Acta Biomaterialia
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2025
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IF 9.6
Mengxian Wang,Zeping Yu,Xinlong Li,Junqiao Li,Jianshu Li,Jun Luo,Jiyao Li,Yan Xiong,Jiaojiao Yang
Septic arthritis is a severe disease that damages articular cartilage and triggers a strong inflammatory response. Current treatments mainly depend on systemic antibiotics and lack effective intra-articular therapies, as well as standardized animal models, and precise detection methods. In this study, we present a drug delivery system responsive to the bacterial microenvironment for targeted inflammation control, along with an effective method for monitoring changes in septic arthritis in SD rats. This system consists a core with pH-sensitive metal-organic frameworks ZIF-8 loading anti-inflammatory drugs indomethacin and a shell with hybrid cell membranes from macrophages (MM) and platelets (PM), refer as MP@ZIF-8@IN. This system, which diverges from traditional treatments, enhances drug utilization, prolongs local retention, and allows for spontaneous release at the treatment site, thereby enabling the exclusive intra-articular treatment of septic arthritis. The drug delivery system inhibits the NF-κB pathway, reduces oxidative stress, and regulates macrophage polarization, preventing cartilage destruction. Additionally, in this standardized animal model utilizing the knee joints of SD rats, we have developed musculoskeletal ultrasound and magnetic resonance imaging for time-based monitoring, thus overcoming the limitation of conventional methods, which are unsuitable for soft tissue analysis. Our findings advance therapeutic strategies for septic arthritis and encourage further application of visualization techniques in related fields. Statement of significance This study presents significant advancements in the treatment and understanding of septic arthritis. Our customized drug delivery system targets bacteria and macrophages, ensuring long-time drug retention and enhanced inflammation control, all while reducing reliance on antibiotics—an important step toward addressing antibiotic resistance. Additionally, we have refined septic arthritis animal models to establish clearer guidelines for intervention timing, grounded in clinical symptoms and imaging data. This addresses a critical gap in current research and offers a practical framework for future therapeutic approaches.
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JOURNAL OF ETHNOPHARMACOLOGY
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2024
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IF 4.8
Ze Li,Jing Yuan,Yue Dai,Yufeng Xia
Ethnopharmacological relevance For centuries, Shaoyao-Gancao-Fuzi decoction (SGFD) has been a reliable traditional Chinese medicine for treating rheumatoid arthritis (RA). Despite its long history of use, the specific active components and underlying mechanisms of its therapeutic effects have yet to be fully understood. Aim of the study The aim of this study was to investigate the active ingredients and therapeutic effects of SGFD on RA, and to further understand its underlying mechanism. Materials and methods The chemical constituents in SGFD extract and in rat serum after oral administration of SGFD were identified and evaluated using ultra-performance liquid chromatography quadrupole-time-flight mass spectrometry (UPLC-Q-TOF/MS) together with various data-processing methods, respectively. The efficacy of SGFD was assessed by using an adjuvant-induced arthritis (AIA) rat model and lipopolysaccharide-stimulated RAW 264.7 cell. Subsequently, cell metabolomic was conducted to clarify the potential biomarkers and pathways. ELISA, RT-qPCR, and WB were used to verify the anti-arthritis mechanism of SGFD. Results A total of 65 chemical constituents were identified in SGFD. 17 active components were distinguished in rat serum samples, of which 13 may be the main active ingredients for SGFD treatment of RA. The remarkable efficacy of SGFD in reducing the symptoms of RA is evident through its ability to alleviate the redness and swelling of the affected paws, as well as reduce the infiltration of inflammatory cells. Cell experiments revealed that rat serum of SGFD reduced IL-1 β , IL-6, and TNF- α secretion in RAW 264.7 cells. 27 potential biomarkers were identified through cell metabolomics analysis. The arachidonic acid (AA) metabolism signaling pathway was activated in RA, which could be reversed by rat serum of SGFD. SGFD effectively inhibited the expression and transformation of AA by downregulating the expression of key enzymes, including phospholipase A and cyclooxygenase. Conclusion SGFD may ameliorate RA symptoms by regulating the AA-PGH 2 -PGE 2 /PGF 2α pathway. The main active components include songorine, fuziline, neoline, albiflorin, paeoniflorin, liquiritin, benzoylmesaconine, isoformononetin, liquiritigenin, isoliquiritigenin, formononetin, glycyrrhizic acid, and glycyrrhetinic acid.
