Study on the physicochemical properties and anti-inflammatory effects of paeonol in rats with TNBS-induced ulcerative colitis

Zong, Shiyu; Pu, Yang; Xu, Benliang; Zhang, Tong; Bing, Wang

doi:10.1016/j.intimp.2016.11.010

Cited by 61 publications

(48 citation statements)

References 40 publications

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“…We selected direct powder compression considering the high influence of the drug product surface properties on drug dissolution. 15,16) Drug directly released from powder after tablet disintegration, which has a considerable dispersion, can accelerate dissolution and can improve rela-tive bioavailability. Moreover, direct powder compression is simple and does not require granulating and drying, thereby ensuring a stable quality of the finished product.…”

Section: Methodsmentioning

confidence: 99%

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Formulation Optimization of Gastro-Retention Tablets of Paeonol and Efficacy in Treatment of Experimental Gastric Ulcer

Zhang

Han

et al. 2017

CHEMICAL & PHARMACEUTICAL BULLETIN

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This study aims to develop a gastroretentive sustained-release drug delivery system of paeonol using floating properties and to investigate its therapeutic effects in rat models. The gastric retention tablets of paeonol (GRT-Ps) were prepared by a direct compression method, and the Box-Behnken design was used to optimize its formulation. The optimized formulation containing 15% NaHCO 3 and a 2 : 1 ratio of paeonol and HPMC-K4M floated within 1 min and remained afloat for more than 8 h in the simulated gastric fluid (200 mL, pH 1.2) and simultaneously showed the desired sustained drug release. Moreover, small tablets (3 mm) were prepared according to the same formulation and the process technology of big tablets (8 mm). A similar drug release behavior was observed between two kinds of tablets ( f 2 52), and then the evaluations of efficacy and retention capacity in vivo were conducted with small tablets. In vivo retention studies showed that the T max (2 h) of GRT-P in rat stomachs was significantly extended compared with the T max (0.5 h) of normal reference preparation. Compared with the model group, low and high doses of GRT-P could significantly inhibit the increase of malondialdehyde (MDA) in serum. Studies showed that the higher MDA content in inflammation tissue increases the inflammatory response. The ulcer inhibition rates of GRT-P in the highdose group were 59.0 and 64.1% in the ranitidine group. Results indicated that GRT-Ps had the potential for a sustained drug release and an enhanced gastric residence time with relatively high drug concentrations in the tissue distribution.Key words paeonol; gastric retention tablet; sustained release; gastric ulcer; efficacy Paeonol, also called peony phenol, is the active component of a traditional Chinese medicine, namely, moutan cortex (Paeonia suffruticosa ANDREWS, Ranunculaceae).1) Paeonol has been extensively studied for its anti-inflammatory, antioxidant, anti-atherosclerosis, anti-diabetic, and anti-mutagenic effects.2,3) However, paeonol has significant growth-inhibitory and apoptosis-inducing effects in gastric cancer cells in vitro and in vivo.4) Moreover, studies have shown that paeonol prevents inflammatory diseases of the alimentary canal, such as irritable gastric ulcer, with minimal side effects.5) However, studies on the ethanol-induced gastric ulcer effect of paeonol are lacking. Currently, the listed paeonol dosages are administered via ordinary oral tablets and injection. However, paeonol has poor water solubility, easy oxidation, and a short biological half-life. [6][7][8] The paeonol products are unable to prolong effective drug concentration in blood to influence the oral bioavailability of a drug. Therefore, the present study, which is based on the properties of paeonol, has been designed to develop gastric retention tablets using modern technology to achieve prolonged presence in the stomach, thereby improving treatment of gastric ulcer. This approach has a profound clinical significance in developing a novel sustained-release delivery syst...

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Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

Formulation Optimization of Gastro-Retention Tablets of Paeonol and Efficacy in Treatment of Experimental Gastric Ulcer

Zhang

Han

et al. 2017

CHEMICAL & PHARMACEUTICAL BULLETIN

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“…Paeonol has been demonstrated to have antioxidant activity when used in ex vitro (Zhang et al, 1999 ; Matsuda et al, 2001 ; Jin et al, 2016 ), in vitro (Tseng et al, 2012 ; Liu et al, 2014 ; Ping et al, 2014 ), and in vivo preparations (Hsieh et al, 2006 ; Liu et al, 2014 ; Ding et al, 2016 ; Jin et al, 2016 ). Paeonol also has anti-inflammatory actions in a number of animal models of diseases other than pulmonary fibrosis (Chou, 2003 ; Du et al, 2010 ; Fu et al, 2012 ; Zhao et al, 2013 ; Chen et al, 2014 ; Liu et al, 2014 ; Ding et al, 2016 ; Zong et al, 2017 ) and in various cell types in response to stimuli (Nizamutdinova et al, 2007 ; Chae et al, 2009 ; Du et al, 2010 ; Himaya et al, 2012 ; Tseng et al, 2012 ; Kong et al, 2013 ; Liu et al, 2014 ; He et al, 2016 ; Jin et al, 2016 ). Thus, the antioxidant and anti-inflammatory properties of paeonol make it a potential drug for the therapy of pulmonary fibrosis.…”

Section: Introductionmentioning

confidence: 99%

Prevention of Bleomycin-Induced Pulmonary Inflammation and Fibrosis in Mice by Paeonol

Liu

Lin

et al. 2017

Front. Physiol.

