JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES
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2023
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IF 3
Laisen Wang,Liyue Hou,Siliang Han,Huaizhong Guo,Ligai Bai
A monolithic solid-phase extraction (SPE) cartridge packed with a composite adsorbent was fabricated via polymerization using dodecene as the monomer with the porous organic cage (POC) material doped, combing with an analytical column through a high-performance liquid chromatography (HPLC) instrument, which was used for the online extraction and separation of 23-acetyl alismol C, atractylodes lactone II and atractylodes lactone III from Zexie Decoction. The POC-doped adsorbent shows porous structure with a relatively high specific surface area of 85.50 m 2 /g, which was obtained from the characterizations of a scanning electron microscope and an automatic surface area and porosity analyser. Efficient extraction and separation of three target terpenoids was achieved by an online SPE-HPLC method based on the POC-doped cartridge, which exhibits strong matrix-removal ability and good terpenoids-retention ability with a high adsorption capacity, due to the interactions of hydrogen bond and hydrophobicity between the terpenoids and the POC-doped adsorbent. Method validation shows good linearity ( r ≥ 0.9998) of the regression equation, and high accuracy with the spiked recovery in the range of 99.2 %-100.8 % of the proposed method. Compared to the generally disposable adsorbent, this work fabricated a reusable monolithic cartridge, which can be used for at least 100 times, with the RSD based on the peak area of the three terpenoids less than 6.6 %.
研究领域:
分析化学
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药学
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中药学
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产品关联
DOI
PubMed
高影响因子
MEDIATORS OF INFLAMMATION
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2022
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IF 4.529
Jieru Han,Wenhao Li,Guangyu Shi,Yunlei Huang,Xutao Sun,Na Sun,Deyou Jiang
Ulcerative colitis (UC) is a complex inflammatory bowel disease (IBD) associated with mitochondrial function. Atractylenolide III (AT III) is a natural product with anti-inflammatory effects. The aim of this work is to investigate the protective effect of AT III on UC and its underlying mechanisms. Herein, dextran sulfate sodium- (DSS-) induced mice and lipopolysaccharide- (LPS-) stimulated intestinal epithelial cells (IEC-6) were employed to mimic UC pathologies in vivo and in vitro. The results showed that in DSS-induced mice, AT III significantly reversed the body weight loss, colon length reduction, disease activity index (DAI) increase, and histological damage. The production of proinflammatory factors and reduction of antioxidants in colitis were suppressed by AT III. In addition, we demonstrated that AT III attenuated the intestinal epithelial barrier destruction and mitochondrial dysfunction induced by DSS, which was similar to the in vitro results in LPS-treated IEC-6 cells. The protein levels of p-AMPK, SIRT1, and PGC-1α along with acetylated PGC-1α were also upregulated by AT III in vivo and in vitro. In conclusion, these findings support that AT III may protect against mitochondrial dysfunction by the activation of the AMPK/SIRT1/PGC-1α signaling pathway during UC development.
研究领域:
药理学
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免疫学
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胃肠病学
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分子生物学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2024
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IF 4.8
Mengdi Wu,Xiangli Yan,Huang Huang,Xiuhui Guo,Ming Bai,Baoying wang,Pan Su,Yucheng Li,Erping Xu
Ethnopharmacological relevance Modified Danzhi Xiaoyao San (MDXS) is an effective clinical prescription for depression in China, which was deprived of Danzhi Xiaoyao San in the Ming Dynasty. MDSX has significant implications for the development of new antidepressants, but its pharmacological mechanism has been rarely studied. Aim of the study To reveal the active components and molecular mechanism of MDXS in treating depression through network pharmacology and experimental verification in vivo and in vitro . Materials and methods UPLC-Q-TOF-MS/MS was used to identify the chemical components in the MDXS freeze-dried powder, drug-containing serum, and cerebrospinal fluid (CSF). Based on the analysis of prototype components in the CSF, the major constituents, potential therapeutic targets and possible pharmacological mechanisms of MDXS in treating depression were investigated using network pharmacological and molecular docking. Then corticosterone (CORT)-induced mice model of depression was established to investigate the antidepressant effects of MDXS. HT22 cells were cultured to verify the neuroprotective effects and core targets of the active components. Results There were 81 compounds in MDXS freeze-dried powder, 36 prototype components in serum, and 13 prototype components in CSF were identified, respectively. Network pharmacology analysis showed that these 13 prototype components in the CSF shared 190 common targets with depression, which were mainly enriched in MAPK and PI3K/AKT signaling pathways. PPI analysis suggested that AKT1 and MAPK1 (ERK1/2) were the core targets. Molecular docking revealed that azelaic acid (AA), senkyunolide A (SA), atractylenolide III (ATIII), and tokinolide B (TB) had the highest binding energy with AKT1 and MAPK1. Animal experiments verified that MDXS could reverse CORT-induced depression-like behaviors, improve synaptic plasticity, alleviate neuronal injury in hippocampal CA3 regions, and up-regulate the protein expression of p-ERK1/2 and p-AKT. In HT22 cells, azelaic acid, senkyunolide A, and atractylenolide III significantly protected the cell injury caused by CORT, and up-regulated the protein levels of p-ERK1/2 and p-AKT. Conclusions These results suggested that MDXS may exert antidepressant effects partially through azelaic acid, senkyunolide A, and atractylenolide III targeting ERK1/2 and AKT.
