Xanthoangelols isolated from <i>Angelica keiskei</i> inhibit inflammatory‐induced plasminogen activator inhibitor 1 (PAI‐1) production

Ohkura, Naoki; Nakakuki, Yoshitaka; Taniguchi, Masahiko; Kanai, Setsuko; Nakayama, Akiko; Ohnishi, Katsunori; Sakata, Toshiyuki; Nohira, Tomoyoshi; Matsuda, Juzo; K, Baba; Atsumi, Gen‐ichi

doi:10.1002/biof.187

Cited by 29 publications

(28 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…TNF-α, a player in inflammation responses, is also involved in the induction of PAI-1 expression. Again, chalcones in ashitaba, namely compounds 2, 3, 5, and 6, were found to suppress activities induced by TNF-α, resulting in a reversal of PAI-1 increase in human umbilical vein endothelial cells [35]. In another study, 1 and 2 illustrated dose-dependent antiplatelet activity against a number of platelet aggregation inducers, including collagen-, phorbol 12-myristate 13-acetate (PMA), and platelet-activating factor (PAF) in washed rabbit platelets [37].…”

Section: Antithrombotic Activitymentioning

confidence: 94%

“…Tumor necrosis factor alpha (TNF-α) has been implicated as an important participant in the induction of inflammation [32] and is regulated by transcription factors activator protein 1 (AP-1) and the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). Ashitaba extract and compound 2 were shown to inhibit inflammation induced by TNF-α in male kwl ICR mice [35]. Another study determined that isolated compounds 1 and 2 had similar TNF-α suppressing effects in RAW264 macrophages [32], and compound 5 induced suppression in porcine aortic endothelial cells [33].…”

Section: Oxidative Stress Relief and Anti-inflammatory Activitymentioning

confidence: 98%

See 1 more Smart Citation

A Review of the Medicinal Uses and Pharmacology of Ashitaba

Caesar

Cech

2016

Planta Med

View full text Add to dashboard Cite

Medicinal plants are commonly employed for therapeutic purposes throughout the world. A recent National Health Interview Survey estimated that nearly 18 % of adults in the United States regularly took non-vitamin, non-mineral dietary supplements in 2012 [1]. Because of the popularity of herbal medicines, it is important to understand the chemical basis behind the purported activities of botanicals. Angelica, a member of the Apiaceae (Umbelliferae) family, is a large genus comprised of over 60 species. Members of the genus have been utilized as medicines across the world, most notably in Asia, to treat numerous ailments, including influenza, hepatitis, arthritis, indigestion, fever, and microbial infections [2]. An increasing number of studies are being conducted on a medicinally promising member of the genus, Angelica keiskei Koidzumi (Apiaceae), or ashitaba. This large leafy perennial plant native to the Pacific coast of Japan is used throughout Asia for its diuretic, laxative, stimulant, and galactagogue properties [3]. In the past decade, several active constituents representing chalcones, flavanones, and coumarins have been isolated and characterized from ashitaba, and several bioactiv-ities have been described. This review presents the current progress on ashitaba pharmacological studies, with a focus on isolated secondary metabolites, biological activity, toxicological data, and clinical relevance. Bioactive Metabolites Isolated from Ashitaba ! Chalcones Most of the literature on the bioactive metabolites from ashitaba concerns the diverse activity of various chalcones (l " Table 1 and Fig. 1), which are most abundant in the root bark of the plant [4]. Chalcones are formed from phenylpropanoid starter units, extended with three malonyl-CoA molecules. The resulting polyketide is folded by the enzyme chalcone synthase to promote Claisen condensations and subsequent enolizations [5]. Interestingly, the bioactive chalcones found in ashitaba are prenylated at the 5′-position (l " Fig. 1), indicating that these molecules have undergone multiple biosynthetic steps, travelling through the acetate, shikimate, and isoprenoid pathways.

show abstract

Section: Antithrombotic Activitymentioning

confidence: 94%

Section: Oxidative Stress Relief and Anti-inflammatory Activitymentioning

confidence: 98%

A Review of the Medicinal Uses and Pharmacology of Ashitaba

Caesar

Cech

2016

Planta Med

View full text Add to dashboard Cite

show abstract

“…We reported that xanthoangelol isolated from Angelica keiskei inhibits PAI-1 increases induced by lipopolysaccharide (LPS) in mouse plasma and by TNF-α in culture media of HUVEC [12]. We also showed that chrysin, a naturally occurring flavone, a type of flavonoid found in plants such as passion flower and chamomile, inhibits the TNF-α induced PAI-1 increase in the culture medium of endothelial cell line [13].…”

Section: Introductionmentioning

confidence: 78%

Effects of Fermented Rice Vinegar Kurozu and Its Sediment on Inflammation-Induced Plasminogen Activator Inhibitor 1 (PAI-1) Increase

