MICROCHEMICAL JOURNAL
·
2019
·
IF 3.206
Hui Guo,Yunfei Chen,Na Song,Xinyi Yang,Shen Yao,Junqing Qian
Bamboo leaf is known as dietic tea for the prevention of obesity in China. To screen lipase inhibitors from bamboo leaf extract rapidly, lipase functionalized magnetic ligand fishing combined with HPLC/MS was established. Firstly, lipase was immobilized on magnetic nanoparticles by dialdehyde starch to obtain lipase-functionalized magnetic nanoparticles (L-MNPs), and then the L-MNPs were incubated with bamboo leaf extract to fish out ligands. Three enzyme inhibitors were obtained and identified as isoorientin, orientin, isovitexin by HPLC/MS. The results provided a powerful evidence for explaining the hypolipidemic effects of bamboo leaf extract, and this ligand fishing method is feasible for screening enzyme inhibitors from complex mixtures.
研究领域:
生物化学
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药物筛选
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食品科学
✓ 已验证
产品关联
DOI
高影响因子
Foods
·
2024
·Vol. 13
·期 5
·777
·
IF 4.7
Jingyu Gao,Longli Xie,Yu Peng,Mo Li,Jingming Li,Yuanying Ni,Xin Wen
Mung beans contain abundant flavonoids like vitexin and isovitexin, which contribute to their strong bioactivities, such as antioxidant effects, so efforts should focus on extracting bioactive flavonoids as well as aligning with the goal of green extraction for specific applications. Deep eutectic solvent coupled with ultrasound-assisted extraction (DES-UAE) was applied to extract flavonoids from mung beans, and eight different DESs were compared on the extraction yield. In addition, the traditional extraction method with 30% ethanol was performed as the reference. The results showed that ethylene glycol-glycolic acid achieved the highest yield among all the DESs, 1.6 times that of the reference values. Furthermore, the DES-UAE parameters were optimized as a 60 mL/g liquid–solid ratio, 30% water content in DES, 200 W ultrasonic power, 67 °C ultrasonic temperature, and 10 min extraction time, leading to the DES extract with the maximum extraction yield of 2339.45 ± 42.98 μg/g, and the significantly stronger DPPH and ABTS radical scavenging ability than the traditional extract. Therefore, employing DES and ultrasonic extraction together offers a green method for extracting flavonoids from mung beans, advancing the development and utilization of plant-derived effective components in a sustainable manner.
研究领域:
化学工程
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食品科学
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药学
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分析化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
·
2019
·
IF 3.743
Zhigang Guo,Hu Guozhang,Hang Wang,Zhaohui Li,Naijie Liu
Glioma is the most common form of malignant brain cancer with high mortality rate in human. Therefore, finding effective therapeutic strategy and revealing the underlying molecular mechanism is necessary. Ampelopsin (Amp), an effective component of the traditional Chinese herb of Ampelopsis grossedentata, is reported to have important biological properties, including anti-inflammatory, anti-cancer, and anti-oxidant activity; however, its effects on human glioma are poorly understood. Here, the in vitro and in vivo study was performed to investigate the anti-glioma ability of Ampelopsin. Human glioma cell lines of U251 and A172 were treated with Ampelopsin (0, 25, 50, and 100 uM) for 24 h, followed by various analysis. And human glioma xenograft models were established by injecting U251, accompanied with administration of Ampelopsin at 50 and 100 mg/kg to confirm the anti-cancer role of Ampelopsin. We found that Ampelopsin could suppress the glioma cell proliferation by modulating G1 and S phase arrest. Incubation with Ampelopsin led to the activity of Caspase-8, Caspase-9, Caspase-3 and poly (ADP-ribose) polymerases (PARP), indicating that Ampelopsin induced apoptotic response via both intrinsic and extrinsic signaling pathways. Additionally, autophagy was also observed in Ampelopsin-treated cancer cells, which is evidenced by autophagosome formation and LC3B-II accumulation. Ampelopsin-caused cancer cell death was obviously regained by apoptosis inhibitors. Further, Ampelopsin activated c-Jun N-terminal protein kinase (JNK) expression and enhanced reactive oxygen species (ROS) generation. Suppressing JNK markedly ameliorated Ampelopsin-induced apoptosis and autophagy, and ROS scavenger exhibited similar results. In vivo, Ampelopsin inhibited tumor growth and progression in mouse xenograft models. In conclusion, our findings indicated that Ampelopsin led to G1 and S phase arrest, triggered apoptosis and autophagy through potentiating ROS generation and JNK activation in human glioma cells. Thus, Ampelopsin might be a promising candidate against human glioma.
