DRUG DEVELOPMENT AND INDUSTRIAL PHARMACY
·
2019
·
IF 2.367
Yu-Jiao Xie,Qi-Long Wang,Michael Adu-Frimpong,Jian Liu,Kang-Yi Zhang,Xi-Ming Xu,Jiang-Nan Yu
Isoliquiritigenin (ISL) possesses a variety of pharmacological activities amid poor solubility in water which has restricted its clinical application. In this study, isoliquiritigenin-loaded F127/P123 polymeric micelles (ISL-FPM) were successfully prepared and evaluated in vitro and in vivo. The particle size, polydispersity index, and zeta potential of the selected formulation were 20.12 ± 0.72 nm, 0.183 ± 0.046, and −38.31 ± 0.33 mV, respectively, coupled with high encapsulation efficiency of 93.76 ± 0.31%. Drug-loading test showed the solubility of ISL after formulating into micelles was 232 times higher than its intrinsic solubility. Moreover, critical micelle concentration (CMC) was tested with fluorescence probe method and turned out to be quite low, which implied high stability of ISL-FPM. Release profile in HCl (pH 1.2), double distilled water, and PBS (pH 7.4) of ISL-FPM reached over 80%, while free ISL was around 40%. Pharmacokinetic research revealed that formulated ISL-FPM significantly increased bioavailability by nearly 2.23-fold compared to free ISL. According to the results of in vitro antioxidant activity, scavenging DPPH activity of ISL was significantly strengthened when it was loaded into polymeric micelles. Altogether, ISL-FPM can act as a promising approach to improve solubility as well as enhance bioavailability and antioxidant activity of ISL.
研究领域:
药剂学
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药物化学
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DOI
PubMed
高影响因子
International Journal of Clinical and Experimental Pathology
·
2015
·
IF 1.891
Shupeng Zhao,Haigang Chang,Pengju Ma,Guojun Gao,Cailing Jin,Xinli Zhao,Wenke Zhou,Baozhe Jin
Objective: To investigate the effect of isoliquiritigenin on the activity of DNA topoisomerase (TOP I) and its inhibitory effect on the growth of U87 glioma cells. Methods: This study investigated the inhibitory effect of isoliquiritigenin on the growth of U87 glioma cells and its cytotoxicity by MTT method and determined the effect of isoliquiritigenin on TOP I activity by agarose gel electrophoresis. On this basis, we studied the interaction between isoliquiritigenin and TOP I and DNA. Finally, we further discussed the effect of isoliquiritigenin on the activity of Caspase 3, the apoptosis protein of U87 glioma cells. Results: Isoliquiritigenin could inhibit the growth of U87 glioma cells (half inhibitory concentration IC50: 0.221 mM) and is of low cytotoxicity to normal cells. Agarose gel electrophoresis showed that isoliquiritigenin had significant inhibitory effect on TOP I activity. Molecular simulation results indicated that isoliquiritigenin took priority of binding to the active center of TOP I, and formed hydrogen bonds with the catalytic site Try723. Finally, Caspase 3 activity detection results suggested that isoliquiritigenin could significantly increase the activity of Caspase 3 (P < 0.05). Conclusion: Isoliquiritigenin had a reversible inhibitory effect on TOP I activity, reduced the rate of single strand DNA unwinding in tumor cells, and thus played an important role in inducing the apoptosis of U87 glioma cells.