Ohkura¹,

Kihara-Negishi²,

Fujii³

et al. 2018

FNS

Self Cite

View full text Add to dashboard Cite

Kurozu is a traditional black rice vinegar in Japan. Kurozu-moromi is the solid sediment that arises during the production of Kurozu. Kurozu is thought to have blood thinning and antithrombotic activities but a specific effect has not been proven. Plasma plasminogen activator inhibitor 1 (PAI-1) inhibits fibrinolysis and when elevated, it is a risk factor for the development of thrombotic diseases. Here, we examined the effects of a diet containing Kurozu and Kurozu-moromi on LPS (lipopolysaccharide)-induced increases in plasma PAI-1 levels in mice and on TNF-α (tumor necrosis factor α) increased PAI-1 production in the medium of a cultured endothelial cell line. Mice were fed with a diet containing 0.25% (w/w) concentrated Kurozu or 0.5% (w/w) Kurozu-moromi for four weeks, and then subcutaneously injected with 0.015 mg/kg of LPS in saline and sacrificed three hours later. Orally administered concentrated Kurozu and Kurozu-moromi significantly suppressed the LPS-induced increase in PAI-1 antigen and its activity in mouse plasma. The ethanol extract of Kurozu-moromi inhibited TNF-α induced increases of PAI-1 in the culture medium of the EA.hy926 endothelial cell line. The present findings showed that Kurozu and Kurozu-moromi contain natural products that decrease thrombotic tendencies by decreasing PAI-1 production in inflammatory states and have potential as antithrombotic foodstuffs.

show abstract

“…Seven chalcones 1-7 (Fig. 1A) were isolated as active principles from A. keiskei by repeated column chromatography and their purity was analyzed by HPLC (Shimadzu HPLC system with UV monitor at 254 nm; l-Bondapak C 18 column, 10 lm, 10 · 300 mm; 60% aqueous MeOH as eluent; flow rate 2.0 mL/min): 4-hydroxyderrcin (1), xanthoangelol E (2), xanthoangelol D (3), xanthokeismin A (4), xanthoangelol B (5), xanthoangelol (6), and xanthoangelol F (7). The structures of these chalcones 1-7 were identified by 1 H-and 13 C-NMR spectra, which were consistent with the previously reported spectroscopic data.…”

Section: Test Materialsmentioning

confidence: 99%

“…It has been reported that A. keiskei contains various bioactive chalcones and coumarins, showing antioxidant, 2 antidiabetic, 3 chemopreventive, 4,5 and anti-inflammatory activities. 6,7 Lee et al reported that the hexane fraction of A. keiskei inhibited the production of lipopolysaccharide (LPS)-induced nitric oxide (NO) and prostaglandin E 2 (PGE 2 ) through downregulation of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) proteins and mRNA. 8 Another study demonstrated that chalcones isolated from A. keiskei attenuate the production of interleukin-6 (IL-6) in tumor necrosis factor-a (TNF-a)-stimulated osteoblast cells.…”

Section: Introductionmentioning

confidence: 99%

Chalcones fromAngelica keiskeiAttenuate the Inflammatory Responses by Suppressing Nuclear Translocation of NF-κB

Chang

Lee

Ryu

2014

Journal of Medicinal Food

View full text Add to dashboard Cite

The ethyl acetate-soluble fraction from the ethanolic extract of Angelica keiskei showed potent inhibitory activity against the production of nitric oxide (NO) in lipopolysaccharide (LPS)-activated RAW 264.7 cells. We identified seven chalcones (1-7) from EtOAc-soluble fractions through the activity-guided separation. Four active principles, identified as 4-hydroxyderrcine (1), xanthoangelol E (2), xanthokeismin A (4), and xanthoangelol B (5), inhibited the production of NO and the expression of proinflammatory cytokines, interleukin (IL)-1β and IL-6, in LPS-activated macrophages. Western blotting and reverse transcription-polymerase chain reaction analysis demonstrated that these chalcones attenuated protein and mRNA levels of inflammatory enzymes such as inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Moreover, these active compounds suppressed the degradation of inhibitory-κBα (I-κBα) and the translocation of nuclear factor κB (NF-κB) into nuclei of LPS-activated macrophages. These data demonstrate that four chalcones (1, 2, 4, and 5) from A. keiskei can suppress the LPS-induced production of NO and the expression of iNOS/COX-2 genes by inhibiting the degradation of I-κBα and nuclear translocation of NF-κB. Taken together, four chalcones from A. keiskei may have efficacy as anti-inflammatory agents.

show abstract

Xanthoangelols isolated from Angelica keiskei inhibit inflammatory‐induced plasminogen activator inhibitor 1 (PAI‐1) production

Cited by 29 publications

References 19 publications

A Review of the Medicinal Uses and Pharmacology of Ashitaba

A Review of the Medicinal Uses and Pharmacology of Ashitaba

Effects of Fermented Rice Vinegar Kurozu and Its Sediment on Inflammation-Induced Plasminogen Activator Inhibitor 1 (PAI-1) Increase

Chalcones fromAngelica keiskeiAttenuate the Inflammatory Responses by Suppressing Nuclear Translocation of NF-κB

Contact Info

Product

Resources

About