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Flavonol and flavonoid compounds are important natural compounds with various biomedical activities. Therefore, it is of great significance to develop a strategy for the specific extraction of flavonol and flavonoid compounds. Quercetin is a well-studied flavonoid possessing many health benefits. This compound is a versatile antioxidant known to possess protective abilities against body tissue injury induced by pathological situations and various drug toxicities. Although quercetin is widely distributed in many plants, its content generally is not very high. Therefore, the specific extraction of quercetin as well as other flavonol and flavonoid compounds has profound significance. In this work, the quercetin molecularly imprinting polymer (QMIP) was successfully prepared, in which a typical flavonol quercetin was selected as the template molecule. QMIP was synthesized by performing the surface molecular imprinting technology on the surface of NH2-MIL-101(Fe). Our study results showed that QMIP exhibited quick binding kinetic behavior, a high adsorption capacity (57.04 mg/g), and the specific recognition ability toward quercetin compared with structurally distinct compounds (selective factor > 2). The specific adsorption ability of quercetin by QMIP was further explained using computation simulation that molecules with non-planar 3D conformations hardly entered the molecularly imprinted cavities on QMIP. Finally, QMIP was successfully used for the specific extraction of quercetin and five other flavonol and flavonoid compounds in the crude extracts from Sapium sebiferum. This study proposes a new strategy to synthesize the molecularly imprinted polymer based on a single template for enriching and loading a certain class of active ingredients with similar core structures from variable botanicals. [ABSTRACT FROM AUTHOR]

Two flavone di-C-glycosides, a pair of isomers, were isolated from Scutellaria baicalensis. The structures of compounds 1 and 2 were elucidated by means of physical data, including 1D and 2D NMR and HR-ESI-MS. Supporting theoretical calculations of the compound conformational landscape has also been conducted for geometry optimization. This is the first report of the natural occurrence of β-furanoarabinoside. In addition, the effects of compounds 1 and 2 on NO, pro-inflammatory cytokines, PGE2 and COX-2 levels were measured in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophage cells. The pair of isomers exhibited significant inhibitory effects on inflammation. [ABSTRACT FROM AUTHOR]

Pulsatilla chinensis (Bunge) Regel is commonly used in Asia, and anemoside B4 (AB4) is its major saponin, with diverse pharmaceutical effects. Previous studies showed that intestinal flora plays an important role in the metabolism of herbs administered orally. In this study, the metabolic profile of AB4 with microflora in rat small and large intestines in vitro was investigated. Gut microflora was collected from different intestinal segments and anaerobically incubated with AB4 at 37°C for 24, 48, 72 and 96 h, respectively. A total of 10 metabolites were detected and identified by ultra- performance liquid chromatography/quadrupole time-of-flight mass spectrometry, involving the products of oxygenation and deglycosylation reactions. Gut microflora in the large intestine generated more comprehensive metabolic pathways, which appears to be attributable to the wider range of bacterial types and numbers of bacteria. Human cancer cell lines SMMC-7721, Hela and MCF-7 were treated with metabolite pools by MTT assay, together with M6 as the greatest deglycosylation product. As a result, M6 exhibited a reduction in cell viability of SMMC-7721 with an IC50 value of 22.28 ± 1.26 μg/mL. The present study provided scientific evidence for AB4 metabolism in small and large intestines, which is helpful to reveal the active forms of AB4 in vivo. [ABSTRACT FROM AUTHOR]

Drug-induced liver injury (DILI) is the most common cause of acute liver failure. Disruption of the Th17/Treg balance can lead to hepatic inflammation, which causes the main symptoms of DILI. Here we investigate the protective mechanisms of (-)-Epigallocatechin-3-gallate (EGCG) on triptolide (TP)-induced DILI that shows the Th17/Treg imbalance. Pretreatment with EGCG (5mg/kg) for 10 days before TP (0.5mg/kg) administration in mice significantly reduced the increased alanine aminotransferase (ALT) level () induced by TP treatment. The hepatic histology analysis further proved that EGCG protected mice from TP-induced liver injury. The imbalance of Th17/Treg was induced by TP treatment, as shown by the upregulation of TLR4 and downregulation of Tim3 expression. EGCG pretreatment can maintain the expression of TLR4 and Tim3 at normal levels to restore the Th17/Treg imbalance. In addition, EGCG can block the TP-induced expression of the downstream targets of TLR4, including MyD88, NFB, and retinoid related orphan receptor (ROR-t), while EGCG can restore the TP inhibition of forkhead/winged-helix family transcriptional repressor p3 (FoxP3) that is the downstream target of Tim3. Consequently, EGCG pretreatment can effectively inhibit the Th17-related pro-inflammatory cytokine (e.g. IL-17 and IL-6) upregulation induced by TP treatment. However, TP inhibition of Treg-related anti-inflammatory cytokine IL-10 production was restored by EGCG pretreatment. Taken together, these results suggest that EGCG possesses significant protective properties against TP-induced hepatic inflammatory injury, and that these properties are carried out via the restoration of the Th17/Treg imbalance by the inhibition of the TLR4 signaling pathway and the enhanced activation of the Tim3 signaling pathway. [ABSTRACT FROM AUTHOR]

