scholarly journals Evaluations and Mechanistic Interrogation of Natural Products Isolated From Paeonia suffruticosa for the Treatment of Inflammatory Bowel Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Kun-Chang Wu ◽  
Der-Yen Lee ◽  
Jeh-Ting Hsu ◽  
Chi-Fang Cheng ◽  
Joung-Liang Lan ◽  
...  

Mu Dan Pi (MDP), a traditional Chinese medicine derived from the root bark of Paeonia suffruticosa Andrews, is used to treat autoimmune diseases due to its anti-inflammatory properties. However, the impact of MDP on inflammatory bowel disease (IBD) and its principal active compounds that contribute to the anti-inflammatory properties are uncertain. Thus, this study systemically evaluated the anti-inflammatory effects of fractionated MDP, which has therapeutic potential for IBD. MDP fractions were prepared by multistep fractionation, among which the ethyl acetate-fraction MDP5 exhibited the highest potency, with anti-inflammatory activity screened by the Toll-like receptor (TLR)-2 agonist, Pam3CSK4, in a cell-based model. MDP5 (at 50 μg/ml, p < 0.001) significantly inhibited nuclear factor kappa-B (NF-κB) reporters triggered by Pam3CSK4, without significant cell toxicity. Moreover, MDP5 (at 10 μg/ml) alleviated proinflammatory signaling triggered by Pam3CSK4 in a dose-dependent manner and reduced downstream IL-6 and TNF-α production (p < 0.001) in primary macrophages. MDP5 also mitigated weight loss, clinical inflammation, colonic infiltration of immune cells and cytokine production in a murine colitis model. Index compounds including paeoniflorin derivatives (ranging from 0.1 to 3.4%), gallic acid (1.8%), and 1,2,3,4,6-penta-O-galloyl-β-D-glucose (1.1%) in MDP5 fractions were identified by LC-MS/MS and could be used as anti-inflammatory markers for MDP preparation. Collectively, these data suggest that MDP5 is a promising treatment for IBD patients.

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Tzu-Fan Chen ◽  
Jeh-Ting Hsu ◽  
Kun-Chang Wu ◽  
Che-Fang Hsiao ◽  
Jou-An Lin ◽  
...  

Abstract Mu Dan Pi (MDP), also known as Moutan Cortex Radicis, is a traditional Chinese medicine used to treat autoimmune diseases. However, the impact of MDP and its principal active compounds on inflammatory bowel disease (IBD) is uncertain. This study therefore systemically assessed the anti-inflammatory effects of MDP and its known active compounds in IBD. The anti-inflammatory activities of water extract and individual compounds were screened by NF-κB and interferon regulatory factor (IRF) reporter assays in THP-1 cells induced with either Toll-like receptor or retinoic acid inducible gene I/melanoma differentiation-associated gene 5 activators and further verified in bone marrow-derived macrophages. MDP water extract significantly inhibited the activation of NF-κB and IRF reporters, downstream signaling pathways and the production of IL-6 and TNF-α, in a dose-dependent manner. Among 5 known active components identified from MDP (1,2,3,4,6-penta-O-galloyl-β-d-glucose [PGG], gallic acid, methyl gallate, paeoniflorin, and paeonol), PGG was the most efficient at inhibiting both reporters (with an IC50 of 5–10 µM) and downregulating IL-6 and TNF-α. Both MDP powder for clinical use and MDP water extract, but not PGG, reduced colitis and pathological changes in mice. MDP and its water extract show promise as a novel therapy for IBD patients.


