XENOBIOTICA
·
2024
·
IF 1.3
Danqing Wu,Rui Luo,Yangnan Chen,Zhiyun Zheng,Shuangying Gui,Ning He
This study explored the distribution of esculin microspheres in rabbit brain tissue following intravitreal injection and investigated the possibility of direct entry of the drug into the brain through the eye, to develop a formulation with enhanced therapeutic efficacy against Parkinson’s disease.Chitosan microspheres of esculin were prepared via an emulsification cross-linking method and their characteristics were evaluated, including angle of repose, bulk density, and swelling ratio. Furthermore, the pharmacokinetic parameters and brain tissue distribution in rabbits were compared among groups administered esculin eye drops, intravitreal esculin solution, and intravitreal esculin microspheres, to determine whether esculin could enter the brain through an ocular route.The results showed that the prepared esculin microspheres were spherical and had good fluidity. Notably, intravitreal administration enhanced the area under the curve (AUC) of esculin in the thalamus. Delivery through microspheres prolonged the drug retention time in both rabbit plasma and brain tissues, as well as the brain-targeting efficiency of esculin.The collective findings indicated that there may be a direct eye-brain pathway facilitating enter of esculin microspheres into brain tissue after intravitreal injection, supporting the utility of intravitreal esculin microspheres as an effective therapeutic formulation for Parkinson’s disease, a long-term chronic condition.
研究领域:
药理学
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神经科学
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药物递送系统
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PubMed
高影响因子
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
·
2026
·
IF 5.2
Yue Zheng,Huan Xu,Dongjing Liu,Liping Feng,Biyang Yao,Ziyu Liao,Yunxuan Zhou,Jingrui Wang,Yanyue Qin,Yingchun Zeng
An esculin-phospholipid complex-based self-nanoemulsifying drug delivery system (EPC-SNEDDS) was successfully developed and optimized. • As The first reported oral nanoformulation for ESC, EPC-SNEDDS significantly improved its oral bioavailability. • The mechanisms by which EPC-SNEDDS improved the oral absorption of ESC were elucidated, including improved stability, enhanced intestinal permeability, and promoted lymphatic absorption. • Oral administration of EPC-SNEDDS normalized serum uric acid (UA) levels in hyperuricemic mice and concurrently exhibited favorable renal protective effects. • Orally administered EPC-SNEDDS not only significantly inhibited UA production, but also potently promoted its excretion. Hyperuricemia (HUA) is the second most prevalent metabolic disease with unmet clinical needs persisting in its pharmacotherapy. Esculin (ESC) is an active coumarin with anti-hyperuricemic effects. However, its poor solubility, low membrane permeability, and significant first-pass effect limit its oral absorption and application. Self-nanoemulsifying drug delivery system (SNEDDS) has attracted extensive attention as a versatile platform to improve the oral bioavailability of poorly soluble and low-permeability drugs. Herein, an ESC-phospholipid complex (EPC) was prepared to enhance the lipophilicity of ESC and consequently its compatibility with SNEDDS. Subsequently, an EPC-loaded SNEDDS (EPC-SNEDDS) was developed for the oral delivery of ESC. Its composition was screened via pseudo-ternary phase diagrams and further optimized via a Box-Behnken design. The optimal formulation consisted of Lauroglycol 90, Tween 80, and Transcutol P (21.6:41.4:37.2, w/w/w ). After aqueous dispersion, EPC-SNEDDS rapidly formed nanoemulsions with a small droplet size (27.78 ± 0.71 nm), narrow particle size distribution (PDI = 0.149 ± 0.007), and high stability. Moreover, the formulation increased the oral bioavailability of ESC by 2.88-fold, which could be ascribed to improved stability, membrane permeability and lymphatic transport. In hyperuricemic mice, oral EPC-SNEDDS effectively suppressed serum and hepatic xanthine oxidase activity and promoted uric acid excretion, exhibiting superior urate-lowering efficacy compared with free ESC and EPC. Collectively, the integration of phospholipid complexes with SNEDDS provides a feasible strategy for efficient oral administration of ESC, and EPC-SNEDDS represents a promising therapeutic approach for HUA treatment. Download: Download high-res image (244KB) Download: Download full-size image
