Nanoencapsulated Syzygium aromaticum oil alleviates acetic acid-induced ulcerative colitis in rats by influencing critical redox, NF-κB/iNOS, and Keap1/Nrf2/HO-1 signaling pathways.

IF 5.3 2区 医学 Q2 IMMUNOLOGY
Gehad E Elshopakey, Shaymaa Rezk, Ahmed Ateya, Tarek A Elkhooly, Alaa A Omar, Ali El-Far, Ekramy M Elmorsy, Hala Magdy Anwer, Mona M Elghareeb
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引用次数: 0

Abstract

Ulcerative colitis (UC) is an autoimmune inflammatory condition characterized by significant mucosal destruction. Although Syzygium aromaticum (Clove oil; CO) oil is well-known for its antioxidant and anti-inflammatory properties, its high volatility, toxicity, and hydrophobicity can compromise its biological efficacy. Therefore, nanoencapsulation is a feasible approach for boosting its therapeutic potential, including stability, bioavailability, and target delivery. Herein, this study was designed to minimize acetic acid-mediated UC using CO alone or encapsulated in nano-vehicles including PCL, CS, and ALG. The developed nano-capsules CO were characterized by Zetasizer, FT-IR, and SEM, and subsequently, the encapsulation efficiency and controlled release profile of CO were determined. Forty adult rats were assigned to five groups (n = 8) as follows: the control (CONT) group, which received dimethyl sulfoxide (DMSO) once daily; the UC group, which received rectal acetic acid (AA) instillation on day 8 of the experiment. CO group: rats were treated orally with clove oil (250 mg/kg) dissolved in DMSO once daily. PCL@CS + ALG group; rats were orally treated with nano-vehicle (250 mg/kg). CONPs group: rats received clove oil nanoparticles (PCL@CO(CS + ALG)NPs, 250 mg/kg). All groups received their respective treatments once a day for seven consecutive days, before and after UC induction. An in silico study revealed the binding affinities of eugenol, the principal bioactive constituent of CO, toward inflammatory molecules at both the mRNA and protein levels. Biologically, the colon outcomes showed that CO, either alone or loaded with nanoparticles (CONPs), significantly decreased MDA and NO levels and elevated antioxidant enzymatic activities (SOD, CAT, , GPx, and GR), with higher GSH levels. Additionally, the treatment of rats with CO or CONPs mitigated colon inflammation by decreasing the MPO activity, TNF-α, IFN-γ, IL-1β, and PGE2 levels, as well as downregulating the expression of NF-κB, IL-6, IL-8, and iNOS genes. Remarkably, CONPs prevented the colon oxidative damage by modulating the mRNA expression of Keap1/Nrf2/HO-1 signaling pathways. Unlike the rats exposed to AA, the treatment with CO and CONPs dramatically restored the mRNA expression of Cdc25c and RNF8 genes. Histologically, the CONPs-treated group showed a clear restoration of colonic tissue architecture toward normal, accompanied by normalization of VEGF and α-SMA immunoexpression patterns. Conclusively, CO, either alone or encapsulated in nanoparticles (CONPs), offers promising therapeutic potential for UC, likely through its anti-inflammatory, antioxidant, and anti-fibrotic effects, as well as superior regulation of angiogenesis compared with pure CO.

