Flos lonicerae flavonoids attenuate experimental ulcerative colitis in rats via suppression of NF-κB signaling pathway

Liu, Daming; Yu, Xiao; Sun, Huiyi; Zhang, Wen; Guo, Lan; Zhu, Liu

doi:10.1007/s00210-020-01814-4

Cited by 36 publications

(21 citation statements)

References 51 publications

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“…A bunch of studies have demonstrated that lonicerin is one of the predominant constituents that possess anti-inflammatory and immunomodulatory activities 14 , 15 . Although lonicerin has recently found effective to prevent 2,4,6-trinitrobenzenesulfonic acid solution-induced colitis in rats, the mechanism related to the inactivation of NF- κ B signaling pathway remains inexplicit 16 . As part of our effort to characterize active natural products 17 , their unique molecular targets 18 , and corresponding mechanism 19 , we herein have verified the lonicerin's protective effect on DSS-induced colitis.…”

Section: Introductionmentioning

confidence: 99%

Lonicerin targets EZH2 to alleviate ulcerative colitis by autophagy-mediated NLRP3 inflammasome inactivation

Yao

Liu

et al. 2021

Acta Pharmaceutica Sinica B

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Aberrant activation of NLRP3 inflammasome in colonic macrophages strongly associates with the occurrence and progression of ulcerative colitis. Although targeting NLRP3 inflammasome has been considered to be a potential therapy, the underlying mechanism through which pathway the intestinal inflammation is modulated remains controversial. By focusing on the flavonoid lonicerin, one of the most abundant constituents existed in a long historical anti-inflammatory and anti-infectious herb Lonicera japonica Thunb., here we report its therapeutic effect on intestinal inflammation by binding directly to enhancer of zeste homolog 2 (EZH2) histone methyltransferase. EZH2-mediated modification of H3K27me3 promotes the expression of autophagy-related protein 5, which in turn leads to enhanced autophagy and accelerates autolysosome-mediated NLRP3 degradation. Mutations of EZH2 residues (His129 and Arg685) indicated by the dynamic simulation study have found to greatly diminish the protective effect of lonicerin. More importantly, in vivo studies verify that lonicerin dose-dependently disrupts the NLRP3–ASC–pro-caspase-1 complex assembly and alleviates colitis, which is compromised by administration of EZH2 overexpression plasmid. Thus, these findings together put forth the stage for further considering lonicerin as an anti-inflammatory epigenetic agent and suggesting EZH2/ATG5/NLRP3 axis may serve as a novel strategy to prevent ulcerative colitis as well as other inflammatory diseases.

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Section: Introductionmentioning

confidence: 99%

Lonicerin targets EZH2 to alleviate ulcerative colitis by autophagy-mediated NLRP3 inflammasome inactivation

Yao

Liu

et al. 2021

Acta Pharmaceutica Sinica B

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“…Moreover, hyperoside, lonicerin, and luteolin from LJFE exhibited possible anti-ulcer activities in an animal model of trinitrobenzenesulfonic acid (TNBS) -induced colitis through NF-κB signaling pathway inhibition. These natural compounds significantly reduced the values of specific serum oxidative and proinflammatory markers (superoxide dismutase, myeloperoxidase, malondialdehyde, prostaglandin E2, TNF-α, IL-β, and C-reactive protein) in TNBS -induced colitis [25].…”

Section: Discussionmentioning

confidence: 95%

Effects of Lonicera japonica Flower Bud Extract on Citrobacter rodentium-Induced Digestive Tract Infection

Minami

Makino

2020

Medicines

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Background: Although antibiotic therapy is currently a gold standard for bacterial infections, it is not used for severe diseases like enterohemorrhagic Escherichia coli, in which the Shiga toxin is overproduced by antibiotic action. The Lonicera japonica flower bud (LJF) is an herbal component used against purulent diseases in traditional Japanese and Chinese medicine. We investigated the effects of LJF extract (LJFE) on Citrobacter rodentium-induced digestive tract infection in a mouse model. Methods:Citrobacter rodentium and LJFE were orally administered to C57BL/6 mice. The survival rate and bacterial colonization in the large intestine, mesenteric lymph node, and blood of mice were evaluated. Cytokines secreted from intraperitoneal macrophages of LJFE-treated mice were measured using ELISA. Moreover, the phagocytic activity of intraperitoneal macrophages against Citrobacter rodentium was compared between LJFE- or chlorogenic acid (CGA)-treated mice. Results: LJFE significantly increased the survival rate and decreased Citrobacter rodentium colonization in mice. Moreover, the values of tumor necrosis factor-α, interleukin-1β, and interferon-γ secreted from macrophages were increased following LJFE treatment. While macrophages of LJFE-treated mice showed a significant phagocytic activity, macrophages of CGA-treated mice only showed a phagocytic tendency. Conclusions: LJF may be useful for treating Citrobacter rodentium-induced digestive tract infection.

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“…Luteolin (3 ,4 ,5,7-tetrahydroxy flavonoids) is present in vegetables (carrots, celery, bell peppers), fruits (apple), and herbs (honeysuckle, chrysanthemum, perilla), which has favorable effects on intestinal barrier function. More specifically, luteolin can attenuate ulcerative colitis, suppress rectal cancer, and prevent irinotecan-induced mucositis [104][105][106][107]. From another perspective, luteolin had a notably alleviative effect on intestinal barrier damage induced by decabromodiphenyl ether (BDE-209) in a Caco-2 cell monolayer model through suppressing the phosphorylation of IκBα and the accumulation of NF-κB p50 and ERK expression [42].…”

Section: Luteolinmentioning

confidence: 99%

Pharmacological Effects of Polyphenol Phytochemicals on the Intestinal Inflammation via Targeting TLR4/NF-κB Signaling Pathway

Wang

Yang

2022

IJMS

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TLR4/NF-κB is a key inflammatory signaling transduction pathway, closely involved in cell differentiation, proliferation, apoptosis, and pro-inflammatory response. Toll like receptor 4 (TLR4), the first mammalian TLR to be characterized, is the innate immune receptor that plays a key role in inflammatory signal transductions. Nuclear factor kappa B (NF-κB), the TLR4 downstream, is the key to accounting for the expression of multiple genes involved in inflammatory responses, such as pro-inflammatory cytokines. Inflammatory bowel disease (IBD) in humans is a chronic inflammatory disease with high incidence and prevalence worldwide. Targeting the TLR4/NF-κB signaling pathway might be an effective strategy to alleviate intestinal inflammation. Polyphenol phytochemicals have shown noticeable alleviative effects by acting on the TLR4/NF-κB signaling pathway in intestinal inflammation. This review summarizes the pharmacological effects of more than 20 kinds of polyphenols on intestinal inflammation via targeting the TLR4/NF-κB signaling pathway. We expected that polyphenol phytochemicals targeting the TLR4/NF-κB signaling pathway might be an effective approach to treat IBD in future clinical research applications.

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Flos lonicerae flavonoids attenuate experimental ulcerative colitis in rats via suppression of NF-κB signaling pathway

Cited by 36 publications

References 51 publications

Lonicerin targets EZH2 to alleviate ulcerative colitis by autophagy-mediated NLRP3 inflammasome inactivation

Lonicerin targets EZH2 to alleviate ulcerative colitis by autophagy-mediated NLRP3 inflammasome inactivation

Effects of Lonicera japonica Flower Bud Extract on Citrobacter rodentium-Induced Digestive Tract Infection

Pharmacological Effects of Polyphenol Phytochemicals on the Intestinal Inflammation via Targeting TLR4/NF-κB Signaling Pathway

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