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Frontiers in Pharmacology
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2024
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IF 4.4
Xin Qiao,Xiaojuan Cao,Shuang Xu,Cunlin Wang,Rui Guo,Xiaojuan Yao,Qiong Zhang
Background: Dysregulated and excessive inflammatory reactions can lead to tissue damage, which is the underlying cause of most human diseases. Menisoxoisoaporphine A (MA), a novel oxoisoaporphine alkaloid, was obtained from Menispermi Rhizoma, a traditional Chinese medicinal herb used in the treatment of inflammatory conditions in clinical practice. This suggests that MA has very promising potential for the development of anti-inflammatory therapeutics. Hence, this study aims to investigate the anti-inflammatory effects and underlying mechanisms of MA.Method: The anti-inflammatory effects of MA were evaluated in lipopolysaccharide (LPS)-induced mouse macrophage RAW264.7 cells. Its underlying mechanisms were explored through RNA sequencing and Western blotting. The binding modes and interactions sites between MA and phosphodiesterase 4B (PDE4B) were predicted using molecular docking and validated by molecular dynamics simulation.Results: MA treatment significantly reduced LPS-induced morphological changes, inflammatory cytokine relesae, and proinflammatory genes expression in RAW264.7 cells compared to the LPS-induced controls. Transcriptome sequencing analysis suggested that PDE4B might be a key target for MA to exert its therapeutic effect. Mechanismly, MA directly acted on Tyr405 site of PDE4B, thus leading to a sustained elevation of the cyclic adenosine monophosphate (cAMP) levels, which subsequently inactivated NF-κB signaling pathway by phosphorylating protein kinase A (PKA). MA inhibited the NF-κB-mediated inflammatory response depending on PDE4B.Conclusion: MA, a natural and novel compound, exerted anti-inflammatory effects in LPS-induced RAW264.7 macrophage cells. It demonstrated a strong binding ability to the Tyr405 sites of PDE4B, thereby inhibiting NF-κB signaling pathway by regulating the cAMP-PKA axis. Elucidating the interaction between MA and PDE4B holds significant potential for the advancement of innovative therapeutic strategies aimed at inflammatory diseases. By strategically modulating this interaction, it may be feasible to achieve more precise regulation of inflammatory responses, thereby offering promising therapeutic benefits for conditions such as rheumatoid arthritis, asthma, and inflammatory bowel disease.
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JOURNAL OF NANOBIOTECHNOLOGY
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2024
·Vol. 22
·期 1
·1-19
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IF 10.6
Tang Bo,Wang Qiuxiang,Zhang Guowei,Zhang Aiwen,Zhu Lu,Zhao Rongrong,Gu Hongwei,Meng Jie,Zhang Junfang,Fang Guihua
Traditional eye drops are administered via topical instillation. However, frequent dosing is needed due to their relatively rapid precorneal removal and low ocular bioavailability. To address these issues, stearoyl L- carnitine-modified nanoemulsions (SC-NEs) were fabricated. The physicochemical properties of SC-NEs in terms of size, morphology, zeta potential, encapsulation efficiency, and in vitro drug release behavior were characterized. The cellular uptake and mechanisms of SC-NEs were comprehensively studied in human corneal epithelial cells and the stearoyl L- carnitine ratio in SC-NEs was optimized. The optimized SC-NEs could target the novel organic cation/carnitine transporter 2 (OCTN2) and amino acid transporter B (0 +) (ATB 0,+ ) on the corneal epithelium, which led to superior corneal permeation, ocular surface retention ability, ocular bioavailability. Furthermore, SC-NEs showed excellent in vivo anti-inflammatory efficacy in a rabbit model of endotoxin-induced uveitis. The ocular safety test indicated that the SC-NEs were biocompatible. In general, the current study demonstrated that OCTN2 and ATB 0,+ -targeted nanoemulsions were promising ophthalmologic drug delivery systems that can improve ocular drug bioavailability and boost the therapeutic effects of drugs for eye diseases. Graphical Abstract