The abnormal expression of N-acetylneuraminic acid (SA) and sialylated glycoproteins in biological fluids are closely associated with various diseases including cancer. However, the low content of SA and the strong interference of complex matrix greatly influence the effective capture of SA in biosamples prior to analysis. Herein, a dual-capture-system strategy based on molecular imprinting and post-imprinting modification (PIM) was proposed to precisely capture SA with improved binding affinity and specificity. After imprinting with SA as template, dynamic imine bonds are introduced by post-imprinting modification, enabling sufficiently high specificity to capture SA through imprinting cavities and the dynamic imine bonds hydrolysis reaction simultaneously. The prepared magnetic PIM polymers (Mag-MIPs-PIM) exhibited significantly high specificity both for SA (IF = 4.24) and sialylated glycoprotein (IF TRF  = 3.50). In addition, the feasibility of Mag-MIPs-PIM for practical application was demonstrated by association with HPLC for the determination of SA in human serum, and an LOD of 0.01 × 10 -2  g L -1 was obtained. The proposed strategy based on molecular imprinting and PIM provides a new inspiration for the improvement of selectivity of the molecularly imprinted polymers., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: To explore the protective effects of quercetin (QE) on triptolide (TP) induced liver injury and the relevant mechanism., Methods: Forty C57BL/6 mice were equally divided into 4 groups, control group, TP model group, 20 mg/kg QE treatment group and 80 mg/kg QE treatment group randomly. The 20 mg/kg and 80 mg/kg QE groups were gastrointestinal administration with QE at the dose of 0.2 mL/10 g for 10 d, twice daily, while other groups were administrated with equivalent normal saline. Four hours post the last dose, animals were gastrointestinal administered with TP at a dose of 500 μg/kg per mouse, except for NS control. All the mice were sacrificed 22 h later, blood and liver tissue samples were collected. The pathologic change of liver tissue was detected by HE staining. The level of aminotransferase (AST) and aspartate alanine aminotransferase (ALT) in serum, and the level of glutathione (GSH), malondialdehyde (MDA) and superoxide dismutase (SOD) in liver tissue homogenates were detected using the commercial kits. The level of interleukin (IL)-17, IL-10 and IL-6 in liver tissue homogenates was measured by ELISA. Hepatic expression of Toll-like receptor 4 (TLR4) was detected by Western blot., Results: Compared with the control group, in the TP model group, hepatic lobule structure atrophied and even disappeared, hepatic cell necrosis and inflammatory cell infiltration are obvious. Additionally, in TP model group, serum ALT, AST and MDA levels were significantly increased, SOD and GSH levels were decreased, IL-6 and IL-17 levels were increased, IL-10 levels were decreased, and TLR4 protein levels were increased ( P < 0.05). Compared with the TP model group, liver tissue injury and inflammatory cell infiltration were reduced in the QE group, and serum levels of ALT, AST, MDA, IL-6 and IL-17 were all decreased. TLR4 expression was down-regulated ( P < 0.05) in both QE groups, and the decease levle was more significant in the high-dose QE group ( P < 0.05, compared with the low-dose QE group)., Conclusion: Quercetin can reduce TP-induced liver injury by reducing oxidative damage, promoting antioxidant and regulating cytokine secretion., (Copyright© by Editorial Board of Journal of Sichuan University (Medical Science Edition).)

Drug-induced liver injury (DILI) is the most common cause of acute liver failure. Disruption of the Th17/Treg balance can lead to hepatic inflammation, which causes the main symptoms of DILI. Here we investigate the protective mechanisms of (-)-Epigallocatechin-3-gallate (EGCG) on triptolide (TP)-induced DILI that shows the Th17/T reg imbalance. Pretreatment with EGCG (5[Formula: see text]mg/kg) for 10 days before TP (0.5[Formula: see text]mg/kg) administration in mice significantly reduced the increased alanine aminotransferase (ALT) level ([Formula: see text]) induced by TP treatment. The hepatic histology analysis further proved that EGCG protected mice from TP-induced liver injury. The imbalance of Th17/T reg was induced by TP treatment, as shown by the upregulation of TLR4 and downregulation of Tim3 expression. EGCG pretreatment can maintain the expression of TLR4 and Tim3 at normal levels to restore the Th17/T reg imbalance. In addition, EGCG can block the TP-induced expression of the downstream targets of TLR4, including MyD88, NF[Formula: see text]B, and retinoid related orphan receptor (ROR-[Formula: see text]t), while EGCG can restore the TP inhibition of forkhead/winged-helix family transcriptional repressor p3 (FoxP3) that is the downstream target of Tim3. Consequently, EGCG pretreatment can effectively inhibit the Th17-related pro-inflammatory cytokine (e.g. IL-17 and IL-6) upregulation induced by TP treatment. However, TP inhibition of T reg -related anti-inflammatory cytokine IL-10 production was restored by EGCG pretreatment. Taken together, these results suggest that EGCG possesses significant protective properties against TP-induced hepatic inflammatory injury, and that these properties are carried out via the restoration of the Th17/T reg imbalance by the inhibition of the TLR4 signaling pathway and the enhanced activation of the Tim3 signaling pathway.