Chemistry-Switzerland
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2023
·Vol. 5
·期 3
·1497-1507
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IF 2.1
Longlong Gao,Rui Tian,Yong Shao
DNAzymes have attracted increasing interest in developments of gene tools, therapies, and biosensors. Among them, G-quadruplexes are widely used as the key structure elements of DNAzymes to activate the catalytic competency of specific cofactors, such as hemin, but there is a great demand to diversify DNAzymes using other more straightforward DNA structures such as fully matched duplex (FM-DNA). However, the perfect base pairs in duplex limit the DNAzyme activity. In this work, a photocatalytic DNAzyme was developed by introducing an abasic site (AP site) into duplex (AP-DNA) to switch its photocatalytic activity. Palmatine (PAL), a photosensitizer from natural isoquinoline alkaloids, served as a cofactor of the DNAzyme by binding at the AP site. The AP site provides a less polarized environment to favor the PAL fluorescence. As a result, dissolved oxygen was converted into singlet oxygen (1O2) via energy transfer from the excited PAL. The oxidation of substrates by the in situ photogenerated1O2served as a readout for the DNAzyme. In addition, the duplex-based DNAzyme was engineered from FM-DNA by the cascade uracil-DNA glycosylase to generate AP-DNA. Our work provides a new way to construct duplex-based DNAzymes.Keywords:DNAzyme;duplex;abasic site;phohocatalysis;isoquinoline alkaloids;palmatine
研究领域:
生物化学
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分子生物学
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催化
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DOI
高影响因子
Food and Bioprocess Technology
·
2024
·
IF 5.3
Fu Jin-Xian,Jiao Jiao,Gai Qing-Yan,He Xiao-Jia,Fu Yu-Jie,Feng Xue,Gao Jie
Baicalein and wogonin, two health-promoting flavonoid aglycones in Scutellaria baicalensis Georgi roots, have better bioactivity and bioavailability than their glycoside precursors (baicalin and wogonoside). The search for novel microorganisms for the fermentation of S. baicalensis roots to improve the yields of baicalein and wogonin is of great interest in the food and nutraceutical industries. In this study, a novel endophytic fungus ( Penicillium rubens ) capable of producing cellulase (0.82 ± 0.12 U/mL) and β-glucosidase (4.55 ± 0.97 U/mL) was used to ferment S. baicalensis roots to obtain high yields of baicalein and wogonin. Semi-solid-state fermentation with homogeneous fungal cultures was found to be the appropriate strategy. Under the optimal fermentation parameters (temperature 30 °C, inoculation dose of fungal cultures 4 mL/g, and time 60 h), the yields of baicalein and wogonin (46.95 ± 4.98 mg/g DW and 31.41 ± 9.36 mg/g DW) from S. baicalensis roots were tremendously increased by 16.13-fold and 15.47-fold over control, respectively. Results of industrial enzyme bioprocessing and scanning electron microscope indicated that the remarkable increase in aglycone product yields could be due to the synergistic effects of cellulase and β-glucosidase produced by P. rubens on cell wall hydrolysis and glycoside deglycosylation. In addition, extracts of S. baicalensis roots fermented by P. rubens showed a significant increase in antioxidant and antimicrobial activities. Overall, the semi-solid-state fermentation of S. baicalensis roots using the novel P. rubens was an effective strategy that could yield high quantities of baicalein and wogonin, which had promising potential in the food and nutraceutical industries. Graphical Abstract
研究领域:
药用植物学
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微生物学
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食品科学
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天然产物化学
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DOI
高影响因子
AQUACULTURE
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2025
·
IF 3.9
Li-Peng Shan,Mao-Mao Wang,Yang Hu,Lei Liu,Bin Zhu,Jiong Chen
Hepatopancreatic microsporidiosis (HPM), caused by Enterocytozoon hepatopenaei (EHP), has emerged as a major threat to the shrimp aquaculture industry. However, no effective strategies have yet been developed to control the spread of this disease. In this study, we assessed the anti-EHP activity of ten monomeric compounds in Penaeus vannamei . The results showed that tetrahydropalmatine reduced the EHP copy number by 73.8 % at a concentration of 20 mg/L. In a therapeutic experiment, feeding EHP-infected shrimp a diet containing 0.1 % tetrahydropalmatine significantly lowered the EHP load. Additionally, the growth-related gene juvenile hormone esterase-like carboxylesterase 1 was significantly upregulated, while ecdysteroid-regulated protein and farnesoic acid O-methyltransferase were significantly downregulated, suggesting that tetrahydropalmatine may enhance the growth potential of EHP-infected shrimp. After 30 days of feeding, the EHP-infected shrimp's body weight in the groups fed with tetrahydropalmatine increased by 19.9 % compared to those fed with the normal diet. In a prevention experiment, healthy shrimp fed a diet containing tetrahydropalmatine and subsequently infected with EHP showed an increase in body weight by day 30 post-infection, compared to the control group, although this difference was not statistically significant. Tetrahydropalmatine can inhibit spore germination and electron dense disc formation, which may be an important reason for its suppression of EHP infection. Moreover, tetrahydropalmatine effectively inhibited the horizontal transmission of EHP, suggesting its potential to limit HPM outbreaks. These findings indicate that tetrahydropalmatine may serve as a feed additive for the treatment of HPM caused by EHP.