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INTERNATIONAL IMMUNOPHARMACOLOGY
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2024
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IF 4.8
Li Guo,Sai Zhang,Cong Zhang,Shuang Ren,Zihan Zhou,Fengyuan Wang,Yuexuan Wang,Qiqi Chen,Yubing Wang,Wen-Hui Lee,Kui Zhu,Di Qin,Yuanyuan Gao,Tongyi Sun
Inflammatory pain is a chronic pain caused by peripheral tissue inflammation, seriously impacting the patient’s life quality. Cinobufacini injection, as a traditional Chinese medicine injection preparation, shows excellent efficacy in anti-inflammatory and analgesic treatment in patients with advanced tumors. In this study, a novel analgesic peptide CI5 with anti-inflammatory and analgesic bio-functions that naturally presents in Cinobufacini injection and its regulatory mechanism are reported. Our results showed that the administration of CI5 significantly relieved the pain of mice in the acetic acid twisting analgesic model and formalin inflammatory pain model. Furthermore, CI5 effectively reduced the inflammatory cytokines (IL-6, TNF-α and IL-1β) and inflammatory mediator (PGE2) expressions, and prevented the carrageenan-induced paw edema in mice. Further LC-MS/MS results showed the anti-inflammatory and analgesic bio-functions of CI5 depended on its interaction with the Rac-2 protein upstream of ERK1/2 and the inflammatory signaling pathway (ERK1/2/COX-2 axis). In summary, CI5, as a novel natural candidate identified from Cinobufacini injection, showed substantial clinical promise for inflammatory pain treatments.
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BIOMACROMOLECULES
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2024
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IF 5.5
Yuhan Yang,Yangyi Chen,Yue Wei,Wei Wu,Qing Wang,Tianyun Xue,Xiaoyan Zhang,Wei Chen,Wei Zhang
A drug delivery system based on silybin-conjugated chitosan (CS-SB) polymeric micelles was developed to improve the oral absorption of doxorubicin (DOX). SB was grafted to CS via succinic acid, and CS-SB was identified by 1H NMR and FT-IR. The DOX-loaded micelles were prepared by self-assembly, and the characteristics of micelles, including a small particle size of 167.8 ± 2.3 nm, a high drug loading capacity of 8.59%, and a low critical micelle concentration of 1.3 × 10–5 g/mL, were demonstrated. The micelles showed oral bioavailability of up to 193% versus DOX·HCl. The cytotoxicity test showed the biosafety of CS-SB and the potential of reductive DOX-induced cardiotoxicity. The inhibition of P-gp efflux and CYP3A4 enzyme in CS-SB micelles was confirmed by cellular uptake and enzyme activity inhibition tests. The endocytosis process of micelles was revealed by an endocytosis inhibition test. The findings exhibited the potential of CS-SB micelles in drug delivery.
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BIOMACROMOLECULES
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2024
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IF 5.5
Xiangyi Liu,Lulu Du,Jia Liu,Yueting Shi,Qipeng Liu,Ying Xu,Yingying Xia,Xiaiting Wang,Dan Ding,Xingyi Li,Deqing Lin
With the advantages of less invasiveness and better shape adaptability, in situ-forming hydrogels are desired biomaterials as scaffolds, drug carriers, and so on. Herein, a negatively charged NaCl-responsive ultrashort peptide sequence (EEH) is reported whose electrostatic repulsion can be reduced through the charge-shielding effect. Under physiological conditions, its AIEgen-capped amphiphile TPE-GEEH of low concentration (1 mg/mL) presents NaCl-triggered morphological transformation from micelle to closely packed fiber with enhanced emission, which can be applied to biosense sodium ion (Na+) with high sensitivity and quick response. At a slightly acidic pH, 10 mg/mL TPE-GEEH undergoes sol–gel transition upon addition of NaCl (100 mM) with improved mechanical properties, which should be useful to develop an in situ-forming hydrogel. Overall, our report provides a simple strategy to construct NaCl-responsive assemblies for potential application in biosensors and drug delivery system.