2019 ◽  
Vol 44 (6) ◽  
pp. 595-605 ◽  
Author(s):  
Corinne E. Metzger ◽  
S. Anand Narayanan ◽  
David C. Zawieja ◽  
Susan A. Bloomfield

Inflammatory bowel disease is a condition that leads to gut pathologies such as abnormal lymphatic architecture, as well as to systemic comorbidities such as bone loss. Furthermore, current therapies are limited to low efficacy and incur side effects. Dietary interventions have been explored minimally, but may provide a treatment for improving gut outcomes and comorbidities. Indeed, plant-based soy protein has been shown to exert anti-inflammatory effects. Here, we tested the impact of a moderately elevated soy protein diet in a chronic, 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis model on gut and bone inflammatory-mediated pathophysiological adaptations. Colitis was induced by intrarectal administration of TNBS. Gut histopathology was scored, and lymphatic structural changes and the local inflammatory state were assessed via immunofluorescence. In addition, the effects of gut inflammation on bone turnover and osteocyte proteins were determined via histomorphometry and immunohistochemistry, respectively. The moderately elevated soy protein diet produced improvements in both colonic and bone tissues. In TNBS animals given the soy protein intervention, colon histological scores were reduced and the abnormal lymphatic architecture resolved. There were also improvements in bone formation and reduced bone resorption. In addition, TNBS increased inflammatory cytokines such as tumor necrosis factor-α and receptor activator of nuclear factor κ-B ligand in the gut and bone, but this was resolved in both tissues with the dietary soy protein intervention. The moderately elevated soy protein diet mitigated gut and bone inflammation in a chronic, TNBS-induced colitis model, demonstrating the potential for soy protein as a potential anti-inflammatory dietary intervention for inflammatory bowel disease.


2021 ◽  
Vol 27 (Supplement_1) ◽  
pp. S38-S38
Author(s):  
Barbara Olednzki ◽  
Vanni Bucci ◽  
Caitlin Cawley ◽  
Ana Maldonado-Contreras

Abstract Background and Aims The inflammatory bowel disease-anti-inflammatory diet (IBD-AID) is a whole food diet designed to favor the development of an anti-inflammatory microbiome and to assist with remission in patients suffering from inflammatory bowel disease (IBD). Herein, we evaluated the effect of the IBD-AID on the gut microbiome and defined the impact of specific foods on bacteria depleted in IBD patients, as well as the clinical response to the IBD-AID. Methods A single-arm, pre-post intervention trial was performed. After a baseline period, a dietary intervention was initiated. We collected stool and blood samples throughout the study and assessed dietary intake and disease severity. We applied advanced computational approaches to define and model complex interactions between the diet, microbiota, and response to the IBD-AID. Results A dense dataset comprising 553 dietary records and 340 stool samples was compiled from 22 subjects participating in the study. The IBD-AID favored bacteria that are normally depleted in IBD cohorts and capable of producing short-chain fatty acids (SCFAs). Consumption of non-starchy vegetables, nuts, and seeds positively correlated with increased abundance of SCFA-producing bacteria, including Roseburia hominis, Eubacterium eligens,and Faecalibacterium prausnitzii. Half of the subjects completing the intervention with high diet adherence (>60%) reported a positive clinical response to the IBD-AID, with a subset of bacterial species predicting diet-induced reduction of symptoms with 67% accuracy. After the intervention, subjects also exhibited a reduction of circulating inflammatory markers. Conclusions The IBD-AID favors the growth of SCFA-producing bacteria that are depleted during IBD dysbiosis. The microbiome signatures emerging after the IBD-AID can predict response to the diet.


Nutrients ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 3204
Author(s):  
Genelle R. Healey ◽  
Larissa S. Celiberto ◽  
Soo Min Lee ◽  
Kevan Jacobson

