Preventive effects of arctigenin from Arctium lappa L against LPS-induced neuroinflammation and cognitive impairments in mice.

Arctigenin (Arc) is a phenylpropanoid dibenzylbutyrolactone lignan in Arctium lappa L, which has been widely applied as a traditional Chinese herbal medicine for treating inflammation. In the present study, we explored the neuroprotective effect and the potential mechanisms of arctigenin against LPS-evoked neuroinflammation, neurodegeneration, and memory impairments in the mice hippocampus. Daily administration of arctigenin (50 mg/kg per day, i.g.) for 28 days revealed noticeable improvements in spatial learning and memory deficits after exposure to LPS treatment. Arctigenin prevented LPS-induced neuronal/synaptic injury and inhibited the increases in Abeta (Aß) generation and the levels of amyloid precursor protein (APP) and ß-site amyloid precursor protein cleavage enzyme 1 (BACE1). Moreover, arctigenin treatment also suppressed glial activation and reduced the production of proinflammatory cytokines. In LPS-treated BV-2 microglial cells and mice, activation of the TLR4 mediated NF-κB signaling pathway was significantly suppressed by arctigenin administration. Mechanistically, arctigenin reduced the LPS-induced interaction of adiponectin receptor 1 (AdipoR1) with TLR4 and its coreceptor CD14 and inhibited the TLR4-mediated downstream inflammatory response. The outcomes of the current study indicate that arctigenin mitigates LPS-induced apoptotic neurodegeneration, amyloidogenesis and neuroinflammation as well as cognitive impairments, and suggest that arctigenin may be a potential therapeutic candidate for neuroinflammation/neurodegeneration-related diseases.

Inhibitory Effect of Supercritical Extracts from Arctium lappa L. on the Lectin Pathway of the Complement System.

The complement system participates in host defense by eliminating microorganisms and triggering inflammation. However, insufficient control or exacerbated complement activation contributes to inflammatory diseases. Since promising antioxidant and anti-inflammatory activities have been identified in Arctium lappa L. extracts, this study aims to explore the effect of A. lappa extracts on the lectin pathway (LP) of complement activation. Four extracts were obtained by supercritical extraction using scCO2 with or without ethanol as co-solvent, at different temperatures and pressures (E1: 2.2 mg/mL, E2: 2.6 mg/mL and E3: 2.0 mg/mL, E4: 1.5 mg/mL). To evaluate the effect of A. lappa extracts on the LP activation, an ELISA assay using mannose binding lectin pathway of complement was carried out with C4 detection. All extracts showed a concentration-dependent inhibitory effect on the activation of complement by the LP. The following IC50 were observed for E1, E2, E3 and E4: 179.4 µg/mL, 74.69 µg/mL, 119.1 µg/mL and 72.19 µg/mL, respectively. Our results suggest that A. lappa extracts are potential candidates for the treatment of inflammatory disorders that are complement-related.

Metabolomics-Based Screening of Biofilm-Inhibitory Compounds against Pseudomonas aeruginosa from Burdock Leaf.

Screening of anti-biofilm compounds from the burdock leaf based on metabolomics is reported here. The crystal violet assay indicated 34% ethanol elution fraction of burdock leaf could completely inhibit biofilm formation of Pseudomonas aeruginosa at 1 mg·mL(-1). Then, the chemical composition of burdock leaf fraction was analyzed by ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) and 11 active compounds (chlorogenic acid, caffeic acid, p-coumaric acid, quercetin, ursolic acid, rutin, cynarin, luteolin, crocin, benzoic acid, and Tenacissoside I) were identified. Lastly, UPLC-MS analysis was employed to obtain the metabolic fingerprints of burdock leaf fractions before and after inhibiting the biofilm of Pseudomonas aeruginosa. The metabolic fingerprints were transformed to data, analyzed with PLS-DA (partial least squares discriminant analysis) and the peaks whose area was significantly changed were found out. Thus, 81 compounds were screened as potential anti-biofilm ingredients. Among them, rutin, ursolic acid, caffeic acid, p-coumaric acid and quercetin were identified and confirmed as the main anti-biofilm compounds in burdock leaf. The study provided basic anti-biofilm profile data for the compounds in burdock leaf, as well as provided a convenient method for fast screening of anti-biofilm compounds from natural plants.

Study on human intestinal bacterium Blautia sp. AUH-JLD56 for the conversion of arctigenin to (-)-3'-desmethylarctigenin.

Arctium lappa L. (A. lappa) is a popularly used vegetable as well as herbal medicine. Human intestinal microflora was reported to convert arctiin, the lignan compound with highest content in the dried fruits of Arctium lappa, to a series of metabolites. However, the specific bacterium responsible for the formation of 3'-desmethylarctigenin (3'-DMAG), the most predominant metabolite of arctiin by rat or human intestinal microflora, has not been isolated yet. In the present study, we isolated one single bacterium, which we named Blautia sp. AUH-JLD56, capable of solely biotransforming arctiin or arctigenin to (-)-3'-DMAG. The structure of the metabolite 3'-DMAG was elucidated by electrospray ionization mass spectrometry (ESI-MS) and (1)H and (13)C nuclear magnetic resonance spectroscopy. The biotransforming kinetics and maximum biotransforming capacity of strain AUH-JLD56 was investigated. In addition, the metabolite 3'-DMAG showed significantly higher 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical-scavenging activity than that of the substrate arctigenin at the concentrations tested.

Plasma pharmacokinetics and tissue distribution of arctiin and its main metabolite in rats by HPLC-UV and LC-MS.

