Anti-Inflammatory and Immunoregulatory Action of Sesquiterpene Lactones

Paço, Ana; Brás, Teresa; Santos, Jacqueline Oliveira dos; Sampaio, Paula; Gomes, Andreia C.; Duarte, Maria F.

doi:10.3390/molecules27031142

Cited by 61 publications

(34 citation statements)

References 148 publications

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“…Little is known about the effects of sesquiterpene lactones on tumor cells, specifically on PDAC and the immunomodulation response, despite allergic reactions of STLs due to activation of immune system has been described [ 131 ]. It seems to have a stimulating role over cytotoxic immune cells, favoring the elimination of tumor cells.…”

Section: Discussionmentioning

confidence: 99%

Sesquiterpene Lactones as Promising Candidates for Cancer Therapy: Focus on Pancreatic Cancer

et al. 2022

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Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive disease which confers to patients a poor prognosis at short term. PDAC is the fourth leading cause of death among cancers in the Western world. The rate of new cases of pancreatic cancer (incidence) is 10 per 100,000 but present a 5-year survival of less than 10%, highlighting the poor prognosis of this pathology. Furthermore, 90% of advanced PDAC tumor present KRAS mutations impacting in several oncogenic signaling pathways, many of them associated with cell proliferation and tumor progression. Different combinations of chemotherapeutic agents have been tested over the years without an improvement of significance in its treatment. PDAC remains as one the more challenging biomedical topics thus far. The lack of a proper early diagnosis, the notable mortality statistics and the poor outcome with the available therapies urge the entire scientific community to find novel approaches against PDAC with real improvements in patients’ survival and life quality. Natural compounds have played an important role in the process of discovery and development of new drugs. Among them, terpenoids, such as sesquiterpene lactones, stand out due to their biological activities and pharmacological potential as antitumor agents. In this review, we will describe the sesquiterpene lactones with in vitro and in vivo activity against pancreatic tumor cells. We will also discuss the mechanism of action of the compounds as well as the signaling pathways associated with their activity.

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Section: Discussionmentioning

confidence: 99%

Sesquiterpene Lactones as Promising Candidates for Cancer Therapy: Focus on Pancreatic Cancer

et al. 2022

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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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“…The chemical structures of SLs allow for different target interactions, mainly due to the α-methylene-γ-lactone moiety, making SLs able to modulate different cellular responses. At the molecular level, SLs impact different signal pathways, being the NF-kB, MAPK, and JAT-STAT the most well-described ones [ 37 ]. The impact of C. cardunculus leaf extracts on the circadian clock had not been addressed in previous studies.…”

Section: Discussionmentioning

confidence: 99%

Antiproliferative Effects of Cynara Cardunculus in Colorectal Cancer Cells Are Modulated by the Circadian Clock

Fuhr

Basti²,

Brás³

et al. 2022

IJMS

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The circadian clock generates 24 h rhythms in behavioural, cellular and molecular processes. Malfunctions of the clock are associated with enhanced susceptibility to cancer, worse treatment response and poor prognosis. Clock-controlled genes are involved in cellular processes associated with tumour development and progression including metabolism of drugs and the cell cycle. Cynara cardunculus, a plant of the Asteraceae family, has been reported to have antiproliferative effects on breast cancer cells. Here, we used the human colorectal cancer (CRC) cell line HCT116 and its knockout variants for different core-clock genes (BMAL1, PER2, NR1D1), to investigate the treatment effect of C. cardunculus lipophilic leaf extract under different clock scenarios. Our results show a direct effect of C. cardunculus on the circadian phenotype of the cells, as indicated by alterations in the phase, amplitude, and period length of core-clock gene oscillations. Furthermore, our data indicate a role for the circadian clock in sensitivity to C. cardunculus treatment. In particular, the treatment inhibited proliferation and induced cytotoxicity and apoptosis in a clock knockout-specific manner, in CRC cells. These results point to a potential effect of C. cardunculus lipophilic leaf extracts as a modulator of the circadian clock, in addition to its anti-proliferative properties.

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Anti-Inflammatory and Immunoregulatory Action of Sesquiterpene Lactones

Cited by 61 publications

References 148 publications

Sesquiterpene Lactones as Promising Candidates for Cancer Therapy: Focus on Pancreatic Cancer

Sesquiterpene Lactones as Promising Candidates for Cancer Therapy: Focus on Pancreatic Cancer

Dietary non-starch polysaccharides impair immunity to enteric nematode infection

Antiproliferative Effects of Cynara Cardunculus in Colorectal Cancer Cells Are Modulated by the Circadian Clock

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