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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分子生物学
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产品关联
DOI
PubMed
高影响因子
Engineering
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2021
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IF 7.553
Lu Zhao,Hao Liu,Yingchao Wang,Shufang Wang,Dejin Xun,Yi Wang,Yiyu Cheng,Boli Zhang
Xuanfeibaidu Formula (XFBD) is a Chinese medicine used in the clinical treatment of coronavirus disease 2019 (COVID-19) patients. Although XFBD has exhibited significant therapeutic efficacy in clinical practice, its underlying pharmacological mechanism remains unclear. Here, we combine a comprehensive research approach that includes network pharmacology, transcriptomics, and bioassays in multiple model systems to investigate the pharmacological mechanism of XFBD and its bioactive substances. High-resolution mass spectrometry was combined with molecular networking to profile the major active substances in XFBD. A total of 104 compounds were identified or tentatively characterized, including flavonoids, terpenes, carboxylic acids, and other types of constituents. Based on the chemical composition of XFBD, a network pharmacology-based analysis identified inflammation-related pathways as primary targets. Thus, we examined the anti-inflammation activity of XFBD in a lipopolysaccharide-induced acute inflammation mice model. XFBD significantly alleviated pulmonary inflammation and decreased the level of serum proinflammatory cytokines. Transcriptomic profiling suggested that genes related to macrophage function were differently expressed after XFBD treatment. Consequently, the effects of XFBD on macrophage activation and mobilization were investigated in a macrophage cell line and a zebrafish wounding model. XFBD exerts strong inhibitory effects on both macrophage activation and migration. Moreover, through multimodal screening, we further identified the major components and compounds from the different herbs of XFBD that mediate its anti-inflammation function. Active components from XFBD, including Polygoni cuspidati Rhizoma , Phragmitis Rhizoma , and Citri grandis Exocarpium rubrum , were then found to strongly downregulate macrophage activation, and polydatin, isoliquiritin, and acteoside were identified as active compounds. Components of Artemisiae annuae Herba and Ephedrae Herba were found to substantially inhibit endogenous macrophage migration, while the presence of ephedrine, atractylenolide I, and kaempferol was attributed to these effects. In summary, our study explores the pharmacological mechanism and effective components of XFBD in inflammation regulation via multimodal approaches, and thereby provides a biological illustration of the clinical efficacy of XFBD.
研究领域:
药理学
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免疫学
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转录组学
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中医药
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生物化学
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产品关联
DOI
PubMed
高影响因子
Cell Metabolism
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2022
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IF 31.373
Zu-Guo Zheng,Yin-Yue Xu,Wen-Ping Liu,Yang Zhang,Chong Zhang,Han-Ling Liu,Xiao-Yu Zhang,Run-Zhou Liu,Yi-Ping Zhang,Meng-Ying Shi,Hua Yang,Ping Li
Summary sn-1,2-diacylglycerol (sn-1,2-DAG)-mediated activation of protein kinase Cε (PKCε) is a key pathway that is responsible for obesity-related lipid metabolism disorders, which induces hepatic insulin resistance and type 2 diabetes. No small molecules have been previously reported to ameliorate these diseases through this pathway. Here, we screened and identified the phytochemical atractylenolide II (AT II) that reduces the hepatic sn-1,2-DAG levels, deactivates PKCε activity, and improves obesity-induced hyperlipidemia, hepatosteatosis, and insulin resistance. Furthermore, using the ABPP strategy, the diacylglycerol kinase family member DGKQ was identified as a direct target of AT II. AT II may act on a novel drug-binding pocket in the CRD and PH domains of DGKQ to thereby allosterically regulate its kinase activity. Moreover, AT II also increases weight loss by activating DGKQ-AMPK-PGC1α-UCP-1 signaling in adipose tissue. These findings suggest that AT II is a promising lead compound to improve obesity-induced insulin resistance.