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高影响因子
JOURNAL OF MICROENCAPSULATION
·
2025
·
IF 3.2
Ning He,Danqing Wu,Rui Luo,Ziqin Cao,Shuang Shan,Qingsong Fei,Jiabao Wu,Shaoyun Bai
This study was to prepare the esculin-loaded chitosan microspheres for intravitreal injection and explore the feasibility of the treatment of macular degeneration. The microspheres were fabricated using an emulsification crosslinking technique. The drug loading, encapsulation efficiency, and mean particle diameter of the optimised esculin-loaded chitosan microspheres were 8.03 ± 1.30%, 93.03 ± 2.16%, and 4.81 ± 1.60 μm, respectively. The thermal stability evaluation at 25 °C demonstrated consistent particle diameter maintenance, with microspheres retaining sizes of 4.73 ± 1.75 μm and 4.89 ± 1.55 μm after 15 and 30 days’ storage periods, respectively. The in vitro release profile demonstrated 80% cumulative drug release from the microspheres over a 72 h period. Subsequent pharmacokinetic analysis revealed significantly enhanced parameters in the vitreous humour following intravitreal administration, with the half-life (t1/2) reaching 879.88 ± 44.00 min and the area under curve (AUC) attaining 150.18 ± 2.28 × 103 mg·min/mL. Intravitreal injection of esculin-loaded chitosan microspheres offers a promising drug delivery system for the treatment of macular degeneration.
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高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2023
·
IF 5.6
Jiangwei Ni,Ge Li,Ningfeng Dai,Zijiao Quan,Haibin Tong,Yu Liu
Objectives Acute lung injury (ALI) poses a serious threat to human health globally, particularly with the Coronavirus 2019 (COVID-19) pandemic. Excessive recruitment and infiltration of neutrophils is the major etiopathogenesis of ALI. Esculin, also known as 6,7-dihydroxycoumarin, is a remarkable compound derived from traditional Chinese medicine Cortex fraxini . Accumulated evidence indicates that esculin has potent anti-inflammatory effects, but its pharmaceutical effect against ALI and potential mechanisms are still unclear. Methods This study evaluated the protective effect of esculin against ALI by histopathological observation and biochemical analysis of lung tissues and bronchoalveolar lavage fluid (BALF) in lipopolysaccharide (LPS)-challenged ALI mice in vivo . The effects of esculin on N-formyl-met-leu-phe (fMLP)-induced neutrophil migration and chemotaxis were quantitatively assessed using a Transwell assay and an automated cell imaging system equipped with a Zigmond chamber, respectively. The drug affinity responsive target stability (DARTS) assay, in vitro protein binding assay and molecular docking were performed to identify the potential therapeutic target of esculin and the potential binding sites and pattern. Results Esculin significantly attenuated LPS-induced lung pathological injury, reduced the levels of pro-inflammatory cytokines in both BALF and lung, and suppressed the activation of NF-κB signaling. Esculin also significantly reduced the number of total cells and neutrophils as well as myeloperoxidase (MPO) activity in the BALF. Esculin impaired neutrophil migration and chemotaxis as evidenced by the reduced migration distance and velocity. Furthermore, esculin remarkably inhibited Vav1 phosphorylation, suppressed Rac1 activation and the PAK1/LIMK1/cofilin signaling axis. Mechanistically, esculin could interact with β 2 integrin and then diminish its ligand affinity with intercellular adhesion molecule-1 (ICAM-1). Conclusions Esculin inhibits β 2 integrin-dependent neutrophil migration and chemotaxis, blocks the cytoskeletal remodeling process required for neutrophil recruitment, thereby contributing to its protective effect against ALI. This study demonstrates the new therapeutic potential of esculin as a novel lead compound.
