Sesquiterpene Lactones Research Articles

A network pharmacology approach to investigate dehydrocostus lactone inhibits the proliferation and epithelial-mesenchymal transition of human gastric cancer cells via regulating the PI3K/Akt and extracellular signal-regulated kinases/mitogen-activated protein kinase signalling pathways.

Dehydrocostus lactone (DHE), a sesquiterpene lactone, has been proven the significant inhibition of multiple cancer cells. However, there are limited reports on the activity of DHE in gastric cancer (GC). In this research, Network pharmacology predicted the anti-GC mechanism of DHE, and the prediction was verified by in-vitro experiments. Network pharmacology confirmed the major effect signalling pathway of DHE in treating GC. Cell viability assay, colony formation assay, wound healing assay, cell migration and invasion assay, apoptosis assay, western blot and real-time quantitative polymerase chain reaction verified the mechanism of DHE in GC cell lines. The results showed that DHE inhibited the growth and metastasis of MGC803 and AGS GC cells. Mechanistically, the analysis results indicated that DHE significantly induced the apoptosis process by suppressing the PI3K/protein kinase B (Akt) signalling pathway, and inhibited epithelial-mesenchymal transition by suppressing the extracellular signal-regulated kinases (ERK)/MAPK signalling pathway. The Akt activator (SC79) inhibited DHE induced apoptosis, and DHE had similar effects with the ERK inhibitor (FR180204). All results suggested that DHE was a potential natural chemotherapeutic drug in GC treatment.

Hypolipidemic Activity of Sesquiterpene Lactones and their Derivatives

BACKGROUND: Despite the available range of lipid-lowering drugs, mainly of synthetic origin, the problem of atherosclerosis therapy and its manifestations remain unresolved. Bioinformatics methods, in particular molecular docking, are considered as a promising direction in terms of developing effective original lipid-lowering drugs. Today, as a promising source of natural lipid-lowering agents, it is advisable to consider natural terpenoids, namely sesquiterpene lactones, which are distinguished by a wide range of pharmacological activity. This article presents the results of a virtual and biological screening of the lipid-lowering activity of sesquiterpene γ-lactones and their chemically modified derivatives. AIM: The aim is to evaluate the lipid-lowering properties of samples of sesquiterpene γ-lactones and their derivatives by virtual and biological screening methods. METHODS: Molecular modeling of the binding energy of the “ligand-target” complex (docking). Molecular docking of the lipid-lowering activity of sesquiterpene γ-lactones and their derivatives was performed using the Glide program from the developer of the Schrodinger Small-Molecule Drug Discovery package using the Extra Precision algorithm (https://www.schrodinger.com/glide). The effect of sesquiterpene lactones on the expression of genes for key enzymes of lipid metabolism in the liver was studied in an in vivo model of hyperlipidemia caused by an atherogenic diet. CONCLUSION: Virtual screening of the lipid-lowering activity of sesquiterpene γ-lactones and their derivatives by molecular docking revealed a number of promising compounds (matricin, matricarin, grossmisin oxime, austricin oxime, 5β (H)-austricin) receptor interactions on the enzyme system cholesterol 7α-hydroxylase (CYP7A1). New mechanisms of lipid-lowering activity for sesquiterpene γ-lactones were proposed, which were established in the study of gene expression of key enzymes of lipid metabolism in the liver in a model of hyperlipidemia caused by an atherogenic diet in rats under in vivo conditions.

Tehranolid and Artemisinin Effects on Ameliorating Experimental Autoimmune Encephalomyelitis by Modulating Inflammation and Remyelination.

