. Taken together, ASB reduced the occurrence of astrocyte-mediated neuroinflammation by targeting menin, thereby attenuating the PIA-induced depressive-like behavior. Our results reveal that ASB may be an attractive antidepressant drug and exert an antidepressant effect in PIA. In terms of drug selection, ASB may be a specific drug for patients with depressive symptoms.
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2.2. Experimental design for drug treatment
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The experimental design and drug treatment schedule are shown in Fig. 1A. The experimental animals were randomly divided into three groups: control, PIA, and PIA+ASB. ASB (DESITE, Chengdu, China)was dissolved in 1% DMSO and diluted with saline. For the PIA+ASB group, LPS and ASB (4 mg/kg/day) were administered intraperitoneally from P3 for 3 days.
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One-Way Intestinal Perfusion of PVP/VA–Poloxamer ...
Turmeric was the dried rhizome of Curcuma longa L., and its extract had important pharmacological effects such as anti-tumor, cholagogic, and antioxidant. However,curcuma extract had poor water solubility and low bioavailability, which had become the main limiting factor for its clinical application. The purpose of this study was to prepare PVP/VA–Poloxamer–188–curcuma extract solid dispersion (PAP–CSD) to improve the solubilityand bioavailability of the curcuma extract. The intestinal absorption mechanism of solid dispersion of this extract was studied by one-way intestinal perfusion in rats. PAP–CSD,PVP/VA–curcuma extract solid dispersion (PA–CSD) and Poloxamer–188–curcuma extract solid dispersion (P–CSD) was able to improve the intestinal absorption of the curcuma extract (P< 0.05), and PAP–CSD (combined use of two carriers) was better than that of PA–CSD and P–CSD. CCK8 method was used to investigate the effects of the curcuma extract and PAP–CSD on the proliferation of hepatic stellate cells (HSC)–T6 cells. The inhibitory effect ofPAP–CSD on the proliferation of HSC-T6 cells, related to the p38 MAPK pathway, was better than that of the curcuma extract.
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Materials
Bisdemethoxycurcumin reference substance, demethoxycurcumin reference substance, and curcumin reference substance were all purchased from Chengdu DST Biotechnology Co., Ltd. (batch number: DST191009-021, DST190910-030, DST200412-014),
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Effects of HSYA on serum and brain cholesterol levels....
Abstract
Hydroxysafflor yellow A (HSYA) has a certain improvement effect on Alzheimer's disease (AD) rats, but its specific mechanism is still unclear. The purpose of this study was to observe the regulatory effect of HSYA on learning and memory ability of AD rats induced by Aβ1-42. To explore the effective targets and potential molecular mechanisms of HSYA in AD treatment based on quantitative proteomics.
Through the Morris water maze experiment, we found that after HSYA treatment, the learning ability of rats in the model group has been significantly improved. Quantitative proteomics results showed that among the 11 common differential proteins between the "model/sham operation" comparison group and the "HSYA treatment/model" comparison group, the cholesterol synthesis rate-limiting enzyme mevalonate decarboxylase (Mvd) Western Blot results are consistent with the results of quantitative proteomics analysis.We found that HSYA can inhibit the expression of BACE protein in hippocampus of AD rats and decrease the level of Aβ1-42. Besides, HSYA could also reduce cholesterol levels in serum and hippocampus. In summary, HSYA can effectively improve learning and memory disorders in AD rats, and exert neuroprotective effects by effectively controlling serum and brain cholesterol to down-regulate the expression of BACE and thus reduce the content of Aβ1-42.
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HSYA (purity > 98%，Fig. 1a) was purchased from Chengdu DeSiTe Biological Accepted ManuscriptTechnology Co., Ltd. (Sichuan, China); 600mg HSYA was dissolved in 200ml double distilled water and prepared into 3 mg/mL HSYA reserve solution and stored at 4℃. The dose of HSYA was 30mg/kg, and the volume of HSYA was calculated according to body weight
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原文链接：https://doi.org/10.1080/00207454.2022.2082964
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A novel ion mobility separation-enabled ......
