Anti-Inflammatory Activities of a Chinese Herbal Formula IBS-20In VitroandIn Vivo

Irritable bowel syndrome (IBS) is a functional bowel disorder and the etiology is not well understood. Currently there is no cure for IBS and no existing medication induces symptom relief in all patients. IBS-20 is a 20-herb Chinese medicinal formula that offers beneficial effects in patients with IBS; however, the underlying mechanisms are largely unknown. This study showed that IBS-20 potently inhibited LPS- or IFNΓ-stimulated expression of pro-inflammatory cytokines, as well as classically activated macrophage marker nitric oxide synthase 2. Similarly, IBS-20 or the component herbCoptis chinensisdecreased LPS-stimulated pro-inflammatory cytokine secretion from JAWS II dendritic cells. IBS-20 or the component herbs also blocked or attenuated the IFNΓ-induced drop in transepithelial electric resistance, an index of permeability, in fully differentiated Caco-2 monolayer. Finally, the up-regulation of key inflammatory cytokines in inflamed colon from TNBS-treated mice was suppressed significantly by orally administrated IBS-20, including IFNΓ and IL-12p40. These data indicate that the anti-inflammatory activities of IBS-20 may contribute to the beneficial effects of the herbal extract in patients with IBS, providing a potential mechanism of action for IBS-20. In addition, IBS-20 may be a potential therapeutic agent against other Th1-dominant gut pathologies such as inflammatory bowel disease.

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Recent Advances: The Imbalance of Cytokines in the Pathogenesis of Inflammatory Bowel Disease

Mediators of Inflammation ◽

10.1155/2017/4810258 ◽

2017 ◽

Vol 2017 ◽

pp. 1-8 ◽

Cited By ~ 42

Author(s):

Qingdong Guan ◽

Jiguo Zhang

Keyword(s):

Ulcerative Colitis ◽

Inflammatory Bowel Disease ◽

Inflammatory Cytokines ◽

Bowel Disease ◽

Intestinal Inflammation ◽

Beneficial Effects ◽

Recent Advances ◽

Inflammatory Bowel ◽

Inflammation Targeting ◽

Anti Inflammatory

Cytokines play an important role in the immunopathogenesis of inflammatory bowel disease (IBD), including Crohn’s disease and ulcerative colitis, where they drive and regulate multiple aspects of intestinal inflammation. The imbalance between proinflammatory and anti-inflammatory cytokines that occurs in IBD results in disease progression and tissue damage and limits the resolution of inflammation. Targeting cytokines have been novel strategies in the treatment of IBD. Recent studies show the beneficial effects of anticytokine treatments to IBD patients, and multiple novel cytokines are found to be involved in the pathogenesis of IBD. In this review, we will discuss the recent advances of novel biologics in clinics and clinical trials, and novel proinflammatory and anti-inflammatory cytokines found in IBD with focusing on IL-12 family and IL-1 family members as well as their relevance to the potential therapy of IBD.

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In vitro evidence for the involvement of H2S pathway in the effect of clodronate during inflammatory response

Scientific Reports ◽

10.1038/s41598-021-94228-y ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Rosangela Montanaro ◽

Alessio D’Addona ◽

Andrea Izzo ◽

Carlo Ruosi ◽

Vincenzo Brancaleone

Keyword(s):

Inflammatory Markers ◽

In Vitro Study ◽

Inos Expression ◽

Beneficial Effects ◽

Tnf Α ◽

Inflammatory State ◽

Anti Inflammatory ◽

Underlying Mechanisms ◽

Inflammatory Effect

AbstractClodronate is a bisphosphonate agent commonly used as anti-osteoporotic drug. Throughout its use, additional anti-inflammatory and analgesic properties have been reported, although the benefits described in the literature could not solely relate to their inhibition of bone resorption. Thus, the purpose of our in vitro study is to investigate whether there are underlying mechanisms explaining the anti-inflammatory effect of clodronate and possibly involving hydrogen sulphide (H2S). Immortalised fibroblast-like synoviocyte cells (K4IM) were cultured and treated with clodronate in presence of TNF-α. Clodronate significantly modulated iNOS expression elicited by TNF-α. Inflammatory markers induced by TNF-α, including IL-1, IL-6, MCP-1 and RANTES, were also suppressed following administration of clodronate. Furthermore, the reduction in enzymatic biosynthesis of CSE-derived H2S, together with the reduction in CSE expression associated with TNF-α treatment, was reverted by clodronate, thus rescuing endogenous H2S pathway activity. Clodronate displays antinflammatory properties through the modulation of H2S pathway and cytokines levels, thus assuring the control of the inflammatory state. Although further investigation is needed to stress out how clodronate exerts its control on H2S pathway, here we showed for the first the involvement of H2S in the additive beneficial effects observed following clodronate therapy.