Multiple sclerosis (MS) is an autoimmune demyelinating disease of the central nervous system. Artemisinin (ART) is a natural sesquiterpene lactone with an endoperoxide bond that is well-known for its anti-inflammatory effects in experimental autoimmune encephalomyelitis (EAE), the most commonly used animal model of MS. Tehranolide (TEH) is a novel compound with structural similarity to ART. In this study, we aimed to investigate the ameliorating effect of TEH on EAE development by targeting proteins and genes involved in this process and compare its effects with ART. Female C57BL/6 mice were immunized with MOG35-55. Twelve days post-immunization, mice were treated with 0.28mg/kg/day TEH and 2.8mg/kg/day ART for 18 consecutive days, and the clinical score was measured daily. The levels of pro-inflammatory and anti-inflammatory cytokines were assessed in mice serum and splenocytes by ELISA. We also evaluated the mRNA expression level of cytokines, as well as genes involved in T cell differentiation and myelination in the spinal cord tissue by qRT-PCR. Administration of TEH and ART significantly alleviated EAE signs. A significant reduction in IL-6 and IL-17 secretion and IL-17 and IL-1 gene expression in spinal cord were observed in the TEH-treated group. ART had similar or less significant effects. Moreover, TGF-β, IL-4, and IL-10 genes were stimulated by ART and TEH in the spinal cord, while the treatments did not affect IFN-γ expression. Both treatments dramatically increased the expression of FOXP3, GATA3, MBP, and AXL. Additionally, the T-bet gene was reduced after TEH administration. The compounds made no changes in RORγt, nestin, Gas6, Tyro3, and Mertk mRNA expression levels in the spinal cord. The study revealed that both TEH and ART can effectively modulate the genes responsible for inflammation and myelination that play a crucial role in EAE. Interestingly, TEH demonstrated a greater potency compared to ART and hence may have the potential to be evaluated in interventions for the management of MS.

A Novel Approaches to Feverfew (<i>Tanacetum Prthenium</i>): A Review

Tanacetum Parthenium is a herbal medicinal plant which is known as feverfew. Asterace is the family of feverfew. It is traditionally applicable in the treatment of stomach aches, fever, arthritis, infertility, migraine, insect bites, menstruation problems, and labour pain during childbirth. Dioscorides was the first Greek physician to which uses feverfew extract for treatment of inflammation. Particularly among Greek and early European herbalists, feverfew plant has ancient historyfor traditionally used as common medicine. This plant is also known as "featherfew" due to its feathery leaves. The leaves have been used in medicinal preparation in past two decades for treatment of arthritis and migraine by both the British and Canadian government. The herbal plant of feverfew cultivated in large area of world that show medicinal importance. Plant grow substantially and show important strongly report in support of therapeutic uses. This aromatic plant look like yellow green leave and give bitter odour and give therapeutic active chemical constituents include pinenes flavonoid and glycoside. It shows various pharmacological properties, like antispasmodic, cardiotonic, anti-inflammatory, anti-cancer, and as an enema for worms. The colour of feverfew plant is yellow and bloom in October to July, which is also used in asthma, dizziness, nausea and vomiting. Parthenolide may experience an acid-induced cyclisation in the presence of excessive moisture, resulting in a sesquiterpene lactone of the guaianolide class, which is frequently present in feverfew. If the composition satisfies pharmacopoeial microbiological quality standards, microbial degradations are unlikely to have a significant impact.

Chemical Compositions of Eupatorium heterophyllum Leaf Samples from Yunnan and Sichuan Provinces of China-Isolation of 13 New Sesquiterpene Lactones.

Eight samples of Eupatorium heterophyllum leaves were collected at different locations in Yunnan and Sichuan provinces in China, and their chemical constituents were investigated. Thirteen previously undescribed sesquiterpene lactones-seven germacranolides, three eudesmanolides, two guaianolides, and a 2-norelemanolide-were isolated, and their structures were elucidated based on extensive spectroscopic analyses. The major constituents in the six samples from northwestern Yunnan and Sichuan are hiyodorilactones A and B, whereas that in the two samples from the region near Kunming, Yunnan is eupatoriopicrin. These results and previously reported results suggest the presence of locality-dependent intra-specific diversity in the chemical constituents of E. heterophyllum leaves.