研究领域:
肿瘤学
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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
BIOMEDICINE & PHARMACOTHERAPY
·
2024
·
IF 6.9
Linhao Xu,Yuxin Jiang,Yanli Bi,Senwen Zheng,Yirong Wu,Yihao Wu,Yizhou Xu,Jian Chen
Chinese herbs have been used to treat small-cell lung cancer (SCLC) due to their low toxicity and significant efficacy. This study focused on oridonin, a natural compound extracted from Rabdosia rubescens, and aimed to investigate its potential antitumor activity on SCLC and to evaluate the synergistic effect of combining oridonin with other small molecules. In this study, oridonin exhibited a dual effect. At lower concentrations, it suppressed the cell viability of SCLC cells (H1688 and H446). At high concentrations, oridonin induced SCLC cell apoptosis, damaged HBE cells in vitro and compromised the function of the liver and heart in vivo . The lower concentration of oridonin induced autophagy by enhancing the expression of p62 and the LC3B-II/LC3B-I ratio. This phenomenon might be associated with the activation of the protein kinase RNA-like ER kinase (PERK)/eukaryotic initiation factor 2 alpha (eIF2α)/growth arrest and DNA damage-inducible gene 153 (CHOP/GAD153) pathway. Therefore, the combined effect of oridonin with GSK2606414 or 3- methyladenine increased apoptosis in SCLC cells and reduced tumor growth. A similar phenomenon was observed after oridonin was combined with p62 or CHOP RNA interference treatment. Simultaneously, the combination of oridonin and GSK2606414 exhibited therapeutic efficacy without manifesting adverse effects. Our findings suggest that oridonin at lower concentrations can induce autophagy by activating the PERK/eIF2α/CHOP signaling pathway. The inhibition of the PERK/eIF2α/CHOP pathway could enhance oridonin therapeutic responses by triggering apoptosis. The novel therapeutic approach of combining oridonin with a PERK inhibitor is promising as a strategy for the treatment of SCLC.
研究领域:
肿瘤学
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药理学
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分子生物学
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细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
·
2023
·
IF 7.5
Yongjian Guo,Chengju Luo,Yuening Sun,Wenjing Guo,Ruitian Zhang,Xin Zhang,Xue Ke,Libin Wei
Mitochondria dynamically change their morphology via fusion and fission, a process called mitochondrial dynamics. Dysregulated mitochondrial dynamics respond rapidly to metabolic cues, and are linked to the initiation and progression of diverse human cancers. Metabolic adaptations significantly contribute to tumor development and escape from tissue homeostatic defenses. In this work, we identified oroxylin A (OA), a dual GLUT1/mitochondrial fusion inhibitor, which restricted glucose catabolism of hepatocellular carcinoma cells and simultaneously inhibited mitochondrial fusion by disturbing SIRT1/PDK2/PARL axis. Based the dual action of OA in metabolic regulation and mitochondrial dynamics, further results revealed that mitochondrial functional status and spare respiratory capacity (SRC) of cancer cells had a close correlation with mitochondrial metabolic plasticity, and played important roles in the susceptibility to cancer therapy aiming at glucose restriction. Cancer cells with healthy mitochondria and high SRC exhibit greater metabolic flexibility and higher resistance to GLUT1 inhibitors. This phenomenon is attributed to the fact that high SRC cells fuse mitochondria in response to glucose restriction, enhancing tolerance to energy deficiency, but undergo less mitochondrial oxidative stress compared to low SRC cells. Thus, inhibiting mitochondrial fusion breaks mitochondrial metabolic plasticity and increases cancer cell susceptibility to glucose restriction therapy. Collectively, these finding indicate that combining a GLUT1 inhibitor with a mitochondrial fusion inhibitor can work synergistically in cancer therapy and, more broadly, suggest that the incorporations of mitochondrial dynamics and metabolic regulation may become the targetable vulnerabilities bypassing the genotypic heterogeneity of multiple malignancies.
