Chlorogenic acid ameliorates experimental colitis in mice by suppressing signaling pathways involved in inflammatory response and apoptosis

Vukelić, Iva; Detel, Dijana; Pučar, Lara Batičić; Potočnjak, Iva; Buljević, Sunčica; Domitrović, Robert

doi:10.1016/j.fct.2018.08.061

Cited by 72 publications

(48 citation statements)

References 43 publications

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“…The activation of MAPKs (p38, ERK and JNK) plays a critical role in the activation of NF-κβ-p65 pathway, which mediates intracellular signal transduction involving the expression of the proinflammatory cytokines IL-1β, IL-6, and TNF-α. Chlorogenic acid (chA), a phenolic compound found in the IA extract, demonstrated its activity in the inhibition of MAPK pathways, such as c-Jun N-terminal kinases 1 (JNK1) and signaling regulated kinases 1 (ERK1), and in the inhibition of the expression of the phosphorylated proteins p-JNK1 and p-ERK1 [43]. Similarly, STAT3-mediated activation of acquired immune responses plays a pathogenic role in colitis by enhancing T cells survival.…”

Section: Discussionmentioning

confidence: 99%

Intestinal Anti-Inflammatory Activity of the Aqueous Extract from Ipomoea asarifolia in DNBS-Induced Colitis in Rats

Silva

Araujo

Araújo

et al. 2018

IJMS

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Inflammatory bowel disease is triggered by an uncontrolled immune response associated with genetic, environmental, and intestinal microbiota imbalance. Ipomoea asarifolia (IA), popularly known as “salsa” or “brave salsa”, belongs to the Convolvulaceae family. The aim of this approach was to study the preventive effect of IA aqueous extract in 2,4-dinitrobenzene sulfonic acid (DNBS)-induced colitis in rats. Rats pretreated with IA extract or sulfasalazine (SSZ) received intracolonic instillation of DNBS in 50% ethanol (v/v). IA extract presented a protective effect against intestinal inflammation, with improvement in the disease activity index and macroscopic damage. IA or SSZ significantly reduced myeloperoxidase activity, and also down-regulation of the gene expression of JNK1, NF-κβ-p65, STAT3, and decreased levels of TNFα, IL-1β, and increased IL-10, associated with a significant improvement of oxidative stress, in addition to a reduction in MDA and an increase of glutathione in colonic tissue. The protective effect of the extract was also confirmed in histological evaluation, showing preservation of the colonic cytoarchitecture. Immunohistochemical analysis revealed down-regulation of NF-κβ-p65, iNOS, IL-17, and up-regulation of SOCs-1 and MUC-2. IA extract presents antioxidant and anti-inflammatory intestinal properties, and proved to be a potential application for preventing damage induced by DNBS.

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Section: Discussionmentioning

confidence: 99%

Intestinal Anti-Inflammatory Activity of the Aqueous Extract from Ipomoea asarifolia in DNBS-Induced Colitis in Rats

Silva

Araujo

Araújo

et al. 2018

IJMS

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“…An in vivo study reported CGA might be useful to treat inflammation and ameliorate colitis severity by inhibiting TNF-α expression and apoptotic signalling pathways. 32 However, whether a decrease in TNF-α induced by CGA is protective against cell apoptosis during heart failure is unclear. Therefore, we investigated the effect of CGA on cardiovascular disease in a mouse model of TAC induced heart failure.…”

Section: Tnf-α-induced Myocyte Apoptosis Involves Complicatedmentioning

confidence: 99%

“…However, despite the multifunctionality of CGA, little is known about its effect on heart failure. An in vivo study reported CGA might be useful to treat inflammation and ameliorate colitis severity by inhibiting TNF‐α expression and apoptotic signalling pathways . However, whether a decrease in TNF‐α induced by CGA is protective against cell apoptosis during heart failure is unclear.…”

Section: Introductionmentioning

confidence: 99%

Chlorogenic acid: A potent molecule that protects cardiomyocytes from TNF‐α–induced injury via inhibiting NF‐κB and JNK signals