研究领域:
水产养殖学
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寄生虫学
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分子生物学
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DOI
高影响因子
BIOCHEMICAL PHARMACOLOGY
·
2020
·
IF 4.96
Cui Li,Liping Li,Yaodong Yi,Wei Wang,Jingqun Yuan,Fuqing Tan,Danbo Fang,Su Zeng,Hui Zhou,Huidi Jiang
Cisplatin is a first-line chemotherapeutic agent that is widely used for treatment of various solid tumors. However, cisplatin-induced adverse effects, particularly severe nephrotoxicity, preclude its application. In this study, we showed that L-tetrahydropalmatine ( L-THP) could selectively inhibit organic cation transporter 2 (OCT2), which plays a crucial role in renal cisplatin uptake from the circulation. Additionally, we demonstrated that L-THP attenuated cisplatin-induced toxicity in mouse primary renal tubular cells. Subsequently, we verified that L-THP reduced the renal accumulation of cisplatin and alleviated cisplatin-induced renal injury in healthy and tumor-bearing nude mice. In healthy mice, co-treatment of L-THP at 5–40 mg/kg reduced cisplatin renal accumulation to 75.0%-49.9% of that in cisplatin alone group (10 mg/kg), and alleviated cisplatin-induced nephrotoxicity. Additionally, it did not alter Pt concentration in the tumor tissue and did not impair its antitumor efficacy in tumor bearing nude mice. The tumor inhibitory rates of cisplatin (10 mg/kg) co-treated with L-THP at 10, 20 and 40 mg/kg were 71.4%, 70.4% and 69.4%, respectively, in H460 tumor bearing nude mice, higher than that of in cisplatin alone group (60.6%), while in HCT116 tumor bearing nude mice, the tumor inhibitory rates in co-treated with 20 mg/kg L-THP was 34.7% ( vs 26.3% in cisplatin alone group). Moreover, L-THP reduced cisplatin accumulation and alleviated cisplatin-induced cytotoxicity in human primary renal tubular cells. Therefore, our findings suggested that concomitant administration of L-THP could attenuate cisplatin-induced renal injury via selective inhibition of OCT2 without impairing its antitumor efficacy.
研究领域:
药理学
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肿瘤学
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毒理学
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产品关联
DOI
PubMed
高影响因子
ChemistrySelect
·
2022
·Vol. 7
·期 42
·e202203178
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IF 2.307
Yuanxiang Fu,Hengdan Si,Juan Chen,Wenjuan Zhang,Shuang Feng,Zhiyou Xiao
Graphical Triplex DNA plays an essential role in molecular recognition, gene regulation, diagnosis, and treatment of genetic diseases. It is crucial to screen intercalators to enhance triplex DNA stability. We established a novel “turn-on” fluorescence sensor for screening triplex DNA binders based upon molecular beacon and target dsDNA. The working principle of DNA fluorescence sensor was confirmed by circular dichroism experiments and melting curve tests. Triplex DNA plays an essential role in molecular recognition, gene regulation, diagnosis, and treatment of genetic diseases. However, triplex DNA has some shortcomings, such as poor internal Hoogsteen hydrogen bond stability and the difficult formation of parallel triplex DNA under physiological conditions, limiting its applications to a certain extent. Therefore, it is crucial to screen intercalators to enhance triplex DNA stability. Herein, we established a novel “turn-on” fluorescence sensor for screening triplex DNA binders based upon molecular beacon. Eight different organic small molecules were screened. The fluorescence of the sensor was significantly enhanced in the presence of berberine, coralyne, palmatine, and neomycin. These four small molecules affect stabilizing triplex DNA as an intercalator; the other four small molecules, kanamycin, tetracycline, ethidium bromide, and 4 ′, 6-diamidino-2-phenylindole did not show any noticeable intercalation effect. The results of circular dichroism and melting curve were consistent with those of the fluorescence spectrum.