The etiology of inflammatory bowel disease (IBD) is complex but is thought to be linked to an intricate interaction between the host’s immune system, resident gut microbiome and environment, i.e., diet. One dietary component that has a major impact on IBD risk and disease management is fiber. Fiber intakes in pediatric IBD patients are suboptimal and often lower than in children without IBD. Fiber also has a significant impact on beneficially shaping gut microbiota composition and functional capacity. The impact is likely to be particularly important in IBD patients, where various studies have demonstrated that an imbalance in the gut microbiome, referred to as dysbiosis, occurs. Microbiome-targeted therapeutics, such as fiber and prebiotics, have the potential to restore the balance in the gut microbiome and enhance host gut health and clinical outcomes. Indeed, studies in adult IBD patients demonstrate that fiber and prebiotics positively alter the microbiome and improve disease course. To date, no studies have been conducted to evaluate the therapeutic potential of fiber and prebiotics in pediatric IBD patients. Consequently, pediatric IBD specific studies that focus on the benefits of fiber and prebiotics on gut microbiome composition and functional capacity and disease outcomes are required.


Nutrients ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 610 ◽  
Author(s):  
Gian Tenore ◽  
Ester Pagano ◽  
Stefania Lama ◽  
Daniela Vanacore ◽  
Salvatore Di Maro ◽  
...  

Under physiological conditions, the small intestine represents a barrier against harmful antigens and pathogens. Maintaining of the intestinal barrier depends largely on cell–cell interactions (adherent-junctions) and cell–matrix interactions (tight-junctions). Inflammatory bowel disease is characterized by chronic inflammation, which induces a destructuring of the architecture junctional epithelial proteins with consequent rupture of the intestinal barrier. Recently, a peptide identified by Bubalus bubalis milk-derived products (MBCP) has been able to reduce oxidative stress in intestinal epithelial cells and erythrocytes. Our aim was to evaluate the therapeutic potential of MBCP in inflammatory bowel disease (IBD). We studied the effect of MBCP on (i) inflamed human intestinal Caco2 cells and (ii) dinitrobenzene sulfonic acid (DNBS) mice model of colitis. We have shown that MBCP, at non-cytotoxic concentrations, both in vitro and in vivo induced the adherent epithelial junctions organization, modulated the nuclear factor (NF)-κB pathway and reduced the intestinal permeability. Furthermore, the MBCP reverted the atropine and tubocurarine injury effects on adherent-junctions. The data obtained showed that MBCP possesses anti-inflammatory effects both in vitro and in vivo. These results could have an important impact on the therapeutic potential of MBCP in helping to restore the intestinal epithelium integrity damaged by inflammation.


2020 ◽  
Vol 25 (46) ◽  
pp. 4893-4913 ◽  
Author(s):  
Fan Cao ◽  
Jie Liu ◽  
Bing-Xian Sha ◽  
Hai-Feng Pan

: Inflammatory bowel disease (IBD) is a chronic, elusive disorder resulting in relapsing inflammation of intestine with incompletely elucidated etiology, whose two representative forms are ulcerative colitis (UC) and Crohn’s disease (CD). Accumulating researches have revealed that the individual genetic susceptibility, environmental risk elements, intestinal microbial flora, as well as innate and adaptive immune system are implicated in the pathogenesis and development of IBD. Despite remarkable progression of IBD therapy has been achieved by chemical drugs and biological therapies such as aminosalicylates, corticosteroids, antibiotics, anti-tumor necrosis factor (TNF)-α, anti-integrin agents, etc., healing outcome still cannot be obtained, along with inevitable side effects. Consequently, a variety of researches have focused on exploring new therapies, and found that natural products (NPs) isolated from herbs or plants may serve as promising therapeutic agents for IBD through antiinflammatory, anti-oxidant, anti-fibrotic and anti-apoptotic effects, which implicates the modulation on nucleotide- binding domain (NOD) like receptor protein (NLRP) 3 inflammasome, gut microbiota, intestinal microvascular endothelial cells, intestinal epithelia, immune system, etc. In the present review, we will summarize the research development of IBD pathogenesis and current mainstream therapy, as well as the therapeutic potential and intrinsic mechanisms of NPs in IBD.


2021 ◽  
Author(s):  
Xiao fan Song ◽  
Lei Qiao ◽  
Shuqi Yan ◽  
Yue Chen ◽  
Xina Dou ◽  
...  