研究领域:
癌症生物学
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分子生物学
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代谢学
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Natural Medicines
·
2020
·Vol. 75
·期 1
·129-141
·
IF 2.055
An Meng-Fei,Wang Ming-Yue,Shen Chang,Sun Ze-Rui,Zhao Yun-Li,Wang Xuan-Jun,Sheng Jun
Abstract Isoorientin (ISO), a natural flavonoid compound, has been identified in several plants and its biological activity is determined and the study on lowering uric acid has not been reported. In view of the current status of treatment of hyperuricemia, we evaluated the hypouricemic effects of ISO in vivo and in vitro, and explored the underlying mechanisms. Yeast extract-induced hyperuricemia animal model as well as hypoxanthine and xanthine oxidase (XOD) co-induced high uric acid L-O2 cell model and enzymatic experiments in vitro were selected. The XOD activity and uric acid (UA) level were inhibited after the treatment of ISO in vitro and in vivo. Furthermore, serum creatinine (CRE) and blood urea nitrogen (BUN) levels were also significantly reduced and liver damage was recovered in pathological histology after the ISO administration in hyperuricemia animal model. The results of mechanism illustrated that protein expressions such as XOD, toll-like receptor 4 (TLR4), cathepsin B (CTSB), NLRP3, and its downstream caspase-1 as well as interleukin-18 (IL-18) were markedly downregulated by ISO intervention in vitro and in vivo. Our results suggest that ISO exerts a urate-lowering effect through inhibiting XOD activity and regulating TLR4-NLRP3 inflammasome signal pathway, thus representing a promising candidate therapeutic agent for hyperuricemia. Graphic abstract Both animal models and in vitro experiments suggested that ISO may effectively lower uric acid produce. The mechanism might be the inhibition of XOD activity and NLRP3 inflammasome of upregulation.
研究领域:
药理学
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生物化学
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分子生物学
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医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF COLLOID AND INTERFACE SCIENCE
·
2023
·
IF 9.9
Jianqin Yan,Chan Shan,Zhuoran Zhang,Fashun Li,Yong Sun,Qian Wang,Bin He,Kui Luo,Jing Chang,Yan Liang
Autophagy inducers increase the sensitivity of tumor cells to chemotherapeutic drugs and enhance anti-tumor efficacy. An autophagy-induced intracellular signaling fractional nano-drug system was constructed for the co-delivery of the autophagy inducer rapamycin (RAPA) and the anti-tumor drug 9-nitro-20(S)-camptothecin (9-NC). Link peptides, including cathepsin B-sensitive peptides (Ala-Leu-Ala-Leu, ALAL), nucleus-targeting peptides (TAT, sequence: YGRKKRRQRRR), and chrysin (CHR)-modified hydrophobic biodegradable polymers (poly(-caprolactone)) (PCL), were grafted onto hyaluronic acid (HA) to yield two amphiphiles, HA-ALAL-PCL-CHR (CPAH) and HA-ALAL-TAT-PCL-CHR (CPTAH). Spherical RAPA- and 9-NC-loaded micelles were obtained by the self-assembly of amphiphiles comprising CPAH and RAPA and CPTAH and 9-NC. In this fractional nano-drug system, RAPA was released earlier than 9-NC, as CPAH as a RAPA carrier lacked a nucleus-targeting TAT (unlike CPTAH as an 9-NC carrier). RAPA induced autophagy in tumor cells and improved their sensitivity, whereas the secondary nucleus-targeting micelles directly delivered 9-NC to the nucleus, considerably improving anti-tumor efficacy. Immunofluorescence staining, acridine orange (AO) staining, and western blotting results demonstrated that the system induced a high level of autophagy in combination chemotherapy. The proposed system possesses a high level of cytotoxicity in vitro and in vivo and provides a potential method for enhancing anti-tumor efficacy in clinical settings.