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CHEMISTRY & BIODIVERSITY
·
2024
·
IF 2.3
Shu-Hang Li,Meng-Ying Li,Tao-Tao Yuan,Guo-Wei Wang,Jian-Bin Zeng,Zhimian Shi,Jian-Hang Liu,Jun-Cheng Su
Osthole (also known as Osthol) is the main anti-inflammatory coumarin found in Cnidium monnieri and severs as the exclusive quality-controlled component according the Chinese Pharmacopoeia. However, its underlying anti-inflammatory mechanism remains unknown. In this study, we demonstrated that Osthole treatment significantly inhibited the generation of TNF-α, but not IL-6 in the classical LPS-stimulated RAW264.7 macrophage model. In addition, LPS induced the activation of both MAPK and NF-κB signalling pathways, of which the former was dose-dependently restrained by Osthole via suppressing the phosphorylation of JNK and P38 proteins, while the phosphorylation of IκB and P65 proteins remained unaffected. Interestingly, Osthole dose-dependently up-regulated the expression of the key cholinergic anti-inflammatory pathway regulator α7nAChR, and the TNF-α inhibition effect of Osthole was also significantly alleviated by the treatment of α7nAChR antagonist methylbetaine. These results demonstrate that Osthole may regulate TNF-α by promoting the expression of α7nAChR, thereby activate the vagus nerve-dependent cholinergic anti-inflammatory pathway.
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Scientific Reports
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2018
·Vol. 8
·期 1
·1-11
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IF 4.122
Li Lili,Zhang Sheng,Xin Yanfei,Sun Junying,Xie Feng,Yang Lin,Chen Zhiqin,Chen Hao,Liu Fang,Xuan Yaoxian,You Zhenqiang
Quzhou Fructus Aurantii (QFA) is an authentic herb of local varieties in Zhejiang, China, which is usually used to treat gastrointestinal illnesses, but its effects on respiratory inflammation have not been reported yet. In our study, the anti-inflammatory activity of QFA extract (QFAE) was evaluated on copper sulfate pentahydrate (CuSO 4 ·5H 2 O)-induced transgenic neutrophil fluorescent zebrafish model. QFAE showed a significant effect of anti-inflammation in CuSO 4 ·5H 2 O-induced zebrafish by reducing the neutrophil number in the inflammatory site. We investigated the anti-inflammatory activity of QFAE on lipopolysaccharide (LPS)-induced acute lung injury (ALI) mice models and RAW 264.7 cells. QFAE had an anti-inflammatory effect on reducing total cells, neutrophils, and macrophages in BALF and attenuated alveolus collapse, neutrophils infiltration, lung W/D ratio, myeloperoxidase (MPO) protein expression and other pulmonary histological changes in lung tissues, as well as hematological changes. Levels of pro-inflammatory cytokines, including TNF, IL-6, IFN-γ, MCP-1, and IL-12p70, were decreased, whereas anti-inflammatory cytokine IL-10 was increased after treatment with QFAE both in vivo and in vitro . In summary, our results suggested that QFAE had apparent anti-inflammatory effects on CuSO 4 ·5H 2 O-induced zebrafish, LPS-induced ALI mice, and RAW 264.7 cells. Furthermore, QFAE may be a therapeutic drug to treat ALI/ARDS and other respiratory inflammations.
