DRUG DELIVERY
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2019
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IF 3.829
Yujia Zhang,Nan Zhang,Hui Song,He Li,Jin Wen,Xiaochuan Tan,Wensheng Zheng
Gout is a kind of joint disease characterized by the accumulation of monosodium urate (MSU) crystals in the joint and its surrounding tissue, causing persistent hyperuricemia. Colchicine is the first choice of treatment for acute gout attacks. Due to strong toxicity of colchicines oral tablets, there are high fluctuations of blood drug concentration and serious irritation of gastrointestinal tract, and hence a transdermal preparation can help to slow down the blood drug concentration, reduce the frequency of drug taking, and improve the patients' compliance of the drug. The ethosome is a lipid carrier with high concentration of ethanol and has been proved to promote the penetration of drugs into the skin. Borneol (BO) is an excellent penetration enhancer in Chinese medicine, which can promote the entry of drugs into the skin. This paper prepared the borneol-physically-modified colchicine ethosome (COL-bpES) and used the prepared borneol-dioleoyl phosphoethanloamine (BO-DOPE) to prepare borneol-chemically-modified colchicine ethosome (COL-bcES). Compared to the free colchicine aqueous solution (free COL) and normal colchicine ethosome (COL-ES), the borneol-modified colchicine ethosome (COL-bES) demonstrated better drug penetration effect, while the particle size of the COL-bcES was lower than that of the COL-bpES. Toxicity, in vitro diffusion, pharmacokinetics and pharmacodynamics are superior to those of COL-bpES, providing a better delivery system for the treatment of small molecule inflammatory drugs.
研究领域:
药剂学
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生物医学工程
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高影响因子
MOLECULES
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2026
·Vol. 31
·期 4
·721
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IF 5.1
Juhua Zhong,Yishuo Zhu,Bin Xia,Faying Jiang,Zhengyue Qiu,Lewei Zhao,Siyu Chen,Hongbao Chen,Haobo Wang,Lin Kang,Tonghe Yang,Shuai Li,Si Liu,Jianguo Zeng,Zhixing Qing
Lilies (Liliumspp.) are highly valued in China for their edible and medicinal properties; however, bitterness in certain varieties limits consumer acceptance. Although historically attributed to colchicine, the presence of alkaloids in lilies remains a subject of debate. This research screened five lily species for colchicine and its 15 biosynthetic precursors, usingGloriosa superbaandColchicum autumnaleas positive controls. While detected in the controls, none were detected in any tissues (bulbs, roots, stems, flowers, and leaves) of the five lilies. A comparative analysis of five lily varieties—Longyahong, Lanzhou,Lilium lancifolium, Longya, and Guiyanghong—revealed that Longyahong exhibited the strongest bitterness, which was localized exclusively in the bulb peels. Based on comparative LC-MS profiling between bitter and non-bitter varieties, three high-abundance compounds were selected for isolation and subsequent sensory evaluation. Two monomeric compounds were isolated and confirmed via chromatographic methods as the primary bitter components. This study provides compelling chemical and biochemical evidence of the presence of colchicine in the examined lilies. By identifying two specific bitter components in Longyahong bulb peels, these findings refute the long-standing misconception regarding colchicine in lilies and provide a chemical foundation for improving the palatability and commercial value of bitter lily varieties.