研究领域:
肿瘤学
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分子生物学
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药理学
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PubMed
高影响因子
CELLULAR SIGNALLING
·
2025
·
IF 3.7
JingjingLi,Juan Gu,SijiaPan,Nuo Deng,Muhammad Khan,Lingyan Li,Xiao Wu,Yongming Li
Despite continuous therapeutic interventions, the prognosis of hepatocellular carcinoma (HCC) remains very poor. Thus, quest for novel treatment strategies to improve therapeutic window of HCC therapy is paramount. Arsenic trioxide (ATO) is commonly used as the first-line treatment for acute promyelocytic leukemia (APL). Isoliquiritigenin (ISL) is a potential plant-based bioactive molecule with versatile biological and pharmacological effects including anticancer effect. The present study aimed to investigate the potential synergistic effects of combination of ISL and ATO in HCC cells. The data revealed that the combination of ISL and ATO synergistically inhibited HCC cell proliferation. The collective data demonstrate that synergistic anticancer effect of combined treatment of ISL + ATO was achieved via cooperative induction of mitochondrial apoptosis through ROS generation and inhibition of PI3K/Akt/mTOR pathway. In addition, ROS generation and suppression of PI3K/Akt/mTOR pathway were found to be two independent events in induction of apoptosis. Finally, we observed that combination treatment effectively suppressed tumor growth in nude mice xenograft model through induction of intrinsic apoptosis and inhibition of PI3K/Akt/mTOR pathway. In conclusion, the findings of this study suggest that both drugs work synergistically to exert anti-tumor effect in HCC, both in-vitro and in-vivo and could offer novel strategy for liver cancer treatment.
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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DOI
PubMed
高影响因子
AAPS PHARMSCITECH
·
2019
·Vol. 20
·期 5
·1-11
·
IF 2.608
Zhang Kangyi,Wang Qilong,Yang Qiuxuan,Wei Qiuyu,Man Na,Adu-Frimpong Michael,Toreniyazov Elmurat,Ji Hao,Yu Jiangnan,Xu Ximing
The aim of this study was to develop a self-microemulsifying drug delivery system (SMEDDS) for enhancement of the oral bioavailability of isoliquiritigenin (ISL) as well as evaluate its in vivo anti-hyperuricemic effect in rats. The ISL-loaded self-microemulsifying drug delivery system (ISL-SMEDDS) was comprised of ethyl oleate (EO, oil phase), Tween 80 (surfactant), and PEG 400 (co-surfactant). The ISL-SMEDDS exhibited an acceptable narrow size distribution (44.78 ± 0.35 nm), negative zeta potential (− 10.67 ± 0.86 mV), and high encapsulation efficiency (98.17 ± 0.24%). The in vitro release study indicated that the release rates of the formulation were obviously higher in different release media (HCl, pH 1.2; PBS, pH 6.8; double-distilled water, pH 7.0) compared with the ISL solution. The oral bioavailability of the ISL-SMEDDS was enhanced by 4.71 times in comparison with the free ISL solution. More importantly, ISL-SMEDDS significantly reduced uric acid level by inhibiting xanthine oxidase (XOD) activity in the model rats. Collectively, the prepared ISL-SMEDDS proved to be potential carriers for enhancing the solubility and oral bioavailability of ISL, as well as ameliorating its anti-hyperuricemic effect.
研究领域:
药剂学
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生物药剂学
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药物代谢动力学
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF MEDICAL MICROBIOLOGY
·
2026
·
IF 3.6
Hui Yu,Nan Wang,Changjiang Sun,Bingfeng Leng,Liping Sun,Xuming Deng,Lei Xu,Zihao Teng,Jianfeng Wang,Lin Wang
Enterotoxigenic Escherichia coli (ETEC), a predominant pathogen responsible for neonatal animal diarrhea, poses a significant threat to global health and results in considerable economic losses in animal husbandry. The pathogenicity of ETEC is primarily mediated by its adherence to intestinal epithelial cells via fimbriae adhesins and the subsequent secretion of enterotoxins. We developed a high-throughput screening platform for chorionic inhibitors. By employing semi-solid motility assays, hemagglutination inhibition assays, and cell adhesion assays, we screened a panel of natural compounds and identified Isogliquiritin (ISL) as the active compound. Subsequent validation using transmission electron microscopy and reverse transcription-polymerase chain reaction (qRT-PCR) revealed that ISL significantly inhibits the synthesis and assembly of ETEC fimbriae, thereby reducing bacterial adhesion to host cells. After assessing its safety, we demonstrated through in vivo experiments that ISL attenuates ETEC-induced diarrhea. In the Galleria mellonella larval model, ISL increased the survival rate, meanwhile in a mouse diarrhea model, ISL reduced inflammation caused by ETEC C83902 and upregulated the expression of tight junction protein (ZO-1, claudin-1, and occluding) genes. Collectively, our findings highlight that ISL is a promising natural compound for the prevention and treatment of ETEC-induced diarrhea. By targeting bacterial virulence factors rather than bacterial growth, ISL provides a novel strategy against antimicrobial resistance and offers a safer alternative for managing ETEC infections in livestock.
