Lactucin

Lactucin induces apoptosis through reactive oxygen species-mediated BCL-2 and CFLARL downregulation in Caki-1 cells.[Pubmed:34302634]

Genes Genomics. 2021 Oct;43(10):1199-1207.

BACKGROUND: Lactucin, a naturally occurring active sesquiterpene lactone, is abundantly found in chicory and romaine lettuce. A recent study reported that Lactucin could induce apoptosis in leukemia cells. However, its cytotoxicity and potential molecular mechanisms underlying cancer cell death remain unclear. OBJECTIVE: Therefore, in this study, we aimed to investigate the direct effect and underlying mechanism of action of Lactucin on renal cancer cells. METHODS: MTT assay and flow cytometry were performed to evaluate the rate of cell proliferation and apoptosis, respectively. Western blotting, reverse transcription polymerase chain reaction, and protein stability analyses were performed to analyze the effect of Lactucin on the expression of apoptosis-related proteins such as B-cell lymphoma 2 (BCL-2) and CFLAR (CASP8 and FADD like apoptosis regulator) long isoform (CFLARL) in Caki-1 human renal cancer cells. In addition, reactive oxygen species (ROS) generation was evaluated using flow cytometry. RESULTS: Lactucin treatment induced apoptosis in Caki-1 cells in a dose-dependent manner via activation of the caspase pathway. It downregulated BCL-2 and CFLARL expression levels by suppressing BCL-2 transcription and CFLARL protein stability, respectively. Pretreatment with N-acetyl-1-cysteine, a ROS scavenger, attenuated the Lactucin-induced apoptosis and restored the BCL-2 and CFLARL expression to basal levels. Lactucin-facilitated BCL-2 downregulation was regulated at the transcriptional level through the inactivation of the NF-kappaB pathway. CONCLUSIONS: Our study is the first to demonstrate that Lactucin-induced apoptosis is mediated by ROS production, which in turn activates the caspase-dependent apoptotic pathway by inhibiting BCL-2 and CFLARL expression in Caki-1 cells.

Comparative Metabolite Profile, Biological Activity and Overall Quality of Three Lettuce (Lactuca sativa L., Asteraceae) Cultivars in Response to Sulfur Nutrition.[Pubmed:34068285]

Pharmaceutics. 2021 May 13;13(5). pii: pharmaceutics13050713.

The main objective of the present study was to assess the effects of sulfur (S) nutrition on plant growth, overall quality, secondary metabolites, and antibacterial and radical scavenging activities of hydroponically grown lettuce cultivars. Three lettuce cultivars, namely, Pazmanea RZ (green butterhead, V1), Hawking RZ (green multi-leaf lettuce, V2), and Barlach RZ (red multi-leaf, V3) were subjected to two S-treatments in the form of magnesium sulfate (+S) or magnesium chloride (-S). Significant differences were observed under -S treatments, especially among V1 and V2 lettuce cultivars. These responses were reflected in the yield, levels of macro- and micro-nutrients, water-soluble sugars, and free inorganic anions. In comparison with the green cultivars (V1 and V2), the red-V3 cultivar revealed a greater acclimation to S starvation, as evidenced by relative higher plant growth. In contrast, the green cultivars showed higher capabilities in production and superior quality attributes under +S condition. As for secondary metabolites, sixteen compounds (e.g., sesquiterpene lactones, caffeoyl derivatives, caffeic acid hexose, 5-caffeoylquinic acid (5-OCQA), quercetin and luteolin glucoside derivatives) were annotated in all three cultivars with the aid of HPLC-DAD-MS-based untargeted metabolomics. Sesquiterpene lactone Lactucin and anthocyanin cyanidin 3-O-galactoside were only detected in V1 and V3 cultivars, respectively. Based on the analyses, the V3 cultivar was the most potent radical scavenger, while V1 and V2 cultivars exhibited antibacterial activity against Staphylococcus aureus in response to S provision. Our study emphasizes the critical role of S nutrition in plant growth, acclimation, and nutritional quality. The judicious-S application can be adopted as a promising antimicrobial prototype for medical applications.