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Journal of Inflammation Research
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2026
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IF 4.6
Chenxi Wu,Xinru Xu,Yueyue Shi,Cantao Li,Fenfen Li,Ziye Xu,Liangxin Chen,Wenjing Xu,Yihuan Wang,Xiaoxi Zhang,Daozong Xia
Objective Neutrophil extracellular traps (NETs) are involved in the pathogenesis of gouty arthritis (GA). This study aimed to investigate whether standardized extract of flavonoids from Smilax glabra Roxb. (SFSG) alleviates GA by targeting NETs formation and to elucidate its underlying mechanisms involving neutrophil-driven inflammation and signaling pathways.Methods SFSG’s effects were evaluated in a monosodium urate (MSU)-induced GA model. Neutrophil depletion (via mAb 1A8 antibody) validated their pathogenic role. SFSG was administered for 7 days to assess joint swelling, histopathology (HE staining), neutrophil infiltration (immunohistochemistry), and inflammatory cytokines (IL-1β and IL-8, measured by ELISA). In MSU and PMA-stimulated neutrophils, SFSG (0–200 μg/mL, non-toxic by CCK8) was tested for NETs formation (immunofluorescence, transmission electron microscopy), oxidative stress (ROS), lactate dehydrogenase (LDH) activity, Raf/ERK signaling, and citrullinated histone H3 (CitH3) (Western blotting).Results Neutrophil depletion significantly alleviated MSU-induced joint inflammation, confirming neutrophils as key drivers of GA pathology. SFSG treatment dose-dependently suppressed MSU-induced joint inflammation in vivo. Notably, the high dose inhibited ankle swelling by ~66% (reducing it from 58.36% to 19.75%), matching the efficacy of colchicine. Concomitant reductions in neutrophil infiltration and IL-1β/IL-8 levels were also observed. Additionally, SFSG attenuated PADI4 and NOX2 gene expression. In vitro, SFSG inhibited NETs formation, ROS production, and LDH release while downregulating Raf/ERK signaling and CitH3 expression.Conclusion SFSG alleviates GA progression by targeting neutrophil-driven inflammation and NETs formation through suppression of Raf/ERK signaling and CitH3 expression, thereby demonstrating its potential as a phytotherapeutic agent for neutrophil-associated pathologies.
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ADVANCED FUNCTIONAL MATERIALS
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2026
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IF 19.9
Xiaoxue He,Tian Liu,Mingjia Sun,Linsheng Wu,Yinghou Wang,Jingdong Xiao,Jin Sun,Qikun Jiang
Small interfering RNAs (siRNAs) have emerged as promising therapeutics for ulcerative colitis (UC) owing to their potent anti-inflammatory effects and favorable biocompatibility. However, effective oral siRNA delivery remains challenging due to limited inflammatory cell targeting, inefficient endosomal escape, and rapid degradation in the gastrointestinal tract. To overcome these barriers, we developed a nano-in-micro modular microbead system for colon-targeted delivery of siRNA against tumor necrosis factor-α (TNF-α). This platform integrates two key components: (i) a library of ginsenoside-based lipid nanoparticles (LNPs) generated by screening natural sterol analogues, among which ginsenoside Rg3-based LNPs (Rg3@siTNF-α) were identified as optimal carriers, enabling enhanced macrophage targeting via glucose transporter-1–mediated recognition and promoting endosomal escape by attenuating Niemann–Pick C1 (NPC1)–dependent recycling; and (ii) a calcium alginate (CA) shell that encapsulated Rg3@siTNF-α to form microbeads (CA@Rg3@siTNF-α), protecting the LNPs from premature degradation in the upper gastrointestinal tract. Upon colon-specific dissolution, CA@Rg3@siTNF-α released Rg3@siTNF-α, facilitating efficient macrophage uptake, rapid endosomal escape, and lipase-responsive siRNA release. Consequently, the microbeads alleviated UC by suppressing inflammation and oxidative stress, restoring epithelial barrier integrity, and rebalancing the gut microbiota. Collectively, this work presents a spatiotemporally controlled strategy for oral siRNA delivery with multi-mechanistic therapeutic actions.
