Pharmacological Reports
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2020
·Vol. 72
·期 2
·400-417
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IF 2.754
Li Yingxue,Jiang Bo,Wang Ruiyin,Wang Jingyun,Li Yachen,Bao Yongming
Background Tanshinone IIA (Tan IIA) and andrographolide (Andro) are natural compounds that are reported to exhibit anticancer activities against various types of cancers. The aim of this study is to evaluate the synergistic anticancer effects of the combination of Tan IIA and Andro, and to investigate the mechanisms of pharmacological effect and their potential applications as an anticancer therapy in clinics.
Methods The anticancer effects of the combination of Tan IIA and Andro on MCF7, SMMC7721, and BGC823 cells were explored. The apoptosis of the cancer cells was determined by MTT and AV-PI dual stain assays. The intracellular GSH level was measured by DTNB assay, and the intracellular levels of reactive oxygen species (ROS) were examined by flow cytometry. The expression of the proteins in the apoptosis pathway was determined by immunobloting. Results The combination of Tan IIA and Andro exhibited significant synergistic anticancer effects against cancer cells, especially at low concentrations. Andro reacted with the thiol group of intracellular GSH, thus disrupting the GSH redox cycle and eventually increasing the level of intracellular ROS. Tan IIA triggered p53 responses and apoptosis by binding to the DNA of cancer cells. The crosstalk between ROS and p53 exhibited a synergistic effect on the apoptosis of cancer cells. Conclusion The combination of Tan IIA and Andro showed significant synergistic effects on cancer cell apoptosis by promoting crosstalk between ROS and p53, providing a novel and effective combination that has the potential to be applied in clinical anticancer therapy. Graphic abstract
研究领域:
肿瘤学
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药理学
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细胞生物学
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DOI
PubMed
高影响因子
REACTIVE & FUNCTIONAL POLYMERS
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2022
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IF 4.966
Lijie Liu,Yaxin Tan,Yuqi Bao,Sen Liao,Duoduo Wang,Qiaorong Ye,Chensi Zeng,Ni Tan
To improve the recognition ability and the controlled release of andrographolide (ADR), it is necessary to prepare a better intelligent drug delivery carrier. In this paper, the magnetic andrographolide imprinted polymer (ADR-MMIP) with pH/redox/light triple stimulus response was successfully prepared by reverse atom transfer radical polymerization (RATRP), where ADR was as the template, β-Cyclodextrin (β-CD) and 4-amino-4′-methacrylamide azobenzene (AMAB) as the bi-functional monomers , and both of N, N′-bis (acryloyl) cystamine (BAC) and ethylene glycol dimethacrylate (EGDMA) as cross-linkers. A series of adsorption experiments indicated that ADR-MMIP had excellent adsorption and selectivity capacities with the maximum adsorption capacity 41.43 mg g −1 and the factors α 4.256 and β 1.940 for the selectivity and relative selectivity, respectively. The adsorption mechanism of ADR-MMIP was investigated the multiphase adsorption with the chemical action on heterogeneous material surface by the linear fitting with the isothermal and kinetic adsorption models, and the in-vitro ADR release showed ADR-MMIP was sensitive to the triple-stimuli of pH/redox/light with the maximum cumulative drug release rate 91.53% when the above three conditions were applied concurrently. The above information demonstrated the ADR-MMIP should be of great application potential in the ADR extraction and isolation from mixture and the intelligent drug delivery system.
研究领域:
药学
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材料科学
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药物递送系统
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产品关联
DOI
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2023
·
IF 5.8
Sicheng Yao,Naiying Chen,Xinxing Sun,Qiuyue Wang,Mingming Li,Yang Chen
Particle size is a key parameter to determine the capacity of nanoparticles to overcome the skin barrier; however, such effect and the possible mechanism remain only partially understood for nanosuspensions. In this work, we examined the skin delivery performance of andrographolide nanosuspensions (AG-NS) ranging in diameter from 250 nm to 1000 nm and analyzed the role of particle size in influencing their ability of skin penetration. The AG-NS with particle sizes of about 250 nm (AG-NS250), 450 nm (AG-NS450), and 1000 nm (AG-NS1000) were successfully prepared by ultrasonic dispersion method and characterized by transmission electron microscopy . The drug release and penetration via the intact and barrier-removed skin were compared by the Franz cell method, and the related mechanisms were probed using laser scanning confocal microscopy (LSCM) via visualization of penetration routes and histopathological study via observation of structural change of the skin. Our finding revealed that drug retention in the skin or its sub-layers was increased with the reduction of particle size, and the drug permeability through the skin also exhibited an obvious dependence on the particle size from 250 nm to 1000 nm. The linear relationship between the in vitro drug release and ex vivo permeation through the intact skin was well established among different preparations and in each preparation, indicating the skin permeation of the drug was mainly determined by the release process. The LSCM indicated that all these nanosuspensions could deliver the drug into the intercellular lipid space, as well as block the hair follicle in the skin, where a similar size dependence was also observed. The histopathological investigation showed that the formulations could make the stratum corneum of the skin loose and swelling without severe irritation. In conclusion, the reduction of particle size of nanosuspension would facilitate topical drug retention mainly via the modulation of drug release.