One new 12, 8-guaianolide sesquiterpene lactone with antihyperglycemic activity from the roots of Cichorium intybus

Three 12, 8-guaianolide sesquiterpene lactones, including a new compound intybusin F (1), and a new natural product cichoriolide I (2), along with six known 12, 6-guaianolide compounds (4–9) were isolated from the roots of Cichorium intybus L. Their structures were determined by extensive spectroscopic analysis. The absolute configurations of new compounds were elucidated based on analysis of the experimental and calculated electronic circular dichroism spectra. Compounds 1, 2, 4, 7, 8 showed significant effects on facilitating the glucose uptake in oleic acid plus high glucose-stimulated HepG2 cells at 50 μM. In addition, compounds 1, 2, 3, 6, 7 exhibited obvious inhibitory effects against NO production, of them, compounds 1, 2, 7 can significantly decrease the secretion of inflammatory cytokines (TNF-α, IL-6 and COX-2) levels in this hyperglycemic HepG2 cell model.

P75 Are ‘hypoallergenic’ personal care products truly safe?

Abstract It is estimated that one-fifth of the general population may have allergic contact dermatitis (ACD) to common environmental allergens. Skincare companies are increasingly advertising their products as ‘hypoallergenic’, targeting consumers who seek personal care products (PCPs) that are less likely to cause an allergic reaction. However, there are no Food and Drug Administration standards to regulate the use of the term hypoallergenic, allowing manufacturers to use the term freely. We evaluated PCPs marketed as hypoallergenic from two health and beauty retailers in the UK for the presence of allergens in the British Society of Cutaneous Allergy (BSCA) baseline series. Product and ingredient lists were obtained from www.boots.com and www.superdrug.com in November 2022 using the term hypoallergenic in the search box. PCPs without the term hypoallergenic in the product description, unrelated products (plasters, jewellery, sanitary towels, tampons, clothing, facial brushes) and duplicates (same products in different sizes) were excluded. In total, 208 PCPs met the inclusion criteria: 47 (22.6%) were rinse-off and 161 (77.4%) were leave-on products. At least one substance from the BSCA baseline series was an ingredient in 79 (38.0%) PCPs. Of these, 54 (26.0%) had 1 potential allergen, 21 (10.2%) had 2, and 4 (1.9%) had 3 potential allergens from the series. The frequently encountered allergens were cetearyl alcohol and paraben mix, found in 42 (20.4%) and 37 (18.0%) of products, respectively. Other BSCA baseline series allergens identified in PCPs included 2-bromo-2-nitropropane-1,3-diol, lanolin, decyl glucoside, diazolidinyl urea, methylisothiazolinone, limonene and linalool. In addition, PCPs had chemicals that were related to and may cross-react with allergens in the BSCA baseline series. Parfum/fragrance, which can cross-react with fragrance mix I and II, was found in 85 (41.3%) PCPs. Sodium benzoate and/or benzoic acid, often used as preservatives in PCPs, were found in 66 (32.0%) products. Forty (19.4%) PCPs had ingredients that belong to the Asteraceae family and therefore may trigger an ACD in those with positive reaction to Compositae and/or sesquiterpene lactone mix. Twenty-three (11.2%) PCPs contained cetyl alcohol and/or stearyl alcohol, the two major components of cetearyl alcohol. Overall, 153 (74.3%) of 206 PCPs marketed as hypoallergenic contained BSCA baseline series allergens or ingredients that may cross-react with them. This highlights the need to increase public awareness and education about the potential dangers of purchasing ‘hypoallergenic’ PCPs.

CD10 (P75) Are ‘hypoallergenic’ personal care products truly safe?

