Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic inflammatory disorder characterized by urothelial barrier disruption, neurogenic inflammation, and persistent pelvic pain. However, the upstream molecular mechanisms linking epithelial dysfunction with inflammatory and vascular alterations remain incompletely understood. In this study, we investigated the involvement of STING-associated signaling in experimental cystitis and evaluated the therapeutic potential of the anti-inflammatory marine-derived briareane diterpenoid excavatolide B (EXCB) and its derivative EXCB79 in a cyclophosphamide (CYP)-induced rat model. CYP-induced cystitis was accompanied by increased immunoreactivity of STING together with elevated TBK1 and NF-κB immunostaining, urothelial barrier disruption, CD11b⁺ myeloid cell infiltration, increased expression of the inflammatory mediators COX-2 and IL-1β, angiogenesis-associated changes, and enhanced pelvic hypersensitivity. At the concentrations selected for subsequent analyses, EXCB (20 µg/mL) and EXCB79 (5 µg/mL) attenuated pelvic hypersensitivity and were associated with reduced bladder inflammation and partial preservation of epithelial barrier integrity. Double immunofluorescence analysis demonstrated altered spatial associations between STING and CD11b, CD31, VEGF, ZO-1, E-cadherin, and vimentin following CYP administration. Pharmacological modulation of STING-associated signaling was accompanied by reduced immunoreactivity of STING-associated markers together with attenuation of inflammatory, vascular, and epithelial barrier-related alterations, including reduced VEGF immunoreactivity. Collectively, these findings support an association between STING-associated signaling and inflammatory, vascular, and epithelial alterations in experimental cystitis and suggest that pharmacological modulation of this pathway may represent a potential therapeutic strategy for bladder inflammation and pain-related symptoms.
Ulcerative colitis (UC) is a chronic inflammatory bowel disease. Titanium dioxide nanoparticles (TiO₂ NPs) are used as a whitening agent in food industry and considered a risk factor for UC. Chia seed oil is nutrient-rich oil with antioxidant and anti-inflammatory properties. NOD-like receptor pyrin domain-containing protein 3 (NLRP3) detects danger signals forming NLRP3 inflammasome complex. This study assessed the attenuating effect of chia seed oil against TiO₂ NPs-induced UC. Forty-eight adult male rats were divided into 4 groups; control, chia: received oral chia seed oil (2.5 ml/kg/day) for 3 weeks, TiO₂: received TiO₂ NPs (100 mg/kg) orally for 2 weeks and TiO₂+chia group: received chia seed oil for 1 week before TiO₂ NPs and continued for 2 weeks. Colon specimens were dissected out for histological and molecular analysis (RT-qPCR) and evaluation of oxidative stress. Serum level of inflammatory cytokines was also measured. Compared to TiO₂ group, TiO₂+chia group showed amelioration of histological changes as preservation of crypts and goblet cell number, attenuation of inflammation, maintenance of junctions, decreased percentage area of fibrosis, Bax, interleukin-1β and proliferating cell nuclear antigen immunostaining. Together with reduced lipid peroxidation, enhanced antioxidant enzymes, downregulation of NLRP3, caspase-1 and interleukin-1β gene expression and reduction of serum inflammatory cytokines. In conclusion, chia seed oil attenuates TiO₂ NPs-induced UC damage through reduction of oxidative stress, downregulation of NLRP3 inflammasome pathway, altered pro-apoptotic signaling, inhibition of fibrosis and cell proliferation; and epithelial barrier preservation. So, it could serve as a prophylactic agent or adjuvant therapy for UC.
Clematis flammula and Fraxinus angustifolia leaves are commonly used in Algeria to treat inflammatory diseases, with potential hypolipidemic effects that have not been investigated so far. The present study explored the in vitro, ex vivo, and in vivo hypolipidemic effects of ethanolic leaf extracts from both plants using two animal models (mice and rabbits) with distinct lipid metabolism. Dyslipidemia was induced by oral administration of Triton X-100, once daily for three consecutive days. Immediately after each Triton X-100 administration, animals received plant extracts (100 and 200 mg/kg bw) or atorvastatin (10 mg/kg bw). Anti-lipase and anti-HMG-CoA reductase activities were evaluated using in vitro and ex vivo assays. Triton X-100 induced marked alterations in serum lipid profiles, characterized by increased LDL-C, VLDL-C, and total cholesterol levels, which were improved by C. flammula and F. angustifolia extracts, particularly at 200 mg/kg bw. While F. angustifolia exhibited greater hypolipidemic efficacy, the lack of improvement in total cholesterol in mice treated with C. flammula, in contrast to rabbits, may suggest species-dependent differences in lipid metabolism, potentially involving CETP-mediated cholesterol transport, which requires further experimental confirmation. In vitro anti-lipase assays showed greater inhibitory potency for F. angustifolia (IC50 = 3.55 µg/mL) than C. flammula (IC50 = 12.10 µg/mL). Both extracts inhibited HMG-CoA reductase activity by over 60
Ormocarpum cochinchinense has long been used in traditional medicine for the management of bone fractures. Despite its widespread ethnomedicinal use, scientific evidence supporting its efficacy and underlying mechanisms in fracture healing remains limited. This study aimed to investigate the safety and fracture-healing potential of the aqueous extract of O. cochinchinense (OCE) with emphasis on angiogenesis and osteogenesis, and to elucidate its role in modulating endothelial cell inflammation. The biological activity of OCE was assessed using a combination of in vitro and in vivo approaches. The phytochemical characterization of the extract was performed using GC–MS analysis. The safety profile of OCE was assessed through in vivo toxicity evaluation and the fracture-healing efficacy was investigated through radiographic and histological analyses. Molecular mechanisms were examined by assessing the expression of angiogenic and osteogenic marker genes. Additionally, endothelial protective effects were evaluated under lipopolysaccharide (LPS)-induced inflammatory conditions by measuring oxidative stress markers and pro-inflammatory mediators. GC–MS analysis identified a total of 25 phytocompounds in OCE. OCE exhibited no observable toxicity in rats. It accelerated fracture healing by promoting advanced callus formation, enhancing collagen-rich matrix deposition, and improving mineralization. OCE significantly upregulated angiogenic (VEGFA, VEGFR2) and osteogenic (BMP2, SP7, RUNX2, ALP, Col1A1, OPN, OCN) gene expression, indicating coordinated activation of bone regeneration pathways. Furthermore, OCE protected endothelial cells from LPS-induced cytotoxicity by reducing reactive oxygen species and nitric oxide levels and downregulating inflammatory mediators including NOX1, NOX2, NOX4, iNOS, IL-1β, IL-6, and TNF-α. OCE promoted fracture healing through a multifaceted mechanism involving enhanced angiogenesis and osteogenesis. It also confers endothelial protection by mitigating inflammation and oxidative stress that might aid in improved endothelial function and thereby fracture healing. These findings validate its traditional use and highlight its potential as a safe and effective natural therapeutic agent for bone regeneration.
The present study aimed to evaluate the effects of topical vildagliptin on experimentally induced hypertrophic scars (HTSs) in a rabbit model. A total of 40 healthy male albino rabbits were randomly assigned to five groups (n = 8): healthy control (CTRL), untreated induced HTS model (HTS model), vehicle-received (VEH), 0.1
