Examination of protective and therapeutic effects of ruscogenin on cerulein-induced experimental acute pancreatitis in rats

PURPOSE: To determine the potential protective and therapeutic effects and action mechanism of ruscogenin on cerulein-induced acute pancreatitis (AP) model in rats. METHODS: Overall, 32 rats were attenuated to the sham (2-mL/kg/day isotonic solution for 4 weeks), control (20-µg/kg cerulein-induced AP for 12 hours), prophylaxis groups (cerulein-induced AP following 3-mL/kg/day ruscogenin for 4 weeks) and treatment (3-mL/kg/day ruscogenin following cerulein-induced AP for 12 hours). Blood samples were collected for biochemical analysis of nitric oxide synthase 1 (NOS1/neuronal NOS), malondialdehyde (MDA) and intercellular adhesion molecule 1 (ICAM-1). After sacrification, pancreas tissues were collected and prepared for light microscopic (hematoxylin and eosin), immunohistochemical (nuclear factor kappa B) and biochemical analysis (tumor necrosis factor-alpha [TNF-α], interleukin-6 and 1β [IL-6 and IL-1β], CRP, high-sensitivity CRP [hs-CRP] amylase, lipase, and ICAM-1). Ultrastructural analysis was performed by transmission electron microscopy. RESULTS: The protective and therapeutic actions of ruscogenin were accomplished by improvements in histopathology, by decreasing blood cytokine levels of CRP, hs-CRP levels, TNF-α, IL-6, IL-1β, ICAM-1, by reducing the pancreatic enzymes amylase and lipase in blood, and by suppressing the expression of nuclear factor kappa B, ICAM-1, and NOS-1, but not MDA in pancreatic tissues. Ruscogenin also improved cerulein-induced ultrastructural degenerations in endocrine and exocrine cells, especially in treatment group. CONCLUSION: The present findings have demonstrated the beneficial protective and therapeutical effects of ruscogenin, nominating it as a highly promising supplementary agent to be considered in the treatment of AP, and even as a protective agent against the damages induced by disease.

Evaluation of prophylactic and therapeutic effects of ruscogenin on acute radiation proctitis: an experimental rat model

PURPOSE: Radiation proctitis (RP) is inflammation and damage to the rectum, manifested secondary to ionizing radiation utilized for treatment. In this study, we evaluated the anti-inflammatory therapeutical and protective effects of ruscogenin in a model of acute RP. METHODS: Thirty-two Sprague-Dawley rats were divided into 4 groups (n = 8) as sham, control, treatment, and prophylaxis groups. Prophylaxis group and treatment group were dosed ruscogenin by oral gavage for 14 days pre- and postradiation. At the end of the 28th day, all subjects were sacrificed. RESULTS: Histopathological analysis showed a significant increase in cryptitis abscess, cryptitis and reactive atypia, and depth of lymphocytic infiltration of the control group, compared to the other groups (P < 0.05), while treatment and prophylaxis groups showed significant decreases (P < 0.05). Immunohistochemical analysis indicated that immunoreactivity were significantly higher in control group (P < 0.05, P < 0.001, and P < 0.01, respectively), but vice versa for treatment and prophylaxis groups. There was not any significant difference for fibroblast growth factor 2 immunoreactivity. The epithelium of control rectums indicated an increase in TNF-α immunoreactivity while other groups had significant decrease (P < 0.01). Electron microscopical findings were parallel to light microscopy. CONCLUSION: In this study, ruscogenin was observed to be effective on prophylaxis or treatment of acute RP. Although there are various reports on the treatment of the rectum damaged by acute RP in the literature, this could be the first study since there is no research indicating the ultrastructural effect of ruscogenin.