Effects of Wine Components in Inflammatory Bowel Diseases

With the rising prevalence of Inflammatory bowel disease (IBD) worldwide, and the rising cost of treatment with novel biological drugs, there is an increasing interest in various diets and natural foods as a potential way to control/modulate IBD. As recent data indicates that diet can modify the metabolic responses essential for the resolution of inflammation, and as wine compounds have been shown to provide substantial anti-inflammatory effect, in this review we aimed to discuss the current evidence concerning the impact of biological compounds present in wine on IBD. A number of preclinical studies brought forth strong evidence on the mechanisms by which molecules in wine, such as resveratrol or piceatannol, provide their anti-inflammatory, anti-oxidative, anti-tumor, and microbiota-modulation effects. However, concerning the effects of alcohol, it is still unclear how the amount of ethanol ingested within the framework of moderate wine consumption (1–2 glasses a day) affects patients with IBD, as human studies regarding the effects of wine on patients with IBD are scarce. Nevertheless, available evidence justifies the conductance of large-scale RCT trials on human subjects that will finally elucidate whether wine can offer real benefits to the IBD population.     

A Potential Role of Plant/Macrofungi/Algae-Derived Non-Starch Polysaccharide in Colitis Curing: Review of Possible Mechanisms of Action

Multiple in vitro and in vivo model investigations have suggested a broad spectrum of potential mechanisms by which plant/macrofungi-derived non-starch polysaccharides may play a role in the treatment of inflammatory bowel disease (IBD). This article reviews the in vivo and in vitro evidence of different plant-derived polysaccharides for IBD therapy. Their underlying mechanisms, particularly the molecular mechanisms associated with protective effects in the treatment and prevention of IDB, have been well summarized, including anti-inflammatory, epithelial barrier repair, and the regulation of intestinal flora. Emerging studies have observed the potent role of probiotics in IBD, particularly its ability to modulate gut microbiota, a well-known key factor for IBD. In summary, plant/macrofungi-derived polysaccharides have the potential to be a promising agent for the adjuvant treatment and prevention of IBD and will contribute to the design of well-designed clinical intervention trials that will ultimately improve the therapy of IBD.     

(Poly)phenols in Inflammatory Bowel Disease and Irritable Bowel Syndrome: A Review

(Poly)phenols (PPs) may have a therapeutic benefit in gastrointestinal (GI) disorders, such as irritable bowel syndrome (IBS) or inflammatory bowel disease (IBD). The aim of this review is to summarise the evidence-base in this regard. Observational evidence does not give a clear indication that PP intake has a preventative role for IBD or IBS, while interventional studies suggest these compounds may confer symptomatic and health-related quality of life improvements in known patients. There are inconsistent results for effects on markers of inflammation, but there are promising reports of endoscopic improvement. Work on the effects of PPs on intestinal permeability and oxidative stress is limited and therefore conclusions cannot be formed. Future work on the use of PPs in IBD and IBS will strengthen the understanding of clinical and mechanistic effects.     

Inflammasome Regulation: Therapeutic Potential for Inflammatory Bowel Disease

Inflammasomes are multiprotein complexes formed to regulate the maturation of pro-inflammatory caspases, in response to intracellular or extracellular stimulants. Accumulating studies showed that the inflammasomes are implicated in the pathogenesis of inflammatory bowel disease (IBD), although their activation is not a decisive factor for the development of IBD. Inflammasomes and related cytokines play an important role in the maintenance of gut immune homeostasis, while its overactivation might induce excess immune responses and consequently cause tissue damage in the gut. Emerging studies provide evidence that some genetic abnormalities might induce enhanced NLRP3 inflammasome activation and cause colitis. In these cases, the colonic inflammation can be ameliorated by blocking NLRP3 activation or its downstream cytokine IL-1β. A number of natural products were shown to play a role in preventing colon inflammation in various experimental colitis models. On the other hand, lack of inflammasome function also causes intestinal abnormalities. Thus, an appropriate regulation of inflammasomes might be a promising therapeutic strategy for IBD intervention. This review aims at summarizing the main findings in these studies and provide an outline for further studies that might contribute to our understanding of the role of inflammasomes in the pathogenesis and therapeutic treatment of IBD.     