Abstract It is estimated that one-fifth of the general population may have allergic contact dermatitis (ACD) to common environmental allergens. Skincare companies are increasingly advertising their products as ‘hypoallergenic’, targeting consumers who seek personal care products (PCPs) that are less likely to cause an allergic reaction. However, there are no Food and Drug Administration standards to regulate the use of the term hypoallergenic, allowing manufacturers to use the term freely. We evaluated PCPs marketed as hypoallergenic from two health and beauty retailers in the UK for the presence of allergens in the British Society of Cutaneous Allergy (BSCA) baseline series. Product and ingredient lists were obtained from www.boots.com and www.superdrug.com in November 2022 using the term hypoallergenic in the search box. PCPs without the term hypoallergenic in the product description, unrelated products (plasters, jewellery, sanitary towels, tampons, clothing and facial brushes) and duplicates (same products in different sizes) were excluded. In total, 208 PCPs met the inclusion criteria: 47 (22.6%) were rinse-off and 161 (77.4%) were leave-on products. At least one substance from the BSCA baseline series was an ingredient in 79 (38.0%) PCPs. Of these, 54 (26.0%) had one potential allergen, 21 (10.2%) had two, and four (1.9%) had three potential allergens from the series. The frequently encountered allergens were cetearyl alcohol and paraben mix, found in 42 (20.4%) and 37 (18.0%) of products, respectively. Other BSCA baseline series allergens identified in PCPs included 2-bromo-2-nitropropane-1,3-diol, lanolin, decyl glucoside, diazolidinyl urea, methylisothiazolinone, limonene and linalool. In addition, PCPs had chemicals that were related to and may cross-react with allergens in the BSCA baseline series. Parfum/fragrance, which can crossreact with fragrance mix I and II, was found in 85 (41.3%) PCPs. Sodium benzoate and/or benzoic acid, often used as preservatives in PCPs, were found in 66 (32.0%) products. Forty (19.4%) PCPs had ingredients that belong to the Asteraceae family and therefore may trigger an ACD in those with positive reaction to Compositae and/or sesquiterpene lactone mix. Twenty-three (11.2%) PCPs contained cetyl alcohol and/or stearyl alcohol, the two major components of cetearyl alcohol. Overall, 153 (74.3%) of 206 PCPs marketed as hypoallergenic contained BSCA baseline series allergens or ingredients that may cross-react with them. This highlights the need to increase public awareness and education about the potential dangers of purchasing ‘hypoallergenic’ PCPs.

Identification and characterization of CYP71 subclade cytochrome P450 enzymes involved in the biosynthesis of bitterness compounds in Cichorium intybus.

Industrial chicory (Cichorium intybus var. sativum) and witloof (C. intybus var. foliosum) are crops with an important economic value, mainly cultivated for inulin production and as a leafy vegetable, respectively. Both crops are rich in nutritionally relevant specialized metabolites with beneficial effects for human health. However, their bitter taste, caused by the sesquiterpene lactones (SLs) produced in leaves and taproot, limits wider applications in the food industry. Changing the bitterness would thus create new opportunities with a great economic impact. Known genes encoding enzymes involved in the SL biosynthetic pathway are GERMACRENE A SYNTHASE (GAS), GERMACRENE A OXIDASE (GAO), COSTUNOLIDE SYNTHASE (COS) and KAUNIOLIDE SYNTHASE (KLS). In this study, we integrated genome and transcriptome mining to further unravel SL biosynthesis. We found that C. intybus SL biosynthesis is controlled by the phytohormone methyl jasmonate (MeJA). Gene family annotation and MeJA inducibility enabled the pinpointing of candidate genes related with the SL biosynthetic pathway. We specifically focused on members of subclade CYP71 of the cytochrome P450 family. We verified the biochemical activity of 14C. intybus CYP71 enzymes transiently produced in Nicotiana benthamiana and identified several functional paralogs for each of the GAO, COS and KLS genes, pointing to redundancy in and robustness of the SL biosynthetic pathway. Gene functionality was further analyzed using CRISPR/Cas9 genome editing in C. intybus. Metabolite profiling of mutant C. intybus lines demonstrated a successful reduction in SL metabolite production. Together, this study increases our insights into the C. intybus SL biosynthetic pathway and paves the way for the engineering of C. intybus bitterness.

