Inhibitory Effects of Naturally Occurring Compounds on Aflatoxin B1Biotransformation

Five new (fusarisolins A–E, 1 to 5) and three known (6 to 8) polyketides were isolated from the marine-derived fungus Fusarium solani H918, along with six known phenolics (9 to 14). Their structures were established by comprehensive spectroscopic data analyses, methoxyphenylacetic acid (MPA) method, chemical conversion, and by comparison with data reported in the literature. Compounds 1 and 2 are the first two naturally occurring 21 carbons polyketides featuring a rare β- and γ-lactone unit, respectively. All isolates (1 to 14) were evaluated for their inhibitory effects against tea pathogenic fungus Pestalotiopsis theae and 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) synthase gene expression. Compound 8 showed potent antifungal activity with an ED50 value of 55 μM, while 1, 8, 13, and 14 significantly inhibited HMG-CoA synthase gene expression.

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Role of serotonergic neurons in the maintenance of the 10-Hz rhythm in sympathetic nerve discharge

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1996.270.1.r174 ◽

1996 ◽

Vol 270 (1) ◽

pp. R174-R181 ◽

Cited By ~ 6

Author(s):

H. S. Orer ◽

M. E. Clement ◽

S. M. Barman ◽

S. Zhong ◽

G. L. Gebber ◽

...

Keyword(s):

Sympathetic Nerve ◽

Peak Frequency ◽

Inhibitory Effects ◽

Receptor Agonists ◽

Naturally Occurring ◽

Medullary Raphe ◽

Receptor Agonists And Antagonists ◽

Raphe Neurons ◽

Nerve Discharge

We studied the effects of serotonin (5-HT)-receptor agonists and antagonists on the naturally occurring 10-Hz rhythm in sympathetic nerve discharge (SND) of urethan-anesthetized, baroreceptor-denervated cats. Intravenous doses of the 5-HT1A-receptor agonists 8-hydroxy-2(di-n-propylamino)-tetralin (8-OH-DPAT) and U-93385E, which inhibit the firing of serotonergic medullary raphe neurons, decreased the power in the 10-Hz band of SND without affecting the power at frequencies < or = 6 Hz. The inhibitory effects of 8-OH-DPAT and U-93385E were reversed by the 5-HT1A-receptor antagonists spiperone and WAY-100135. Microinjection of 8-OH-DPAT into medullary raphe nuclei also selectively eliminated the 10-Hz rhythm in SND. Intravenous administration of the 5-HT2-receptor antagonist methysergide blocked the 10-Hz rhythm in SND, whereas the 5-HT2-receptor agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-amino-propane increased peak frequency and power in the 10-Hz band of SND. Microinjection of N-methyl-D-aspartic acid into the medullary raphe also enhanced the 10-Hz rhythm in SND. These data support the view that the naturally occurring discharges of serotonergic medullary raphe neurons preferentially enhance the 10-Hz rhythm in SND.

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Inhibitory Effects of Naturally Occurring Furan Fatty Acids on Hemolysis of Erythrocytes Induced by Singlet Oxygen

YAKUGAKU ZASSHI ◽

10.1248/yakushi1947.110.9_665 ◽

1990 ◽

Vol 110 (9) ◽

pp. 665-672 ◽

Cited By ~ 5

Author(s):

Youji OKADA ◽

Haruo OKAMJIMA ◽

Misaka TERAUCHI ◽

Hirokazu KONISHI ◽

IMin LIU ◽

...

Keyword(s):

Fatty Acids ◽

Singlet Oxygen ◽

Inhibitory Effects ◽

Furan Fatty Acids ◽

Naturally Occurring

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Isolation and identification of polar auxin transport inhibitors from Saussurea costus and Atractylodes japonica

Acta Agrobotanica ◽

10.5586/aa.1700 ◽

2017 ◽

Vol 70 (3) ◽

Cited By ~ 4

Author(s):

Yuta Toda ◽

Hideyuki Shigemori ◽

Junichi Ueda ◽

Kensuke Miyamoto

Keyword(s):

Auxin Transport ◽

Polar Auxin Transport ◽

Inhibitory Effects ◽

Medicinal Species ◽

Isolation And Identification ◽

Naturally Occurring ◽

Structure Activity ◽

Atractylodes Japonica ◽

Transport Inhibitors ◽

Dehydrocostus Lactone

An intensive survey of naturally-occurring regulators of polar auxin transport (PAT) was conducted in two oriental medicinal species from the Asteraceae, Saussurea costus and Atractylodes japonica, using the radish hypocotyl bioassay system and physicochemical analyses. Costunolide and santamarine were identified as well as dehydrocostus lactone from S. costus roots, and atractylenolide II and (+)-eudesma-4(14),7(11)-dien-8-one from Atractylodes japonica rhizomes as physiologically novel compounds possessing inhibitory activities of PAT. Costunolide and santamarine showed ca. 40% inhibition of PAT in the radish hypocotyl segments at a dose of 2.5 μg/plant and 1 μg/plant, respectively. Inhibitory effects of atractylenolide II and (+)-eudesma-4(14),7(11)-dien-8-one were ca. 10 times lower than those of costunolide and santamarine. Structure–activity relationships and possible mechanisms to inhibit PAT are also discussed.