Emerging nanomedicine and prodrug delivery strategies for the treatment of inflammatory bowel disease

Inflammatory bowel disease (IBD) is a chronic and recurrent disease of the gastrointestinal tract, mainly including Crohn's disease (CD) and ulcerative colitis (UC). However, current approaches against IBD do not precisely deliver drugs to the inflammatory site, which leads to life-long medication and serious side effects that can adversely impact patients’ adherence. It is necessary to construct optimal drug delivery systems (DDSs) that can target drugs to the region of inflammation, thereby improve therapeutic efficacy and reduce side effects. With the burgeoning development of nanotechnology-based nanomedicines (NMs) and prodrug strategy, remarkable progresses in the treatment of IBD have been made in recent years. Herein, the latest advances are outlined at the intersection of IBD treatment and nanotherapeutics as well as prodrug therapy. First, the pathophysiological microenvironment of inflammatory sites of IBD is introduced in order to rationally design potential NMs and prodrugs. Second, the necessity of NMs for the IBD therapy is elaborated, and the representative nanotherapeutics via passive targeted and active targeted NMs developed to treat the IBD are overviewed. Furthermore, the emerging prodrug-based therapeutics are summarized, including 5-aminosalicylic acid-, amino acid-, and carbohydrate-conjugated prodrugs. Finally, the design considerations and perspectives of these NMs and prodrugs-driven IBD therapeutics in the clinical translation are spotlighted.     

Pharmacological Insights into Halophyte Bioactive Extract Action on Anti-Inflammatory,Pain Relief and Antibiotics-Type Mechanisms

The pharmacological activities in bioactive plant extracts play an increasing role in sustainable resources for valorization and biomedical applications. Bioactive phytochemicals, including natural compounds, secondary metabolites and their derivatives, have attracted significant attention for use in both medicinal products and cosmetic products. Our review highlights the pharmacological mode-of-action and current biomedical applications of key bioactive compounds applied as anti-inflammatory, bactericidal with antibiotics effects, and pain relief purposes in controlled clinical studies or preclinical studies. In this systematic review, the availability of bioactive compounds from several salt-tolerant plant species, mainly focusing on the three promising species Aster tripolium, Crithmum maritimum and Salicornia europaea, are summarized and discussed. All three of them have been widely used in natural folk medicines and are now in the focus for future nutraceutical and pharmacological applications.     

Inflammation,It’s Regulation and Antiphlogistic Effect of the Cyanogenic Glycoside Amygdalin

The inflammatory reaction accompanies in part or in full any disease process in the vascularized metazoan. This complicated reaction is controlled by regulatory mechanisms, some of which produce unpleasant symptomatic manifestations of inflammation. Therefore, there has been an effort to develop selective drugs aimed at removing pain, fever, or swelling. Gradually, however, serious adverse side effects of such inhibitors became apparent. Scientific research has therefore continued to explore new possibilities, including naturally available substances. Amygdalin is a cyanogenic glycoside present, e.g., in bitter almonds. This glycoside has already sparked many discussions among scientists, especially about its anticancer potential and related toxic cyanides. However, toxicity at different doses made it generally unacceptable. Although amygdalin given at the correct oral dose may not lead to poisoning, it has not yet been accurately quantified, as its action is often affected by different intestinal microbial consortia. Its pharmacological activities have been studied, but its effects on the body’s inflammatory response are lacking. This review discusses the chemical structure, toxicity, and current knowledge of the molecular mechanism of amygdalin activity on immune functions, including the anti-inflammatory effect, but also discusses inflammation as such, its mediators with diverse functions, which are usually targeted by drugs.     

CYP450 Epoxygenase Metabolites,Epoxyeicosatrienoic Acids,as Novel Anti-Inflammatory Mediators