Cichorium pumilum Jacq Extract Inhibits LPS-Induced Inflammation via MAPK Signaling Pathway and Protects Rats From Hepatic Fibrosis Caused by Abnormalities in the Gut-Liver Axis.[Pubmed:33995112]

Front Pharmacol. 2021 Apr 29;12:683613.

The development of liver fibrosis is closely related to the gut microbiota, and the "gut-liver axis" is the most important connection between the two. ethyl acetate extract of Cichorium pumilum Jacq (CGEA) is an herbal extract consisting mainly of sesquiterpenoids. The anti-inflammatory and hepatoprotective effects of CGEA have been reported, but the anti-fibrotic effects of CGEA via intestinal microbes and the "gut-liver axis" cycle have rarely been reported. In this study, we observed that CGEA not only directly attenuated inflammatory factor levels in inflamed mice, but also attenuated liver inflammation as well as liver fibrosis degeneration in rats with liver fibrosis caused by colitis. We observed in vitro that CGEA significantly promoted the growth of Bifidobacterium adolescentis. Similarly, fecal 16S rDNA sequencing of liver fibrosis rats showed that CGEA intervention significantly altered the composition of the intestinal microbiota of liver fibrosis rats. CGEA increased the abundance of intestinal microbiota, specifically, CGEA increased the ratio of Firmicutes to Bacteroidetes, CGEA could significantly increase the levels of Ruminococcus. In addition, CGEA intervention significantly protected intestinal mucosal tissues and improved intestinal barrier function in rats. Lactucin is the main sesquiterpenoid in CGEA, and HPLC results showed its content in CGEA was up to 6%. Lactucin has been reported to have significant anti-inflammatory activity, and in this study, we found that Lactucin decreased p38 kinases (p38), phosphorylation of the extracellular signal-regulated kinase (ERK) and protein kinase B (AKT) protein phosphorylation in lipopolysaccharide (LPS)-activated RAW264.7 cells, thereby reducing mRNA expression and protein expression of pro-inflammatory factors inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), and inhibiting the release of inflammatory factors interleukin (IL)-6 and nitric oxide (NO), exerting anti-inflammatory effects. In summary, the prevention of liver fibrosis caused by intestinal inflammation by CGEA may be achieved by regulating the intestinal microbiota and restoring the intestinal barrier thereby improving the "gut-liver axis" circulation, reducing liver inflammation, and ultimately alleviating liver fibrosis. Notably, the direct anti-inflammatory effect of CGEA may be due to its content of Lactucin, which can exert anti-inflammatory effects by inhibiting the phosphorylation of Mitogen-activated protein kinase (MAPK) and Akt signaling pathways.

Low Oral Bioavailability and Partial Gut Microbiotic and Phase II Metabolism of Brussels/Witloof Chicory Sesquiterpene Lactones in Healthy Humans.[Pubmed:33260567]

Nutrients. 2020 Nov 28;12(12). pii: nu12123675.

Free and glycosylated sesquiterpene lactones (SLs), which are abundant in leafy vegetables including Brussels/witloof chicory, possess health-promoting effects in vivo. However, the pharmacokinetics of dietary source of SLs remain largely unknown. In this open-label and single-dose trial, sixteen healthy volunteers consumed 150 g of Brussels/witloof chicory juice containing 48.77 mumol SLs in 5 min. Blood, urine, and fecal samples were collected before and after chicory consumption in 24 h. No SLs were detected in the serum, urine, and fecal samples before chicory consumption in all of the participants. Chicory consumption increased Lactucin, 11beta,13-dihydroLactucin, and their glucuronide/sulfate conjugates, rather than lactucopicrin and 11beta,13-dihydrolactucopicrin, as well as glycosylated SLs in biological samples. The peak concentration of total SLs in serum reached 284.46 nmol/L at 1 h, while, in urine, this peak was 220.3 nmol between 2 and 6 h. The recovery of total SLs in blood, urine, and feces was 7.03%, 1.13%, and 43.76% of the ingested dose, respectively. Human fecal suspensions with intestinal microbiota degraded glycosylated SLs in chicory, and converted lactucopicrin and 11beta,13-dihydrolactucopicrin to Lactucin and 11beta,13-dihydroLactucin, respectively. Collectively, Brussels/witloof chicory SLs are poorly bioavailable and they undergo partial gut microbial and phase II metabolism in humans.