研究领域:
药理学
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免疫学
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病理生理学
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分子生物学
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高影响因子
Journal of Biomedical Nanotechnology
·
2024
·Vol. 20
·期 9
·1457-1466
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IF 2.9
Shi Feng,Sun Weigang,Yin Wenxiong,Xia Xiaoli,Adu-Frimpong Michael,Cao Xia,Ji Hao,Wang Qilong,Xu Ximing,Yu Jiangnan
In this study, Esculin (ES)-loaded liposomes modified with TPGS (ES-TPGS-Ls) were successfully prepared to enhance bioavailability and hepatoprotective activity of this coumarin glucoside. We utilize thin-film dispersion to fabricate ES-TPGS-Ls. The size, polydispersed index (PDI),
Zeta potential (Z-potential), morphology, and encapsulation effectiveness of the liposomes were all evaluated afterwards. The storage stability of ES-TPGS-Ls at 4 °C was investigated. The findings showed that ES-TPGS-Ls had spherical nanoparticles with 194.47±8.54 nm as the mean
size, 0.239±0.011 as PDI, and −21.16±0.97) mV as Z-potential coupled with encapsulation efficiency (EE) of 91.85±0.44%. Storage stability of liposomes at 4 °C was maintained within one week. Pharmacokinetic study showed that the relative oral bioavailability
of ES-TPGS-Ls increased by 2.38 times. Pharmacodynamic studies showed that the developed liposomes could enhance the hepatoprotective activity of ES. Overall, the ES-TPGS-Ls significantly enhanced the bioavailability of esculin, thereby enhancing the in vivo hepatoprotective effect
of ES.
研究领域:
药剂学
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药物代谢动力学
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肝脏保护研究
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高影响因子
MOLECULAR NEUROBIOLOGY
·
2026
·Vol. 63
·期 1
·432
·
IF 5.5
Lin Jinyu,You Bowen,Yang Xin,Li Xue,Sun Wenjuan,Xu Zhongyu,Zhang Yi,Tong Xuhui,Dong Shuying
Cerebral ischemia/reperfusion injury (CIRI) refers to the secondary brain injury that occurs when blood supply is restored to ischemic cerebral tissue, and represents one of the primary causes of adult disability and mortality. Current evidence indicates that aesculin exhibits antioxidative and anti-inflammatory activities; however, its therapeutic effects on CIRI remain to be elucidated. The objective of this study was to investigate the potential role of Esculin (ESCU) in protecting against CIRI and to elucidate its underlying mechanisms. Adult male mice were used to establish the middle cerebral artery occlusion/reperfusion (MCAO/R) model. The mice were administered varying doses of ESCU or a reference positive control drug. To evaluate the neuroprotective effects of ESCU, neurological deficit scores were assessed, and cerebral blood flow was measured. 2,3,5-triphenyltetrazolium chloride staining, H&E staining, and Nissl staining were used to determine neuronal damage. NLRP3-related markers and mitophagy-related markers were determined to investigate the mechanism of action of ESCU. ESCU afforded robust neuroprotection in mice, ameliorating functional deficits, reducing infarct size, and preserving neuronal structure. It potently alleviated oxidative stress and restored mitochondrial function (reduced ROS, improved cristae morphology, and increased mitochondrial membrane potential). Mechanistically, ESCU activated mitophagy (upregulating LC3Ⅱ, PINK1, and Parkin; downregulating p62) and inhibited the NLRP3 inflammasome (downregulating NLRP3, GSDMD-N, cleaved caspase-1, IL-1β, and IL-18). Notably, the mitophagy inhibitor Mdivi-1 abolished ESCU’s inhibition of the NLRP3 pathway, establishing a causal relationship. Thus, ESCU mitigates cerebral ischemia-reperfusion injury by coordinately enhancing mitophagy and suppressing NLRP3 inflammasome activation. Our study demonstrates that ESCU attenuates CIRI mechanistically by promoting PINK1/Parkin-mediated mitophagy, thereby suppressing NLRP3 inflammasome activation. These findings not only elucidate a novel pathway underlying ESCU’s neuroprotection but also position it as a promising therapeutic candidate for CIRI, warranting further investigation into its precise targets and clinical potential.