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DRUG METABOLISM AND DISPOSITION
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2026
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IF 4
Dingsheng Wen,Liping Zhang,Peiwen Deng,Huaan Li,Xiaohua Feng,Lu Wen,Gang Chen
Effective drug delivery to the inner ear is severely limited by the restrictive nature of the round window membrane (RWM). In this study, coumarin-6 labeled chitosan nanoparticles were administered via intratympanic injection in guinea pigs to investigate their spatiotemporal transport across the RWM and entry into the inner ear. The nanoparticles exhibited prolonged residence on the RWM and efficient presence in the perilymph in a time- and concentration-dependent manner. Mechanistic analyses demonstrated that nanoparticle transport occurred through coordinated paracellular and transcellular pathways. Transient modulation of tight junctions facilitated paracellular diffusion, while active transcellular transport involved multiple endocytic routes. Following cellular uptake, nanoparticles underwent intracellular trafficking and were released into the perilymph via Golgi-mediated exocytosis. Collectively, these findings reveal an in vivo, RWM-specific transport cascade characterized by coordinated paracellular tight-junction modulation, multiroute endocytic uptake, and Golgi-mediated exocytotic release into the perilymph, providing mechanistic insight into nanoparticle disposition in the inner ear and supporting their potential for local drug delivery. Significance statement This study defines an in vivo, RWM-specific transport cascade governing nanoparticle disposition in the inner ear. It demonstrates coordinated paracellular and transcellular transport enabling nanoparticle entry into the perilymph, advancing mechanistic insight into physiological barrier regulation of inner ear drug delivery and supporting rational design of nanocarrier-based otologic therapies.
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Nutrients
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2026
·Vol. 18
·期 14
·2360
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IF 5.8
Xiaoxi Zhang,Gaoyang Fu,Xinyu Zhao,Yan Huang,Fenfen Li,Daozong Xia
Background/Objectives:Gouty arthritis (GA) is an inflammatory disease caused by increased purine metabolism. The limitations of current anti-GA therapies remain a major challenge. Astilbin, the main flavonoid in Smilax glabra Roxb., was found to exert potential anti-GA effects in our previous study.Methods:In this study, a mouse model of monosodium urate (MSU)-induced arthritis and an inflammatory model using mouse bone marrow-derived macrophages (BMDMs) were established.Results:Our data showed that astilbin reduced MSU-induced joint swelling and inflammatory infiltration in mice, restored lipopolysaccharide (LPS)/MSU-induced reductions in cell viability, and inhibited the expression levels of inflammatory factors IL-1β, IL-6 and TNF-α. Further studies showed that astilbin significantly reduced MSU-induced increases in NLRP3 and P-p65 protein levels, as well as the expression of ASC, P-IKKα, P-IκBα, and cleaved-caspase-1.Conclusions:This study suggests that astilbin may be a promising natural product for the treatment of GA by inhibiting the activation of the NLRP3 inflammasome and NF-κB signaling pathway.
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Materials Horizons
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2025
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IF 10.7
Ziqing Yuan,Jiasu Xu,luyao li,Hongxia Li,Jie He,Kaiwen Bao,Lai Jiang,Guangxia Shen,Xianting Ding
Visualization of proteins and nucleic acids with super-resolution is a persistent need. Expansion microscopy (ExM) permits nanoscale imaging of biomolecules on conventional microscope by physically expanding biological specimens embedded in a stretchable hydrogel. However, achieving simultaneous super-resolution co-imaging of proteins and nucleic acids on ExM has remained a general challenge. Here, we present photoclick dual anchoring expansion microscopy (Phan-ExM), which employs an unorthodox anchoring reagent, N-(3-methacrylamidopropyl)-3-(2-methyl-1 H-pyrrol-1-yl)-2 H-tetrazole-2-carboxamide (MAP-mPyTC), for rapid and concurrent retention of proteins and nucleic acids within the ExM gel matrix through photoclick chemistry. We demonstrated MAP-mPyTC could anchor both protein and mRNA biomolecules within 10 minutes, significantly reducing the time compared to typical ExM techniques, which usually take several hours to overnight. Moreover, we showed that Phan-ExM significantly enhanced the fluorescence intensity of protein and RNA spots compared to previous method. With Phan-ExM, we achieved high-resolution co-imaging of multiplex proteins and nucleic acids on a single specimen at ~85 nm resolution. We revealed that paclitaxel and colchicine treatment significantly disrupted mitochondrial dynamics in BALB/c 3T3 cells, with an associated aggregation of ACTB mRNA observed at sites of mitochondrial damage. Phan-ExM provides a platform technique for super-resolution colocalization of nucleic acids and proteins on the same specimen with conventional microscope.
