CHEMICAL ENGINEERING JOURNAL
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2026
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IF 12.5
Li Zhu,Yue Zheng,Mengjuan Yu,Shan Yu,Yiyun Luo,Ravin Narain,Kaihui Nan,Yangjun Chen
Corneal neovascularization (CNV), a major cause of vision impairment, requires improved therapeutic strategies. While Celastrol (Cel), a natural product extracted from traditional Chinese herbs, demonstrates anti-angiogenic potential for CNV treatment, its clinical application can be hindered by poor aqueous solubility and ocular bioavailability. To address this, we developed mucoadhesive micelles using phenylboronic acid (PBA)- and stearic acid (SA)-modified chitosan oligosaccharides (COS) for encapsulation and enhanced ocular delivery of Cel. The Cel-loaded micelles (COSA-PBA@Cel) exhibited a positive Zeta potential of approximately +27 mV, facilitating electrostatic interaction with negatively charged ocular mucin. PBA integration further enabled dynamic covalent bonding with sialic acid residues, synergistically prolonging corneal retention. Therefore, COSA-PBA@Cel nanomicelles exhibited remarkably prolonged ocular surface retention time. In vitro experiments demonstrated that COSA-PBA@Cel micelles effectively inhibited the migration and tube formation of human umbilical vein endothelial cells (HUVECs), showcasing potent anti-neovascular activity. In a mouse model of alkali burn-induced CNV, COSA-PBA@Cel micelles significantly suppressed pathological angiogenesis, primarily through enhanced Cel delivery that modulates the HIF-1α/VEGF signaling pathway. This nanoplatform overcomes key ocular drug delivery challenges while leveraging Cel's therapeutic potential, offering a promising topical solution for CNV management.
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Advanced Science
·
2026
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IF 14.1
Jinrun Chen,Yuqin Wu,Bofei Xu,Jiabei Hou,Yijing Li,Yuhan Hu,Yutuo Zhu,Wenqiao Zhang,Shuqi Feng,Huanting Jin,Yuchen Cheng,Yuanyuan Jin,Jianhong Zhou,Xingyi Li
Activation of retina-specific CD4 + T cells capable of breaking through the blood-retinal barrier (BRB) was significantly associated with the onset and progression of autoimmune uveitis (AU). Antigen-presenting cells (APCs) orchestrate this process by presenting retinal antigens to naïve CD4 + T cells and driving their differentiation into autoreactive CD4 + T cells. Here, we report an intestinal APCs-targeted strategy for treating AU based on orally administered nanoCEL (diameter: 37.06 ± 0.12 nm), a pH-responsive nanomedicine exhibiting a great gastric acid stability and a pH-responsive drug release behavior. After oral administration, nanoCEL effectively penetrates the intestinal mucus barrier and targets APCs in the intestine. Using an experimental autoimmune uveitis rat model, oral administration of nanoCEL (2 mg/kg) exhibits a superior therapeutic efficacy than free CEL treatment by suppressing the antigen-presenting ability of APCs and impairing pathogenic T cell differentiation. Additionally, nanoCEL medication protects the BRB from the damage of pathogenic T cells by the reduction of the infiltration of peripheral immune cells and the activation of retinal glial cells. Compared to free CEL, oral administration of nanoCEL remarkably enhances drug bioavailability and improves biosafety without apparent systemic toxicity. Thus, the proposed APC-targeted nanodrug delivery system might be a promising strategy to treat AU.
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JOURNAL OF FOOD COMPOSITION AND ANALYSIS
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2026
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IF 5.3
Huan Liu,Liying Liang,Minggang Wang,Qinfeng Huang,Yu Pan,Xiaojie Wei,Wenchao Zhang
The naturally occurring pentacyclic triterpenoid compounds ursolic acid (UA) and oleanolic acid (OA) are commonly found together in various fruits and find broad applications in pharmaceuticals, cosmetics, food and agricultural fields. In this study, a sensitive and practical icELISA method was developed based on a monoclonal antibody (mAb) YC23-101, with a median inhibitory concentration (IC 50 ) of 15.56 ng/mL and a linear range of 5.26 to 54.1 ng/mL. The limits of detection (LOD) ranges from 0.98-5.11 ng/mL in fruit matrices and the recoveries were 94.03-112.21% with coefficients of variation below 5.73%. Cross-reactivity analysis showed that mAb YC23-101 could also specifically recognize OA with similar sensitivity to UA, indicating feasibility for the simultaneously quantification of UA and OA in fruits. The developed icELISA was applied to several fruits, and the results showed good correlation with that of HPLC. Molecular docking analysis predicted equal binding energy of UA and OA to the mAb with hydrophobic interactions playing a predominant role. All these findings demonstrated that this icELISA is reliable, sensitive, and suitable for the high-throughput quantification of total UA and OA content in fruits composition analysis.