Inflammation plays a crucial role in the initiation and development of a wide range of systemic illnesses. Epoxyeicosatrienoic acids (EETs) are derived from arachidonic acid (AA) metabolized by CYP450 epoxygenase (CYP450) and are subsequently hydrolyzed by soluble epoxide hydrolase (sEH) to dihydroxyeicosatrienoic acids (DHETs), which are merely biologically active. EETs possess a wide range of established protective effects on many systems of which anti-inflammatory actions have gained great interest. EETs attenuate vascular inflammation and remodeling by inhibiting activation of endothelial cells and reducing cross-talk between inflammatory cells and blood vessels. EETs also process direct and indirect anti-inflammatory properties in the myocardium and therefore alleviate inflammatory cardiomyopathy and cardiac remodeling. Moreover, emerging studies show the substantial roles of EETs in relieving inflammation under other pathophysiological environments, such as diabetes, sepsis, lung injuries, neurodegenerative disease, hepatic diseases, kidney injury, and arthritis. Furthermore, pharmacological manipulations of the AA-CYP450-EETs-sEH pathway have demonstrated a contribution to the alleviation of numerous inflammatory diseases, which highlight a therapeutic potential of drugs targeting this pathway. This review summarizes the progress of AA-CYP450-EETs-sEH pathway in regulation of inflammation under different pathological conditions and discusses the existing challenges and future direction of this research field.     

Exploring Effects of Chitosan Oligosaccharides on the DSS-Induced Intestinal Barrier Impairment In Vitro and In Vivo

Intestinal barrier dysfunction is an essential pathological change in inflammatory bowel disease (IBD). The mucus layer and the intestinal epithelial tight junction act together to maintain barrier integrity. Studies showed that chitosan oligosaccharide (COS) had a positive effect on gut health, effectively protecting the intestinal barrier in IBD. However, these studies usually focused on its impact on the intestinal epithelial tight junction. The influence of COS on the intestinal mucus layer is still poorly understood. In this study, we explored the effect of COS on intestinal mucus in vitro using human colonic mucus-secreted HT-29 cells. COS relieved DSS (dextran sulfate sodium)-induced mucus defects. Additionally, the structural characteristics of COS greatly influenced this activity. Finally, we evaluated the protective effect of COS on intestinal barrier function in mice with DSS-induced colitis. The results indicated that COS could manipulate intestinal mucus production, which likely contributed to its intestinal protective effects.     

Anti-Cancer Potential of Synthetic Oleanolic Acid Derivatives and Their Conjugates with NSAIDs

Naturally occurring pentacyclic triterpenoid oleanolic acid (OA) serves as a good scaffold for additional modifications to achieve synthetic derivatives. Therefore, a large number of triterpenoids have been synthetically modified in order to increase their bioactivity and their protective or therapeutic effects. Moreover, attempts were performed to conjugate synthetic triterpenoids with non-steroidal anti-inflammatory drugs (NSAIDs) or other functional groups. Among hundreds of synthesized triterpenoids, still the most promising is 2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oic acid (CDDO), which reached clinical trials level of investigations. The new group of synthetic triterpenoids are OA oximes. The most active among them is 3-hydroxyiminoolean-12-en-28-oic acid morpholide, which additionally improves the anti-cancer activity of standard NSAIDs. While targeting the Nrf2 and NF-κB signaling pathways is the main mechanism of synthetic OA derivatives′ anti-inflammatory and anti-cancer activity, most of these compounds exhibit multifunctional activity, and affect cross-talk within the cellular signaling network. This short review updates the earlier data and describes the new OA derivatives and their conjugates in the context of modification of signaling pathways involved in inflammation and cell survival and subsequently in cancer development.     

蒙脱石负载氧化铈纳米酶用于克罗恩肠炎治疗

通过水热法合成由临床用药蒙脱石(Montmorillonite, MMT)负载的高效纳米酶氧化铈(Cerium dioxide, CeO₂), 通过开展体内外实验, 拓展其在炎症性肠病治疗中的普适性. 结果显示, CeO₂@MMT具有良好的类超氧化物歧化酶活性及类过氧化氢酶活性, 并且在小鼠克罗恩病的治疗中体现了明显的疗效及优异的生物安全性, 为CeO₂@MMT的应用拓宽了方向.     

