PHYTOMEDICINE
·
2024
·
IF 6.7
Xiaoliang Dong,Lu Qu,Bingxin Wang,Xiaowei Sha,Bo Wu,Yudong Sun,Xiaohua Pan,Juan Xiong,Jia Sun,Li-Long Pan
ABSTRACT Background Cardiovascular disease is one of the main causes of global mortality, and there is an urgent need for effective treatment strategies. Gut microbiota-dependent metabolite trimethylamine-N-oxide (TMAO) promotes the development of cardiovascular diseases, and shizukaol C, a natural sesquiterpene isolated from Chloranthus multistachys with various biological activities, might exhibit beneficial role in preventing TMAO-induced vascular inflammation. Purpose The purpose of this study was to investigate the anti-inflammatory effects and the underlying mechanisms of shizukaol C on TMAO-induced vascular inflammation. Methods The effect and underlying mechanism of shizukaol C on TMAO-induced adhesion molecules expression, bone marrow-derived macrophages (BMDM) adhesion to VSMC were evaluated by western blot, cell adhesion assay, co-immunoprecipitation, immunofluorescence assay, and quantitative Real-Time PCR, respectively. To verify the role of shizukaol C in vivo , TMAO-induced vascular inflammation model were established using guidewire-induced injury on mice carotid artery. Changes in the intima area and the expression of GSTpi, VCAM-1, CD68 were examined using haematoxylin-eosin staining, and immunofluorescence assay. Results Our data demonstrated that shizukaol C significantly suppressed TMAO-induced adhesion molecule expression and the bone marrow-derived macrophages (BMDM) adhesion in vascular smooth muscle cells (VSMC). Mechanically, shizukaol C inhibited TMAO-induced c-Jun N-terminal kinase (JNK)-nuclear factor-kappa B (NF-κB)/p65 activation, and the JNK inhibition was dependent on the shizukaol C-mediated glutathione-S-transferase pi (GSTpi) expression. By further molecular docking and protein-binding analysis, we demonstrated that shizukaol C directly binds to Keap1 to induce Nrf2 nuclear translocation and upregulated GSTpi expression. Consistently, our in vivo experiment showed that shizukaol C elevated the expression level of GSTpi in carotid arteries and alleviates TMAO-induced vascular inflammation. Conclusion : Shizukaol C exerts anti-inflammatory effects in TMAO-treated VSMC by targeting Keap1 and activating Nrf2-GSTpi signaling and resultantly inhibits the downstream JNK-NF-κB p65 activation and VSMC adhesion, and alleviates TMAO-induced vascular inflammation in vivo , suggesting that shizukaol C may be a potential drug for treating TMAO-induced vascular diseases.
研究领域:
药理学
·
心血管疾病
·
炎症
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Drug Design Development and Therapy
·
2024
·
IF 4.7
Qi Wu,Kexin Liu,Ruijuan Hou,Xingxing Wu,Xiaoyu Ruan,Mao Wang,Zhiting Sun,Lingchang Meng,Guoliang Dai,Changyin Li,Jing Wu,Genglin Mu
Purpose Inflammatory bowel disease (IBD) is a serious disease that affects the metabolism and inflammatory responses of human beings. From the perspective of traditional Chinese medicine, damp-heat syndrome is one of the main syndromes of IBD. Rhizoma Paridis, also known as the root of Paris polyphylla, a well-known herbal medicine used in China, is used to treat IBD with damp-heat syndrome (IBD-DH). However, uncertainty still exists regarding the underlying mechanisms and the impact of Rhizoma Paridis on IBD-DH.Methods The rats in the model (DAT) and medication administration (Rhizoma Paridis total saponins (RPTS) and Pennogenin (PN)) groups were given a high temperature and high humidity environment, high fat and high sugar diet combined with 2,4,6-trinitrobenzene sulfonic acid (TNBS) to establish the model of experimental colitis of damp-heat type, and the normal control group (RNC) rats were given a normal diet at normal temperature and humidity. Damp-heat control group (DNC) was set with the same condition as DAT without TNBS. Hematoxylin-Eosin (HE) staining was used to observe the histopathological morphology of the rat colorectum. The expression of the metabolism-related genes (Phospholipase A2 (sPLA2, cPLA2), and phosphatidylethanolamine N-methyltransferase (PEMT)) was assessed by using real-time quantitative PCR analysis (RT–qPCR). And the levels of the metabolism-related proteins (sPLA2, cPLA2), S100A8/9, Arg-1, and cytokines were detected by enzyme-linked immunosorbent assay (ELISA) kit. To investigate lipids and amino acids which closely associated with the IBD and IBD-DH, lipid pseudotargeted metabolomics with UHPLC-TQ/MS analysis method, as well as targeted quantitative amino acid analysis were performed.Results Our data showed that RPTS (50 mg/kg) and PN (20 mg/kg) significantly ameliorated the severity of TNBS-induced colitis and downregulated the levels of circulating proinflammatory cytokines. Compared with RNC group, lipid pseudotargeted metabolomics demonstrated that glycerophospholipids, sphingolipids, carnitine, and glycerolipids were the four most perturbed lipid classes, and amino acids targeted metabolomics demonstrated that serine, N-acetylneuraminic acid, histidine, proline, taurine, and kynurenine changed significantly in DAT group . Correlation analyses showed tight associations between most of differential metabolites and proinflammatory cytokines. RPTS and PN both regulated glycerophospholipid metabolism and sphingolipid metabolism. However, both of them did not have a significant effect on amino acid modulation. RPTS and PN potentially regulated sPLA2, cPLA2, and PEMT.Conclusion These results showed that RPTS (50 mg/kg) and PN (20 mg/kg) effectively alleviated rats’ colitis of damp-heat type, affected cytokines, and altered lipid metabolism without significant modulation on amino acid metabolism.