The pharmacokinetic profile of arctiin, the major active lignan in fruits of Arctium lappa L., was investigated. Its main meta"bolite arctigenin was identified by an LC-MS method, and an HPLC-UV technique was developed for the simultaneous quantification of the metabolite and arctiin in plasma and organs. Chromatographic separation was performed on an Agilent™ C18 HPLC column with acetonitrile and water by linear gradient elution. Arctiin and arctigenin were identified on-line by LC-MS. The pharmacokinetics and tissue distribution of arctiin and arctigenin were determined for the first time by using a simple, selective, and accurate HPLC method. The AUC0-t values of arctigenin were larger compared with arctiin after oral administration of arctiin. The concentration of the metabolite was significantly higher than the concentration of arctiin in the stomach and small intestine in rats after oral administration of arctiin, indicating that the stomach and small intestine were the major organs of arctiin metabolism. These findings could provide support for the clinical studies conducted with Fructus Arctii.

Comparative analysis of caffeoylquinic acids and lignans in roots and seeds among various burdock (Arctium lappa) genotypes with high antioxidant activity.

Caffeoylquinic acids and lignans in the crude extracts of both roots and seeds from different burdock ( Arctium lappa L.) genotypes were simultaneously characterized and systematically compared by LC-MS and matrix-assisted laser desorption/ionization quadrupole ion trap time-of-flight mass spectrometry (MALDI-QIT-TOF MS), and their antioxidant activities were also investigated. A total of 14 lignans were identified in burdock seeds and 12 caffeoylquinic acids in burdock roots. High levels of caffeoylquinic acids were also detected in burdock seeds, but only trace amounts of lignans were found in burdock roots. Burdock seeds contained higher concentrations of lignans and caffeoylquinic acids than burdock roots. Quantitative analysis of caffeoylquinic acids and lignans in roots and seeds of various burdock genotypes was reported for the first time. Great variations in contents of both individual and total phenolic compounds as well as antioxidant activities were found among different genotypes. Burdock as a root vegetable or medicinal plants possessed considerably stronger antioxidant activity than common vegetables and fruits.

Antifungigrama para comprovar o potencial de ação dos extratos vegetais hidroglicólicos sobre Candida sp. (Berkhout) / Etest to confirm the action potential of plant hydroglycol extracts on Candida sp. (Berkhout)

A candidíase vaginal é uma doença causada, na maioria das vezes, pelo fungo do gênero Candida sp, que habita o trato gastrintestinal e geniturinário da espécie humana e pode tornar-se patogênico sob determinadas condições. A maioria dos indivíduos desenvolve defesas imunológicas que impedem a proliferação e desenvolvimento de candidíase localizada ou disseminada. Embora a causa exata do aumento de espécies não-albicans seja desconhecida, há evidências de que a própria terapia antifúngica possa estar contribuindo para o processo. Linhagens de C. glabrata são mais resistentes aos imidazólicos do que a C. albicans, sendo necessária uma concentração 10 vezes superior de miconazol para eliminar a C. glabrata quando comparada a C. albicans. Foi realizado um antifungigrama testando o potencial de ação de produtos vegetais sobre o fungo Candida sp. Foi observado que, ocorreu inibição do fungo no contato com os extratos hidroglicólicos das plantas Arctium lappa L., Calendula officinalis L., Stryphnodendron adstringens (Mart.) Coville e Tabebuia avellanedae Lorentz ex Griseb. A importância deste trabalho reside na possibilidade de desenvolvimento de tratamento complementar, menos agressivo, de menor custo e sem toxidade, o que possibilitaria melhor qualidade de vida para portadoras de candidíase vaginal recorrente ou não.

Vaginal candidiasis is a disease caused, in most cases, by the fungus of the genus Candida sp., which inhabits the gastrointestinal and genitourinary tracts of the human species and can become pathogenic under certain conditions. Most individuals develop immune defenses that prevent the proliferation and the development of localized or disseminated candidiasis. Although the exact cause of the increase in non-albicans species is unknown, there is evidence that antifungal therapy itself may have contributed to it. Strains of C. glabrata are more resistant to imidazole than C. albicans, and a 10-fold higher concentration of miconazole is required to eliminate C. glabrata compared to C. albicans. Etest was performed by testing the action potential of plant products on the fungus Candida sp. Inhibition of the fungus occurred when it was in contact with the hydroglycol extracts of plants Arctium lappa L., Calendula officinalis L., Stryphnodendron adstringens (Mart.) Coville and Tabebuia avellanedae Lorentz ex Griseb. The importance of this study lies in the possibility of developing a complementary treatment, less aggressive, of lower cost and without toxicity, which would allow better life quality for women with vaginal candidiases that are recurrent or not.

Biological activities of Fructus arctii fermented with the basidiomycete Grifola frondosa.

Fructus arctii extract containing phenolic glycosides was cultured with Grifola frondosa mycelia to produce ß-glucosidase and its biological activities were studied. This ß-glucosidase converted the glycosides (arctiin and caffeic acid derivatives) into aglycones (arctigenin and caffeic acid). Fermented Fructus arctii extract (G-FAE) with G. frondosa had antioxidant and 5-lipoxygenase inhibitory activities. The photoprotective potential of G-FAE was tested in human dermal fibroblasts (HDF) exposed to ultra-violet A (UVA). It was revealed that G-FAE had an inhibitory effect on human interstitial collagenase (matrix metalloproteinase, MMP-1) expression in UVA-irradiated HDF. The treatment of UVA-irradiated HDF with G-FAE resulted in a dose-dependent decrease in the expression level of MMP-1 mRNA. G-FAE also showed notable stimulation of collagen biosynthetic activity for fibroblasts. These diverse functionalities suggest that G-FAE could be a promising cosmetic ingredient.