Assessing the Intestinal Permeability and Anti-Inflammatory Potential of Sesquiterpene Lactones from Chicory.[Pubmed:33228214]

Nutrients. 2020 Nov 19;12(11). pii: nu12113547.

Cichorium intybus L. has recently gained major attention due to large quantities of health-promoting compounds in its roots, such as inulin and sesquiterpene lactones (SLs). Chicory is the main dietary source of SLs, which have underexplored bioactive potential. In this study, we assessed the capacity of SLs to permeate the intestinal barrier to become physiologically available, using in silico predictions and in vitro studies with the well-established cell model of the human intestinal mucosa (differentiated Caco-2 cells). The potential of SLs to modulate inflammatory responses through modulation of the nuclear factor of activated T-cells (NFAT) pathway was also evaluated, using a yeast reporter system. Lactucopicrin was revealed as the most permeable chicory SL in the intestinal barrier model, but it had low anti-inflammatory potential. The SL with the highest anti-inflammatory potential was 11beta,13-dihydroLactucin, which inhibited up to 54% of Calcineurin-responsive zinc finger (Crz1) activation, concomitantly with the impairment of the nuclear accumulation of Crz1, the yeast orthologue of human NFAT.

Human Gut Microbiota Metabolism of Dietary Sesquiterpene Lactones: Untargeted Metabolomics Study of Lactucopicrin and Lactucin Conversion In Vitro and In Vivo.[Pubmed:32970341]

Mol Nutr Food Res. 2020 Nov;64(21):e2000619.

SCOPE: 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. METHODS AND RESULTS: 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. CONCLUSION: 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.

Sedative Effects of Latexes Obtained from Some Lactuca L. Species Growing in Turkey.[Pubmed:32235622]

Molecules. 2020 Mar 30;25(7). pii: molecules25071587.

Lactuca L. species belong to the Asteraceae family and these plants are traditionally used for therapeutic purposes around the world. The dried milky latex of L. serriola is known as "lettuce oil" and is used as a sedative in Turkey. This study aimed to evaluate the sedative effects and analyze the chemical compositions of latexes obtained from some Lactuca species growing in Turkey. The sedative effects were evaluated through various behavioral tests on mice. For this purpose, latexes were obtained from L. glareosa Boiss., L. viminea (L.) J. Presl and C. P, L. mulgedioides (Vis and Pancic) Boiss. and Kotschy ex. Boiss., L. saligna L., and L. serriola L. The latex from L. saligna showed the highest sedative effects, whilst L. serriola and L. viminea latexes also displayed significant sedative effects compared to the control group at a dose of 100 mg/kg. However, the latexes from L. glareosa and L. mulqedioides did not exhibit any sedative effects on mice. Characteristic sesquiterpene lactones (Lactucin, lactucopicrin, 11,13beta-dihydroLactucin, and 11,13beta-dihydrolactucopicrin) were determined qualitatively and quantitatively by high-performance liquid chromatography (HPLC). Lactucin was identified as the main component.

A Potential Nutraceutical Candidate Lactucin Inhibits Adipogenesis through Downregulation of JAK2/STAT3 Signaling Pathway-Mediated Mitotic Clonal Expansion.[Pubmed:32023857]

Cells. 2020 Jan 31;9(2). pii: cells9020331.

