Boswellic acid coated zinc nanoparticles attenuate NF-κB-mediated inflammation in DSS-induced ulcerative colitis in rats

Abstract

Introduction Ulcerative colitis (UC) is a chronic non-specific inflammatory bowel disease, and until now therapeutic agents for UC still cannot exert satisfied effects. Therefore, this study aimed to investigate the ameliorative effect of boswellic acid coated zinc nanoparticles (BAs-ZnNPs) on dextran sodium sulphate (DSS) induced-UC in rats. Methods Rats were divided into five groups; control, BAs-ZnNPs, DSS, DSS+BAs, and DSS + BAs-ZnNPs. The activity of alkaline phosphatase (ALP) was determined colorimetrically, while the concentration of IgM, IgG, TNF-α, IL-1β, and IL-8 were measured by ELISA. Levels of gene expression of NF-κB and COX-2 genes were evaluated by RT-qPCR, while the expression of protein levels of PI3K and STAT-3 were done by western blotting. Finally, histopathological examination of colon tissues of different groups of rats was done. Results The depicted ball-like structure of the BAs-ZnNPs in the TEM images ranging in size from 50 to 100 nm in diameter while their formation was confirmed by UV–visible spectroscopy with a sharp peak of maximum absorbance at 266 nm. Our results revealed that BAs-ZnNPs exerted an anti-inflammatory effect in the experimental model of colitis, demonstrated histologically and biochemically as shown by the improvement of ALP, IgM, IgG, and the gene expression levels of NF-κB and COX-2. Also, this beneficial effect was associated with the reduction in the expression of TNF-α, IL-1β, IL-8, PI3K, and STAT-3. Thus, this effect improves the altered immune response associated with the colonic inflammation. Conclusion BAs-ZnNPs can be proposed as a therapeutic candidate to attenuate UC. The potential underlying mechanism includes suppression of ALP, IgM, IgG, IL-1β, and IL-8 levels via regulation of NF-κB and COX-2 gene expression and STAT-3 and PI3K protein expression in a UC rat model.

The progression of inorganic nanoparticles and natural products for inflammatory bowel disease

“…This anti-inflammatory effect was evident from the improvements observed in ALP, IgM, and IgG levels, as well as in the expression levels of NF-κB and COX-2 in both histological and biochemical experiments. The potential mechanisms involve the regulation of NF-κB and COX-2 gene expression, along with STAT-3 and PI3K protein expression, leading to a reduction in ALP, IgM, IgG and IL-8 levels in a rat model of ulcerative colitis [ 81 ].…”

Pathological mechanism and targeted drugs of ulcerative colitis: A review

“…[ 53 , 54 ] HIF-1α, COX-2, IL-6, IL-1β, and TNF-α are influenced by NF-κB and induce and regulate the development of body immunity and inflammation through different pathways. [ 55 ] HIF-1α can be produced in large amounts in hypoxic environments, regulates the neovascularization, and participates in several response processes such as inflammation, [ 56 ] and UC The large number of immune cells aggregating at the site of intestinal inflammation creates a local hypoxic environment where HIF-1α is activated, which in turn promotes the synthesis of IL-10 and COX-2 and enhances the inflammatory response. [ 57 , 58 ] COX-2, the rate-limiting enzyme that catalyzes the synthesis of prostaglandins from arachidonic acid, is highly expressed in the UC mucosal epithelium and crypt, which can lead to an increase in prostaglandin E2, [ 59 ] COX-2 expression is also regulated by the NF-κB pathway, and its expression is enhanced under conditions of tissue injury and inflammation, resulting in increased prostaglandins in UC patients, causing vasodilation, increased permeability, mucosal congestion and edema, and symptoms of abdominal pain and diarrhea.…”

Development, Analytical Characterization, and Bioactivity Evaluation of Boswellia serrata Extract-Layered Double Hydroxide Hybrid Composites

“…The main drawback in the use of BSE is related to its poor aqueous solubility and limited bioavailability. In this respect, different inclusion strategies have been proposed to enhance its solubility, dissolution rate, and body absorption, mainly based on the employment of phospholipids, cyclodextrins, or, in general, polymer-based vehicles or emulsions [ 5 , 6 , 7 , 8 ].Recently, many delivery vehicles for pentacyclic triterpenes, including microemulsions [ 9 ], nanoparticles [ 10 , 11 ], nanomicelles [ 12 ], and solid lipid nanoparticles (SLNs) [ 13 ], have been developed to solve the poor aqueous solubility and absorption. Nevertheless, these vehicles could provide a low loading capacity, high costs, and potential safety concerns.…”