Selenium (Se) as an essential micronutrient that has implications in human diseases, including inflammatory bowel disease (IBD), especially with respect to Se deficiencies. Recently, selenium nanoparticles (SeNPs) have attracted significant...


Marine Drugs ◽  
2021 ◽  
Vol 19 (4) ◽  
pp. 196
Author(s):  
Muhammad Bilal ◽  
Leonardo Vieira Nunes ◽  
Marco Thúlio Saviatto Duarte ◽  
Luiz Fernando Romanholo Ferreira ◽  
Renato Nery Soriano ◽  
...  

Naturally occurring biological entities with extractable and tunable structural and functional characteristics, along with therapeutic attributes, are of supreme interest for strengthening the twenty-first-century biomedical settings. Irrespective of ongoing technological and clinical advancement, traditional medicinal practices to address and manage inflammatory bowel disease (IBD) are inefficient and the effect of the administered therapeutic cues is limited. The reasonable immune response or invasion should also be circumvented for successful clinical translation of engineered cues as highly efficient and robust bioactive entities. In this context, research is underway worldwide, and researchers have redirected or regained their interests in valorizing the naturally occurring biological entities/resources, for example, algal biome so-called “treasure of untouched or underexploited sources”. Algal biome from the marine environment is an immense source of excellence that has also been demonstrated as a source of bioactive compounds with unique chemical, structural, and functional features. Moreover, the molecular modeling and synthesis of new drugs based on marine-derived therapeutic and biological cues can show greater efficacy and specificity for the therapeutics. Herein, an effort has been made to cover the existing literature gap on the exploitation of naturally occurring biological entities/resources to address and efficiently manage IBD. Following a brief background study, a focus was given to design characteristics, performance evaluation of engineered cues, and point-of-care IBD therapeutics of diverse bioactive compounds from the algal biome. Noteworthy potentialities of marine-derived biologically active compounds have also been spotlighted to underlying the impact role of bio-active elements with the related pathways. The current review is also focused on the applied standpoint and clinical translation of marine-derived bioactive compounds. Furthermore, a detailed overview of clinical applications and future perspectives are also given in this review.


2020 ◽  
Vol 4 (1) ◽  
pp. e000786
Author(s):  
Abbie Maclean ◽  
James J Ashton ◽  
Vikki Garrick ◽  
R Mark Beattie ◽  
Richard Hansen

The assessment and management of patients with known, or suspected, paediatric inflammatory bowel disease (PIBD) has been hugely impacted by the COVID-19 pandemic. Although current evidence of the impact of COVID-19 infection in children with PIBD has provided a degree of reassurance, there continues to be the potential for significant secondary harm caused by the changes to normal working practices and reorganisation of services.Disruption to the normal running of diagnostic and assessment procedures, such as endoscopy, has resulted in the potential for secondary harm to patients including delayed diagnosis and delay in treatment. Difficult management decisions have been made in order to minimise COVID-19 risk for this patient group while avoiding harm. Initiating and continuing immunosuppressive and biological therapies in the absence of normal surveillance and diagnostic procedures have posed many challenges.Despite this, changes to working practices, including virtual clinic appointments, home faecal calprotectin testing kits and continued intensive support from clinical nurse specialists and other members of the multidisciplinary team, have resulted in patients still receiving a high standard of care, with those who require face-to-face intervention being highlighted.These changes have the potential to revolutionise the way in which patients receive routine care in the future, with the inclusion of telemedicine increasingly attractive for stable patients. There is also the need to use lessons learnt from this pandemic to plan for a possible second wave, or future pandemics as well as implementing some permanent changes to normal working practices.In this review, we describe the diagnosis, management and direct impact of COVID-19 in paediatric patients with IBD. We summarise the guidance and describe the implemented changes, evolving evidence and the implications of this virus on paediatric patients with IBD and working practices.


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