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Journal of Food Measurement and Characterization
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2023
·Vol. 17
·期 3
·2978-2987
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IF 3.4
Zhang Lin,Dong Yi,Lu Yunhao,Mo Rui,He Qiang
The photolysis of colchicine under ultraviolet and visible light irradiation was studied by ultraviolet (UV) scanning and HPLC-MS. The photoproduct was proposed and the cytotoxicity change before and after irradiation was investigated. Results showed that both ultraviolet and visible light irradiation could effectively degrade colchicine into deacetamido-lumicolchicine. The process conformed to first-order kinetics, in which a high degradation rate (K = 0.5862 h − 1 ) was observed when colchicine was dissolved in ethanol and irradiated by UV light. Cell viability and cell cycle studies proved that a photolysis treatment of colchicine could weaken the cytotoxicity effectively. Colchicine inhibited the division of BRL 3 A cells in G2/M phase with an IC 50 value of 0.48 µg/mL, while the toxic effect could be reduced significantly with IC 50 2.1 µg/mL when colchicine was exposed to UV irradiation. Results are beneficial to the toxicity elimination of colchicine in the processing of daylily flower in food industry, and can also provide photochemistry reference for colchicine-related studies.
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CARBOHYDRATE POLYMERS
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2022
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IF 10.723
Yuhan Yang,Yangyi Chen,Dianpeng Li,Shiyuan Lin,Hui Chen,Wei Wu,Wei Zhang
A novel delivery system based on linolenic acid (LA) conjugated chitosan (CS) polymeric micelles were proposed for improving the oral absorption of doxorubicin (DOX) through targeting intestinal fatty acid transporter. LA, as a ligand of the transporter, was grafted into CS to construct CS-LA micelles, and DOX was encapsulated into the micelles. The synthesized micelle material was identified by 1 H NMR and FT-IR. The micelles showed regular spherical shapes with a particle size of 117.1 ± 1.6 nm, drug loading of 8.77 ± 0.02 %, and critical micelle concentration (CMC) of 23.6 μg/ml. The pharmacokinetics studies showed the relative bioavailability of 166 % versus DOX·HCl. The fatty acid transport protein 4-mediated intestinal uptake process of micelles was confirmed by the intracellular uptake, immunofluorescent imaging and permeation test. These findings confirmed the potential of CS-LA micelles as an effective oral delivery vehicle, and fatty acid transporter as a target spot for enhancing intestinal drug absorption.
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Biomaterials Advances
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2022
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IF 0
Fenglei Zhang,Xuejing Pei,Xiaoxia Peng,Dongxia Gou,Xiao Fan,Xuefei Zheng,Chengcheng Song,Yifa Zhou,Sisi Cui
Pectin-based drug delivery systems hold great potential for oral insulin delivery, since they possess excellent gelling property, good mucoadhesion and high stability in the gastrointestinal (GI) tract. However, lack of enterocyte targeting ability and premature drug release in the upper GI tract of the susceptible ionic-crosslinked pectin matrices are two major problems to be solved. To address these issues, we developed folic acid (FA)-modified pectin nanoparticles (INS/DFAN) as insulin delivery vehicles by a dual-crosslinking method using calcium ions and adipic dihydrazide (ADH) as crosslinkers. In vitro studies indicated insulin release behaviors of INS/DFAN depended on COOH/ADH molar ratio in the dual-crosslinking process. INS/DFAN effectively prevented premature insulin release in simulated GI fluids compared to ionic-crosslinked nanoparticles (INS/FAN). At an optimized COOH/ADH molar ratio, INS/DFAN with FA graft ratio of 18.2% exhibited a relatively small particle size, high encapsulation efficiency and excellent stability. Cellular uptake of INS/DFAN was FA graft ratio dependent when it was at/below 18.2%. Uptake mechanism and intestinal distribution studies demonstrated the enhanced insulin transepithelial transport by INS/DFAN via FA carrier-mediated transport pathway. In vivo studies revealed that orally-administered INS/DFAN produced a significant reduction in blood glucose levels and further improved insulin bioavailability in type I diabetic rats compared to INS/FAN. Taken together, the combination of dual crosslinking and FA modification is an effective strategy to develop pectin nano-vehicles for enhanced oral insulin delivery.