研究领域:
药学
·
纳米技术
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肿瘤学
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MATERIALS & DESIGN
·
2024
·
IF 7.6
Chengjun Peng,Guichun Wang,Jiaxin Li,Yuxiao Wang,Zixuan Shu,Maomao Tang,Xiaodong Ma,Jian Guo,Shuangying Gui
Periodontitis is characterized by local inflammatory response and the resultant alveolar bone resorption. The elevated reactive oxygen species (ROS) level not only aggravates local inflammation but also prohibits osteogenesis. Hence, simultaneously scavenging ROS and triggering the activity of osteoblasts may produce synergism in periodontium regeneration. Herein, we developed an injectable hydrogel system, CC-B-CAPE@CY-NPs, for periodontitis treatment, in which caffeic acid phenethyl ester (CAPE), a naturally-occurring anti-inflammatory ingredient, was caged by aryl borate for ROS-responsive release. Meanwhile, the nanoparticles incorporating Chrysin (CY), another natural product with osteogenetic property, were also coated in the hydrogel. In vitro, the hydrogel was capable of scavenging the excessive ROS and modulating the polarization of M1 macrophages, highlighting its anti-inflammatory potency. In addition, its osteogenetic effect was verified by the increased ALP activity in the hydrogel-treated periodontal ligament stem cells (PDLSCs). Our studies revealed the anti-inflammatory stemmed from its ablation of NF-κB signaling, while the activation of Wnt/β-catenin cascade accounted for its osteogenetic potency. In a rat periodontitis model, the capability of reducing ROS levels, modulating macrophage polarization, and promoting osteogenesis was transformed into the recovery of destructed alveolar bone. All above, the hydrogel possesses great potential as a promising remedy for periodontitis.
研究领域:
口腔医学
·
药剂学
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组织工程
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炎症研究
·
骨再生
✓ 已验证
产品关联
DOI
高影响因子
Frontiers in Plant Science
·
2024
·
IF 4.1
Wang Miaomiao,Shen Qiuyu,Pang Jianyu,Mao Yu,Li Xiaofei,Tao Yanxia,Tang Wenru,Sun Ruifen,Zhou Xuhong
Objective: Carnation is a plant that holds high value in terms of its edibility, medicinal properties, and ornamental appeal. Creating no sense he aim of this study was to evaluate the antioxidant and antitumor properties of extracts derived from various parts of the carnation plant. Metabolomics technology was employed to identify the primary chemical constituents.Methods: Initially, we measured the total phenolic and total flavonoid contents in carnation roots, stems, leaves, and flowers, followed by assessing the antioxidant and anti-tumor capabilities of each component using diverse experimental methods. Subsequently, UPLC-MS/MS was employed to identify metabolites in different parts of carnation and investigate their roles in antioxidant and anti-tumor activities.Results: Mention numerical value- for better underatnding- Results of the study indicated that the methanol extract obtained from carnation flowers and roots exhibited superior antioxidant capacity compared to that from the stems and leaves. This disparity may be attributed to the abundance of polyphenols, flavonoids, and antioxidants present in the flowers, including methyl ferulate and luteolin-4’-O-glucoside. Furthermore, the significant presence of the anthraquinone compound rhein-8-O-glucoside in carnation roots may contribute to their enhanced antioxidant properties. Ten distinct compounds were isolated and recognized in carnation flowers, with Isoorientin 2”-O-rhamnoside and Kurarinone demonstrating notable antioxidant activity and binding affinity to SOD1 and SOD3, as validated through antioxidant screening and molecular docking.Conclusion: Overall, the findings from this study have expanded our knowledge of the phytochemical composition across different anatomical regions of the carnation plant, providing valuable insights for its holistic utilization.
研究领域:
植物学
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药理学
·
分析化学
·
药物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY
·
2015
·
IF 2.084
Shimei Qi,Xianjuan Kou,Jun Lv,Zhilin Qi,Liang Yan
Our results showed that ampelopsin significantly inhibited cell viability of hepatoma HepG2 cells using MTT assay. We further investigated the mechanism of anticancer activity by ampelopsin, it showed that ampelopsin induced apoptosis of HepG2 cells using DAPI assay and flow cytometry, which was confirmed by activation of PARP. Next, activation of the caspase cascades were demonstrated, including caspase-8, -9 and -3. We also found that ampelopsin increased the levels of death receptor 4 (DR4), death receptor 5 (DR5) and decreased the expression of Bcl-2 protein, which led to an increase of the Bax/Bcl-2 ratio. Meanwhile, the release of cytochrome c from mitochondria was observed. Ampelopsin decreased the levels of iNOS and COX-2 but had no impact on the level of reactive oxygen species (ROS). In addition, ampelopsin activated ERK1/2 and P38, but little JNK1/2 activation was detected. Further investigation showed that suppression of P38 activation by SB203580 increased the cell viability and also prevented cleavage of caspase-3 and PARP, inhibition of ERK1/2 with U0126 had the opposite action. In conclusion, our results indicated that ampelopsin mainly elicited apoptosis through extrinsic and intrinsic pathway and that ERK1/2 and P38 had opponent effects on the apoptosis.
