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Paeoniflorin prevents postoperative peritoneal adhesion formation in an experimental rat model.

ABSTRACT: Although materials and modern surgical techniques have been developed to suppress postoperative adhesions, adhesion formation can still occur, and thus, a novel effective anti-adhesion drug is greatly needed. In the present study, we explored the efficacy of paeoniflorin treatment against postoperative peritoneal adhesions and examined the anti-oxidative stress and anti-inflammatory properties of PE. Forty-eight male Sprague-Dawley rats were randomly divided into 6 groups for the study: the sham, control, hyaluronan and three concentrations (10, 20 and 40 mg/kg/d) paeoniflorin groups. Abdominal adhesions were created by abrasion of the caecum and its opposite abdominal wall. In the paeoniflorin groups, the rats were administered daily oral doses of paeoniflorin for 7 days. The abdominal cavities of the rats were reopened with a U-shaped incision to macroscopically grade the adhesions. Histologic analysis was performed, and oxidative stress, inflammatory cytokine, collagen fiber degradation and cytokeratin levels were measured. Macroscopic and histopathological measurements revealed that paeoniflorin reduced peritoneal adhesion and inflammation. Notably, treatment with paeoniflorin reduced the protein levels of TGF-?1, IL-6 and COX-2. The collagen fiber fractions were distinctly lower in the PE groups than in the control group. Western blotting analyses showed that paeoniflorin increased MMP-9 and superoxide dismutase-2 protein expression and sharply reduced ?-SMA and COX-2 protein expression. Peritoneal mesothelium cells were more continuous and complete in animals treated with paeoniflorin. Our study suggests that paeoniflorin can be used to ameliorate peritoneal adhesions via anti-oxidative stress and anti-inflammatory actions during the postoperative period.

SUBMITTER: Gao Q

PROVIDER: S-EPMC5706843 | biostudies-other | 2017 Nov

REPOSITORIES: biostudies-other

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Paeoniflorin prevents postoperative peritoneal adhesion formation in an experimental rat model.

Gao Qi Q Wei Guangbing G Wu Yunhua Y Yao Na N Zhou Cancan C Wang Kai K Wang Kang K Sun Xuejun X Li Xuqi X

Oncotarget 20170928 55

Although materials and modern surgical techniques have been developed to suppress postoperative adhesions, adhesion formation can still occur, and thus, a novel effective anti-adhesion drug is greatly needed. In the present study, we explored the efficacy of paeoniflorin treatment against postoperative peritoneal adhesions and examined the anti-oxidative stress and anti-inflammatory properties of PE. Forty-eight male Sprague-Dawley rats were randomly divided into 6 groups for the study: the sham ...[more]

PMID: 29212197

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Project description:Postoperative peritoneal adhesion (PPA) is a major clinical complication after open surgery or laparoscopic procedure. Ligustrazine is the active ingredient extracted from the natural herb Ligusticum chuanxiong Hort, which has promising antiadhesion properties. This study is aimed at revealing the underlying mechanisms of ligustrazine in preventing PPA at molecular and cellular levels. Both rat primary peritoneal mesothelial cells (PMCs) and human PMCs were used for analysis in vitro. Several molecular biological techniques were applied to uncover the potential mechanisms of ligustrazine in preventing PPA. And molecular docking and site-directed mutagenesis assay were used to predict the binding sites of ligustrazine with PPARγ. The bioinformatics analysis was further applied to identify the key pathway in the pathogenesis of PPA. Besides, PPA rodent models were prepared and developed to evaluate the novel ligustrazine nanoparticles in vivo. Ligustrazine could significantly suppress hypoxia-induced PMC functions, such as restricting the production of profibrotic cytokines, inhibiting the expression of migration and adhesion-associated molecules, repressing the expression of cytoskeleton proteins, restricting hypoxia-induced PMCs to obtain myofibroblast-like phenotypes, and reversing ECM remodeling and EMT phenotype transitions by activating PPARγ. The antagonist GW9662 of PPARγ could restore the inhibitory effects of ligustrazine on hypoxia-induced PMC functions. The inhibitor KC7F2 of HIF-1α could repress hypoxia-induced PMC functions, and ligustrazine could downregulate the expression of HIF-1α, which could be reversed by GW9662. And the expression of HIF-1α inhibited by ligustrazine was dramatically reversed after transfection with si-SMRT. The results showed that the benefit of ligustrazine on PMC functions is contributed to the activation of PPARγ on the transrepression of HIF-1α in an SMRT-dependent manner. Molecular docking and site-directed mutagenesis tests uncovered that ligustrazine bound directly to PPARγ, and Val 339/Ile 341 residue was critical for the binding of PPARγ to ligustrazine. Besides, we discovered a novel nanoparticle agent with sustained release behavior, drug delivery efficiency, and good tissue penetration in PPA rodent models. Our study unravels a novel mechanism of ligustrazine in preventing PPA. The findings indicated that ligustrazine is a potential strategy for PPA formation and ligustrazine nanoparticles are promising agents for preclinical application.

Project description:BackgroundAmong all the common complications that occur after abdominal surgery, intestinal adhesion is perhaps the most unpleasant one. However, current methods to treat and prevent intestinal adhesion are limited; thus, exploring new methods to prevent and treat intestinal adhesion is greatly needed. In this study, we demonstrated that Danhong injection (DHI) may be used as a promising method to prevent and treat intra-abdominal adhesion in a rat model.Materials and methodsForty-eight rats were randomly divided into six groups. Except for the sham-operated group, all rats underwent cecal abrasion to establish an adhesion model. After the operation, the rats in the DHI-treated groups received different doses of DHI via the tail vein daily, while the other group was treated with the same volume of saline solution. Seven days after the operation, all rats were sacrificed, and the degree of adhesion was evaluated by Nair's scoring system. The extent of inflammation in the adhesion tissue was detected by HE staining and the expression of tumor necrosis factor-α (TNF-α) and transforming growth factor-β (TGF-β). The collagen deposition was assessed by Sirius red staining and α-SMA, MMP9, t-PA, and PAI-1 levels. Oxidative stress was indicated by the level of reactive oxygen species (ROS) in adhesion tissues and by immunohistochemical labeling of Nrf2. Furthermore, rat primary peritoneal mesothelial cells (RPMCs) were treated with H2O2 and DHI, and NF-κB phosphorylation was detected to illustrate the effect of DHI on oxidative stress.ResultsThe intra-abdominal adhesion scores were significantly decreased in the groups treated with a high dose of DHI compared with the control groups, and the degree of inflammation, fibrosis, and oxidative stress was also significantly decreased. DHI treatment significantly reduced the levels of TNF-α, TGF-β1, and PAI and increased the expression levels of MMP9, Nrf2, and t-PA in the adhesion tissues. ROS levels and NF-κB phosphorylation were significantly reduced in DHI-treated RPMCs compared with the control RPMCs.ConclusionDHI alleviates the formation of postoperative intra-abdominal adhesions by inhibiting inflammation, collagen deposition, and oxidative stress in a rat model and may serve as a promising drug to prevent intra-abdominal adhesions.

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Paeoniflorin prevents postoperative peritoneal adhesion formation in an experimental rat model.

Publications

Paeoniflorin prevents postoperative peritoneal adhesion formation in an experimental rat model.

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