Artemisia argyi extract alleviates inflammation in a DSS-induced colitis mouse model and enhances immunomodulatory effects in lymphoid tissues.

BACKGROUND: The incidence of inflammatory bowel disease (IBD), an inflammatory disorder of the gastrointestinal system has increased. IBD, characterized by aberrant immune responses against antigens, is thought to be caused by the invasion of enterobacteria. The pathogenesis of IBD is complicated, hence novel effective therapeutic agents are warranted. Therefore, this study evaluates the potential of Artemisia argyi, a medicinal herb, in alleviating IBD. METHODS: The effectiveness of the A. argyi ethanol extract was verified both in vitro and in vivo. Inflammation was induced in RAW 264.7 cells by 1 µg/mL of lipopolysaccharide (LPS) and by 3% dextran sodium sulfate (DSS) in a DSS-induced colitis mouse model. During the ten-day colitis induction, 200 mg/kg of A. argyi ethanol extract was orally administered to the treatment group. Levels of inflammation-related proteins and genes were analyzed in the colon, serum, and lymphoid tissues, i.e., Peyer's patches (PPs) and spleen. The chemical constituent of the A. argyi ethanol extract was identified using an ultra-high performance liquid chromatography mass spectrometry (UPLC-MS/MS) analysis. RESULTS: A. argyi ethanol extract treatment ameliorated IBD symptoms and reduced the expression of inflammation-related proteins and genes in the colon and serum samples. Furthermore, A. argyi treatment induced the activation of anti-oxidative associated proteins, such as nuclear factor-erythroid factor 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1); and the treatment have also inhibited nuclear factor-κB (NF-κB), a central mediator of inflammatory responses. A. argyi enhanced the immunomodulatory effects in the PPs and spleen, which may stem from interleukin-10 (IL-10) upregulation. Chemical analysis identified a total of 28 chemical compounds, several of which have been reported to exert anti-inflammatory effects. CONCLUSIONS: The effectiveness of the A. argyi ethanol extract in alleviating IBD was demonstrated; application of the extract successfully mitigated IBD symptoms, and enhanced immunomodulatory responses in lymphoid tissues. These findings suggest A. argyi as a promising herbal medicine for IBD treatment.

Susceptibility of Campylobacter Strains to Selected Natural Products and Frontline Antibiotics.

Campylobacter species have developed resistance to existing antibiotics. The development of alternative therapies is, therefore, a necessity. This study evaluates the susceptibility of Campylobacter strains to selected natural products (NPs) and frontline antibiotics. Two C. jejuni strains (ATCC® 33560TM and MT947450) and two C. coli strains (ATCC® 33559TM and MT947451) were used. The antimicrobial potential of the NPs, including plant extracts, essential oils, and pure phytochemicals, was evaluated by broth microdilution. The growth was measured by spectrophotometry and iodonitrotetrazolium chloride. Antibiotic resistance genes (tet(O) and gyrA) were characterized at the molecular level. The minimum inhibitory concentrations (MICs) and the minimum bactericidal concentrations (MBCs) ranged from 25 to 1600 µg/mL. Cinnamon oil, (E)-Cinnamaldehyde, clove oil, eugenol, and baicalein had the lowest MIC and MBC values (25-100 µg/mL). MT947450 and MT947451 were sensitive to erythromycin and gentamicin but resistant to quinolones and tetracycline. Mutations in gyrA and tet(O) genes from resistant strains were confirmed by sequencing. The findings show that NPs are effective against drug-sensitive and drug-resistant Campylobacter strains. The resistance to antibiotics was confirmed at phenotypic and genotypic levels. This merits further studies to decipher the action mechanisms and synergistic activities of NPs.

Improvement in host metabolic homeostasis and alteration in gut microbiota in mice on the high-fat diet: A comparison of calcium supplements.

Despite the previously reported health benefits of calcium intake for the attenuation of metabolic disease, few studies have investigated the relationships among calcium intake, gut microbiota, and host metabolism. In this study, we assessed the effects of calcium supplementation on host microbial community composition and metabolic homeostasis. Mice were fed a high-fat diet with different calcium concentrations (4 and 12 g/kg) of 2 calcium supplements, calcium carbonate and calcium citrate. Supplementation with the higher concentration of calcium citrate significantly prevented body weight gain and decreased plasma biomarkers for metabolic disorder compared to calcium carbonate supplementation. Both calcium supplementation led to changes in microbial composition, increased propionate production and increased anorexigenic GLP-1 gene expression. The calcium citrate groups also experienced less metabolic endotoxemia. Our findings suggested that calcium supplementation could ameliorate host metabolic disorder caused by a high-fat diet, due to gut microbiota changes as well as decreased intestinal inflammation.

Daurinol, a catalytic inhibitor of topoisomerase IIα, suppresses SNU-840 ovarian cancer cell proliferation through cell cycle arrest in S phase.