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COLLOIDS AND SURFACES B-BIOINTERFACES
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2024
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IF 5.4
Wei Gu,Qinfu Zhao,Ye He,Shengyu Wang,Yuanqi Yang,Yian Li,Shuaipeng Feng,Siling Wang
Mesoporous carriers have gained significant attention for enhancing the solubility and bioavailability of Biopharmaceutics Classification System (BCS) Class II drugs. However, the contribution of mesoporous carriers with varying morphologies to the physical stability of these drugs is not well-defined. In this work, mesoporous carbon nanoparticles (MCN) and hollow carbon mesoporous nanoparticles (HMC) were prepared, while the weakly acidic Indomethacin (IMC) and alkaline Celecoxib (CXB) were incorporated into these carriers in the amorphous state by the solvent evaporation method. Notably, HMC demonstrated superior drug loading efficiencies (approximately 43 %) for both IMC and CXB owning to its hollow structure. The mesoporous drug loading systems significantly enhanced dissolution rates in comparison with both self-made amorphous drugs and raw drugs. Furthermore, under accelerated and long-term storage conditions, the mesoporous carriers effectively prevented drugs loaded from crystallization, maintaining constant dissolution profiles for over 12 months. Intriguingly, CXB exhibited a slower rate of crystallization after loading into the mesoporous carriers, likely due to the formation of hydrogen bonds between the carbonaceous carrier material and the amino groups of CXB. Compared with loaded drugs, the self-made amorphous drugs exhibited a crystallinity increase beyond 60 % within the initial month. Collectively, these findings highlighted the potential of mesoporous carbon carriers to elevate the dissolution behaviors of BCS Class II drugs while preserving the physical stability of the loaded amorphous drugs.
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World Journal of Traditional Chinese Medicine
·
2024
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IF 4.3
Gao Hong-Xue,Liu Zhi-Qiang,Hou Zong,Song Feng-Rui,Xing Jun-Peng,Zheng Zhong,Liu Shu
Objective: This study aimed to elucidate the active components and mechanisms of Plantago asiatica L. (PAL) in the treatment of gout. Materials and Methods: Based on its polarity, PAL was partitioned into three parts, P1, P2, and P3, through gradient elution using AB-8 macroporous resin columns. The primary constituents of these fractions include iridoids, phenylethanoid glucosides, and flavonoids. Subsequently, a comprehensive in vitro and in vivo screening and evaluation model was developed considering the fundamental pathological processes of gout, including the inhibition of uric acid (UA) production, augmentation of UA excretion, and anti-inflammatory effects. This model was used to analyze the anti-gout activity of P1, P2, P3, and the overall extracts derived from PAL. Results: All the PAL parts exhibited specific therapeutic properties as part of gout therapy. Specifically, the P2 part demonstrated the ability to diminish interleukin-1 beta levels, lower UA concentrations, suppress joint inflammation in rats, and restore abnormal parameters associated with gout, such as creatinine and urea nitrogen. These findings highlight the significant effect of P2 on gout treatment. Conclusions: Following a thorough assessment of the outcomes derived from diverse anti-gout experiments, P2 exhibited superior anti-gout properties compared to the remaining parts. P2 demonstrated a restorative effect on the aberrant parameters associated with gout, thereby comprehensively elucidating the therapeutic mechanism of P2 against gout. This study provides substantial evidence and serves as a reference for future investigations regarding the material foundation of PAL in gout treatment.
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EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
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2024
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IF 4.4
Xiaoxiao Liang,Shiyuan Liu,Zebin Li,Yuehua Deng,Yanbin Jiang,Huaiyu Yang
Cocrystal engineering, which involves the self-assembly of two or more components into a solid-state supramolecular structure through non-covalent interactions, has emerged as a promising approach to tailor the physicochemical properties of active pharmaceutical ingredient (API). Efficient coformer screening for cocrystal remains a challenge. Herein, a prediction strategy based on machine learning algorithms was employed to predict cocrystal formation and seven reliable models with accuracy over 0.890 were successfully constructed. Imatinib was selected as the model drug and the models established were applied to screen 31 potential coformers. Experimental verification results indicated RF-8 is the optimal model among seven models with an accuracy of 0.839. When the seven models were combined for coformer screening of Imatinib, the combinational model achieved an accuracy of 0.903, and eight new solid forms were observed and characterized. Benefiting from intermolecular interactions, the obtained multicomponent crystals displayed enhanced physicochemical properties. Dissolution and solubility experiments showed the prepared multicomponent crystals had higher cumulative dissolution rate and remarkably improved the solubility of imatinib , and IM-MC exhibited comparable solubility to Imatinib mesylate α form. Stability test and cytotoxicity results showed that multicomponent crystals exhibited excellent stability and the drug-drug cocrystal IM-5F exhibited higher cytotoxicity than pure API.
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危险品化学品经营许可证（带存储）