Sesquiterpene Lactones: Promising Natural Compounds to Fight Inflammation

Matos, Melanie S.; Anastácio, José D; Santos, Cláudia N.

doi:10.3390/pharmaceutics13070991

Cited by 58 publications

(49 citation statements)

References 102 publications

(182 reference statements)

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“…Bioactive dietary components play a large role in regulating gut health and resistance to enteric pathogen infections. Our recent work with chicory has identified that SL have a clear anthelmintic activity, and it is known that SL (especially those derived from chicory) are anti-inflammatory and antibacterial compounds [32, 33]. Thus, we examined the effects on parasitic infection and gut microbiota in mice.…”

Section: Discussionmentioning

confidence: 99%

Dietary non-starch polysaccharides impair immunity to enteric nematode infection

Valente

Jensen

Myhill

et al. 2022

Preprint

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The influence of diet on immune function and resistance to enteric infection and disease is becoming ever more established. Highly processed, refined diets can lead to inflammation and gut microbiome dysbiosis, whilst health-promoting dietary components such as phytonutrients and fermentable fibres are thought to promote a healthy microbiome and balanced mucosal immunity. Chicory (Cichorium intybus) is a leafy green vegetable rich in fibres and bioactive compounds that may promote gut health. Unexpectedly, we here show that incorporation of chicory into semisynthetic AIN93G diets renders mice susceptible to infection with enteric helminths. Mice fed a high level of chicory leaves (10% dry matter) had a more diverse gut microbiota, but a diminished type-2 immune response to infection with the intestinal roundworm Heligmosomoides polygyrus. Furthermore, the chicory-supplemented diet significantly increased burdens of the caecum-dwelling whipworm Trichuris muris, concomitant with a highly skewed type-1 immune environment in caecal tissue. The chicory-supplemented diet was rich in non-starch polysaccharides, particularly uronic acids (the monomeric constituents of pectin). In accordance, mice fed pectin-supplemented AIN93G diets had higher T. muris burdens and reduced IgE production and expression of genes involved in type-2 immunity. Importantly, treatment of pectin-fed mice with exogenous IL-25 restored type-2 responses and was sufficient to allow T. muris expulsion. Collectively, our data suggest that increasing levels of fermentable, non-starch polysaccharides in refined diets compromises immunity to helminth infection in mice. This diet-infection interaction may inform new strategies for manipulating the gut environment to promote resistance to enteric parasites.

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Section: Discussionmentioning

confidence: 99%

Dietary non-starch polysaccharides impair immunity to enteric nematode infection

Valente

Jensen

Myhill

et al. 2022

Preprint

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“…Anti-in ammatory effect of 8deoxylactucin is mediated by two mechanisms: 1) inhibition of NF-kB activity and 2) cyclooxygenase (COX-2) inhibition [26]. In an in vitro study, it has been shown that SLs extracted from chicory root, in a dose-dependent manner downregulated the genes expression of COX-2, inducible nitric oxide synthase (iNOS), TNF-α and IL-1β in LPS-stimulated macrophages [27]. It was observed that lactucin and lactucopicrin, found in CI, exerted an analgesic effect in the tail-ick and hot plate tests in mice and their antinociceptive activity was similar to ibuprofen [17,28].…”

Section: Discussionmentioning

confidence: 99%

Protective Effect of Cichorium Intybus Root Extract and Esculetin on Lipopolysaccharide-Induced Pain and Inflammation in Male Mice: A Potential Role for Tumor Necrosis Factor-α and Interleukin-1β