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Isoquinolinequinone Derivatives from a Marine Sponge (Haliclona sp.) Regulate Inflammation in In Vitro System of Intestine

Marine Drugs ◽

10.3390/md19020090 ◽

2021 ◽

Vol 19 (2) ◽

pp. 90

Author(s):

Yun Kim ◽

Yeong Ji ◽

Na-Hyun Kim ◽

Nguyen Van Tu ◽

Jung-Rae Rho ◽

...

Keyword(s):

Nitric Oxide ◽

Marine Sponge ◽

Nuclear Translocation ◽

Hydroxyl Group ◽

Subsequent Increase ◽

Inflammatory Bowel ◽

Anti Inflammatory ◽

Key Functional Groups ◽

Oxide Synthase

Using bio-guided fractionation and based on the inhibitory activities of nitric oxide (NO) and prostaglandin E2 (PGE2), eight isoquinolinequinone derivatives (1–8) were isolated from the marine sponge Haliclona sp. Among these, methyl O-demethylrenierate (1) is a noble ester, whereas compounds 2 and 3 are new O-demethyl derivatives of known isoquinolinequinones. Compound 8 was assigned as a new 21-dehydroxyrenieramycin F. Anti-inflammatory activities of the isolated compounds were tested in a co-culture system of human epithelial Caco-2 and THP-1 macrophages. The isolated derivatives showed variable activities. O-demethyl renierone (5) showed the highest activity, while 3 and 7 showed moderate activities. These bioactive isoquinolinequinones inhibited lipopolysaccharide and interferon gamma-induced production of NO and PGE2. Expression of inducible nitric oxide synthase, cyclooxygenase-2, and the phosphorylation of MAPKs were down-regulated in response to the inhibition of NF-κB nuclear translocation. In addition, nuclear translocation was markedly promoted with a subsequent increase in the expression of HO-1. Structure-activity relationship studies showed that the hydroxyl group in 3 and 5, and the N-formyl group in 7 may be key functional groups responsible for their anti-inflammatory activities. These findings suggest the potential use of Haliclona sp. and its metabolites as pharmaceuticals treating inflammation-related diseases including inflammatory bowel disease.

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The nitric oxide synthase 2 pathway is targeted by both pro- and anti-inflammatory treatments in the immature human intestine

Nitric Oxide ◽

10.1016/j.niox.2017.03.003 ◽

2017 ◽

Vol 66 ◽

pp. 53-61 ◽

Cited By ~ 10

Author(s):

Emanuela Ferretti ◽

Eric Tremblay ◽

Marie-Pier Thibault ◽

David Grynspan ◽

Karolina M. Burghardt ◽

...

Keyword(s):

Nitric Oxide ◽

Nitric Oxide Synthase ◽

Human Intestine ◽

Anti Inflammatory ◽

Nitric Oxide Synthase 2 ◽

Oxide Synthase

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Anti-Inflammatory Effects of Cumin Essential Oil by Blocking JNK, ERK, and NF-κB Signaling Pathways in LPS-Stimulated RAW 264.7 Cells

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2015/474509 ◽

2015 ◽

Vol 2015 ◽

pp. 1-8 ◽

Cited By ~ 12

Author(s):

Juan Wei ◽

Xitong Zhang ◽

Yang Bi ◽

Ruidong Miao ◽

Zhong Zhang ◽

...

