lactucin and intybin

Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases, and there are no effective drugs available so far. Lactucin and Lactucopicrin belong to sesquiterpene lactones and are extracted from Cichorium glandulosum Boiss. et Huet (CG) possesses multiple biopharmacological activities. However, the therapeutic effects of both Lactucin and Lactucopicrin on many diseases and their underlying mechanisms remain largely unknown. Here, we analyzed the both natural compounds hypolipidemic effects on FFA-induced HepG2 cells and their potential mechanisms based on transcriptomics and experimental tests. Our results indicated that Lactucin (10 μM) and Lactucopicrin (20 μM) remarkably reduced TG accumulation. Transcriptomics analysis identified 1960, 1645, and 1791 differentially expressed genes (DEGs) and obtained 611 and 635 specific genes in different comparisons, respectively. The enrichment analysis and experimental validations (RT-qPCR and Western Blot) showed that their hypolipidemic activities were most probably exerted via regulating numerous key DEGs involved in lipid metabolism. Taken together, both Lactucin and Lactucopicrin may represent potent hepatoprotective agents. Both of them exhibited therapeutic effects against liver diseases such as NAFLD by regulating multi-gene and proteins like HADHA, ADAM17, SQSTM1, and GBA and modulating multi-pathways like fatty acid oxidation metabolic signaling.

Topics: Hep G2 Cells; Humans; Lactones; Lipid Metabolism; Non-alcoholic Fatty Liver Disease; Phorbols; Sesquiterpenes

Gut microbiota converts dietary phytochemicals into metabolites and modulates their health effects. The microbial metabolism of dietary terpenoids, as the sesquiterpene lactones of leafy vegetables, is unknown.. In vitro fermentation of lactucopicrin, lactucin, and romaine lettuce with gut microbiota from independent donors, show their extensive metabolism through untargeted metabolomics of the fecal incubations. Dehydroxylations and double bond hydrogenations are the main catabolic reactions. Isomers of dihydrolactucopicrin, tetrahydrolactucopicrin, and deoxylactucin, are observed after lactucopicrin metabolism. Tetrahydrolactucin and hexahydrolactucin are also found after lactucin metabolism. Lettuce fermentation shows similar metabolic conversions. Phase II conjugates of most of these metabolites are detected in the urine of healthy volunteers after escarole salad intake. Glucuronides, and sulfates, of dihydrolactucopicrin, tetrahydrolactucopicrin, dihydrolactucin, and deoxylactucin, are detected in the urine although with large inter-subject variability.. This is the first report on the gut microbiota metabolism of sesquiterpene lactones in humans, and one of the first reports to describe that dietary terpenoids of widely consumed leafy vegetables are extensively catabolized by human gut microbiota. A large inter-subject variation in the metabolism of sesquiterpene lactones also reflects differences in gut microbiota composition. It suggests that inter-individual differences in their health effects should be expected.

Topics: Adult; Asteraceae; Feces; Female; Fermentation; Gastrointestinal Microbiome; Humans; Lactones; Lactuca; Male; Metabolomics; Phorbols; Sesquiterpenes; Vegetables

This study was conducted to investigate the effects of the extracts of green romaine lettuce (GRE) on sleep enhancement. GRE contains 1071.7 and 199.2 µg/g of extracts of lactucin and lactucopicrin, respectively, known as sleep enhancement substances. When 100 mg/kg of GRE was administered orally, sleep latency and duration time were significantly increased compared to controls (p < 0.05). Rapid eye movement (REM) sleep decreased with 100 mg/kg of GRE administration and non-REM (NREM) sleep also increased. There was no significant difference between REM and NREM among the oral GRE administration groups receiving 100, 120, and 160 mg/kg GRE. In the caffeine-induced insomnia model, total sleep time was significantly increased by 100 mg/kg GRE administration compared to the caffeine-treated group (p < 0.05). In addition, GRE inhibited the binding of [

Topics: Animals; Lactones; Lactuca; Male; Mice, Inbred ICR; Phorbols; Plant Extracts; Plant Leaves; Rats, Sprague-Dawley; Receptors, GABA-A; Sesquiterpenes; Sleep

Lactucin (1) and its derivatives lactucopicrin (2) and 11beta,13-dihydrolactucin (3), which are characteristic bitter sesquiterpene lactones of Lactuca virosa and Cichorium intybus, were evaluated for analgesic and sedative properties in mice. The compounds showed analgesic effects at doses of 15 and 30 mg/kg in the hot plate test similar to that of ibuprofen, used as a standard drug, at a dose of 30 mg/kg. The analgesic activities of the compounds at a dose of 30 mg/kg in the tail-flick test were comparable to that of ibuprofen given at a dose of 60 mg/kg. Lactucopicrin appeared to be the most potent analgetic of the three tested compounds. Lactucin and lactucopicrin, but not 11beta,13-dihydrolactucin, also showed sedative properties in the spontaneous locomotor activity test.

Topics: Analgesics; Animals; Cichorium intybus; Furans; Hypnotics and Sedatives; Lactones; Male; Mice; Molecular Structure; Motor Activity; Pain; Phorbols; Plant Leaves; Plant Roots; Sesquiterpenes; Sesquiterpenes, Guaiane; Structure-Activity Relationship

Topics: Furans; Lactones; Phorbols; Plants; Sesquiterpenes