The prevalence of obesity has increased dramatically worldwide in the past ~50 years. Searching for safe and effective anti-obesity strategies are urgently needed. Lactucin, a plant-derived natural small molecule, is known for anti-malaria and anti-hyperalgesia. The study is to investigate whether Lactucin plays a key role in adipogenesis. To this end, in vivo male C57BL/6 mice fed a high-fat diet (HFD) were treated with 20 mg/kg/day of Lactucin or vehicle by gavage for seven weeks. Compared with vehicle-treated controls, Lactucin-treated mice showed lower body mass and mass of adipose tissue. Consistently, in vitro 3T3-L1 cells were treated with 20 muM of Lactucin. Compared to controls, Lactucin-treated cells showed significantly less lipid accumulation during adipocyte differentiation and lower levels of lipid synthesis markers. Mechanistically, we showed the anti-adipogenic property of Lactucin was largely limited to the early stage of adipogenesis. Lactucin-treated cells fail to undergo mitotic clonal expansion (MCE). Further studies demonstrate that Lactucin-induced MCE arrests might result from reduced phosphorylation of JAK2 and STAT3. We then asked whether activation of JAK2/STAT3 would restore the inhibitory effect of Lactucin on adipogenesis with pharmacological STAT3 activator colivelin. Our results revealed similar levels of lipid accumulation between Lactucin-treated cells and controls in the presence of colivelin, indicating that inactivation of STAT3 is the limiting factor for the anti-adipogenesis of Lactucin in these cells. Together, our results provide the indication that Lactucin exerts an anti-adipogenesis effect, which may open new therapeutic options for obesity.

Sesquiterpene lactones from Sonchus palustris L. (Asteraceae, Cichorieae).[Pubmed:31731238]

Phytochemistry. 2020 Feb;170:112196.

Seven previously undescribed sesquiterpene lactones, three known sesquiterpene lactones (ixerin D, 15-p-hydroxyphenylacetylLactucin, and 15-p-hydroxyphenylacetylLactucin-8-sulfate), and two known quinic acid derivatives (3-O-feruloylquinic acid and 3,5-di-O-caffeoylquinic acid) were isolated from Sonchus palustris L. roots. Four formerly undescribed compounds were elucidated to be 3beta,14-dihydroxycostunolide-3-O-beta-D-glucopyranosyl-(2-O-p-hydroxyphenylacety l)-14-O-p-hydroxyphenylacetate, 15-p-methoxyphenylacetylLactucin, 15-p-methoxyphenylacetylLactucin-8-sulfate, and 8-p-hydroxyphenylacetylLactucin-15-sulfate. Additionally, three undescribed conjugates of Lactucin and a eudesmanolide type sesquiterpenic acid, sonchpalustrin, 4''-O-methylsonchpalustrin, and isosonchpalustrin, were characterized. The structures of the newly discovered natural products were elucidated using 1D and 2D NMR spectroscopy and UHPLC-HRMS. 15-p-HydroxyphenylacetylLactucin and 15-p-methoxyphenylacetylLactucin showed significant in vitro cytotoxicity against CEM and BJ cells with IC50 values ranging from 3.9 to 9.8muM. Compounds 3 and 4 showed also strong anti-inflammatory activity in vitro.

Silencing of germacrene A synthase genes reduces guaianolide oxalate content in Cichorium intybus L.[Pubmed:31668117]

GM Crops Food. 2020;11(1):54-66.

Chicory (Cichorium intybus L.) is a medicinal and industrial plant from the Asteraceae family that produces a variety of sesquiterpene lactones (STLs), most importantly bitter guaianolides: Lactucin, lactucopicrin and 8-deoxyLactucin as well as their modified forms such as oxalates. These compounds have medicinal properties; however, they also hamper the extraction of inulin - a very important food industry product from chicory roots. The first step in guaianolide biosynthesis is catalyzed by germacrene A synthase (GAS) which in chicory exists in two isoforms - GAS long (encoded by CiGASlo) and GAS short (encoded by CiGASsh). AmiRNA silencing was used to obtain plants with reduced GAS gene expression and level of downstream metabolites, guaianolide-15-oxalates, as the major STLs in chicory. This approach could be beneficial for engineering new chicory varieties with varying STL content, and especially varieties with reduced bitter compounds more suitable for inulin production.

Effectiveness of the Sleep Enhancement by Green Romaine Lettuce (Lactuca sativa) in a Rodent Model.[Pubmed:31582660]

Biol Pharm Bull. 2019;42(10):1726-1732.