研究领域:
生物化学
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分子生物学
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遗传学
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DOI
高影响因子
RSC Advances
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2016
·Vol. 6
·期 75
·71351-71359
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IF 3.289
Haihang Wang,Haiyun Zhai,Zuanguang Chen,Zhixian Liang,Shumei Wang,Qing Zhou,Yufang Pan
A novel electrochemical sensor was designed to determine tetrahydropalmatine (THP) by using a nickel nanoparticles deposited on sulfonated graphene sheets-modified glassy carbon electrode (NiNPs/SGS/GCE). The components and morphological properties of the NiNPs/SGS nanocomposites were investigated by scanning electron microscopy. The anodic peak current (Ipa) of THP at the GCE modified with NiNPs/SGS was much higher than those at the bare GCE and SGS/GCE due to the enhanced effect of the modified nanomaterials. Differential pulse voltammetry (DPV) disclosed a good linear relationship between Ipa and concentrations of THP (0.50–20.0 μM), with a limit of detection of 0.17 μM. Finally, the modified electrode was successfully applied for the determination of THP in Yuanhu Zhitong capsules.
研究领域:
分析化学
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药学
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生物医学工程
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产品关联
DOI
高影响因子
Analytical Methods
·
2014
·Vol. 6
·期 9
·2998-3008
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IF 1.938
Guanghui Liu,Wei He,Hao Cai,Xiuman Sun,Waner Hou,Manna Lin,Zhiyong Xie,Qiongfeng Liao
A rapid and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed to simultaneously determine berberine, palmatine, coptisine, epiberberine and jatrorrhizine in rat plasma, using tetrahydropalmatine as an internal standard. The separation of the five compounds was carried out on a C18 column using a mobile phase consisting of acetonitrile and water (containing 5 mmol ammonium acetate adjusted to pH 5.0 with formic acid). The detection was performed in the multiple reaction monitoring (MRM) mode via the electrospray ionization (ESI) source operating in the positive ionization mode. Linear calibration curves were obtained over the concentration range of 0.20–200.0 ng ml−1 for berberine, and 0.20–100.0 ng ml−1 for palmatine, coptisine, epiberberine and jatrorrhizine. The accuracy, precision and extraction recovery of the five analytes were all satisfactory. The validated method was successfully applied to study the pharmacokinetic differences of the five protoberberine-type alkaloids after the oral administration of Rhizoma coptidis (RC) and Jiao-Tai-Wan (JTW) extract. It was found that the Tmax values of the five ingredients in the JTW extract were significantly increased (P < 0.05) when compared with those in RC. In addition, the AUC0–t of palmatine, coptisine and epiberberine were significantly increased (P < 0.05).