Keyword(s):

Essential Oil ◽

Transcriptional Activation ◽

Raw 264.7 Cells ◽

Raw 264.7 ◽

Extracellular Signal ◽

Mitogen Activated Protein ◽

Anti Inflammatory ◽

Underlying Mechanisms ◽

Oxide Synthase ◽

Inducible Nitric Oxide

Cumin seeds (Cuminum cyminumL.) have been commonly used in food flavoring and perfumery. In this study, cumin essential oil (CuEO) extracted from seeds was employed to investigate the anti-inflammatory effects in lipopolysaccharide- (LPS-) stimulated RAW 264.7 cells and the underlying mechanisms. A total of 26 volatile constituents were identified in CuEO by GC-MS, and the most abundant constituent was cuminaldehyde (48.773%). Mitochondrial-respiration-dependent 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium (MTT) reduction assay demonstrated that CuEO did not exhibit any cytotoxic effect at the employed concentrations (0.0005–0.01%). Real-time PCR tests showed that CuEO significantly inhibited the mRNA expressions of inducible nitric oxide synthase (iNOS), cyclooxygenase (COX-2), interleukin- (IL-) 1, and IL-6. Moreover, western blotting analysis revealed that CuEO blocked LPS-induced transcriptional activation of nuclear factor-kappa B (NF-κB) and inhibited the phosphorylation of extracellular signal regulated kinase (ERK) and c-Jun N-terminal kinase (JNK). These results suggested that CuEO exerted anti-inflammatory effects in LPS-stimulated RAW 264.7 cells via inhibition of NF-κB and mitogen-activated protein kinases ERK and JNK signaling; the chemical could be used as a source of anti-inflammatory agents as well as dietary complement for health promotion.

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Sudachinoid- and Ichangensin-Type Limonoids from Citrus junos Downregulate Pro-Inflammatory Cytokines

International Journal of Molecular Sciences ◽

10.3390/ijms21186963 ◽

2020 ◽

Vol 21 (18) ◽

pp. 6963

Author(s):

Jihun Shin ◽

Hwa Young Song ◽

Mina Lee

Keyword(s):

Inflammatory Cytokines ◽

Human Colon ◽

Dominant Group ◽

Citrus Junos ◽

Mouse Macrophages ◽

Inflammatory Bowel ◽

Anti Inflammatory ◽

Factor Α ◽

Necrosis Factor ◽

Pro Inflammatory Cytokines

Limonoids, a dominant group of phytochemicals in the Rutaceae family, are known to exhibit several pharmacological activities. To identify natural products having efficacy against inflammatory bowel disease (IBD), we isolated 13 limonoids including a new compound, methyl sudachinoid A, from the seeds of Citrus junos and investigated their anti-inflammatory effects by assessing the expression of pro-inflammatory cytokines in lipopolysaccharide-stimulated RAW 264.7 mouse macrophages and HT-29 human colon epithelial cells. Our findings revealed that limonoids significantly downregulated the pro-inflammatory cytokines, such as interleukin (IL)-1β, IL-6, IL-8, tumor necrosis factor-α, and nuclear transcription factor κB. In particular, sudachinoid-type compounds, methyl sudachinoid A and sudachinoid B, and ichangensin-type compound, 1-O-methyichangensin downregulated the expression of pro-inflammatory cytokines more potently than other limonoids, nomilin and limonin, which have been previously reported to exhibit anti-inflammatory activities in other cells; nomilin and limonin were therefore employed as positive controls in this study. Herein, we reveal that the anti-inflammatory activities of limonoids including a new compound methyl sudachinoid A from C. junos were mediated via the downregulation of pro-inflammatory cytokines and these limonoids can be employed as potential therapeutic phytochemicals for IBD.

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A novel indazolo-triazolo-benzotriazepine exerts anti-inflammatory effects by inhibition of cyclooxygenase-2 activity and nitric oxide synthase-2 expression

Naunyn-Schmiedeberg s Archives of Pharmacology ◽

10.1007/s00210-003-0768-6 ◽

2003 ◽

Vol 368 (1) ◽

pp. 26-32 ◽

Cited By ~ 8

Author(s):

Patricia Fern�ndez ◽

M. Isabel Guill�n ◽

Amalia Ubeda ◽

Pablo L�pez-Cremades ◽

Enrique Aller ◽

...

Keyword(s):

Nitric Oxide ◽

Nitric Oxide Synthase ◽

Cyclooxygenase 2 ◽

Anti Inflammatory ◽

Nitric Oxide Synthase 2 ◽

Oxide Synthase

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Apple peel polyphenols: a key player in the prevention and treatment of experimental inflammatory bowel disease

Clinical Science ◽

10.1042/cs20160524 ◽

2016 ◽

Vol 130 (23) ◽

pp. 2217-2237 ◽

Cited By ~ 26

Author(s):

Marie-Claude Denis ◽

Denis Roy ◽

Pantea Rahmani Yeganeh ◽

Yves Desjardins ◽

Thibault Varin ◽

...