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Naturally occurring Batatasins and their derivatives as α-glucosidase inhibitors

RSC Advances ◽

10.1039/c5ra15328j ◽

2015 ◽

Vol 5 (100) ◽

pp. 82153-82158 ◽

Cited By ~ 12

Author(s):

Wei-ping Hu ◽

Guo-dong Cao ◽

Jin-hua Zhu ◽

Jia-zhong Li ◽

Xiu-hua Liu

Keyword(s):

Drug Development ◽

Inhibitory Effects ◽

Antidiabetic Drug ◽

Naturally Occurring ◽

Glucosidase Inhibitors

Naturally occurred Batatasins and derivatives displayed remarkable inhibitory effects against α-glucosidase, which provide promising chemical scaffolds for antidiabetic drug development.

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Effects of modification of the hydrophobic C-1–C-16 segment of tautomycin on its affinity to type-1 and type-2A protein phosphatases

Biochemical Journal ◽

10.1042/bj3500081 ◽

2000 ◽

Vol 350 (1) ◽

pp. 81-88

Author(s):

Akira TAKAI ◽

Katsunori TSUBOI ◽

Masayoshi KOYASU ◽

Minoru ISOBE

Keyword(s):

Monoclonal Antibody ◽

Absolute Configuration ◽

Protein Phosphatases ◽

Side Chains ◽

Inhibitory Effects ◽

Catalytic Subunits ◽

Lower Affinity ◽

Naturally Occurring ◽

Determining Factors

Among the naturally occurring toxins that are known to have specific inhibitory effects on type-1 and type-2A protein phosphatases (PP1 and PP2A), tautomycin (TM) is unique in that it exhibits significantly higher affinity to PP1 than to PP2A. The ratio of the dissociation constant for the PP1–TM interaction to that for the PP2A–TM interaction (the PP1/PP2A ratio) is 0.01–0.03. The aim of the present study was to evaluate the possible contributions of the C-1–C-16 segment of TM to the affinity characteristics of the toxin. The relatively hydrophobic segment contains a spiroketal motif whose enantiomeric form is present in okadaic acid (OA), which exhibits exceedingly higher affinity to PP2A than to PP1. We therefore synthesized two TM analogues: TM1 in which the side chains of the spiroketal motif of TM were removed but its absolute configuration was retained, and TM2 in which the spiroketal motif of TM1 was replaced with its enantiomeric form. The effects of TM, TM1 and TM2 on the activities of the native catalytic subunits of PP1 (PP1C) and PP2A and a recombinant γ isoform of PP1 (PP1γ) were examined. The PP1/PP2A ratio determined thereby was 0.2–0.5 for TM1 and 5–10 for TM2. Both the presence of the side chains and the stereochemistry of the spiroketal moieties may be major determining factors for the affinity characteristics of TM. We also show that a monoclonal antibody raised against OA binds to TM2 albeit with much lower affinity than to OA, whereas it exhibits no measurable affinities to TM and TM1.

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Effects of nucleotide substitutions within the T-loop of precursor tRNAs on interaction with ATP/CTP:tRNA nucleotidyltransferases from Escherichia coli and yeast

Biochemical Journal ◽

10.1042/bj3140049 ◽

1996 ◽

Vol 314 (1) ◽

pp. 49-53 ◽

Cited By ~ 13

Author(s):

Zengji LI ◽

Kimberly A. GILLIS ◽

Lisa A. HEGG ◽

Jianchao ZHANG ◽

David L. THURLOW

Keyword(s):

Escherichia Coli ◽

Wild Type ◽

Inhibitory Effects ◽

Nucleotide Substitutions ◽

E Coli ◽

Naturally Occurring ◽

Base Substitutions

Recognition of tRNA and tRNA-like substrates by the enzyme ATP/CTP:tRNA nucleotidyltransferase requires chemically intact nucleotides within the T-loop, especially at positions 57 and 58, which are invariant purines among naturally occurring tRNAs. To test the effects of base substitutions at these positions, which are distant from the site of catalysis, we synthesized mutant tRNAGlu molecules. These in vitro-synthesized RNAs also contained an extra 33 bases at the 5´ end and lacked post-transcriptionally modified bases. The precursor tRNAs were used as substrates for nucleotidyltransferases from Escherichia coli and yeast. Substitution of cytidines at either position 57 or 58 had dramatic inhibitory effects on recognition by both enzymes, including raising the apparent Km and lowering the apparent Vmax.; substitution of an adenosine at position 57 or a uridine at position 58 inhibited the reaction only slightly by comparison. Our results demonstrate that the identities of nucleotides at positions 57 and 58 are relevant to recognition by nucleotidyltransferase, and that a purine is required at position 57. The extra bases at the 5´ end and the lack of post-transcriptionally modified bases did not substantially inhibit interaction with the enzyme, as judged by the wild-type precursor tRNAGlu acting as an effective substrate for both enzymes in the presence of equal concentrations of appropriate tRNA substrates isolated from E. coli.