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 microg/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 [(3)H]-flumazenil in a concentration-dependent manner, and affinity of both Lactucin and lactucopicrin to gamma-aminobutyric acid (GABA)A-benzodiazepine (BDZ) receptor was 80.7% and 55.9%, respectively. Finally, in the pentobarbital-induced sleep mouse model, the sleep enhancement effect of GRE was inhibited by flumazenil, an antagonist of BDZ. Thus, these results demonstrate that GRE acts via a GABAergic mechanism to promote sleep in a rodent model.

Identification and quantification of selected metabolites in differently pigmented leaves of lettuce (Lactuca sativa L.) cultivars harvested at mature and bolting stages.[Pubmed:31384804]

BMC Chem. 2019 Apr 19;13(1):56.

Background: Identification and screening of cultivars rich in bioactive phytoconstituents can be potentially useful to make nutrient-dense dishes and in medicinal formulations. In this study, we have identified, characterized and quantified caffeoylquinic acids, dicaffeoylquinic acid, dicaffeoyltartaric acid, kaempferol conjugates, quercetin malonylglucoside, sesquiterpene lactones, and cyanidin in 22 lettuce cultivars at mature and bolting stages using UPLC-PDA-Q-TOF-HDMS, UPLC, and HPLC. Results: The composition and contents of the studied metabolites and antioxidant activity varied significantly and depend on leaf color, cultivar type and stage of maturity. The main phenolic acid components of lettuce were quinic and tartaric acid derivatives, whereas kaempferol derivatives were the dominant flavonoids. The sum of the content of phenolic acids ranged from 18.3 to 54.6 mg/100 g DW and 15.5 to 54.6 mg/100 g DW, whereas the sum of the contents of flavonoids ranged from 9.2 to 25.9 mg/100 g DW and 14.9 to 83.0 mg/100 g DW in mature and bolting stage cultivars, respectively. The content of cyanidin, Lactucin, lactucopicrin, and ABTS radical antioxidant activity were in the range of 0.3 to 9.7 (mature stage) and 0.5 to 10.2 mg/g DW (bolting stage), 1.8 to 41.9 (mature stage) and 9.7 to 213.0 (bolting stage) microg/g DW, 9.9 to 344.8 (mature stage) and 169.2 to 3888.2 (bolting stage) microg/g DW, and 12.1 to 29.0 (mature stage) and 15.7 to 30.3 (bolting stage) mg TE/g DW, respectively. The principal component analysis (PCA) showed that the green and red pigmented lettuce cultivars were grouped to the negative and positive sides of PC1, respectively, while the green/red pigmented cultivars were distributed throughout the four quadrants of the PCA plots with no prominent grouping. The loading plot showed that phenolic acids, flavonoids, and cyanidin are the most potent contributors to the radical scavenging activity of lettuce extracts. Conclusions: Lettuce at the bolting stage accumulate relatively high amount of sesquiterpene lactones (SLs), quercetin malonylglucoside (QMG), methylkaempferol glucuronide (MKGR), kaempferol malonylglucoside (KMG), and 3-O-caffeoylquinic acid (3-CQA) compared to the mature stage. Higher amount of phytoconstituents were found to be accumulated in the red pigmented lettuce leaves compared to the green lettuce leaves. In addition, the contents of most of the metabolites in lettuce seem to increase with age of the leaves. The presence of the two bitter SLs, Lactucin and lactucopicrin, in significantly high amount in lettuce leaves at bolting stage could diminish consumer acceptance. However, alternatively, these leaves could be utilized by nutraceutical companies working to recover these compounds.

Sesquiterpenoids with diverse carbon skeletons from the roots of Cichorium glandulosum and their anti-inflammatory activities.[Pubmed:31085308]

Fitoterapia. 2019 Jul;136:104170.

A total of thirteen sesquiterpenoids with diverse skeletons including four new sesquiterpenoids, glandulosines A-D (1-4), a new natural product, glandulosine E (5), and eight known sesquiterpene lactones (6-13) were isolated from the roots of Cichorium glandulosum Boiss. et Huet (Asteraceae). Their structures were determined by extensive spectroscopic experiments including NMR, electronic circular dichroism (ECD), calculated ECD, Rh2(OCOCF3)4-induced ECD, and single-crystal X-ray diffraction analysis, as well as chemical methods. This is the first report of the crystal structure of 11beta,13-dihydroLactucin (11). Thirteen isolated sesquiterpenoids (1-13) were evaluated for their anti-inflammatory activities in vitro, and three guaiane sesquiterpene lactones, glandulosine E (5), scorzoside (9), and Lactucin (10) showed moderate inhibitory activity against LPS-induced nitric oxide (NO) production in RAW 264.7 macrophages.