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高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2023
·
IF 5.4
Yong-Yu Yang,Jing-Jing Qi,Si-Yi Jiang,Ling Ye
Ethnopharmacological relevance Cortex fraxini (also known as qinpi)—the bark of Fraxinus rhynchophylla Hance (Oleaceae)—is widely used as a Chinese traditional medicinal for its anti-inflammatory and anti-hyperuricemic activities. Aim of the study Obesity-induced insulin resistance (IR) is driving the rising incidence of type 2 diabetes mellitus and is related to pathological adipose tissue remodeling. Esculin, a major active component of Cortex fraxini , has anti-diabetic effects. However, whether esculin improves obesity-induced IR by regulating adipose tissue remodeling is unclear. The aims of the present study were to assess the effects of esculin on obesity-induced IR and to explore the underlying mechanisms. Materials and methods Obese IR C57BL/6J mice were treated with esculin (40 or 80 mg/kg/day) for 4 weeks. Oral glucose tolerance tests were used to assess insulin sensitivity. Histological analyses were performed to analyze the number and size distribution of adipocytes. Glucose uptake was assessed using 2-NBDG. Results Esculin had no effect on body weight gain but reduced fasting blood glucose, improved oral glucose tolerance, and increased insulin sensitivity. Esculin reduced adipocyte size and the expression levels of collagen 4A1 and tumor necrosis factor α and increased the number of adipocytes and the expression of vascular endothelial growth factor A. Esculin promoted the differentiation of 3T3-L1 cells and upregulated the mRNA expression of CCAAT/enhancer-binding protein α and peroxisome proliferator-activated receptor-γ, activated the insulin receptor substrate 1 (IRS1)/phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway, and enhanced the translocation of glucose transporter type 4 (GLUT4) and glucose uptake in adipocytes treated with palmitic acid. Conclusions These data suggest that esculin increases insulin sensitivity by improving adipose tissue remodeling and activating the IRS1/PI3K/AKT/GLUT4 pathway.
研究领域:
药理学
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内分泌学
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代谢
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中药
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PubMed
高影响因子
FOOD CHEMISTRY
·
2025
·
IF 9.8
Le Zhang,Ruiyang Ma,Shuangju Song,Weihua Liu,Qiuhua Wu,Zhi Wang
A green and hydroxyl functionalized hypercrosslinked polymer (Esc/BCMBP 1:2 -HCP) was synthesized for solid-phase extraction (SPE) of diamide insecticides by using natural esculin as monomer for the first time. It exhibited an excellent adsorption performance for the diamides. The major SPE influencing parameters were investigated, and then, a new analytical approach coupling the Esc/BCMBP 1:2 -HCP based SPE with HPLC-DAD detection was developed for the analysis of the diamide insecticides. Under optimal conditions, a good linearity was achieved in the analytes concentration range of 0.2–100.0 ng mL −1 , 3.0–500.0 ng g −1 , and 3.0–500.0 ng g −1 for water, rice and soil samples, respectively, with the coefficients of determination>0.9936. The limits of detection were in the range of 0.06–0.30 ng mL −1 , 0.90–1.60 ng g −1 and 0.80–1.80 ng g −1 , respectively. The method recoveries for the spiked samples were from 87.0 % to 111 %, with the relative standard deviations < 7.5 %.
研究领域:
环境科学
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高分子化学
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分析化学
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农药残留分析
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高影响因子
JOURNAL OF FISH DISEASES
·
2021
·Vol. 45
·期 1
·59-68
·
IF 2.767
Li-Peng Shan,Xu Zhang,Yang Hu,Lei Liu,Jiong Chen
White spot syndrome virus (WSSV) is a pathogenic and threatening virus in shrimp culture for which there is no effective control strategy. Finding antiviral lead compounds for the development of anti-WSSV drugs is urgent and necessary; in this study, esculin from 12 monomeric compounds exhibited an excellent anti-WSSV activity. The results showed that esculin increased the survival rate of WSSV-infected shrimps by 59% and reduced the virus copy number in vivo over 90% at 100 μM. In the pre-treatment and post-treatment experiments, esculin could prevent and treat WSSV infection. Compared with the control group, the virus copy number decreased by 30% after 6 h of esculin pre-incubation with WSSV particles and inhibited horizontal transmission of WSSV to a certain extent. Considering that the antiviral activity of esculin was stable in the aquacultural water for 2 days, we evaluated the dosing pattern of continuous medication changes. Obviously, the survival rate of WSSV-infected shrimps was 0% at 108 h when no esculin exchange was made, while at 120 h the survival rate was over 40% at continuous medicine changes. In addition, esculin significantly increased the expression of antimicrobial peptides and thus improved the ability of shrimp to resist WSSV. Overall, our findings suggest that esculin has the potential to be developed into an anti-WSSV medicine.
研究领域:
水产养殖
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病毒学
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海洋生物学
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高影响因子
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