PLANT SCIENCE
·
2019
·
IF 3.785
Changping Deng,Xiaolong Hao,Min Shi,Rong Fu,Yao Wang,Yi Zhang,Wei Zhou,Yue Feng,Nokwanda P. Makunga,Guoyin Kai
Tanshinones are the main bioactive diterpenes in Salvia miltiorrhiza Bunge , are widely used for treating cardiovascular and cerebrovascular diseases. However, the biosynthetic mechanisms of these compounds have not yet been fully explained. In this study, a transcription factor named SmWRKY2 was isolated and functionally characterized. Multiple sequence analysis indicated it was classified into subgroup I of the WRKY family. Expression pattern showed that SmWRKY2 was mainly expressed in the stem and leaf and was inducible by methyl jasmonate (MeJA) treatment. Subcellular localization showed that SmWRKY2 was localized in the nucleus. Overexpression of SmWRKY2 in S. miltiorrhiza hairy roots significantly increased the expression of SmDXS2 and SmCPS , resulting in increased accumulation of tanshinones and the highest total tanshinone content was detected in OE-SmWRKY2-1 line, which was 1.83 times of the control. Meanwhile, tanshinone production was slightly reduced in the antisense-SmWRKY2 line. Dual-Luciferase assay showed that SmWRKY2 can positively regulate SmDXS2 and SmCPS expression, However, Y1H and EMSA experiments indicate that SmWRKY2 only binds to the W-box of the SmCPS promoter. Our study shows that SmWRKY2 is a positive regulator of tanshinone biosynthesis by mainly activating SmCPS. This study thus sheds new light on the regulatory role of SmWRKY2 in tanshinone biosynthesis.
研究领域:
植物学
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分子生物学
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药用植物研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Scientific Reports
·
2020
·Vol. 10
·期 1
·1-4
·
IF 3.998
Jing Yun-Rong,Zhou Wei,Wang Xiang-Yang
In an attempt to improve the oral bioavailability of taxanes, a series of new analogues were synthesized and tested in a panel of human tumor cell lines and cellular permeability assays. Compounds T-13 and T-26 showed potent cytotoxicity and exhibited the highest permeability, so they were selected for pharmacokinetic studies. Here, pharmacokinetics of T-13 and T-26 were studied after intravenous injection (5 mg/kg) and oral administration (60 mg/kg) in male Sprague-Dawley (S.D.) rats, respectively. Plasma concentrations were characterized using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The oral bioavailability of T-13 and T-26 was determined to be 10.71% and 65.79%, respectively. Compounds T-13 and T-26 were both poor substrates of P-glycoprotein (P-gp), and they had a much higher bioavailability than paclitaxel, especially T-26. T-26 with good oral bioavailability represented a potential candidate for potent antitumor activity given oral administration.
研究领域:
药理学
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肿瘤学
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药物代谢
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DOI
PubMed
高影响因子
DRUG DEVELOPMENT RESEARCH
·
2025
·Vol. 86
·期 6
·e70143
·
IF 4.2
Qilong Wang,Xiaowen Wang,Qinyang Hua,Feng Shi,Xia Jiang,Minjie Gong,Tingyuan Li,Jiaying Li,Elmurat Toreniyazov,Jiangnan Yu,Michael Adu-Frimpong,Xia Cao,Ximing Xu
Liver cancer is the fourth most deadly cancer worldwide, but existing treatment options are insufficient, thus highlighting the urgent need for new therapeutic agents. Taxanes, known for their anticancer properties, provide a promising avenue for intervention. In this study, a tetracyclic taxane compound with antitumor activity (taxinine) was extracted and isolated from Taxus chinensis ( T. chinensis ) seeds. It was then formulated into liposomes using lecithin, cholesterol, and D- α -tocopheryl polyethylene glycol succinate (TPGS) as excipients to enhance its solubility and antitumor efficacy. The isolation of taxinine was achieved through ultrasound-assisted ethanol extraction, followed by silica gel column chromatography, MTT activity screening, and recrystallization. Afterward, the structure of taxinine was confirmed using nuclear magnetic resonance and mass spectrometry. Taxinine liposomes were prepared via the thin film dispersion method, while the particle size, polydispersity index, zeta potential, and encapsulation efficiency of the nanoliposomes were discovered to be 186.76 ± 0.08 nm, 0.226 ± 0.012, −44.34 ± 0.77 mV, and 93.75 ± 1.29%, respectively. They also showed good stability with a release rate of 85.77% ± 2.43% in phosphate-buffered solution (PBS, pH 7.4). Toxicity tests conducted on zebrafish larvae indicated that taxinine liposomes were safe in vivo. Tissue distribution study showed that the concentration of taxinine liposomes increased to varying degrees in tissues (especially liver). In vitro experiments demonstrated that taxinine liposomes significantly enhanced the inhibitory effect of taxinine on HepG2 cell growth. Overall, the nanoliposomal formulation improved the anti-liver cancer activity of taxinine, thus suggesting its potential as a therapeutic agent.
研究领域:
肿瘤学
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药剂学
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纳米医学
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分子药理学
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药物代谢
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天然产物化学
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转化医学
✓ 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）