<i>Perilla frutescens</i> extract ameliorates DSS-induced colitis by suppressing proinflammatory cytokines and inducing anti-inflammatory cytokines

Urushima, Hayato; Nishimura, Junichi; Mizushima, Tsunekazu; Hayashi, Noriyuki; Maeda, Kazuhisa; Ito, Toshinori

doi:10.1152/ajpgi.00294.2014

Cited by 46 publications

(31 citation statements)

References 48 publications

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“…As inflammatory mediators like TNF-α and IL-6 play critical roles in the pathogenesis of murine colitis, we analysed their expression by qPCR and Western blot. Consistent with previous reports [65][66][67][68][69][70], the levels of these pro-inflammatory cytokines in DSSinduced mice were found positively correlated to the severity of colitis in the current study. Furthermore, DAPP significantly provided suppressive effects on intrinsic TNF-α and IL-6 elevations under experimental colitis condition, which probably halts the pathological progression of pro-inflammatory cascade.…”

Section: Discussionsupporting

confidence: 93%

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

et al. 2016

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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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Section: Discussionsupporting

confidence: 93%

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

et al. 2016

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“…While our study was in progress, Urushima et al (2015) reported that 0.54% PE administered for 7 days simultaneously with 1.5% DSS or for 10 days following 1.5% DSS treatment for 5 days ameliorated pathogenic symptoms of colitis in 8-week-old C57BL/6 female mice while it improved the body weight loss. They found that serum levels of TNF-α, IL-17A, and IL-10 were significantly reduced by co-administration of PE.…”

Section: Discussionmentioning

confidence: 69%

“…Luteolin suppressed production of proinflammatory cytokines, such as TNF-α, IL-1β, IL-6, and IL-17A in cultured monocytes derived from the 8-week-old wild-type C57/BL6 female mice. Apigenin also suppressed secretion of IL-17A while it increased the anti-inflammatory cytokine IL-10, whereas rosmarinic acid increased the regulatory T cell population ( Urushima et al, 2015 ). Rosmarinic acid has recently been shown to suppresses DSS-induced colitis which is attributed to its dual inhibition of NF-κB and STAT3 activation ( Jin et al, 2017 ).…”

Section: Discussionmentioning

confidence: 99%

Perilla frutescens Extracts Protects against Dextran Sulfate Sodium-Induced Murine Colitis: NF-κB, STAT3, and Nrf2 as Putative Targets

et al. 2017

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Perilla frutescens is a culinary and medicinal herb which has a strong anti-inflammatory and antioxidative effects. In the present study, we investigated the effects of Perilla frutescens extract (PE) against dextran sulfate sodium (DSS)-induced mouse colitis, an animal model that mimics human inflammatory bowel disease (IBD). Five-week-old male ICR mice were treated with a daily dose of PE (20 or 100 mg/kg, p.o.) for 1 week, followed by administration of 3% DSS in double distilled drinking water and PE by gavage for another week. DSS-induced colitis was characterized by body weight loss, colon length shortening, diarrhea and bloody stool, and these symptoms were significantly ameliorated by PE treatment. PE administration suppressed DSS-induced expression of proinflammatory enzymes, including cyclooxygenase-2 and inducible nitric oxide synthase as well as cyclin D1 , in a dose-dependent fashion. Nuclear factor-kappa B (NF-κB) and signal transducer and activator of transcription 3 (STAT3) are major transcriptional regulators of inflammatory signaling. PE administration significantly inhibited the activation of both NF-κB and STAT3 induced by DSS, while it elevated the accumulation of Nrf2 and heme oxygenase-1 in the colon. In another experiment, treatment of CCD841CoN human normal colon epithelial cells with PE (10 mg/ml) resulted in the attenuation of the tumor necrosis factor-α-induced expression/activation of mediators of proinflammatory signaling. The above results indicate that PE has a preventive potential for use in the management of IBD.

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“…In addition, RA possess anti-inflammatory properties in carrageenan-induced paw oedema rat model and liver ischaemia-reperfusion and thermal injury rat models16. Furthermore, it has been reported that RA, as the biologically active element of Perilla frutescens , increases the regulatory T cell population in the DSS-induced colitis model17. However, there has yet to be a study evaluating the detailed in vivo biological efficacies of RA or demonstrating its underlying molecular mechanism in mice with DSS-induced colitis.…”

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confidence: 99%

Rosmarinic acid suppresses colonic inflammation in dextran sulphate sodium (DSS)-induced mice via dual inhibition of NF-κB and STAT3 activation

Jin

Chung

Cheon

et al. 2017

Sci Rep

143

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Ulcerative colitis (UC), a type of inflammatory bowel disease (IBD), is a chronic inflammatory disorder of the colon. Although UC is generally treated with anti-inflammatory drugs or immunosuppressants, most of these treatments often prove to be inadequate. Rosmarinic acid (RA) is a phenolic ester included in various medicinal herbs such as Salvia miltiorrhiz and Perilla frutescens. Although RA has many biological and pharmacological activities, the anti-inflammatory effect of RA in colonic tissue remains unclear. In this study, we investigated the anti-inflammatory effects and underlying molecular mechanism of RA in mice with dextran sulphate sodium (DSS)-induced colitis. In the DSS-induced colitis model, RA significantly reduced the severity of colitis, as assessed by disease activity index (DAI) scores, colonic damage, and colon length. In addition, RA resulted in the reduction of the inflammatory-related cytokines, such as IL-6, IL-1β, and IL-22, and protein levels of COX-2 and iNOS in mice with DSS-induced colitis. Furthermore, RA effectively and pleiotropically inhibited nuclear factor-kappa B and signal transducer and activator of transcription 3 activation, and subsequently reduced the activity of pro-survival genes that depend on these transcription factors. These results demonstrate that RA has an ameliorative effect on colonic inflammation and thus a potential therapeutic role in colitis.

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Perilla frutescens extract ameliorates DSS-induced colitis by suppressing proinflammatory cytokines and inducing anti-inflammatory cytokines

Abstract: Urushima H, Nishimura J, Mizushima T, Hayashi N, Maeda K, Ito T. Perilla frutescens extract ameliorates DSS-induced colitis by suppressing proinflammatory cytokines and inducing anti-inflammatory cytokines.

Cited by 46 publications

References 48 publications

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

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

Perilla frutescens Extracts Protects against Dextran Sulfate Sodium-Induced Murine Colitis: NF-κB, STAT3, and Nrf2 as Putative Targets

Rosmarinic acid suppresses colonic inflammation in dextran sulphate sodium (DSS)-induced mice via dual inhibition of NF-κB and STAT3 activation

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