International Journal of Nanomedicine
·
2023
·
IF 8
Yanan Dong,Rongzhan Fu,Jing Yang,Pei Ma,Lihua Liang,Yu Mi,Daidi Fan
Background and purpose Ginsenoside Rg5 (Rg5), a triterpene saponin, extracted from the natural herbal plant ginseng, is one of the most potent anticancer drugs against various carcinoma cells. However, the therapeutic potential of Rg5 is limited by its low solubility in water, poor bioavailability, and nontargeted delivery. Therefore, we prepared folic acid (FA)-modified bovine serum albumin (BSA) nanoparticles (FA-Rg5-BSA NPs) to improve the therapeutic efficacy and tumor targetability of Rg5.Methods Various aspects of the FA-Rg5-BSA NPs were characterized, including size, polydispersity, zeta potential, morphology, entrapment efficiency (EE), drug loading (DL), in vitro drug release, thermal stability, in vitro cytotoxicity, cell apoptosis, cellular uptake, in vivo antitumor effects and in vivo biodistribution imaging.Results The FA-Rg5-BSA NPs showed a particle size of 201.4 nm with a polydispersity index of 0.081, uniform spherical shape, and drug loading of 12.64±4.02%. The aqueous solution of FA-Rg5-BSA NPs had favorable stability for 8 weeks at 4°C. The FA-Rg5-BSA NPs dissolved under acidic conditions. Moreover, the Rg5-BSA NPs and FA-Rg5-BSA NPs had advanced anticancer activity compared with Rg5 in MCF-7 cells, while poor cytotoxicity was observed in L929 cells. The FA-Rg5-BSA NPs facilitated cellular uptake and induced apoptosis in MCF-7 cells. In addition, in an MCF-7 xenograft mouse model, the in vivo antitumor evaluation revealed that FA-Rg5-BSA NPs were more effective in inhibiting tumor growth than Rg5 and Rg5-BSA NPs. The in vivo real-time bioimaging study showed that the FA-Rg5-BSA NPs exhibited superior tumor accumulation ability.Conclusion The results suggested that FA-Rg5-BSA NPs could serve as a promising system to improve the antitumor effect of Rg5.
研究领域:
药学
·
纳米技术
·
肿瘤学
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Ginseng Research
·
2025
·
IF 5.6
Weimin Wang,Kaixuan Zhou,Zengshuai Fu,Yucheng Huang,Jianjun Deng,Daidi Fan,Haixia Yang
Background Alcohol-induced liver injury contributes to various liver diseases, with dietary interventions of ginsenosides being a promising solution. Ginsenosides, the major active compounds of Panax ginseng Meyer , are divided into protopanaxadiol (PPD) and protopanaxatriol (PPT) based on C-3 or C-6 glycosylation, which have anti-inflammatory and antioxidant effects, but structure-activity relationships remain unclear. Methods Using C57BL/C mice with alcohol-induced liver injury, we evaluated Rg5 and F4 effects on liver function, inflammation, lipid deposition, apoptosis, alcohol metabolism, and lipid synthesis. Results Rg5 (60 mg/kg) demonstrated significantly superior efficacy to F4 in alleviating alcohol-induced liver injury, reducing lipid deposition through 33.9% and 25.8% decreases in serum triglyceride (TG) and total cholesterol (TC) levels versus the F4 group. Additionally, Rg5 attenuated hepatic apoptosis by reducing BAX and cleaved-CASPASE-3 protein expression by 26.3% and 28.4% compared to F4. Rg5 enhanced alcohol metabolism through activation of alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase (ALDH), thereby restoring AMP-activated protein kinase (AMPK) phosphorylation by 26.1% while reducing sterol regulatory element-binding protein 1 (SREBP-1) expression by 27.8% (compared to F4), with efficacy approaching that of positive control silymarin. Molecular docking revealed that the C-6 sugar moiety of F4 induced hydrogen bond donor repulsion, increasing hydrogen bond length and weakening binding stability with ADH, ALDH and AMPK, providing a structural basis for Rg5's superior hepatoprotective activity. Conclusion These findings highlight the critical influence of glycosylation position on hepatoprotective activity of ginsenosides, and provide insights into the structural modification of ginsenosides, which could contribute to the treatment of alcohol-related liver disease.
研究领域:
药理学
·
生物化学
·
药物化学
·
分子生物学
·
营养学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2022
·
IF 5.988
Dong Rong,Zhang Yougang,Chen Shanjun,Wang Huan,Hu Kaiqing,Zhao Huanxin,Tian Qingping,Zeng Kewu,Wang Songsong,Han Liwen
Background: American ginseng (Panax quinquefolium L., AG) is a traditional Chinese medicine with multiple cardiovascular protective properties. Many bioactive components have been discovered in AG over these years. However, the understanding of these key pharmacodynamic components of activity against heart failure is insufficient.Methods: A heart failure model was established using AB line wild-type zebrafish (Danio rerio) to evaluate the anti-heart failure activity of AG. Untargeted metabolomics analysis based on ultra-high performance liquid chromatography-quadrupole electrostatic field orbitrap-mass spectrometry technology (UHPLC-QE-Orbitrap-MS) was performed to screen differential components from AG samples. The potential active components were verified using the zebrafish model. Simultaneously, network pharmacology and molecular docking techniques were used to predict the possible mechanism. Finally, the key targets of six key pharmacodynamic components were verified in zebrafish using quantitative real-time-polymerase chain reaction (Q-PCR) techniques.Results: The heart failure model was successfully established in 48 h of post-fertilization (hpf) zebrafish larvae by treating with verapamil hydrochloride. The zebrafish assay showed that the anti-heart failure effects of AG varied with producing regions. The result of the herbal metabolomic analysis based on UHPLC-QE-Orbitrap-MS indicated that ginsenoside Rg3, ginsenoside Rg5, ginsenoside Rg6, malic acid, quinic acid, L-argininosuccinic acid, 3-methyl-3-butenyl-apinosyl (1→6) glucoside, pseudoginsenoside F11, and annonaine were differential components, which might be responsible for variation in efficacy. Further analysis using zebrafish models, network pharmacology, and Q-PCR techniques showed that ginsenoside Rg3, ginsenoside Rg5, ginsenoside Rg6, malic acid, quinic acid, and pseudoginsenoside F11 were the pharmacodynamic markers (P-markers) responsible for anti-heart failure.Conclusion: We have rapidly identified the P-markers against heart failure in AG using the zebrafish model and metabolomics technology. These P-markers may provide new reference standards for quality control and new drug development of AG.
研究领域:
药理学
·
心脏病学
·
代谢组学
·
斑马鱼模型
✓ 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）