Pharmacotherapeutics Applications and Chemistry of Chalcone Derivatives

Chalcones have been well examined in the extant literature and demonstrated antibacterial, antifungal, anti-inflammatory, and anticancer properties. A detailed evaluation of the purported health benefits of chalcone and its derivatives, including molecular mechanisms of pharmacological activities, can be further explored. Therefore, this review aimed to describe the main characteristics of chalcone and its derivatives, including their method synthesis and pharmacotherapeutics applications with molecular mechanisms. The presence of the reactive α,β-unsaturated system in the chalcone’s rings showed different potential pharmacological properties, including inhibitory activity on enzymes, anticancer, anti-inflammatory, antibacterial, antifungal, antimalarial, antiprotozoal, and anti-filarial activity. Changing the structure by adding substituent groups to the aromatic ring can increase potency, reduce toxicity, and broaden pharmacological action. This report also summarized the potential health benefits of chalcone derivatives, particularly antimicrobial activity. We found that several chalcone compounds can inhibit diverse targets of antibiotic-resistance development pathways; therefore, they overcome resistance, and bacteria become susceptible to antibacterial compounds. A few chalcone compounds were more active than conventional antibiotics, like vancomycin and tetracycline. On another note, a series of pyran-fused chalcones and trichalcones can block the NF-B signaling complement system implicated in inflammation, and several compounds demonstrated more potent lipoxygenase inhibition than NSAIDs, such as indomethacin. This report integrated discussion from the domains of medicinal chemistry, organic synthesis, and diverse pharmacological applications, particularly for the development of new anti-infective agents that could be a useful reference for pharmaceutical scientists.     

Evaluation of Anti-Inflammatory and Antioxidant Effectsof Chrysanthemum Stem and Leaf Extract on Zebrafish Inflammatory Bowel Disease Model

Present studies have shown that Flos Chrysanthemi has anti-inflammatory and other effects and regulates intestinal function, while the chrysanthemum stem and leaf as non-medicinal parts of chrysanthemum have similar chemical components with chrysanthemum, but the activity and mechanisms are rarely elucidated. Therefore, this study used a DSS-induced zebrafish inflammatory bowel disease model to study the anti-inflammatory and antioxidant effects of chrysanthemum stem and leaf extracts. The results indicate that DSS induction leads to increased secretion of acidic mucin in the intestines of juvenile fish, enlargement of the intestinal lumen and the emergence of intestinal inflammation. Compared with the model group, each administration group differentially inhibited the expression of IL-1β, IL-8 and MMP9 in DSS-induced zebrafish, while upregulating the activity of superoxide dismutase. The quantitative analysis results showed that the flavonoids (including Linarin, Diosmetin-7-glucoside, Tilianin, etc.) and phenolic acids (including Isochlorogenic acid C, Isochlorogenic acid A, 1,3-Dicaffeoylquinic acid, etc.) in the alcohol extract were closely related with both anti-inflammatory and antioxidant activity, while the polysaccharides were also shown a certain anti-inflammatory and antioxidant activity. In conclusion, this study suggests that the flavonoids, phenolic acids and polysaccharides from chrysanthemum stem and leaf extracts can improve inflammatory bowel disease of zebrafish by regulating the expressions of IL-1β, IL-8 and MMP9.     

Nutraceutic Potential of Bioactive Compounds of Eugenia dysenterica DC in Metabolic Alterations

The fruit and leaves of Eugenia dysenterica DC., locally known as cagaita, are rich in antioxidant glycosylated quercetin derivatives and phenolic compounds that have beneficial effects on diabetes mellitus, hypertension and general inflammation. We conducted a literature search to investigate the nutraceutical potentials of these phenolic compounds for treating obesity, diabetes mellitus and intestinal inflammatory disease. The phenolic compounds in E. dysenterica have demonstrated effects on carbohydrate metabolism, which can prevent the development of these chronic diseases and reduce LDL (low-density lipoprotein) cholesterol and hypertension. E. dysenterica also improves intestinal motility and microbiota and protects gastric mucosa, thereby preventing inflammation. However, studies are necessary to identify the mechanism by which E. dysenterica nutraceutical compounds act on such pathological processes to support future research.     

Synthesis of azo derivatives of 4-aminosalicylic acid

For searching a better 4-aminosalicylic acid derivative with higher activity and less side effects against the inflammatory bowel disease, 4-aminosalicylic acid (4-ASA) was protected by benzyloxycarbonyl and acetyl, respectively. The resultant was hydrogenized to remove protective group of amino group, then the product was reacted with NaNO2 to give diazonium salt, which was conjugated with salicylic acid, hydroxybenzene, TV-salicyloyl glycine acid to get azo derivatives of 4-ASA. The azo derivatives were hydrolyzed under the alkaline condition to get the target products. All compounds were characterized by FT-IR, 1H NMR, 13C NMR spectra in details. New derivatives of 4-ASA were characterized. The synthetic route was reasonable and feasible.