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Materials Today Bio
·
2026
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IF 11
Yangwang Jin,Fei Qin,Ranxing Yang,Wenzhuo Fang,Kaile Zhang,Meng Liu,Ming Yang,Ying Wang,Qiang Fu
The dynamic pathological microenvironment formed post-urethral injury drives an inflammatory-fibrotic cascade, leading to urethral stricture. Herein, we designed a novel hydrogel dressing (CPT-Cel) to modulate this dynamic urethral microenvironment for scarless reconstruction. The hydrogel responsively degrades and releases its contents upon encountering acidic environments and ROS bursts, interrupting the severe oxidative stress-inflammation cycle and creating a favorable regenerative microenvironment in the early wound phase. The incorporated celastrol continuously releases into the late repair phase, inhibiting the hyperactivation of urethral fibroblasts via the TGF-β/NF-κB pathway in urethral microenviroment, thereby preventing excessive collagen secretion. Furthermore, the dressing, featuring an ECM-mimicking microstructure, effectively adheres to and integrates with the injury site, providing hemostatic and antibacterial functions. In animal models of urethral injury, CPT-Cel accelerated urethral repair within the inflammatory milieu, significantly reduced collagen deposition and ultimately improved stricture outcomes. This study not only validates the core mechanism by which an intelligent drug-loaded hydrogel modulates the dynamic urethral microenvironment but also proposes a new paradigm for urethral tissue engineering.
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OncoTargets and Therapy
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2022
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IF 4.345
Xiaoli Li,Guangbei Zhu,Xintong Yao,Ning Wang,Ronghui Hu,Qingxin Kong,Duanfang Zhou,Liangyuan Long,Jiali Cai,Weiying Zhou
Background Celastrol is a major active component of the thunder god vine (Tripterygium wilfordii) used in traditional Chinese medicine to treat chronic inflammatory and autoimmune diseases. Celastrol inhibits PI3K–Akt–mTOR signaling, which is frequently dysregulated in tumors and critical for tumor-cell proliferation and survival, but the underlying mechanisms are still not fully understood. In the present study, we investigated detailed mechanisms of celastrol inhibition of mTOR signaling in breast cancer cells.Methods First, we evaluated the effect of celastrol on breast cancer-cell growth using MTT assays. Second, we examined the effects of celastrol on mTOR phosphorylation and expression using Western blot. Furthermore, we investigated the cause of mTOR downregulation by celastrol using immunoprecipitation assays. In addition, we evaluated the effect of celastrol on an MDA-MB231 cell-derived xenograft model.Results Celastrol suppressed breast cancer cell growth in vitro and in vivo. Celastrol inhibited mTOR phosphorylation and induced mTOR ubiquitination, resulting in its proteasomal degradation. Mechanistically, we found that mTOR is a client of Hsp90–Cdc37 chaperone complex, and celastrol disrupts mTOR interaction with chaperone Hsp90 while promoting mTOR association with cochaperone Cdc37.Conclusion Our study reveals that celastrol suppresses mTOR signaling, at least in part through regulating its association with chaperones and inducing its ubiquitination.
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JOURNAL OF DRUG TARGETING
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2022
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IF 5.016
Qiang Chen,Chunjing Guo,Zhongxin Liu,Min Cao,Wenxin Wang,Dandan Zhang,Hongxu Geng,Ningning Diao,Daquan Chen
Metabolic syndromes are a group of metabolic disorders for which the molecular mechanisms are still unclear. An increasing number of studies have implicated metabolic syndrome in the association with inflammation. Currently, lipsomes is known to improve nanoparticle hydrophobicity. Meanwhile, in drug delivery systems the application of cholesterol, which is commonly used to stabilise liposomal structures, has essentially no pharmacological effect on liposomes. Herein, we developed an ‘anti-inflammatory liposome’ (Phy-Lip) to effectively handle these challenges via employing Phytosterol instead of cholesterol. Different with the conventional liposomes, Phy-Lip is a much more brilliant nanoparticle with anti-inflammatory functions. In Phy-Lip, cholesterol was substituted by Phy, which works as membrane stabiliser, anti-inflammatory adjuvant at the same time. The experimental results show that Phy-Lip has a strong anti-inflammatory effect, and improves Metabolic syndromes. This study aims to provide a way to solve the challenge.