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Pulmonary fibrosis is a severe and progressive disease that is characterized by an abnormal deposition of extracellular matrix, such as collagens. The pathogenesis of this disease may be initiated by oxidative damage of lung epithelial cells by fibrogenic stimuli, leading to lung inflammation, which in turn promotes various lung fibrotic responses. The profibrogenic effect of transforming growth factor-β1 (TGF-β1) on lung fibroblasts is crucial for the pathogenesis of this disease. Paeonol, the main phenolic compound present in the Chinese herb Paeonia suffruticosa, has antioxidant and anti-inflammatory properties. However, whether paeonol has therapeutic effects against pulmonary fibrosis remains unclear. Using a murine model, we showed that 21 days after the insult, intratracheal bleomycin caused pulmonary inflammation and fibrosis, as evidenced by lung histopathological manifestations and increase in various indices. The inflammatory indices included an increase in total cell count, differential cell count, and total protein concentration in bronchoalveolar lavage fluid. The fibrotic indices included an increase in lung levels of TGF-β1, total collagen, type 1α1 collagen (COL1A1), and α-smooth muscle actin (α-SMA; a marker of myofibroblasts). Bleomycin also was found to cause an increase in oxidative stress as reflected by increased levels of malondialdehyde and 4-hydroxynonenal in the lungs. Importantly, all these pathophysiological events were suppressed by daily treatment with paeonol. Using human lung fibroblasts, we further demonstrated that exposure of human lung fibroblasts to TGF-β1 increased productions of α-SMA and COL1A1, both of which were inhibited by inhibitors of Jun N-terminal kinase (JNK), p38, and Smad3. JNK and p38 are two subfamily members of mitogen-activated protein kinases (MAPKs), whereas Smad3 is a transcription factor. TGF-β1 exposure also increased the phosphorylation of JNK, p38, and Smad3 prior to the induction of α-SMA and COL1A1. Notably, all these TGF-β1-induced cellular events were suppressed by paeonol treatment. Our findings suggest that paeonol has antioxidant, anti-inflammatory, and anti-fibrotic functions against bleomycin-induced pulmonary fibrosis in mice. The beneficial effect of paeonol may be, at least in part, mediated through the inhibition of the MAPKs/Smad3 signaling.

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“…The DAI was assessed at the same time daily after the TNBS administration using a previously described method, which was scored based on weight loss, stool consistency, and rectal bleeding. Each of these three categories was scored from 0 (none) to 4 (most severe), and the sum of the three was defined as the DAI score …”

Section: Methodsmentioning

confidence: 99%

A novel method of sacral nerve stimulation for colonic inflammation

Zhang

Jiang

et al. 2020

Neurogastroenterology Motil

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Background Vagal nerve stimulation has been reported to treat inflammation with promising results. The aims of our study were to optimize sacral nerve stimulation (SNS) methodologies for colonic inflammation in a rodent model of colitis and to investigate autonomic and cytokine mechanisms. Methods Three major efforts were made in optimizing SNS: (a) to determine the best stimulation duration: SNS‐0.5h daily, SNS‐1h daily, and SNS‐3h daily with the parameters set at 5 Hz, 10 seconds on, 90 seconds off; (b) to determine the best stimulation position: bilateral, bipolar, and unipolar stimulation; (c) to determine the best stimulation parameters: our 5 Hz intermittent stimulation vs 14 Hz‐210 μs continuous stimulation. Inflammatory responses were assessed by the disease activity index (DAI), histological analyses, and the myeloperoxidase (MPO) activity. Levels of inflammatory cytokines, norepinephrine (NE), and pancreatic polypeptide (PP) in both plasma and colon tissues were assessed. Key Results Both SNS‐1h and SNS‐3h significantly ameliorated intestinal inflammation; SNS‐1h was superior to SNS‐3h. Bipolar but not bilateral or unipolar stimulation improved the inflammation in colitis. SNS with 5 Hz intermittent stimulation but not the 14 Hz continuous SNS was better for treating colitis in rats. SNS with the optimized stimulation parameters increased vagal activity and decreased sympathetic activity. Conclusion & Inferences Bipolar stimulation for 1 hour daily using intermittent 5 Hz parameters is most effective in improving colonic inflammation in TNBS‐treated rats by inhibiting pro‐inflammatory cytokines and increasing anti‐inflammatory cytokines via the modulation of the autonomic function.

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Study on the physicochemical properties and anti-inflammatory effects of paeonol in rats with TNBS-induced ulcerative colitis

Cited by 61 publications

References 40 publications

Formulation Optimization of Gastro-Retention Tablets of Paeonol and Efficacy in Treatment of Experimental Gastric Ulcer

Formulation Optimization of Gastro-Retention Tablets of Paeonol and Efficacy in Treatment of Experimental Gastric Ulcer

Prevention of Bleomycin-Induced Pulmonary Inflammation and Fibrosis in Mice by Paeonol

A novel method of sacral nerve stimulation for colonic inflammation

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