研究领域:
药理学
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分析化学
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中医药学
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DOI
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
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2021
·
IF 4.932
Yifan Wang,Wen Zhu,Dandan Lu,Chuzhao Zhang,Yue Wang
Activation of NACHT, LRR, and PYD domains-containing protein 3 (NLRP3) inflammasome plays a crucial role in the inflammatory responses of monosodium urate (MSU) crystal-induced gouty arthritis. Therefore, the molecular basis of NLRP3 inflammasome is very valuable in developing potential therapeutic drugs for gout. Tetrahydropalmatine (THP), the main active component of the traditional Chinese medicinal herb Corydalis yanhusuo, has shown prominent anti-inflammatory and analgesic activities, but to date, these effects have not been investigated exhaustively on gout. This study indicated that THP attenuated pain and swelling in an MSU-induced acute gout model by decreasing pro-inflammatory cytokine production and inflammatory cell infiltration. THP exerted its actions by suppressing NLRP3 inflammasome activation and subsequent formation of caspase-1. Furthermore, results showed that THP alleviated MSU-induced reactive oxygen species (ROS) generation, upstream of NLRP3 inflammasome activation, by an increase in the activities of antioxidant enzymes both in vitro and in vivo. In conclusion, our study suggests that THP suppressed ROS-mediated NLRP3 inflammasome activation in MSU-induced inflammatory responses, which highlights its therapeutic potential in gouty arthritis.
研究领域:
药理学
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免疫学
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风湿病学
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产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2024
·
IF 6.6
Yunyan Chen,Ziwei Zhang,Zhilei Qian,Rui Ma,Minna Luan,Yu Sun
Background A sequential release co-delivery system is an effective strategy to improve anti-cancer efficacy. Herein, multicomponent-based liposomes (TET-CTM/L) loaded with tetrandrine (TET) and celastrol (CEL)-loaded coix seed oil microemulsion (CTM) were fabricated, which showed synergistic anti-liver cancer activities. By virtue of Enhanced Permeability and Retention (EPR) effect, TET-CTM/L can achieve efficient accumulation at the tumor site. TET was released initially to repair abnormal vessels and decrease the fibroblasts, and CTM was released subsequently for eradication of tumor tissue.Methods TEM (transmission electron microscopy) and DLS (dynamic light scattering) were adopted to characterize the TET-CTM/L. Flow cytometry was adopted to examine the cellular uptake and cytotoxicity of HepG2 cells. The HepG2 xenograft nude mice were adopted to evaluate the anti-tumor efficacy and systemic safety of TET-CTM/L.Results TEM images of TET-CTM/L showed the structure of small particle size of CTM within large-size liposomes, indicating that CTM can be encapsulated in liposomes by film dispersion method. In in vitro studies, TET-CTM/L induced massive apoptosis toward HepG2 cells, indicating synergistic cytotoxicity against HepG2 cells. In in vivo studies, TET-CTM/L displayed diminished systemic toxicity compared to celastrol or TET used alone. TET-CTM/L showed the excellent potential for tumor-targeting ability in a biodistribution study.Conclusion Our study provides a new strategy for combining anti-cancer therapy that has good potential not only in the treatment of liver cancer but also can be applied to the treatment of other solid tumors.
研究领域:
药学
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肿瘤学
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纳米技术
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产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
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2024
·
IF 4.4
Li Lin,Jingchuan Yan,Jin Sun,Jianfeng Zhang,Bo Liao
Objective: The PRAS40 is an essential inhibitory subunit of the mTORC1 complex, which regulates autophagy. It has been suggested that Erxian Decoction (EXD) could treat spinal cord injury (SCI) via the autophagy pathway. However, the mechanism of whether EXD acts through PRAS40 remains unclear. Methods: With the help of immobilized PRAS40, isothermal titration calorimetry (ITC) and molecular docking, the bioactive metabolites in the EXD were screened. To establish in vitro SCI models, PC12 cells were exposed to hydrogen peroxide (H2O2) and then treated with the identified EXD substances. Furthermore, Western blot assay was carried out to identify potential molecular mechanisms involved. For assessing the effect of metabolites in vivo , the SCI model rats were first pretreated with or without the metabolite and then subjected to the immunohistochemistry (IHC) staining, Basso, Beattie & Bresnahan (BBB) locomotor rating scale, and H&E staining. Results: The immobilized PRAS40 isolated indole, 4-nitrophenol, terephthalic acid, palmatine, sinapinaldehyde, and 3-chloroaniline as the potential ligands binding to PRAS40. Furthermore, the association constants of palmatine and indole as 2.84 × 106 M-1 and 3.82 × 105 M-1 were elucidated via ITC due to the drug-like properties of these two metabolites. Molecular docking results also further demonstrated the mechanism of palmatine binding to PRAS40. Western blot analysis of PC12 cells demonstrated that palmatine inhibited the expression of p-mTOR by binding to PRAS40, activating the autophagic flux by markedly increasing LC3. The injection of palmatine (10μM and 20 μM) indicated notably increased BBB scores in the SCI rat model. Additionally, a dose-dependent increase in LC3 was observed by IHC staining. Conclusion: This research proved that EXD comprises PRAS40 antagonists, and the identified metabolite, palmatine, could potentially treat SCI by activating the autophagic flux.