Cynaropicrin disrupts tubulin and c-Myc-related signaling and induces parthanatos-type cell death in multiple myeloma

The majority of blood malignancies is incurable and has unforeseeable remitting-relapsing paths in response to different treatments. Cynaropicrin, a natural sesquiterpene lactone from the edible parts of the artichoke plant, has gained increased attention as a chemotherapeutic agent. In this study, we investigated the effects of cynaropicrin against multiple myeloma (MM) cells in vitro and assessed its in vivo effectiveness in a xenograft tumor zebrafish model. We showed that cynaropicrin exerted potent cytotoxicity against a panel of nine MM cell lines and two leukemia cell lines with AMO1 being the most sensitive cell line (IC50 = 1.8 ± 0.3 µM). Cynaropicrin (0.8, 1.9, 3.6 µM) dose-dependently reduced c-Myc expression and transcriptional activity in AMO1 cells that was associated with significant downregulation of STAT3, AKT, and ERK1/2. Cell cycle analysis showed that cynaropicrin treatment arrested AMO1 cells in the G2M phase along with an increase in the sub-G0G1 phase after 24 h. With prolonged treatment times, cells accumulated more in the sub-G0G1 phase, implying cell death. Using confocal microscopy, we revealed that cynaropicrin disrupted the microtubule network in U2OS cells stably expressing α-tubulin-GFP. Furthermore, we revealed that cynaropicrin promoted DNA damage in AMO1 cells leading to PAR polymer production by PARP1 hyperactivation, resulting in AIF translocation from the mitochondria to the nucleus and subsequently to a novel form of cell death, parthanatos. Finally, we demonstrated that cynaropicrin (5, 10 µM) significantly reduced tumor growth in a T-cell acute lymphoblastic leukemia (T-ALL) xenograft zebrafish model. Taken together, these results demonstrate that cynaropicrin causes potent inhibition of hematopoietic tumor cells in vitro and in vivo.

Anti-Oxidant, Anti-Mutagenic Activity and Safety Evaluation of Antrocin

Antrocin is a novel compound isolated from Antrodia cinnamomea, and is classified as a sesquiterpene lactone. The therapeutic efficacy of antrocin has been studied, and it has shown an antiproliferative effect on various cancers. The aim of this study was to evaluate the anti-oxidant activity, potential genotoxicity, and oral toxicity of antrocin. Ames tests with five different strains of Salmonella typhimurium, chromosomal aberration tests in CHO-K1 cells, and micronucleus tests in ICR mice were conducted. The results of anti-oxidant capacity assays showed that antrocin has great anti-oxidant activity and is a moderately strong antimutagenic agent. In the results of the genotoxicity assays, antrocin did not show any mutagenic potential. In the 28-day oral toxicity test, Sprague Dawley rats were gavaged with 7.5 or 37.5 mg/kg of antrocin for 28 consecutive days. In addition, 7.5 mg/kg sorafenib, an anti-cancer drug, was used as a positive control for toxicity comparison. At the end of the study, antrocin did not produce any toxic effects according to hematology, serum chemistry, urine analysis, or histopathological examinations. According to the results of the genotoxicity and 28-day oral toxicity study, antrocin, at a dose of 37.5 mg/kg, did not cause adverse effects and can be a reference dose for therapeutic agents in humans.