Taleghani

Rasouli

Rostampour

et al. 2022

Preprint

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Lipopolysaccharide (LPS) has been widely used in animal modeling of inflammation-induced hyperalgesia. Proinflammatory cytokines (TNF-α, IL-1β) are involved in the pathogenesis of pain. Cichorium intybus (CI) contains many compounds which inhibit inflammatory mediators. The present study was designed to evaluate the effect of CI root hydro-alcoholic extract (CE) and Esculetin (ESC) - a bioactive coumarin compound of CI- on LPS-induced pain and inflammation in male mice. CE constituents were evaluated by GC-MS. Two different concentration of CE (300 and 500 mg/kg/p.o.) and ESC (40 mg/kg/i.p.,o.) were used for experiments. Drugs were administered once daily for 7 days. On day 7, LPS (0.83 mg/kg/i.p.) was injected 30 min after the last drug administration. Blood samples were collected 90 min after LPS injection. Hot plate and formalin tests were performed 24 hours after LPS injection. Serum TNF-α and IL-1β levels were measured using ELISA. LPS significantly increased the response time of animals in hot plate and both phases of formalin tests. CE (300 and 500 mg/kg/p.o.) significantly reduced the response time in comparison with the LPS group in hot plate and both phases of formalin tests. CE (500 mg/kg/p.o.) reduced serum TNF-α and IL-1β levels. Esculetin increased the response time in hot plate and the second phase of formalin test compared to the LPS group and also decreased IL-1β level, significantly. Our results demonstrated that CE exhibited anti-nociceptive and anti-inflammatory effects better than esculetin. The probable mechanism of anti-hyperalgesic effect of CE is related to inhibition of inflammatory cytokines IL-1β and TNF-α.

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“…The α-methylene-γ-lactone moiety of these molecules is a reactive entity, capable of Michael-type addition with biological nucleophiles, in particular with the sulfhydryl groups of proteins [4] (Figure 8). BRT has been shown to bind covalently to a cysteine residue (Cys-151) of Keap1 [85], and helenalin shows a high reactivity toward specific thiolcontaining proteins, such as the p65 subunit of NFκB [10,11].…”

Section: Thiol Reactivitymentioning

confidence: 99%

“…They usually display prominent antioxidant and anti-inflammatory properties. Many natural products in this large family have been considered for the treatment of human diseases, including inflammatory diseases, metabolic syndrome, parasitic diseases and cancers [2][3][4].…”

Section: Introductionmentioning

confidence: 99%

Anticancer Targets and Signaling Pathways Activated by Britannin and Related Pseudoguaianolide Sesquiterpene Lactones

Bailly

2021

Biomedicines

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Sesquiterpene lactones (SLs) are abundant in plants and display a large spectrum of bioactivities. The compound britannin (BRT), found in different Inula species, is a pseudoguaianolide-type SL equipped with a typical and highly reactive α-methylene-γ-lactone moiety. The bioproperties of BRT and related pseudoguaianolide SLs, including helenalin, gaillardin, bigelovin and others, have been reviewed. Marked anticancer activities of BRT have been evidenced in vitro and in vivo with different tumor models. Three main mechanisms are implicated: (i) interference with the NFκB/ROS pathway, a mechanism common to many other SL monomers and dimers; (ii) blockade of the Keap1-Nrf2 pathway, with a covalent binding to a cysteine residue of Keap1 via the reactive α-methylene unit of BRT; (iii) a modulation of the c-Myc/HIF-1α signaling axis leading to a downregulation of the PD-1/PD-L1 immune checkpoint and activation of cytotoxic T lymphocytes. The non-specific reactivity of the α-methylene-γ-lactone moiety with the sulfhydryl groups of proteins is discussed. Options to reduce or abolish this reactivity have been proposed. Emphasis is placed on the capacity of BRT to modulate the tumor microenvironment and the immune-modulatory action of the natural product. The present review recapitulates the anticancer effects of BRT, some central concerns with SLs and discusses the implication of the PD1/PD-L1 checkpoint in its antitumor action.

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Sesquiterpene Lactones: Promising Natural Compounds to Fight Inflammation

Cited by 58 publications

References 102 publications

Dietary non-starch polysaccharides impair immunity to enteric nematode infection

Dietary non-starch polysaccharides impair immunity to enteric nematode infection

Protective Effect of Cichorium Intybus Root Extract and Esculetin on Lipopolysaccharide-Induced Pain and Inflammation in Male Mice: A Potential Role for Tumor Necrosis Factor-α and Interleukin-1β

Anticancer Targets and Signaling Pathways Activated by Britannin and Related Pseudoguaianolide Sesquiterpene Lactones

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