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PubMed
高影响因子
Scientific Reports
·
2024
·Vol. 14
·期 1
·1-12
·
IF 3.8
Hu Deliang,Yang Yuqing,Fang Lei,Fan Shijie,Lin Ling,Luo Puying,Xiong Yuanhuan,Su Yufang
Isoliquiritigenin (ISL), a naturally occurring flavonoid derived from licorice root, exhibits antioxidant, anticancer, anti-inflammatory, and anti-allergic properties, and is frequently detected in both environmental and human samples. Previous studies from our lab have demonstrated that ISL exposure can lead to developmental deformities and aberrant immune responses. However, the molecular mechanisms underlying ISL toxicity in zebrafish embryos remain incompletely elucidated. Therefore, this study aimed to elucidate the effects of ISL exposure on endoplasmic reticulum (ER) stress in zebrafish embryos by assessing the expression levels of ER stress markers HSPA5 and CHOP , along with associated apoptosis factors, under various ISL concentrations, with tunicamycin (TM) serving as a positive control. Furthermore, targeted analyses of ER stress-related pathways were conducted using RNA transcriptome sequencing, and the up-regulated gene was verified by western blot. The results revealed that ISL exposure significantly elevated the expression levels of HSPA5 and CHOP , concomitantly activating ER stress pathways, including pPERK-eIF2α-ATF4 and ATF6 pathways in zebrafish embryos. These findings suggest that the activation of endoplasmic reticulum stress signaling pathways may contribute to the developmental deformities observed in zebrafish embryos following ISL exposure, thereby highlighting the potential ecological risks associated with ISL usage.
研究领域:
毒理学
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发育生物学
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分子生物学
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环境科学
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PubMed
高影响因子
ENVIRONMENTAL TOXICOLOGY
·
2023
·Vol. 38
·期 3
·654-665
·
IF 4.5
Yufang Su,Lei Fang,Kaili Zhong,Ting Wang,Mingjie Bao,Ting Zhou,Yuan Zhu
Isoliquiritigenin (ISL) is used in many households' personal hygiene and medicinal products, and the average human daily ISL exposure is 1–2 mg/kg. However, the molecular mechanisms of ISL toxicity in zebrafish embryos have not been fully elucidated. We investigated whether exposure to ISL induces oxidative stress and inflammatory responses in zebrafish. And exposure to ISL significantly affects the expression of immune response-related genes in zebrafish embryos following oxidative stress and the release of pro-inflammatory mediators through Toll-like receptor signaling.
研究领域:
毒理学
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分子生物学
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环境科学
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产品关联
DOI
PubMed
高影响因子
RSC Advances
·
2016
·Vol. 6
·期 89
·86640-86649
·
IF 3.289
Mingyan Liao,Yudan Zhao,Lizi Huang,Biao Cheng,Kun Huang
Parkinson's disease (PD), with widespread aggregation of α-synuclein in the form of Lewy bodies as a neuropathological hallmark, is a rising threat for ageing society. Glycyrrhiza uralensis is an herbal medicine and sweets used for centuries in Asia and Europe, its major pharmacologically active ingredients include isoliquiritigenin (ILG), liquiritin (LT), liquiritigenin (LG) and glycyrrhizic acid (GA). Here, we investigated the effects of Glycyrrhiza uralensis ethanol extract (GUE) and the above four compounds, on the aggregation of α-synuclein in vitro and in a transgenic Caenorhabditis elegans PD model NL5901. In vitro, ILG, LT and GUE inhibit the amyloid formation of α-synuclein and alleviate the toxicity caused by aggregates; moreover, ILG could disaggregate preformed fibrils. In vivo, ILG, LT and GUE not only reduce amyloid formation in C. elegans NL5901, but also extend its life span. Together, these data suggest that ILG and LT may be further considered as candidates for PD treatment.