研究领域:
药理学
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代谢
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内分泌学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Journal of Inflammation Research
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2022
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IF 4.631
Ling Li,Yaoyao Du,Yang Wang,Ning He,Bing Wang,Tong Zhang
Background Gastric ulcer (GU) is the most common multifactor gastrointestinal disorder affecting millions of people worldwide. There is evidence that gut microbiota is closely related to the development of GU. Atractylone (ATR) has been reported to possess potential biological activities, but research on ATR alleviating GU injury is unprecedented.Methods Helicobacter pylori (H. pylori)-induced GU model in zebrafish and ethanol-induced acute GU model in rat were established to evaluate the anti-inflammatory and ulcer inhibitory effects of ATR. Then, 16S rRNA sequencing and metabolomics analysis were performed to investigate the effect of ATR on the microbiota and metabolites in rat feces and their correlation.Results Therapeutically, ATR inhibited H. pylori-induced gastric mucosal injury in zebrafish. In the ulceration model of rat, ATR mitigated the gastric lesions damage caused by ethanol, decreased the ulcer area, and reduced the production of inflammatory factors. Additionally, ATR alleviated the gastric oxidative stress injury by increasing the activity of superoxide dismutase (SOD) and decreasing the level of malondialdehyde (MDA). Furthermore, ATR played a positive role in relieving ulcer through reshaping gut microbiota composition including Parabacteroides and Bacteroides and regulating the levels of metabolites including amino acids, short-chain fatty acids (SCFAs), and bile acids.Conclusion Our work sheded light on the mechanism of ATR treating GU from the perspective of the gut microbiota and explored the correlation between gut microbiota, metabolites, and host phenotype.
研究领域:
药理学
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胃肠病学
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微生物学
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代谢组学
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动物模型
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产品关联
DOI
PubMed
高影响因子
TECHNOLOGY AND HEALTH CARE
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2023
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IF 1.6
Song Xiaolong,Wang Lei,Liu Min,Pan Renyou,Song Jun,Kong Junhong
BACKGROUND: Hypertension is a well-recognized risk factor for cardiovascular, which is also a critical factor in causing myocardial fibrosis (MF). OBJECTIVE: The study aimed to explore the effect of Atractylenolide II (ATL-II) on MF and oxidative stress in spontaneous hypertension rats (SHR). METHODS: The body weight of rats after injection of ATL-II was quantitatively analyzed. The left ventricular function of SHR was evaluated by Echocardiographic. HE staining, Masson trichrome staining, left ventricular mass index (LVMI) and immunofluorescence was applied to investigate the effects of ATL-II on MF. RT qPCR was used to detect the Collagen I, α-SMA, Fibronectin, and Vimentin mRNA expression levels in myocardial slices. The effect ATL-II on cardiomyocyte apoptosis was detected by TUNEL staining and western blot. An immunohistochemistry assay was conducted to detect α-SMA protein and TGF-β1 protein. The contents of H2O2, GSH-PX, SOD, and MDA were measured by colorimetry. RESULTS: ATL-II could dose-dependently improve the BW of SHRs (P< 0.05) and enhance myocardial function. Moreover, ATL-II effectively reduced cardiomyocyte apoptosis in SHRs. Alternatively, ATL-II could inhibit the Collagen I, α-SMA, Fibronectin, and Vimentin mRNA and protein expression levels in SHRs. ATL-II could ameliorate oxidative stress by improving the activities of SOD and GSH-PX and lowering the contents of H2O2 and MDA in ATL-II-treated SHRs, which reach about 80%. CONCLUSION: ATL-II could exert an inhibiting effect on MF and oxidative stress in SHRs. Hence, ATL-II may hold promise for the treatment of MF and oxidative stress in Spontaneous Hypertension.
研究领域:
心脏病学
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药理学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Science
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2024
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IF 14.3
Xietao Ye,Yuping Liu,Liangyin Wei,Yeyang Sun,Xiaoran Zhang,Hong Wang,Hong Guo,Xiaoying Qin,Xiaoqi Li,Ding Qu,Jiege Huo,Yan Chen
Microsatellite-stable colorectal cancer (MSS-CRC) exhibits resistance to programmed cell death protein-1 (PD-1) therapy. Improving the infiltration and tumor recognition of cytotoxic T-lymphocytes (CTLs) is a promising strategy, but it encounters huge challenges from drug delivery and mechanisms aspects. Here, a zeolitic imidazolate framework (ZIF) coated with apoptotic body membranes derived from MSS-CRC cells is engineered for the co-delivery of ginsenoside Rg1 (Rg1) and atractylenolide-I (Att) to MSS-CRC, named as Ab@Rg1/Att-ZIF. This system is selectively engulfed by Ly-6C + monocytes during blood circulation and utilizes a “hitchhiking” mechanism to migrate toward the core of MSS-CRC. Ab@Rg1/Att-ZIF undergoes rapid disassembly in the tumor, released Rg1 promotes the processing and transportation of tumor antigens in dendritic cells (DCs), enhancing their maturation. Meanwhile, Att enhances the activity of the 26S proteasome complex in tumor cells, leading to increased expression of major histocompatibility complex class-I (MHC-I). These coordinated actions enhance the infiltration and recognition of CTLs in the center of MSS-CRC, significantly improving the tumor inhibition of PD-1 treatment from ≈5% to ≈69%. This innovative design, involving inflammation-guided precise drug co-delivery and a rational combination, achieves synergistic engineering of the tumor microenvironment, providing a novel strategy for successful PD-1 treatment of MSS-CRC.
研究领域:
肿瘤学
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药学
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免疫治疗
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纳米技术
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癌症生物学
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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）