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Pharmaceutics
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2022
·Vol. 14
·期 9
·1765
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IF 6.525
Bo Yu,Yiping Shen,Xuejie Zhang,Lijuan Ding,Zheng Meng,Xiaotong Wang,Meihua Han,Yifei Guo,Xiangtao Wang
Owing to its pH-sensitive property and chelating Cu2+effect, poly(methacrylate citric acid) (PCA) can be utilized as a dual functional nanocarrier to construct a nanodelivery system. Negatively charged carboxyl groups can interact with positively charged antineoplastic drugs through electrostatic interaction to form stable drug nanoparticles (NPs). Through drug experimental screening, doxorubicin (DOX) was selected as the model drug, PCA/DOX NPs with a diameter of 84 nm were prepared, and the drug-loading content was 68.3%. PCA/DOX NPs maintained good stability and a sustained release profile. Cell experiments presented that PCA/DOX NPs could inhibit effectively the growth of 4T1 cells; the IC50value was decreased by approximately 15-fold after incubation for 72 h. The cytotoxicity toward H9C2 was decreased significantly. Moreover, based on its ability to efficiently adsorb copper ions, PCA showed good vascular growth inhibition effect in vitro. Furthermore, animal experiments showed that PCA/DOX NPs presented stronger anticancer effects than DOX; the tumor inhibition rate was increased by 1.5-fold. Myocardial toxicity experiments also confirmed that PCA reduced the cardiotoxicity of DOX. In summary, PCA/DOX NPs show good antitumor efficacy and low toxicity, and have good potential for clinical application.Keywords:poly(methacrylate citric acid);doxorubicin;pH sensitive;chelating Cu2+effect
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Frontiers in Pharmacology
·
2021
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IF 5.811
Lin Jingpan,Gao Lu,Lin Yanke,Wang Shuai,Yang Zemin,Ren Shujing,Chen Min,Wu Baojian
Rheumatoid arthritis is a systemic autoimmune disease characterized by synovial inflammation and bone destruction. Identifying drugs with time-varying efficacy and toxicity, and elucidating the mechanisms would help to improve treatment efficacy and reduce adverse effects. Here, we aimed to determine the chronoefficacy of semen strychni (SS) and tripterygium glycoside tablet (TGT) against rheumatoid arthritis in mice, and to investigate a potential role of circadian pharmacokinetics in generating chronoefficacy. SS extract and TGT suspension were prepared with ultrasonication. Effects of SS and TGT on collagen-induced arthritis (CIA) were evaluated by measuring TNF-α and IL-6 levels. SS dosed at ZT18 was more effective in protecting against CIA than drug dosed at ZT6 (i.e., lower levels of key inflammatory factors at ZT18 than at ZT6). This was accompanied by higher systemic exposure levels of strychnine and brucine (two main putative active ingredients of SS) in ZT18-treated than in ZT6-treated CIA mice. TGT dosing at ZT2 showed a better efficacy against CIA as compared to herb doing at ZT14. Consistently, ZT2 dosing generated a higher exposure of triptolide (a main putative active ingredient of TGT) as compared to ZT14 dosing in CIA mice. Moreover, strychnine, brucine, and triptolide significantly inhibited the proliferation of fibroblast-like synoviocytes, and reduced the production of TNF-α and IL-6 and the mRNAs of TNF-α, IL-6, COX-2, and iNOS, suggesting that they possessed an anti-arthritis activity. In conclusion, SS and TGT display chronoefficacy against rheumatoid arthritis in mice, that is attributed to circadian pharmacokinetics of main active ingredients. Our findings have implications for improving treatment outcomes of SS and TGT via timed delivery.
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Frontiers in Chemistry
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2020
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IF 3.693
Niu Weina,Wang Jianguo,Wang Qinyao,Shen Jianjun
Ovarian cancer is a gynecological cancer from which it is difficult to be completely cured. It is common to use regimens as an effective treatment for ovarian cancer, but these inevitably bring serious side effects. New treatment strategies and special drugs are needed to improve the prognosis of patients. Celastrol is a natural product, isolated from traditional medicine, that has been proven to be curative for inflammation and cancers. However, the non-targeting and low solubility of celastrol limit its clinical application. We prepared celastrol-loaded nanoparticles for the efficient treatment of ovarian cancer via oxidative stress amplification. In this work, a tumor-targeted, ROS-sensitive nanoparticle was designed, synthesized, and assembled into a drug delivery system that used celastrol. Folic acid (FA) groups on the surface of nanoparticles guide them to actively target the surface of the tumor cell membrane. Thioketal (TK) bonds in nanoparticles can be oxidized and broken into -SH within the ROS level of tumor tissues, which causes the breaking of the PEG hydrophilic shell layer of nanoparticles and promotes the release of celastrol. The released celastrol further stimulated the production of ROS and amplified the intracellular ROS level to promote the apoptosis of tumor cells, thus achieving a therapeutic effect on the celastrol treated ovarian cancer.