研究领域:
药理学
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神经科学
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中医
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生物化学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF CHROMATOGRAPHY A
·
2024
·
IF 3.8
Liang Qi,Xinting Zhang,Ying Gao,Pin Gong,Jian-Wu Xie
The determination of isoquinoline alkaloids (IQAs) is crucial for maximizing the pharmacological benefits of Rhizoma coptidis (RC). In this study, the dendritic silica sphere (dSiO 2 ) was covalently modified with cyanuric chloride (CNCl) to synthesize a porous dNSiO 2 -CNCl NP. The fluorescence of berberine (Ber), palmatine (Pal), coptisine (Cop), and jatrorrhizine (Jat) was remarkably enhanced by dNSiO 2 -CNCl NP for at least 38-fold, inspiring the accurate determination of the isoquinoline total alkaloids (IQTAs) in RC using fluorometry. The method exhibited good linearity within the concentration range of 0.005 to 1 μM, with a limit of detection (LOD) and quantitation (LOQ) of 0.001 and 0.004 μM. Specially, Jat was discovered to form a stable covalent linkage with dNSiO 2 -CNCl, showing an innovative and enduring fluorescent nanoparticle derived from a natural product. Furthermore, using dNSiO 2 -CNCl as a substrate for fluorescence enhancement and a dispersive solid-phase extraction (d-SPE) sorbent, a fluorescence-mediated HPLV-UV method was developed to monitor Ber, Pal, and Cop in serum. Rapid qualitative analysis using fluorescence was initially performed. In chromatography analysis, the linear range for Cop was 0.20 to 10 μM, with LOD and LOQ at 0.035 and 0.110 μM, while Pal and Ber showed good linearity in the range of 0.05 to 10 μM, with LODs and LOQs at 0.013 and 0.040 μM. The spiked recovery rates ranged from 90.4% to 99.8% for the three IQAs, with intra-day precision below 7.9% and inter-day precision below 9.9%. The dual-functional dNSiO 2 -CNCl NP exhibited promising prospect in fluorescence sensing and separation applications for detecting drugs.
研究领域:
分析化学
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纳米技术
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药学
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
PLANTA MEDICA
·
2021
·Vol. 88
·期 11
·921-932
·
IF 3.356
Xinchi Feng,Kun Wang,Shijie Cao,Liqin Ding,Feng Qiu
Rhizoma coptidis has been clinically used for a long time for the treatment of various diseases in China, such as hypertension, diabetes, and inflammation. Previous studies have shown that alkaloid components of Rhizoma coptidis extract could be extensively metabolized and the metabolites were also considered to be the therapeutic material basis. However, until now, pharmacokinetic studies of the in vivo metabolites have not been revealed yet. The aim of the present study was to characterize the pharmacokinetics and excretions of five main alkaloids (berberine, jatrorrhizine, palmatine, epiberberine, and coptisine) and their seven metabolites (berberrubine, demethyleneberberine, jatrorrhizine-3-O-β-D-glucuronide, thalifendine-10-O-β-D-glucuronide, berberrubine-9-O-β-D-glucuronide, demethyleneberberine-2-O-sulfate, and demethyleneberberine-2-O-β-D-glucuronide) in rats after oral administration of Rhizoma coptidis extract. Meanwhile, comparative pharmacokinetics and excretions of these analytes in diabetic model rats were also investigated, since Rhizoma coptidis is widely used for the treatment of diabetes. Our results showed that the in vivo existing forms of alkaloid components were phase II metabolites, highlighting the glucuronidation metabolic pathway. In diabetic model rats, the utilization of Rhizoma coptidis alkaloids was significantly increased and the biotransformation of berberine into berberrubine was significantly inhibited.
研究领域:
药理学
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代谢
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糖尿病研究
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中药
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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）