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载地奥司明纳米颗粒对Wistar大鼠弗氏佐剂诱导的多关节炎的改善作用;一项机制研究。

Amelioration of Freund's adjuvant-induced polyarthritis by Diosmin-loaded nanoparticles in Wistar rats; a mechanistic study.

作者信息

Mehmood Hamna, Saleem Ammara, Akhtar Muhammad Furqan, Mobashar Aisha

机构信息

Department of Pharmacology, Faculty of Pharmaceutical Sciences, Government College University Faisalabad, Faisalabad, 38000, Pakistan.

Riphah Institute of Pharmaceutical Sciences, Riphah International University, Lahore Campus, Lahore, 5400, Pakistan.

出版信息

Inflammopharmacology. 2025 Mar 31. doi: 10.1007/s10787-025-01654-9.

DOI:10.1007/s10787-025-01654-9
PMID:40159583
Abstract

The current study aims to synthesize diosmin-loaded nanoparticles (DNPs) to make available an alternative safe treatment for adjuvant-induced polyarthritis. DNPs were formulated using chitosan biopolymer and characterized. Acute toxicity study was also performed and acute anti-inflammatory potential was accessed using phologistic agents. For anti-arthritic potential, disease was inoculated by injecting 0.15-ml Freund's adjuvant at day 1 to all groups except normal control in left hind paw. Therapy using DNPs at 5-20 mg/kg and diosmin 20 mg/kg and methotrexate was started from day 8-28 orally. The DNPs of size 223 nm, potential 2.9 Mv, polydisparity index > 0.7 and spherical shape particles as revealed by scanning electron microscopy and amorphous nature were revealed by X-ray diffraction. DNPs dose dependently ameliorated arthritic scoring, pain, paw swelling and body weight in contrary to disease control. DNPs and free drug restored significantly altered blood parameters, oxidation status and neurotransmitters level in treated animals as evident by histologic examination of tissues. Treatment with DNPs and free drug profoundly downregulated the expression of cyclooxygenase-2, interleukin (IL)-6, TNF-α, NF-κβ and increased IL-4 and IL-10 in arthritic animals. DNP 20 mg/kg revealed noteworthy anti-arthritic, anti-inflammatory and anti-nociceptive potential in counter to diosmin and methotrexate treated animals.

摘要

当前的研究旨在合成载有地奥司明的纳米颗粒(DNPs),为佐剂诱导的多关节炎提供一种安全的替代治疗方法。使用壳聚糖生物聚合物制备了DNPs并对其进行了表征。还进行了急性毒性研究,并使用致炎剂评估了急性抗炎潜力。对于抗关节炎潜力,除正常对照组外,在第1天向所有组的左后爪注射0.15 ml弗氏佐剂以诱发疾病。从第8天至28天开始口服给予5-20 mg/kg的DNPs、20 mg/kg的地奥司明和甲氨蝶呤进行治疗。扫描电子显微镜显示DNPs粒径为223 nm,电位为2.9 Mv,多分散指数>0.7,呈球形颗粒,X射线衍射显示为无定形性质。与疾病对照组相反,DNPs剂量依赖性地改善了关节炎评分、疼痛、爪肿胀和体重。组织学检查表明,DNPs和游离药物显著恢复了治疗动物体内明显改变的血液参数、氧化状态和神经递质水平。在关节炎动物中,用DNPs和游离药物治疗可显著下调环氧合酶-2、白细胞介素(IL)-6、肿瘤坏死因子-α、核因子-κβ的表达,并增加IL-4和IL-10的表达。与地奥司明和甲氨蝶呤治疗的动物相比,20 mg/kg的DNP显示出显著的抗关节炎、抗炎和抗伤害感受潜力。

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本文引用的文献

1
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Int J Biol Macromol. 2025 Feb;290:138926. doi: 10.1016/j.ijbiomac.2024.138926. Epub 2024 Dec 18.
2
Appraisal of anti-arthritic potential of Coronopus didymus (L.) Sm. aqueous extract and its safety study in Wistar rats.评价 Coronopus didymus (L.) Sm. 水提物的抗关节炎潜力及其在 Wistar 大鼠中的安全性研究。
Inflammopharmacology. 2023 Dec;31(6):3167-3182. doi: 10.1007/s10787-023-01374-y. Epub 2023 Nov 14.
3
Effect of Diosmin on Selected Parameters of Oxygen Homeostasis.
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Int J Mol Sci. 2023 Aug 18;24(16):12917. doi: 10.3390/ijms241612917.
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Curative potential of Populus ciliata Wall ex. Royle extract against adjuvant-induced arthritis and peripheral neuropathy in Wistar rats.杨叶胡枝子提取物对 Wistar 大鼠佐剂性关节炎及周围神经病变的治疗作用。
Inflammopharmacology. 2023 Dec;31(6):3081-3100. doi: 10.1007/s10787-023-01248-3. Epub 2023 Jun 2.
5
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