纳米包封的丁香油通过影响关键氧化还原、NF-κB/iNOS和Keap1/Nrf2/HO-1信号通路减轻醋酸诱导的大鼠溃疡性结肠炎。
溃疡性结肠炎(UC)是一种自身免疫性炎症,其特征是显著的粘膜破坏。虽然丁香油以其抗氧化和抗炎特性而闻名,但其高挥发性、毒性和疏水性会损害其生物功效。因此,纳米胶囊化是一种提高其治疗潜力的可行方法,包括稳定性、生物利用度和靶向递送。在此,本研究旨在通过单独使用CO或封装在纳米载体(包括PCL, CS和ALG)中来减少醋酸介导的UC。采用Zetasizer、FT-IR和SEM对制备的纳米CO胶囊进行了表征,并对其包封效率和控释谱进行了表征。将40只成年大鼠分为5组(n = 8):对照组(CONT),每日1次给予二甲亚砜(DMSO);UC组于试验第8天进行直肠灌胃乙酸(AA)。CO组:大鼠口服丁香油(250 mg/kg)溶于DMSO,每日1次。PCL@CS + ALG组;大鼠口服纳米载体(250 mg/kg)。CONPs组:大鼠给予丁香油纳米颗粒(PCL@CO(CS + ALG)NPs, 250 mg/kg)。各组在UC诱导前、诱导后均给予相应治疗,每天1次,连续7 d。一项计算机研究揭示了丁香酚(CO的主要生物活性成分)在mRNA和蛋白质水平上对炎症分子的结合亲和力。生物学上,结肠结果显示,CO单独或负载纳米颗粒(CONPs),显著降低MDA和NO水平,提高抗氧化酶活性(SOD, CAT, GPx和GR),升高GSH水平。此外,用CO或CONPs治疗大鼠通过降低MPO活性、TNF-α、IFN-γ、IL-1β和PGE2水平,以及下调NF-κB、IL-6、IL-8和iNOS基因的表达来减轻结肠炎症。值得注意的是,CONPs通过调节Keap1/Nrf2/HO-1信号通路的mRNA表达来预防结肠氧化损伤。与AA处理不同,CO和CONPs处理显著恢复了Cdc25c和RNF8基因的mRNA表达。组织学上,conps处理组结肠组织结构明显恢复正常,VEGF和α-SMA免疫表达模式正常化。总之,一氧化碳,无论是单独使用还是包裹在纳米颗粒(CONPs)中,都具有治疗UC的潜力,可能是通过其抗炎、抗氧化和抗纤维化作用,以及与纯一氧化碳相比,对血管生成的优越调节。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Inflammopharmacology
Inflammopharmacology IMMUNOLOGYTOXICOLOGY-TOXICOLOGY
CiteScore
8.00
自引率
3.40%
发文量
200
期刊介绍: Inflammopharmacology is the official publication of the Gastrointestinal Section of the International Union of Basic and Clinical Pharmacology (IUPHAR) and the Hungarian Experimental and Clinical Pharmacology Society (HECPS). Inflammopharmacology publishes papers on all aspects of inflammation and its pharmacological control emphasizing comparisons of (a) different inflammatory states, and (b) the actions, therapeutic efficacy and safety of drugs employed in the treatment of inflammatory conditions. The comparative aspects of the types of inflammatory conditions include gastrointestinal disease (e.g. ulcerative colitis, Crohn''s disease), parasitic diseases, toxicological manifestations of the effects of drugs and environmental agents, arthritic conditions, and inflammatory effects of injury or aging on skeletal muscle. The journal has seven main interest areas: -Drug-Disease Interactions - Conditional Pharmacology - i.e. where the condition (disease or stress state) influences the therapeutic response and side (adverse) effects from anti-inflammatory drugs. Mechanisms of drug-disease and drug disease interactions and the role of different stress states -Rheumatology - particular emphasis on methods of measurement of clinical response effects of new agents, adverse effects from anti-rheumatic drugs -Gastroenterology - with particular emphasis on animal and human models, mechanisms of mucosal inflammation and ulceration and effects of novel and established anti-ulcer, anti-inflammatory agents, or antiparasitic agents -Neuro-Inflammation and Pain - model systems, pharmacology of new analgesic agents and mechanisms of neuro-inflammation and pain -Novel drugs, natural products and nutraceuticals - and their effects on inflammatory processes, especially where there are indications of novel modes action compared with conventional drugs e.g. NSAIDs -Muscle-immune interactions during inflammation [...]
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