Keyword(s):

Fruits And Vegetables ◽

Intestinal Inflammation ◽

Therapeutic Effects ◽

Microbial Composition ◽

Beneficial Effects ◽

Apple Peel ◽

Bowel Diseases ◽

Clinical Benefits ◽

Inflammatory Bowel ◽

Underlying Mechanisms

Diets rich in fruits and vegetables may reduce oxidative stress (OxS) and inflammation via several mechanisms. These beneficial effects may be due to their high polyphenol content. The aims of the present study are to evaluate the preventive and therapeutic aspects of polyphenols in dried apple peel powder (DAPP) on intestinal inflammation while elucidating the underlying mechanisms and clinical benefits. Induction of intestinal inflammation in mice was performed by oral administration of the inflammatory agent dextran sulfate sodium (DSS) at 2.5% for 10 days. Physiological and supraphysiological doses of DAPP (200 and 400 mg/kg/day respectively) were administered by gavage for 10 days pre- and post-DSS treatment. DSS-mediated inflammation caused weight loss, shortening of the colon, dystrophic detachment of the epithelium, and infiltration of mono- and poly-morphonuclear cells in the colon. DSS induced an increase in lipid peroxidation, a down-regulation of antioxidant enzymes, an augmented expression of myeloperoxidase (MPO) and cyclooxygenase-2 (COX-2), an elevated production of prostaglandin E2 (PGE2) and a shift in mucosa-associated microbial composition. However, DAPP normalized most of these abnormalities in preventive or therapeutic situations in addition to lowering inflammatory cytokines while stimulating antioxidant transcription factors and modulating other potential healing pathways. The supraphysiological dose of DAPP in therapeutic situations also improved mitochondrial dysfunction. Relative abundance of Peptostreptococcaceae and Enterobacteriaceae bacteria was slightly decreased in DAPP-treated mice. In conclusion, DAPP exhibits powerful antioxidant and anti-inflammatory action in the intestine and is associated with the regulation of cellular signalling pathways and changes in microbiota composition. Evaluation of preventive and therapeutic effects of DAPP may be clinically feasible in individuals with intestinal inflammatory bowel diseases.

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Efficient and Divergent Enantioselective Syntheses of DHPVs and Anti-Inflammatory Effect on IEC-6 Cells

Molecules ◽

10.3390/molecules25092215 ◽

2020 ◽

Vol 25 (9) ◽

pp. 2215

Author(s):

Hyun Su Kim ◽

Sungkyun Chung ◽

Moon-Young Song ◽

Changjin Lim ◽

Hyeyoung Shin ◽

...

Keyword(s):

Beneficial Effects ◽

Asymmetric Dihydroxylation ◽

Cross Metathesis ◽

Molecular Therapeutics ◽

Inflammatory Bowel ◽

Anti Inflammatory ◽

Enantioselective Syntheses ◽

Precise Molecular Mechanism ◽

Significant Attention ◽

Inflammatory Effect

Despite numerous reports on the beneficial effects of catechin or epicatechin contained in tea and cacao extract on human health, a conclusive and precise molecular mechanism has not been elucidated. Metabolism of chemical compounds in gut microbiota recently gained significant attention, and extensive studies have been devoted in this field. In conjunction with these results, our group focused on the anti-inflammatory effects of both enantiomers of DHPV (5-(3′,4′-dihydroxyphenyl)-γ-valerolactone), produced in the intestine by microbiota metabolism, on IEC-6 cells. Divergent and efficient enantioselective synthesis of (S)- and (R)-DHPV was efficiently achieved by cross-metathesis and Sharpless asymmetric dihydroxylation as a key reaction for four steps in 16% and 14% overall yields, respectively. The anti-inflammatory effects of two enantiomers were tested on IEC-6 cells, and we found that (S)-DHPV was more active than (R)-DHPV. This result implicates that the metabolite produced in the gut has beneficial effects on IEC-6 cells of rat intestines, and the chirality of the metabolite is important for its anti-inflammatory activity. This also provided information for the future discovery of novel small molecular therapeutics for the treatment of inflammatory bowel disease.

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