研究领域:
中医
·
药理学
·
代谢组学
·
炎症
·
胃肠病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF MEDICINAL CHEMISTRY
·
2024
·
IF 6.8
Zhongyuan Cai,Lingling Jiang,Yingzi Cao,Shengxiang Fu,Shasha Wang,Yuting Jiang,Haojie Gu,Na Li,Xiaomin Fu,Shimin Tang,Jiang Zhu,Weidong Cao,Lei Zhong,Zhuzhong Cheng,Chunchao Xia,Su Lui,Bin Song,Qiyong Gong,Hua Ai
Effective vascular and hepatic enhancement and better safety are the key drivers for exploring gadolinium-free hepatobiliary contrast agents. Herein, a facile strategy proposes that the high lipophilicity may be favorable to enhancing sequentially vascular and hepatobiliary signal intensity based on the structure–activity relationship that both hepatic uptake and interaction with serum albumins partly depend on lipophilicity. Therefore, 11 newly synthesized derivatives of manganese o-phenylenediamine-N,N,N′,N′-tetraacetic acid (MnLs) were evaluated as vascular and hepatobiliary agents. The maximum signal intensities of the heart, liver, and kidneys were strongly correlated with log P, a key indicator of lipophilicity. The most lipophilic agent, MnL6, showed favorable relaxivity when binding with serum albumin, good vascular enhancement, rapid excretion, and reliable hepatobiliary phases comparable to a classic hepatobiliary agent, gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) for in vivo liver tumor imaging. Inhibition experiments confirmed the hepatic targeting of MnL6 is mediated by organic anion-transporting polypeptides.
研究领域:
医学成像
·
药物化学
·
放射学
✓ 已验证
DOI
PubMed
高影响因子
ANALYTICAL AND BIOANALYTICAL CHEMISTRY
·
2024
·Vol. 416
·期 28
·6621-6638
·
IF 3.8
Chen Chang,Zheng Ting,Chen Yang,Li Zegeng,Wu Huan
The preparation of cellular metabolomics samples and how to achieve comprehensive coverage of different polar metabolites in cell samples in the analysis pose a challenge for cellular metabolomics. In this study, we optimized a metabolomics protocol based on ultra-high-performance liquid chromatography high-resolution mass spectrometry (UPLC/HRMS) for the extraction and detection of metabolites in A549 cells and exploration of the intervention effect of Qi-Yu-San-Long decoction (QYSLD) on A549 cells. The results indicate that the lowest level of ATP leakage was observed when A549 cells were quenched under liquid nitrogen. MeOH/chloroform/H 2 O (1:2:1) extraction yielded more chromatographic peaks and excellent reproducibility, and the relative extraction efficiency of most target metabolites was also high. And we optimized the chromatographic separation conditions in both HILIC and RPLC modes, enabling comprehensive detection and analysis of metabolites with varying polarities. Then, we applied the optimized method to UPLC-Q-TOF/MS-based metabolomics of A549 cells to study the mechanism of QYSLD intervention in non-small cell lung cancer (NSCLC). The CCK-8, EdU staining, and cell cycle assay showed that QYSLD inhibited the proliferation of A549 cells by interfering with the cell cycle and blocking them in the G1 phase. A total of 36 differential metabolites associated with the antitumor effects of QYSLD on NSCLC were identified, mainly involving nicotinate and nicotinamide metabolism, sphingolipid metabolism, and glycerophospholipid metabolism. And western blotting confirmed that the change in 1-methylnicotinamide levels after QYSLD intervention was associated with the inhibition of nicotinamide N-methyltransferase expression in A549 cells. Graphical Abstract
研究领域:
癌症生物学
·
药理学
·
代谢组学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Case Studies in Thermal Engineering
·
2024
·
IF 6.4
Wenjun Zhao,Zhisheng Xu,Long Yan,Guoqing Niu
The research of short-chain fluorocarbon surfactants is crucial in effectively and environmentally extinguishing petrochemical fires. In this study, a short-chain fluorocarbon surfactant named 2 H ,2 H -perfluorooctanoic acid sodium salt (PFH-CA) was synthesized, and then characterized its chemical structure, thermal stability, surface activity, and foam property. Subsequently, PFH-CA was compounded with hydrocarbon surfactants including sodium dodecyl sulfate (SDS), dodecyl trimethyl ammonium chloride (DTAC), and N , N -dimethyldodecylamine- N -oxid (OB-2) at different molar ratios. The surface tension, interaction parameters, and foam property of the PFH-CA/hydrocarbon surfactant compounding systems were investigated. The analysis indicates that PFH-CA exhibits excellent surface activity and thermal stability concomitant with poor foam property. Introducing SDS, DTAC, and OB-2 enhances the foam performance and reduces the consumption of PFH-CA through synergistic interactions. Especially, PFH-CA/DTAC (1:4) system possesses the strongest interactions and the best performance, with critical micelle concentration ( CMC ) and surface tension at CMC ( γ CMC ) of 0.11 mmol/L and 20.90 mN/m, respectively. When concentration of PFH-CA exceeds 0.5 mmol/L, the foaming ability and foam stability stabilize at 30 cm and 90 %, respectively. The enhanced performance of PFH-CA/DTAC system is attributed to the electrostatic attraction between anionic and cationic surfactants, which facilitates the formation of micelles, subsequently leading to better surface activity and foam properties.
研究领域:
化学
·
材料科学
·
消防安全工程
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）