Phytochemical prospecting and biological activities of the floral extract from [Impatiens walleriana (Hook.)] (Balsaminaceae)

Impatiens walleriana is a plant species that presents diversity and variety of colors among flowers. This plant species has wide distribution and is easily cultivable throughout the world including natural gardens, greenhouses and parks. This study aims at evaluating the floral extracts of I. walleriana in terms of their qualitative phytochemical constitution and antifungal activities on Sclerotinia sclerotiorum, Colletotrichum gloeosporioides and Colletotrichum acutatum, as well as on the reduction of DPPH free radical and on the inhibition of acetylcholinesterase (AChE). Flowers were collected from two cultivars Pink and White of I. walleriana and the extract produced by maceration. The phytochemical qualitative assay was carried out using different reagents for determination by precipitation or colorimetric alteration. The antifungal test was carried out in Petri dishes with different concentrations of floral extract on S. sclerotiorum, C. gloeosporioides and C. acutatum. The DPPH reduction assay was performed by percentage and as standard antioxidant ascorbic acid. The acetylcholinesterase inhibition test was performed in percentage using Electrophorus electricus. Positive results were observed for phenolics, anthocyanins, organic acids, alkaloids, catechins, tannins, carboxylic acids, hemolytic saponins and sesquiterpene lactones. Fungal inhibition effect was better observed for cv. Pink with 10-26%, 6% and between 9-11% on S. sclerotiorum, C. gloeosporioides and C. acutatum, respectively. The DPPH reduction activity showed satisfactory results for cv. Pink 49% followed by cv. White 41%. And for inhibition of AChE cv. Pink with 30% and cv. White with 27%. The floral extracts of Impatiens walleriana show good results for the biological activities tested, especially for cv. Pink.

Study on the metabolism of natural sesquiterpene lactones in human liver microsomes using LC-Q-TOF-MS/MS

Sesquiterpene lactones are naturally occurring, highly active ­specialised metabolites, which are biosynthesized by important medicinal plants, fulfilling many functions. The in vitro metabolism of parthenolide (1), grosheimin (2), carbetolide C (3), 8α-O-(3,4-dihydroxy-­methylenebutanoyloxy)-dehydromelitensin (4) and arteludovicinolide A (5) was examined using human liver microsomes. Phase I, phase II (glucuronidation), as well as combined phase I + II metabolism were studied. Metabolites were identified via liquid chromatography-high resolution quadrupole time-of-flight mass spectrometry. Monohydroxylated, hydrated, carboxylated, methylated derivatives, together with corresponding monoglucuronides were detected, suggesting that the metabolism of sesquiterpene lactones is changeable due to structural features and scaffold diversity, though the lactone ring is the main site of metabolism.

Sesquiterpene lactones from Artemisia verlotorum and their anti-inflammatory activities

Seven new sesquiterpenoids (1–7) and 19 known analogues were isolated from the whole plant of Artemisia verlotorum. Their structures were determined by extensive analysis of 1D and 2D NMR and HRESIMS data, electronic circular dichroism (ECD) spectra, density functional theory (DFT) NMR calculations, and time dependent density functional theory (TDDFT) ECD calculations. The absolute configurations of 1, 3, 5 and 7 were confirmed by single crystal X-ray diffraction experiments. Compounds 1 and 2 possess a rarely reported 5/8-bicyclic skeleton, while both compounds 3 and 4 were uncommon iphionane-type sesquiterpenoids. Eudesmane sesquiterpenoids (5–17) reported in this study are all 7,8-cis-lactones, of which, compound 7 represents the first eudesmane sesquiterpene with an oxygen bridge connecting C-5 and C-11. All the compounds were tested in vitro for their anti-inflammatory activities in LPS-stimulated RAW 264.7 murine macrophages. Compound 18 showed a potent inhibitory effect on NO production, with IC50 values of 3.08 ± 0.61 μM.

Ergolide mediates anti-cancer effects on metastatic uveal melanoma cells and modulates their cellular and extracellular vesicle proteomes