研究领域:
神经科学
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药理学
·
分子生物学
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DOI
高影响因子
JOURNAL OF APPLIED POLYMER SCIENCE
·
2026
·
IF 2.8
Jinhui Liang,Lin Xie,Junhong Zhang,Tiancheng Zhao,Fuping Xie,Zhenhao Yao,Kan Zhang
In this study, two main-chain type benzoxazines (poly(ILG-ddm) main and poly(ILG-pdfa) main ) based on isoliquiritigenin were successfully synthesized, and their structures and properties were systematically characterized and evaluated. FT-IR and NMR analyses confirmed the chemical structures of benzoxazines, verifying the successful formation of the oxazine ring. DSC studies showed that both bio-based thermosetting systems exhibited lower curing temperatures compared to traditional petroleum-based benzoxazines. Notably, poly(ILG-pdfa) main displayed a significantly lower apparent activation energy (~127 kJ/mol) than poly(ILG-ddm) main (~148 kJ/mol), indicating its easier curing and superior processability. TGA results demonstrated that the resulting cured sample, poly(ILG-ddm) main X , possessed higher thermal stability ( T d5 = 352°C, char yield at 800°C = 58.4%). Although poly(ILG-pdfa) main X showed slightly lower thermal stability ( T d5 = 319°C, char yield = 49.8%), it still maintained excellent performance among fully bio-based polymeric materials. DMA analysis revealed that poly(ILG-pdfa) main X exhibited high storage modulus and a high glass transition temperature (266.2°C) due to the strong intermolecular forces and π–π stacking between the furan and chalcone structures. The isoliquiritigenin-derived polybenzoxazines exhibit an optimal balance between low polymerization temperature and high thermal stability, providing a robust matrix for their application in high-performance and sustainable composites.
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BIOMEDICINE & PHARMACOTHERAPY
·
2024
·
IF 6.9
Ya-ling Zhang,Yuan Qu,Huan-huan Song,Guo Cheng,Fen Lu,Ting-ting Cui,Ye Gong,Xiao-li Ding,Yang Yang,Qian Zhang,Lu-ting Yang,Ya-ping Yan
Multiple sclerosis (MS) is an autoimmune-mediated chronic inflammatory demyelinating disease of the central nervous system (CNS) that poses significant treatment challenges. Currently, it is believed that inflammatory and neuroprotective reactive astrocytes, along with other resident CNS cells and immune cells, contribute to the pathophysiology of MS. In our study, we found that isoliquiritigenin (ILG), a bioactive chalcone compound, significantly reduces the clinical scores of experimental autoimmune encephalomyelitis (EAE) by 44 % ( P < 0.05). Additionally, ILG significantly decreases the pathological scores of spinal cord inflammation and demyelination by 61 % and 65 %, respectively (both P < 0.0001). Furthermore, ILG affects the populations of CD4, Th1, Th17, and Treg cells in vivo . More importantly, ILG significantly promotes the activation of astrocytes in EAE ( P < 0.0001). Additionally, ILG treatment indirectly inhibits inflammatory reactive astrocytes and promotes neuroprotective reactive astrocytes. It reduces spleen levels of TNFα, IL1α, C1qa, IL1β, and IL17A by 95 % ( P < 0.001), 98 % ( P < 0.01), 46 % ( P < 0.05), 97 % ( P < 0.001), and 60 % ( P < 0.001), respectively. It also decreases CNS levels of TNFα, IL1α, C1qa, IL1β, and IL17A by 53 % ( P < 0.05), 88 % ( P < 0.05), 64 % ( P < 0.01), 57 % ( P < 0.05), and 60 % ( P < 0.001), respectively. These results indicate that ILG exerts an immunoregulatory effect by inhibiting the secretion of pro-inflammatory cytokines. Consequently, ILG inhibits inflammatory reactive astrocytes, promotes neuroprotective reactive astrocytes, alleviates inflammation and improves EAE. These findings provide a theoretical basis and support for the application of ILG in the prevention and treatment of MS.