研究领域:
药剂学
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皮肤科学
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纳米技术
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产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2023
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IF 8
Hongzhi Qiao,Lihua Chen,Tianqi Rui,Jingxian Wang,Ting Chen,Tingming Fu,Junsong Li,Liuqing Di
Andrographolide (ADG) is a diterpenoid isolated from Andrographis paniculata with a wide spectrum of biological activities, including anti-inflammatory, anticancer and hepatoprotective effects. However, its poor water solubility and efflux by P-glycoprotein have resulted in lower bioavailability. In this study, ADG nanosuspensions (ADG-NS) were prepared using a wet media milling technique followed by freeze drying. d-α-Tocopheryl polyethylene glycol 1000 succinate (TPGS), a surfactant that inhibits P-glycoprotein function, and sodium lauryl sulfate were used as surface stabilizers. A Box–Behnken design was used to optimize the nanosuspension preparation. The products of these optimal preparation conditions were amorphous and possessed much faster dissolution in vitro than a coarse powder of ADG. The particle size and redispersibility index of the freeze-dried ADG-NS were 244.6±3.0 nm and 113%±1.14% (n=3), respectively. A short-term stability study indicated that the freeze-dried ADG-NS could remain highly stable as nanosuspensions during the testing period. A test of transport across a Caco-2 cell monolayer revealed that the membrane permeability (Papp) of ADG-NS was significantly higher than the permeability of the ADG coarse powder or ADG-NS without TPGS (P<0.01). Compared to the ADG coarse powder, a physical mixture, commercial dripping pills and ADG-NS without TPGS, ADG-NS exhibited significantly higher plasma exposure with significant enhancements in Cmax and area under the curve of plasma concentration versus time from zero to the last sampling time (AUC0−t) (P<0.01). An evaluation of the anti-inflammatory effect on Carr-induced paw edema demonstrated that the ADG-NS were more effective in reducing the rate of paw swelling, producing a greater increase in the serum levels of nitric oxide (NO), Interleukin-1 (IL-1) and tumor necrosis factor-α (TNF-α) (P<0.01) and an increase in superoxide dismutase activity (P<0.05) compared to the ADG coarse powder. This study indicated that nanosuspensions could act as an effective delivery device for ADG to enhance its oral bioavailability and biological efficacy.
研究领域:
药剂学
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药理学
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药物递送系统
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生物药剂学
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炎症
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癌症研究
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制药技术
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DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2022
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IF 5.714
Fengkun Guan,Huijuan Luo,Jiazhen Wu,Mengyao Li,Liping Chen,Ning Huang,Guilan Wei,Juan Nie,Baoyi Chen,Ziren Su,Xie Zhang,Yuhong Liu
Ulcerative colitis (UC), an inflammatory disease, is widely thought to be associated with colonic barrier damage and inflammatory response. With the destruction of the colonic barrier, lipopolysaccharide (LPS) enters the liver through the portal vein and causes liver injury. Liver injury in turn exacerbates UC to form a vicious cycle, so the treatment of liver injury cannot be ignored. Andrographolide (Andro) has a protective effect against colitis and liver injury, but with low bioavailability. Andrographolide sodium bisulfite (ASB), a water-soluble sulfonate of Andro, has better bioavailability, whether it has a better curative effect against UC and liver injury is rarely reported. Hence, we investigated the protective effect and potential mechanism of ASB against dextran sulfate sodium (DSS)-induced UC and liver injury in mice. The results showed that treatment with ASB significantly relieved the clinical symptoms of UC and liver injury by reducing disease activity index, inhibiting gut-derived LPS leakage, and improving colonic and hepatic injury, and its curative effect was better than Andro. Moreover, ASB effectively decreased the YAP-mediated colonic inflammation and TLR4/MyD88/NF-κB-mediated pro-inflammatory factor release in the liver. Both colonic and hepatic inflammation were associated with macrophage proinflammatory polarization, but they were significantly inhibited by ASB. ASB showed good safety in the treatment of UC and liver injury and has no nephrotoxicity as previously described. In conclusion, ASB has an effective protective effect on DSS-induced UC and liver injury, mainly by suppressing macrophage proinflammatory polarization from the gut-liver axis.
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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肝病学
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DOI
PubMed
高影响因子
Microbiology Spectrum
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2025
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IF 3.8
Lianzhan Huang,Buliduhong Halihaman,Yiyue Han,Jieru Zhou,Changjiang Liu,Haoxue Bai,Xuansheng Ding
Respiratory syncytial virus (RSV) infection causes severe burdens and harms worldwide every year, lacking specific therapeutic drugs. Andrographolide is a marketed agent, whose antiviral mechanisms between RSV and the host remain unknown. In this report, we first uncover the global disease burdens caused by RSV infection via Global Burden of Disease database analysis to raise public awareness. Results showed that the overall RSV infection mortality and trends decreased globally during 1990–2021, but children and the elderly remained high-risk populations, and the disease burdens are still severe. Then, an in vitro experiment was performed to reveal the effects of andrographolide, a promising anti-RSV strategy, on the RSV lifecycle and key processes. Meanwhile, molecular docking, cellular heat migration assays (cellular thermal shift assay [CETSA]), and immunoblotting were integrated to screen and identify the efficacy of andrographolide on key RSV adsorption receptors. Notably, the inhibition of andrographolide on RSV viral adsorption was found to be better than ribavirin, and the corresponding key adsorption receptor was further identified as CX3CR1. Subsequently, downstream targets and signaling pathways were unveiled via network pharmacological analysis. Finally, andrographolide was validated to significantly inhibit the expression of reactive oxygen species (ROS), TNF-α, IL-6, and IL-1β after RSV infection via the regulation of the ROS/TXNIP/NF-κB pathway. Our findings highlight that the disease burdens caused by RSV infection are still grim, deserving attention. Andrographolide, a promising anti-RSV drug, was first identified as suppressing RSV adsorption to host cells by affecting CX3CR1 and inhibiting the ROS/TXNIP/NF-κB pathway, thereby reducing oxidative stress and inflammatory responses.
研究领域:
病毒学
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药理学
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流行病学
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分子生物学
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传染病学
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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）