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JOURNAL OF PHARMACY AND PHARMACOLOGY
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2020
·Vol. 72
·期 12
·1854-1864
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IF 2.571
Zhao Huan,Tong Yongbin,Lu Danyi,Wu Baojian
ObjectivesWe aimed to determine the diurnal rhythm of Tripterygium wilfordii (TW) hepatotoxicity and to investigate a potential role of metabolism and pharmacokinetics in generating chronotoxicity.MethodsHepatotoxicity was determined based on assessment of liver injury after dosing mice with TW at different circadian time points. Circadian clock control of metabolism, pharmacokinetics and hepatotoxicity was investigated using Clock-deficient (Clock−/−) mice.Key findingsHepatotoxicity of TW displayed a significant circadian rhythm (the highest level of toxicity was observed at ZT2 and the lowest level at ZT14). Pharmacokinetic experiments showed that oral gavage of TW at ZT2 generated higher plasma concentrations (and systemic exposure) of triptolide (a toxic constituent) compared with ZT14 dosing. This was accompanied by reduced formation of triptolide metabolites at ZT2. Loss of Clock gene sensitized mice to TW-induced hepatotoxicity and abolished the time-dependency of toxicity that was well correlated with altered metabolism and pharmacokinetics of triptolide. Loss of Clock gene also decreased Cyp3a11 expression in mouse liver and blunted its diurnal rhythm.ConclusionsTripterygium wilfordii chronotoxicity was associated with diurnal variations in triptolide pharmacokinetics and circadian expression of hepatic Cyp3a11 regulated by circadian clock. Our findings may have implications for improving TW treatment outcome with a chronotherapeutic approach.
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International Journal of Pharmaceutics-X
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2023
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IF 4.7
Ping Sheng,Chao Bu,Tanyue Hui,Lili Zhou,Hao Chen,Guoliang Zhou
Synergistic chemotherapy and photothermal therapy (PTT) holds the promise of addressing the weakness of individualized chemotherapy and PTT. In this study, we synthesized a chemotherapeutic agent, PDA-Ce-CDs, which combines the photothermal conversion ability and the generation of hydroxyl radicals (•OH), enabling synergistic enhancement of antitumor effects. Furthermore, the localized heating effect of NIR radiation promoted the uptake of the PDA-Ce-CDs and enhances the sensitivity of intracellular reactive oxygen species (ROS). Finally, the antitumor activity of the PDA-Ce-CDs was evaluated through cell experiments and tumor-bearing mice experiments, confirming its excellent antitumor efficacy in vivo and in vitro . Our work presents a new strategy in cancer treatment by utilizing carbon dots in combination with photothermal agents for synergistic chemotherapy-photothermal therapy. This innovative approach offers a new therapeutic avenue for synergistic tumor treatment by harnessing the combined effects of photothermal therapy and chemotherapy.
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INTERNATIONAL IMMUNOPHARMACOLOGY
·
2023
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IF 5.6
Jiwen Fan,Meng Ren,Weiwei Chen,Haodong Wang,Yuquan He
Background Myocardial infarction (MI) triggers a strong inflammatory response mediating by NLRP3 inflammasome which is associated with cardiac fibrosis. The key players in this response are Interleukin (IL)-1 and IL-18, which are regulated by NLRP3 inflammasomes. Celastrol, a traditional Chinese medicine with strong anti-inflammatory activity, has recently reported as a cardioprotective agent. However, the mechanisms by which celastrol is cardioprotective in MI remain elusive. We hypothesized that Celastrol could reduce IL-1β and IL-18 expression and ameliorate myocardial fibrosis after myocardial infarction in rats, improve poor heart remodeling, and preserve heart function. Methods Myocardial infarction (MI) was caused by ligating the left anterior descending of male SD rats. Celastrol (1 mg/kg) or saline was administered every other day for 4 weeks. Heart function and fibrosis were assessed. Inflammatory and fibrotic markers in the myocardia were evaluated with immunohistochemistry, western blot, and ELISA. Molecular docking was employed to predict Celastrol's binding to NLRP3 protein. The effects of Celastrol on the expression of NLRP3 inflammasome and myocardial fibrosis genes were then examined in vitro . Results Celastrol maintained the left ventricular fractional shortening (FS) and ejection fraction (EF). Fibrosis was significantly reduced in animals treated with 1 mg/kg Celastrol (15.17 ± 1.82%) relative to controls (29.88 ± 4.28%). Celastrol also significantly reduced the NLRP3, IL-18, and IL-1β levels, together with macrophage and neutrophil infiltration in the myocardium. Molecular docking predicted that NLRP3 would bind tightly to Celastrol [Docking energy: −8.9 (kcal/mol)]. In vitro experiments showed reduced NLRP3 inflammasome and myocardial fibrosis-associated proteins expression in neonatal rat cardiac fibroblasts treated with Celastrol. Conclusions In post-MI rats, Celastrol, a naturally occurring active ingredient, was able to reduce myocardial fibrosis and improve cardiac function, according to our study. These effects may result from inhibiting the NLRP3 inflammasome and attenuating the early inflammatory storm after MI, suggesting that Celastrol may be useful in treating acute MI.
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