ABSTRACT
To elucidate the chemical composition of a traditional Chinese medicine (TCM) formula necessitates the development of more potent analytical strategies, because of the complexity as a result of the superposition of multiple drugs. Fangji Huangqi Decoction (FHD) is a fourcomponent TCM formula composed by complicated chemical constituents. By using the VionTM ion mobility quadrupole time-of-flight (IM-QTOF) mass spectrometer, we present a novel IM separation-enabled and precursor ions list (PIL)-included high-definition data-dependent acquisition (HDDDA) approach, and apply it to the multicomponent characterization of FHD by cou-pling to ultra-high performance liquid chromatography.
Chromatographic separation was conducted on a CORTECS UPLC T3 column, while HDDDA was employed for MS2 data acquisition in both the negative and positive electrospray-ionization (ESI) modes. The PILs of FHD in two ESI modes were created based on the phytochemical knowledge of four component drugs and mass defect filtering, which ultimately could obtain 316 and 258 targeted masses, respectively, from the full-scan MS1 data. Interestingly, the additional inclusion of PILs in HDDDA could improve the coverage on the target components by 12% (ESI–) and 48% (ESI + ). Structural elucidation was performed by in-house database-driven automatic peak annotation using UNIFITM. We could identify or tentatively characterize 203 components from FHD, involving 25 alkaloids, 86 flavonoids, 48 triterpenoids (saponins), 16 lactones, and 28 others). It is the first report regarding the method development of HDDDA that targets the global TCM components characterization, and the findings obtained would benefit the quality control and the secondary development of FHD.
Reagents and chemicals
Chengdu Desite Biotechnology Co., Ltd. (Chengdu, China), were used as the reference compounds in this work.
原文链接：http://creativecommons.org/licenses/by-nc-nd/4.0/
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A novel hybrid scan approach enabling the ion-mobility......
ABSTRACT
Data-dependent acquisition (DDA) and data-independent acquisition (DIA)-based MSn strategies are extensively applied in metabolites characterization. DDA gives accurate MSn information, but receives low coverage, while DIA covers the entire mass range, but the precursor-product ions matching often yields false positives. Currently available MS scan approaches rarely integrate DIA and DDA within a dutycircle. Utilizing a Vion™IM-QTOF (ion mobility-quadrupole time-of-flight) mass spectrometer, we report a novel hybrid scan approach, namely HDDIDDA, which involves three scan events: 1) IM-enabled full scan (MS1), 2) high-definition MSE (HDMSE) of all precursor ions (MS2); and 3) high-definition DDA (HDDDA) of top N precursors (MS2).
As a proof-of-concept, the HDDIDDA approach combined with offline two-dimensional liquid chromatography (2D-LC) was applied to characterize the multiple ingredients from a reputable Chinese patent medicine, Compound Danshen Dripping Pill (CDDP) used for treating the cardiovascular diseases. An off-line 2D-LC system by configuring an XBridge Amide column and an HSS T3 column showed a measurable orthogonality of 0.92 and enhanced the separation of coeluting components. A fit-for-purpose HDDIDDA methodology was developed in the negative mode to characterize saponins and salvianolic acids, while tanshinones in the positive mode. Computational workflows to efficiently process the acquired HDMSE and HDDDA data were established, and the searching of an in-house CDDP library (recording 712 compounds) eventually characterized 403 components from CDDP, indicating approximate 12-fold improvement compared with the previous report. The HDDIDDA approach can measure collision cross section of each component, and merges the merits ofDIA and DDA in MS2 data acquisition.
Chemicals and reagents
Desite Biotechnology Co., Ltd. (Chengdu, China), were used as the reference compounds with their chemical structures and information detailed in Fig. S1 and Table S1, respectively.
原文链接：https://doi.org/10.1016/j.aca.2021.339320
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