Mebendazole (MBZ) is an efficacious anthelmintic with known anti-inflammatory and fibrinolytic properties. In this study, we aimed to explore the protective effects of this FDA-approved drug against DSS-induced colitis in a murine model either alone or in combination with Sulfasalazine (SSZ), a standard therapy for ulcerative colitis. We found that MBZ significantly improved colitis disease activity index as assessed by changes in body weight, degree of stool consistency, rectal bleeding, and prolapse. We also found that MBZ ameliorated the colon histopathological score by attenuating crypt loss, mucosal damage, and inflammation score in colitis tissues. Similarly, DSS-induced colon shortening, colon weight loss, and increase in spleen weight were all abrogated in the presence of MBZ. Moreover, MBZ decreased inflammation, possibly by reducing oxidative stress markers, suppressing inflammatory cell infiltration, and down-regulation of inflammatory genes in colon tissues. Furthermore, MBZ potently reduced fibrosis by decreasing collagen deposition and down-regulating pro-fibrotic genes including Col 1a1 and Col 1a2 in colitis tissue homogenates. In conclusion, our study showed that this broad-spectrum anthelminthic could be repurposed as a novel therapy for ulcerative colitis without any observed side effects, however, regarding the concerns about the potential toxicity of MBZ in UC patients, future experiments on MBZ therapy in other models of UC is needed to completely address the toxicity concerns.
Background Adhesion band formation is a common cause of morbidity for patients undergoing surgeries. Anti-inflammatory and anti-fibrotic properties of curcumin, a pharmacologically active component of Curcuma longa, have been investigated in several studies. The aim of this study is to explore the therapeutic potential of curcumin in attenuating post-operative adhesion band (PSAB) formation in both peritoneal and peritendinous surgeries in animal models. Methods Bio-mechanical, histological and quantitative evaluation of inflammation, and total fibrosis scores were graded and measured in the presence and absence of phytosomal curcumin. Results Results showed that phytosomal curcumin significantly decreased severity, length, density and tolerance of mobility of peritendinous adhesions as well as incidence and severity of abdominal fibrotic bands post-surgery. Curcumin may decrease inflammation by attenuating recruitment of inflammatory cells and regulating oxidant/anti-oxidant balance in post-operative tissue samples. Moreover, markedly lower fibrosis scores were obtained in the adhesive tissues of phytosomal curcumin-treated groups which correlated with a significant decrease in quantity, quality and grading of fibers, and collagen deposition in animal models. Conclusion These results suggest that protective effects of phytosomal curcumin against PSAB formation is partially mediated by decreasing inflammation and fibrosis at site of surgery. Further studies are needed to investigate the therapeutic potential of this molecule in preventing PSAB.
Background: Protective effects of probiotics in human diseases have been well documented in recent years. In this study, the anti-inflammatory and fibrinolytic properties of two newly isolated probiotic bacteria, Lactiplantibacillus plantarum and Lactococcus lactis either alone or in combination with standard therapy, Mesalazine (MSZ), have been investigated in a murine model for ulcerative colitis. Methods: Characterization of newly isolated probiotic were assessed by performing antibacterial activity, antibiotic resistance, acid and bile tolerance, and hemolytic activity assays. Hematoxylin-Eosin and Masson's trichrome staining were used to evaluate inflammation and collagen deposition in colon tissue sections. Expression of inflammatory- and Fibrotic-associated genes were analyzed using Real-time PCR and ELISA assays. Results: Results showed that administration of probiotics significantly attenuated DSS-induced colon shortening, colon weight loss, and increase in spleen weight in colitis mice. Compared to the colitis mice, disease activity index as assessed by changes in body weight, degree of stool consistency, rectal bleeding, and prolapse was decreased in probiotic-treated group. Mix of probiotics potently improved histopathological score by attenuating crypt loss, mucosal damage, and inflammation score in colitis tissues. Consistently, mRNA and protein levels of pro-inflammatory genes as well as oxidative stress markers were suppressed in the presence of probiotics in colon tissues. Furthermore, probiotic bacteria reduced fibrosis by down-regulating pro-fibrotic genes including Col 1a1 and α-SMA in colon tissue homogenates. Conclusion: These results showed that mix of these newly isolated probiotic bacteria is as potent as the standard treatment and could be utilize as a novel therapy for ulcerative colitis without any observed side effects. Future experiments on these probiotics in other models of UC is needed to completely address the efficacy potency and safety concerns.
Background: Peritoneal adhesions (PA) are a common complication of abdominal operations. Previous studies indicate that inhibition of inflammation and fibrosis at sites of peritoneal damage may prevent the development of intra-abdominal adhesions. Zingiber officinalis Roscoe (ginger) and Panax ginseng (p. ginseng) are herbal products with antioxidant and anti-inflammatory effects which can have restorative properties. Objective: This research aimed to examine the impact of ginger and p. ginseng on prevention of PA in a rat model after surgery. Methods: Following a laparotomy, the wall of the cecum was rubbed to induce intra-abdominal adherence in Wistar rats. Ginger (400mg/kg) and p. ginseng (500mg/kg) were administered to the animals. The animals were sacrificed on 10 days after surgery, and the Nair and Leach scoring system was used to assess adhesion. The microscopic histology of the induced cecal adhesions was evaluated. An enzyme-linked immunosorbent assay (ELISA) was used to determined tissue levels of transforming growth factor-beta (TGF-β) on homogenized PA tissue. Real-time PCR was performed to quantify the mRNA expression of IL-1β, TNF-α, Col 1a1, and Col 3a1 in rat tissue. Result: The adhesion score and histopathological rating based on the Nair and Leach scoring criteria showed lower adhesion scores in the group of rats treated with p. ginseng compared to the control group (P<0.05). Treatment with ginger and p. ginseng was associated with reduced tissue level of TGF-β and mRNA expression of TNF-α and IL-1β. The gene expression level of Col 1a1 and Col 3a1 were markedly decreased in the p. ginseng group. Conclusion: The study's outcome recommends that p. ginseng could be an effective agent for preventing the PA and inflammation during the post-operative stage.
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