Daurinol, a lignan from the ethnopharmacological plant Haplophyllum dauricum, was recently reported to be a novel topoisomerase II inhibitor and an alternative to the clinical anticancer agent etoposide based on a colorectal cancer model. In the present study, we elucidated the detailed biochemical mechanism underlying the inhibition of human topoisomerase IIα by daurinol based on a molecular docking study and in vitro biochemical experiments. The computational simulation predicted that daurinol binds to the ATP-binding pocket of topoisomerase IIα. In a biochemical assay, daurinol (10-100 µM) inhibited the catalytic activity of topo-isomerase IIα in an ATP concentration-dependent manner and suppressed the ATP hydrolysis activity of the enzyme. However, daurinol did not inhibit topoisomerase I activity, most likely because topoisomerase I does not contain an ATP-binding domain. We also evaluated the anti-proliferative activity of daurinol in ovarian, small cell lung and testicular cancer cells, common target cancers treated with etoposide. Daurinol potently inhibited SNU-840 human ovarian cancer cell proliferation through cell cycle arrest in S phase, while etoposide induced G2/M phase arrest. Daurinol induced the increased expression of cyclin E, cyclin A and E2F-1, which are important proteins regulating S phase initiation and progression. Daurinol did not induce abnormal cell and nuclear enlargement in SNU-840 cells, in contrast to etoposide. Based on these data, we suggest that daurinol is a potential anticancer drug candidate for the treatment of human ovarian cancer with few side effects.

Inhibition of gastrointestinal lipolysis by green tea, coffee, and gomchui (Ligularia fischeri) tea polyphenols during simulated digestion.

Green tea, coffee, and gomchui (Ligularia fischeri) tea, which are rich in polyphenols, may exhibit antiobesity effects by inhibiting pancreatic lipase. However, the bioavailability of some polyphenols is poor due to either degradation or absorption difficulties in the gastrointestinal tract, thus making their beneficial effects doubtful. This study was conducted to evaluate the inhibitory effect of three beverages on lipolysis and the contribution of their major polyphenols during simulated digestion. During simulated digestion, gomchui tea was the most potent at inhibiting gastrointestinal lipolysis, whereas green tea was the least potent. The strongest lipase inhibitor among purified major polyphenols was a green tea polyphenol, (-)-epigallocatechin gallate (EGCG, IC(50) = 1.8 ± 0.57 µM), followed by di-O-caffeoylquinic acid isomers (DCQA, IC(50) from 12.7 ± 4.5 to 40.4 ± 2.3 µM), which are gomchui tea polyphenols. However, the stability of DCQA was greater than that of EGCG when subjected to simulated digestion. Taken together, gomchui tea, which has DCQA as the major polyphenol, showed stronger lipolysis inhibitory activity during simulated digestion compared to both green tea and coffee.

Isolation and identification of antioxidant compounds from Ligularia fischeri.

The plant Ligularia fischeri var. spiciformis Nakai, a well-known edible medicinal herb in Korea, has been used to treat maladies such as jaundice, scarlet fever, rheumatoid arthritis, and hepatic function failure. In this research, 4 major antioxidant compounds were detected from this plant's leaves using an on-line high-performance liquid chromatography (HPLC)-ABTS screening system, which can determine the antioxidant activity based on a decrease in absorbance at 734 nm after postcolumn reaction of HPLC-separated antioxidants with the 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) radicals (ABTS(*)). In order to isolate these active compounds, a preparative HPLC was applied and their chemical structures were identified as 5-O-caffeoylquinic acid (5-CQA), 3,4-di-O-caffeoylquinic acid (3,4-DCQA), 3,5-di-O-caffeoylquinic acid (3,5-DCQA), and 4,5-di-O-caffeoylquinic acid (4,5-DCQA) by ESI/MS(n) and (1)H NMR. These 4 isomers comprised over 10% of the dried leaves, with 3,5-DCQA being the most abundant compound. The radical scavenging activity of each isomer was also evaluated simultaneously through the on-line HPLC-ABTS method, which showed 94% antioxidant activity of the ethanol extract derived from caffeoylquinic acids. Among these isomers, 3,4-DCQA contained the most strong antioxidant activity while 3,5-DCQA accounted for the highest radical scavenging capacity due to having the highest content.

Rapid identification of furanocoumarins in Angelica dahurica using the online LC-MMR-MS and their nitric oxide inhibitory activity in RAW 264.7 cells.

INTRODUCTION: Angelica dahurica (Fisch. Ex hoffm.) Benth. Et Hook. is a perennial herb that grows throughout Korea whose dried roots have been used to treat various diseases in Korean traditional medicine. The root extract contains diverse constituents, and it is necessary to determine the active compounds. OBJECTIVE: To investigate the nitric oxide (NO) inhibitory activity in a root extract of A. dahurica and identify the most active compounds using LC-NMR-MS. METHODOLOGY: In search of the anti-inflammatory constituents of A. dahurica extract, the HPLC-based activity profiling approach was used to investigate the extract's NO inhibitory activity. To directly identify the compounds, a hyphenated LC-NMR-MS technique was applied. Reversed-phase isocratic chromatography was performed using the acetonitrile-water solvent system on a C(30) column. The identification of the compounds was based on information from ESI/MS and 1H-NMR. RESULTS: NO inhibitory activities for five main fractions of the extract were evaluated, which were identified by LC-NMR-MS as containing furanocoumarins: byakangelicol, oxypeucedanin, imperatorin, phellopterin and isoimperatorin. CONCLUSION: The results obtained showed that the anti-inflammatory activities of A. dahurica could be linked to imperatorin and phellopterin.