Background: Uveal melanoma is a poor prognosis cancer. Ergolide, a sesquiterpene lactone isolated from Inula Brittanica, exerts anti-cancer properties. The objective of this study was to 1) evaluate whether ergolide reduced metastatic uveal melanoma (MUM) cell survival/viability in vitro and in vivo; and 2) to understand the molecular mechanism of ergolide action. Methods: Ergolide bioactivity was screened via long-term proliferation assay in UM/MUM cells and in zebrafish MUM xenograft models. Mass spectrometry profiled proteins modulated by ergolide within whole cell or extracellular vesicle (EVs) lysates of the OMM2.5 MUM cell line. Protein expression was analyzed by immunoblots and correlation analyses to UM patient survival used The Cancer Genome Atlas (TCGA) data. Results: Ergolide treatment resulted in significant, dose-dependent reductions (48.5 to 99.9%; p<0.0001) in OMM2.5 cell survival in vitro and of normalized primary zebrafish xenograft fluorescence (56%; p<0.0001) in vivo, compared to vehicle controls. Proteome-profiling of ergolide-treated OMM2.5 cells, identified 5023 proteins, with 52 and 55 proteins significantly altered at 4 and 24 hours, respectively (p<0.05; fold-change >1.2). Immunoblotting of heme oxygenase 1 (HMOX1) and growth/differentiation factor 15 (GDF15) corroborated the proteomic data. Additional proteomics of EVs isolated from OMM2.5 cells treated with ergolide, detected 2931 proteins. There was a large overlap with EV proteins annotated within the Vesiclepedia compendium. Within the differentially expressed proteins, the proteasomal pathway was primarily altered. Interestingly, BRCA2 and CDKN1A Interacting Protein (BCCIP) and Chitinase Domain Containing 1 (CHID1), were the only proteins significantly differentially expressed by ergolide in both the OMM2.5 cellular and EV isolates and they displayed inverse differential expression in the cells versus the EVs. Conclusions: Ergolide is a novel, promising anti-proliferative agent for UM/MUM. Proteomic profiling of OMM2.5 cellular/EV lysates identified candidate pathways elucidating the action of ergolide and putative biomarkers of UM, that require further examination.

Atractylodes macrocephala Koidz's rhizomes contain anti-inflammatory sesquiterpenes.

Two new compounds, named eudesm-4(15),7-diene-3α,9β,11-triol (1) and eudesm-4(15),7-diene-1β,3α,9β,11-tetraol (2) together with three known sesquiterpene lactones (1S,5R,7R,10R)-secoatractylolactone (3), (1S,5R,7R,10R)-secoatractylolactone-11-O-β-D-glucopyranoside (4) atractylenolide III (5) were isolated from the rhizomes of Atractylodes macrocephala. Their structures were elucidated by using 1D and 2D-NMR spectra and HRESIMS data. Compound 5 exhibited the most active anti-inflammatory activity with IC50 values of 27.5 μM in inhibiting of nitric oxide production. Compounds 1, 2, and 3 showed moderate effects while compound 4 was inactive.

Occupational Contact Dermatitis Caused by Artichokes.

Introduction: Few cases of skin diseases caused by exposure to artichokes have been published. Artichokes contain sesquiterpene lactones, which are known to be sensitizing. Irritant contact dermatitis (ICD) has also been diagnosed. To our knowledge, no protein contact dermatitis (PCD) has yet been reported to be induced by artichoke. Objectives: The aim of this study was to identify the different types of contact dermatitis that may be due to occupational exposure to artichokes and the professions concerned. Materials and Methods: We conducted a descriptive study, retrieving data from the French national database of occupational diseases for the period of 2001 to 2018. Results: Fifty-six cases were retrieved, and 10 cases were included in this study after data analysis and reading the clinical reports: 7 allergic contact dermatitis (ACD), 2 PCD, and 1 ICD caused by artichokes. Patients were farmers (4), agri-food workers (3), market gardener (1), cashier (1), and store employee (1). Conclusions: This is the first series of occupational contact dermatitis that can be induced by artichokes. Exposure to artichokes can lead to ICD, ACD, PCD, and perhaps contact urticaria. The sesquiterpene lactone mix patch test is not always sufficient to confirm an ACD by artichokes. Irritant contact dermatitis can be associated with ACD from artichokes or evolve on its own.