研究领域:
神经科学
·
免疫学
·
药理学
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DOI
PubMed
高影响因子
SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY
·
2025
·
IF 4.6
Yi Zhang,Ziyi Zhao,Hui Wu
Fluorescence nanosensor based on carbon dots (CDs) is an up-and-coming platform for precise determination of isoliquiritigenin (ISO), ensuring human health and environmental safety. Herein, biomass nitrogen-doped carbon dots (BN-CDs) were assembled through a one-pot hydrothermal platform with lemon peel and melamine as precursors, which could be developed as distinguished sensors to detect ISO. The structure and optical properties of BN-CDs were explored in detail through some analytical methods. The BN-CDs indicated excellent UV resistance performance and biocompatibility. Moreover, after the addition of ISO, the blue fluorescence could be significantly quenched, and an eminent linear relationship was acquired between ln(F 0 /F) and ISO concentrations. The fitting equation was ln(F 0 /F) = 0.054[ISO] + 0.0085 (R 2 = 0.9978) with the concentration range of 0–50 μM. 0.056 μM of detection limit was obtained based on the 3b/k. This nanosensor was successfully carried out in real samples with satisfactory recoveries of 93.3–103.9 %. This research offered a theoretical foundation towards ISO determination via blue-emitting CDs and indicated huge application potential.
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2019
·
IF 4.213
Jian Liu,Qilong Wang,Michael Adu-Frimpong,Qiuyu Wei,Yujiao Xie,Kangyi Zhang,Chunmei Wei,Wen Weng,Hao Ji,Elmurat Toreniyazov,Ximing Xu,Jiangnan Yu
Isoliquiritigenin (ISL) has a great variety of pharmacological effects especially liver cancer therapy, but its poor solubility, bioavailability and liver targeting have limited its clinical use. In order to solve the aforementioned shortcomings, the TPGS-modified proliposomes loaded with ISL (ISL-TPGS-PLP) was prepared in this study. ISL-TPGS-PLP was fabricated via thin-film dispersion method and was characterized by the appearance, particle size, zeta potential and morphology. HPLC was used to evaluate entrapment efficiency (EE), in vitro release and stability of ISL-TPGS-PLP single or combined while appropriate physicochemical parameters were measured with DLS . Meanwhile, the pharmacokinetics and tissue distribution were also studied after oral administration. The results demonstrated that ISL-TPGS-PLP had a mean size of 23.8 ± 0.9 nm , high EE of 97.33 ± 0.40%. More importantly, nearly 90% ISL was released from ISL-TPGS-PLP within 24 h while only 50% was released from ISL suspension. In the pharmacokinetics study, the area under the curve (AUC 0-24h) of ISL-TPGS-PLP was 1.53 times higher than that of ISL suspension. The Tissue distribution study showed that the ISL released from ISL-TPGS-PLP was higher in the liver than the free ISL suspension. Altogether, ISL-TPGS-PLP could ameliorate the ISL solubility, bioavailability and liver targeting ability, suggesting that ISL-TPGS-PLP could serve as a promising nanocarrier for liver cancer therapy.
研究领域:
药剂学
·
肿瘤学
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DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）