Tian

Wang

et al. 2019

J Cellular Molecular Medi

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The traditional Chinese herb Lonicerae Japonicae Flos has shown significant clinical benefits in the treatment of heart failure, but the mechanism remains unclear. As the main active ingredient found in the plasma after oral administration of Lonicerae Japonicae Flos , chlorogenic acid (CGA) has been reported to possess anti‐inflammatory, anti‐oxidant and anti‐apoptosis function. We firstly confirmed the cardioprotective effects of CGA in transverse aortic constriction (TAC)‐induced heart failure mouse model, through mitigating the TNF‐α–induced toxicity. We further used TNF‐α‐induced cardiac injury in human induced pluripotent stem cell‐derived cardiomyocytes (hiPSC‐CMs) to elucidate the underlying mechanisms. CGA pre‐treatment could reverse TNF‐α–induced cellular injuries, including improved cell viability, increased mitochondrial membrane potential and inhibited cardiomyocytes apoptosis. We then examined the NF‐κB/p65 and major mitogen‐activated protein kinases (MAPKs) signalling pathways involved in TNF‐α–induced apoptosis of hiPSC‐CMs. Importantly, CGA can directly inhibit NF‐κB signal by suppressing the phosphorylation of NF‐κB/p65. As for the MAPKs, CGA suppressed the activity of only c‐Jun N‐terminal kinase (JNK), but enhanced extracellular signal‐regulated kinase1/2 (ERK1/2) and had no effect on p38. In summary, our study revealed that CGA has profound cardioprotective effects through inhibiting the activation of NF‐κB and JNK pathway, providing a novel therapeutic alternative for prevention and treatment of heart failure.

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“…Nitric oxide synthase [ 47 – 49 ], interleukin-6 [ 50 ], and tumor necrosis factor [ 51 ] also revealed the same effect as prostaglandin in the regulation of IBD. Additionally, the apoptosis-related targets, such as bax, bcl-2, caspase-3 and caspase-9, also have crucial role in the pathogenesis of IBD [ 52 ]. By analyzing the top 20 KEGG pathways of the 54 putative targets, we found that positive regulation of the nitric oxide biosynthetic process was the most correlated pathway.…”

Section: Discussionmentioning

confidence: 99%

Herbal pair Huangqin-Baishao: mechanisms underlying inflammatory bowel disease by combined system pharmacology and cell experiment approach

Huang

Chen

et al. 2020

BMC Complement Med Ther

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Background Inflammatory bowel disease (IBD) is a severe digestive system condition, characterized by chronic and relapsing inflammation of the gastrointestinal tract. Scutellaria baicalensis Georgi (Huangqin, HQ) and Paeonia lactiflora Pall (Baishao, BS) from a typical herbal synergic pair in traditional Chinese medicine (TCM) for IBD treatments. However, the mechanisms of action for the synergy are still unclear. Therefore, this paper aimed to predict the anti-IBD targets and the main active ingredients of the HQ-BS herbal pair. Methods A systems pharmacology approach was used to identify the bioactive compounds and to delineate the molecular targets and potential pathways of HQ-BS herbal pair. Then, the characteristics of the candidates were analyzed according to their oral bioavailability and drug-likeness indices. Finally, gene enrichment analysis with DAVID Bioinformatics Resources was performed to identify the potential pathways associated with the candidate targets. Results The results showed that, a total of 38 active compounds were obtained from HQ-BS herbal pair, and 54 targets associated with IBD were identified. Gene Ontology and pathway enrichment analysis yielded the top 20 significant results with 54 targets. Furthermore, the integrated IBD pathway revealed that the HQ-BS herbal pair probably acted in patients with IBD through multiple mechanisms of regulation of the nitric oxide biosynthetic process and anti-inflammatory effects. In addition, cell experiments were carried out to verify that the HQ-BS herbal pair and their Q-markers could attenuate the levels of nitric oxide (NO), prostaglandin E2 (PGE2), inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in lipopolysaccharide (LPS)-stimulated THP-1-derived macrophage inflammation. In particular, the crude materials exerted a much better anti-inflammatory effect than their Q-markers, which might be due to their synergistic effect. Conclusion This study provides novel insight into the molecular pathways involved in the mechanisms of the HQ-BS herbal pair acting on IBD.

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Chlorogenic acid ameliorates experimental colitis in mice by suppressing signaling pathways involved in inflammatory response and apoptosis

Cited by 72 publications

References 43 publications

Intestinal Anti-Inflammatory Activity of the Aqueous Extract from Ipomoea asarifolia in DNBS-Induced Colitis in Rats

Intestinal Anti-Inflammatory Activity of the Aqueous Extract from Ipomoea asarifolia in DNBS-Induced Colitis in Rats

Chlorogenic acid: A potent molecule that protects cardiomyocytes from TNF‐α–induced injury via inhibiting NF‐κB and JNK signals

Herbal pair Huangqin-Baishao: mechanisms underlying inflammatory bowel disease by combined system pharmacology and cell experiment approach

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