Transcriptome driven characterization of curly- and smooth-leafed endives reveals molecular differences in the sesquiterpenoid pathway.[Pubmed:30603088]

Hortic Res. 2019 Jan 1;6:1.

Endives (Cichorium endivia L.) are popular vegetables, diversified into curly/frisee- and smooth/broad-leafed (escaroles) cultivar types (cultigroups), and consumed as fresh and bagged salads. They are rich in sesquiterpene lactones (STL) that exert proven function on bitter taste and human health. The assembly of a reference transcriptome of 77,022 unigenes and RNA-sequencing experiments were carried out to characterize the differences between endives and escaroles at the gene structural and expression levels. A set of 3177 SNPs distinguished smooth from curly cultivars, and an SNP-supported phylogenetic tree separated the cultigroups into two distinct clades, consistently with the botanical varieties of origin (crispum and latifolium, respectively). A pool of 699 genes maintained differential expression pattern (core-DEGs) in pairwise comparisons between curly vs smooth cultivars grown in the same environment. Accurate annotation allowed the identification of 26 genes in the sesquiterpenoid biosynthesis pathway, which included several g ermacrene A s ynthase, g ermacrene A o xidase and co stunolide s ynthase members (GAS/GAO/COS module), required for the synthesis of costunolide, a key precursor of lactucopicrin- and Lactucin-like sesquiterpene lactones. The core-DEGs contained a GAS gene (contig83192) that was positively correlated with STL levels and recurrently more expressed in curly than smooth endives, suggesting a cultigroup-specific behavior. The significant positive correlation of GAS/GAO/COS transcription and STL abundance (2.4-fold higher in frisee endives) suggested that sesquiterpenoid pathway control occurs at the transcriptional level. Based on correlation analyses, five transcription factors (MYB, MYB-related and WRKY) were inferred to act on contig83192/GAS and specific STL, suggesting the occurrence of two distinct routes in STL biosynthesis.

Preparation of Magnetic Nanoliposomes of Sesquiterpene-Rich Fraction from Cichorium glandulosum and Its Tissue Distribution in Mice.[Pubmed:30420898]

Evid Based Complement Alternat Med. 2018 Oct 18;2018:8549519.

Objective: To prepare and study the distribution of magnetic nanoliposomes of Sesquiterpene-Rich Fraction from Cichorium glandulosum (SRF-MLN) (under magnetic field) in the main organs of mice. Methods: The SRF-MLN was prepared by ethanol injection-sonication precipitation method. The quality of its pharmaceutical properties was investigated by the active ingredient Lactucin. The drug concentration and distribution of Lactucin in different tissues and organs including whole blood, liver, heart, spleen, lung, and kidney were evaluated with Sesquiterpene-Rich Fraction from Cichorium glandulosum (SRF-LP) as a control. Results: The prepared SRF-MLN was spherical and monodispersed with an average particle diameter of 65 +/- 1 nm, encapsulation efficiency of 91.3% +/- 1.5% (RSD% = 1.5), and drug loading rate of 4.7% +/- 0.3% (RSD% = 0.7). Dispersion coefficient PDI was 0.157 and Zeta potential was -17.5 mV. The Lactucin concentration of SRF-MLN after 10 min of intravenous injection in heart, liver, spleen, lung, and kidney was significantly higher than that of SRF-LP group. The AUC0-12h values of liver tissue were obviously higher than other tissues and MRT was significantly prolonged under the action of the magnetic field (p<0.01). Conclusion: The prepared SRF-MLN can change the distribution of drugs in different tissues and organs, prolonging the action time of the drugs in the body, and it has certain specificity under the action of applied magnetic field.