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PHYTOMEDICINE
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2022
·
IF 6.656
Baogui Xu,Jiawen Zheng,Xiaoxiao Tian,Falei Yuan,zhongliang Liu,Yafeng Zhou,Zuisu Yang,Xianjun Ding
Background Chemical or drug-induced kidney damage has been recognized as a critical cause of kidney failure. The oxidative stress, inflammation, and imbalance of intestinal flora caused by carbon tetrachloride (CCl 4 ) play a fundamental role in chronic kidney damage. Guizhi Fuling pills (GZFL) is a traditional formula consisting of five traditional Chinese medicinal herbs, which can promote blood circulation and improve kidney function. The underlying mechanisms of GZFL improving kidney damage are not fully understood yet. Aim The current study aimed to explore the effects of GZFL on CCl 4 -induced kidney damage and intestinal microbiota in mice. Methods Male ICR mice were intraperitoneally administered with 20% CCl 4 (mixed in a ratio of 1:4 in soybean oil) twice a week, for 4 weeks to induce kidney damage. Creatinine (CRE), urea nitrogen, antioxidant enzymes, and inflammatory cytokines were measured and the histology of the kidney, jejunum, and colon examination to assess kidney and intestinal damage. The expressions of nuclear factor-erythroid 2-related factor 2 (Nrf2) family members, nucleotide-binding domain and leucine-rich repeat protein 3 (NLRP3) inflammasome in kidney tissues, and the tight junction proteins in colonic tissues were detected by Western blot. The gut microbiota was analyzed through 16S rRNA gene sequencing. Results GZFL treatment decreased the serum CRE and urea nitrogen levels. Moreover, GZFL reduced the levels of pro-inflammatory cytokines and increased antioxidant enzyme activities in kidney and colonic tissues. GZFL improved the kidney, jejunum, and colon histology. Furthermore, GZFL inhibited the expressions of NLRP3, ASC, and cleaved-Caspase-1, while Nrf2, HO-1, NQO1, GCLM, and tight junction proteins were increased. The dysbiosis of intestinal microbiota improved after GZFL treatment. Conclusions This study showed that GZFL could improve kidney damage, which might be mainly via the integrated regulations of the Nrf2 pathway, NLRP3 inflammasome, and composition of intestinal microbiota.
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Bioengineered
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2021
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IF 3.269
Jihui Zhang,Hongwei Lei,Xiu Li
Gout is a common and complex form of arthritis that has brought great inconveniences to the normal lives of patients. It is reported that oxidative stress and nod-like receptor family protein 3 (NLRP3) inflammasome-mediated inflammatory reactions are involved in the pathogenesis of gout arthritis. S14G-humanin (S14G-HNG) is a modified peptide of HNG with higher inhibitory activity on the accumulation and deposition of Aβ. Recently, S14G-HNG has been reported to exert great anti-inflammatory effects. The present study proposed to explore the possible therapeutic property of S14G-HNG against gout arthritis. An animal model was established by stimulation with mono-sodium urate (MSU) crystals, followed by treatment with colchicine and S14G-HNG, respectively. The elevated Gait score promoted synovitis score and activated myeloperoxidase (MPO) observed in MSU crystals-treated mice were significantly reversed by colchicine and S14G-HNG. Bone marrow-derived macrophages (BMDMs) were isolated from mice and stimulated with MSU crystals, followed by being treated with 25 and 50 μM S14G-HNG. The increased mitochondrial reactive oxygen species (ROS) and Malondialdehyde (MDA) levels, upregulated NADPH oxidase-4 (NOX-4), activated NLRP3 inflammasome, and elevated production of inflammatory factors in MSU crystals-treated BMDMs were dramatically reversed by S14G-HNG, accompanied by the upregulation of sirtuin type-1 (SIRT1). Lastly, the protective effects of S14G-HNG against MSU crystals-induced NLRP3 inflammasome activation were significantly abolished by the knockdown of SIRT1. In conclusion, our data reveal that S14G-HNG could possess potential benefits against MSU crystals-induced gout arthritis, with colchicine displaying a better effect.
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