Chemical Composition of Plants of the Genus Zaluzania

The chemical structure of compounds identified in species of the genus Zaluzania is reported herein, highlighting the contributions by Professor Pedro Joseph-Nathan to the chemistry of these plants. Although 36 names have been proposed for Zaluzania, only 14 species are currently accepted in the genus, and they are reported to be a rich source of sesquiterpene lactones and flavonoids. Their essential oils also contain several terpenoids, especially ent-kaurene-type diterpenes. In addition, we identified the guaianolides zaluzanin A and zaluzanin B, zaluzanin C, and zaluzanin D, and the eudesmanolides ivalin and ivalin acetate as the major constituents in infusions of aerial parts of Zaluzania augusta, Zaluzania parthenioides, and Zaluzania triloba, respectively. These sesquiterpene lactones were characterized by their physical and spectroscopic data, including 1H and 13C nuclear magnetic resonance (NMR). Likewise, the structures of zaluzanins C and ivalin were confirmed by X-ray diffraction analysis. The presence of guaianolides in Z. parthenioides and eudesmanolides in Z. triloba could be used as a biomarker to differentiate these 2 species, which were previously considered synonymous.

Parthenolide targets NLRP3 to treat inflammasome-related diseases

Natural products have attracted extensive attention from researchers in medical fields due to their abundant biological activities. Parthenolide (PTL) is a sesquiterpene lactone originally purified from herb Feverfew (Tanacetum parthenium), recent studies have showed its potential activities of anti-cancer and anti-inflammatory. Acting as the most studied inflammasome, NLRP3 inflammasome played an important role in human diseases including type-2 diabetes (T2D), Alzheimer's disease (AD) and cryopyrin-associated periodic syndromes (CAPS). In this article, we show that PTL specially inhibits the activation of NLRP3 inflammation by block the upstream signal and prevent the assembly of NLRP3 inflammasome complex. Furthermore, we showed the treatment of PTL significantly attenuates the symptoms of lipopolysaccharide (LPS)-induced systemic inflammation and dextran sulfate sodium (DSS)-induced colitis in mice models. Thus, our results demonstrate that PTL alleviates inflammation by targeting NLRP3 inflammasome, which indicate that PTL acting as a promising natural product for the treatment of NLRP3 inflammasome-related diseases.

Brevilin A shows an anti-tumor role in prostate cancer via the lncRNA H19/miR-194/E2F3 signaling pathway.

Brevilin A, a natural sesquiterpene lactone extracted from Centipeda minima, has been found with antitumor properties. Our study probed the functions of Brevilin A in prostate cancer cells and the mechanisms among Brevilin A, lncRNA H19, miR-194, and E2F3 on the biological behaviors of the cells. CCK8, Transwell, and TUNEL staining assays examined the impact of Brevilin A on prostate cancer cell proliferation, migration, invasion, and apoptosis, respectively. qRT-PCR and western blot determined lncRNA H19, miR-194, and E2F3 profiles. The influence of Brevilin A on the profiles of lncRNA H19, miR-194, and E2F3 was measured. A xenograft model of prostate cancer nude mice was taken to confirm the impact of Brevilin A and lncRNA H19 on cancer cell growth. Consequently, Brevilin A dampened prostate cancer cell proliferation, migration, and invasion, suppressed the expressions of lncRNA H19 and E2F3, and enhanced miR-194 level. LncRNA H19 and E2F3 were uplifted, whereas miR-194 was abated in prostate cancer cells and tissues. LncRNA H19 targeted miR-194 to positively modulate E2F3 expression, boosted DU145 cell proliferation, invasion, and migration, and curbed apoptosis. In the xenograft model, Brevilin A repressed tumor growth, whereas lncRNA H19 fostered tumor growth. Brevilin A suppressed the promotive effect of lncRNA H19 in PC cell growth in vivo. To conclude, Brevilin A modulates the biological behaviors of prostate cancer cells via the lncRNA H19/miR-194/E2F3 axis. Brevilin A exerts an anti-tumor function in prostate cancer.