研究领域:
癌症生物学
·
分子生物学
·
细胞生物学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biomaterials Science
·
2023
·
IF 6.6
Xinyan Tao,Yuan Liu,Zhenhua Ding,Shuang Xie,Wenxiong Cao,Xiaohong Li
Obesity has become a worldwide public health problem and continues to be one of the leading causes of chronic diseases. Obesity treatment is challenged by large drug doses, high administration frequencies and severe side effects. Herein, we propose an antiobesity strategy through the local administration of HaRChr fiber rods loaded with chrysin and grafted with hyaluronic acid and AtsFRk fiber fragments loaded with raspberry ketone and grafted with adipocyte target sequences (ATSs). The hyaluronic acid grafts double the uptake levels of HaRChr by M1 macrophages to promote phenotype transformation from M1 to M2 through upregulating CD206 and downregulating CD86 expressions. ATS-mediated targeting and sustained release of raspberry ketone from AtsFRk increase the secretion of glycerol and adiponectin, and Oil red O staining shows much fewer lipid droplets in adipocytes. The combination treatment with AtsFRk and the conditioned media from HaRChr-treated macrophages elevates adiponectin levels, suggesting that M2 macrophages may secrete anti-inflammatory factors to stimulate adipocytes to produce adiponectin. Diet-induced obese mice showed significant weight losses of inguinal (49.7%) and epididymal (32.5%) adipose tissues after HaRChr/AtsFRk treatment, but no effect was observed on food intake. HaRChr/AtsFRk treatment reduces adipocyte volumes, lowers serum levels of triglycerides and total cholesterol and restores adiponectin levels to those of normal mice. In the meantime, HaRChr/AtsFRk treatment significantly elevates the gene expression of adiponectin and interleukin-10 and downregulates tissue necrosis factor-α expression in the inguinal adipose tissues. Thus, local injection of cell-targeting fiber rods and fragments demonstrates a feasible and effective antiobesity strategy through improving lipid metabolism and normalizing the inflammatory microenvironment.
研究领域:
药理学
·
内分泌学
·
代谢学
·
生物技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Food Science & Nutrition
·
2023
·
IF 3.9
Yufeng Chen,Guobin Xia,Chunfeng Wang,Huawei Wu,Xiaogang Xu,Genxiang Mao,Jiong Wu,Zhenlei Zhao
7,8-dihydroxyflavone (7,8-DHF) is a biologically active flavone with various physiological activities, including neuroprotection, anti-inflammation, and weight loss. Previous studies have found that the efflux protein P-glycoprotein (P-gp) significantly affects the transepithelial transport of 7,8-DHF in the intestine, resulting in its low oral bioavailability. Based on this, in this study, a Caco-2 monolayer cell model was used to investigate 14 dietary plant flavonoids as potential P-gp inhibitors, and their effects on the transepithelial transport and in vitro digestion of 7,8-DHF were explored. The results showed that among the 14 plant flavonoids, hesperetin, epigallocatechin gallate, fisetin, kaempferol, quercetin, and isoorientin increased and the apparent permeability coefficients ( P app ) of 7,8-DHF at AP → BL direction and lowered P app value at BL → AP direction to varying degrees, reducing the efflux ratio of 7,8-DHF less than 1.5. In particular, kaempferol and quercetin exhibited the best effect on promoting the transepithelial transport of 7,8-DHF, especially when used at molar concentration ratios of 1:1 and 1:2 with 7,8-DHF. This is beneficial for improving the oral bioavailability of 7,8-DHF. Meanwhile, 7,8-DHF was found to maintain structural stability in simulated saliva, gastric juice, and intestinal juice, and its stability was not affected by the coexistence of quercetin and kaempferol. Overall, this study provided a theoretical basis for seeking natural and safe P-gp inhibitors to improve the oral absorption of natural products.
研究领域:
药理学
·
营养学
·
细胞生物学
·
药剂学
✓ 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）