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Insights into the mechanism of natural terpenoids as NF-kB inhibitors: an overview on their anticancer potential

Experimental Oncology ◽

10.31768/2312-8852.2016.38(3):158-168 ◽

2016 ◽

Vol 38 (3) ◽

pp. 158-168 ◽

Cited By ~ 15

Author(s):

H Jain ◽

N Dhingra ◽

T Narsinghani ◽

R Sharma

Keyword(s):

Oxidative Stress ◽

Nuclear Factor Kappa B ◽

Physiological Responses ◽

Pharmacological Action ◽

Nuclear Factor ◽

Inhibitory Effects ◽

Naturally Occurring ◽

Anti Cancer ◽

Inducible Protein ◽

Transcription Factor Nuclear Factor

The transcription factor, nuclear factor kappa B (NF-kB) is one of the principal inducible protein in mammals known to control the gene expression in many critical physiological responses such as oxidative stress, inflammation etc. and has been shown to play an important role in the pathogenesis of cancer. Terpenoids are major constituents present in nutritionally used fruits, vegetables and different spices which possess various pharmacological action including anticancer activity. Various terpenoids, viz. monoterpenoids, sesquiterpenoids, diterpenoids, sesterterpenoids, triterpenoids, tetraterpenoids and polyterpenoids inhibit NF-kB signaling pathway through IkB phosphorylation, DNA binding, p65 translocation etc. Keeping in mind these facts, the present review revealed the anti-cancer potential of naturally occurring terpenoids highlighting their mechanism of NF-kB inhibition. This review also focuses on some of the naturally occurring terpenoids belonging to various chemical categories with potential inhibitory effects on NF-kB and their role in the treatment of cancer.

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The Quenching Effect of Flavonoids on 4-Methylumbelliferone, a Potential Pitfall in Fluorimetric Neuraminidase Inhibition Assays

CrossRef Listing of Deleted DOIs ◽

10.1177/1087057111409221 ◽

2011 ◽

Vol 16 (7) ◽

pp. 755-764 ◽

Cited By ~ 24

Author(s):

Jarinrat Kongkamnerd ◽

Adelaide Milani ◽

Giovanni Cattoli ◽

Calogero Terregino ◽

Ilaria Capua ◽

...

Keyword(s):

Pearson Correlation ◽

Experimental Uncertainty ◽

Inhibition Assay ◽

Inhibitory Effects ◽

Quenching Effect ◽

Acetylneuraminic Acid ◽

Naturally Occurring ◽

Neuraminidase Inhibition ◽

Hydrolysis Of ◽

Positive Results

Many assays aimed to test the inhibitory effects of synthetic molecules, and naturally occurring products on the neuraminidase activity exploit the hydrolysis of 2′-O-(4-methylumbelliferyl)-N-acetylneuraminic acid (4-MUNANA). The amount of the released product, 4-methylumbelliferone (4-MU), is then measured fluorimetrically. The authors attempted an analysis of the inhibitory properties of 35 naturally occurring flavonoids on neuraminidase N3, where only 29 of them were sufficiently soluble in the assay medium. During the analysis, the authors noticed a strong quenching effect due to the test compounds on the fluorescence of 4-MU. The quenching constants for the flavonoids were determined according to the Stern-Volmer approach. The extent of fluorescence reduction due to quenching and the magnitude of the fluorescence reduction measured in the inhibition assays were comparable: for 11 of 29 compounds, the two values were found to be coincident within the experimental uncertainty. These data were statistically analyzed for correlation by calculating the pertinent Pearson correlation coefficient. Inhibition and quenching were found to be positively correlated (r = 0.71, p(uncorr) = 1.5 × 10−5), and the correlation was maintained for the whole set of tested compounds. Altogether, the collected data imply that all of the tested flavonoids could produce false-positive results in the neuraminidase inhibition assay using 4-MUNANA as a substrate.

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Therapeutic Potential of Ursonic Acid: Comparison with Ursolic Acid

Biomolecules ◽

10.3390/biom10111505 ◽

2020 ◽

Vol 10 (11) ◽

pp. 1505

Author(s):

Juhyeon Son ◽

Sang Yeol Lee

Keyword(s):

Ursolic Acid ◽

Therapeutic Potential ◽

Antioxidant Activities ◽

Biological Activities ◽

Inhibitory Effects ◽

Beneficial Effects ◽

Pentacyclic Triterpenoid ◽

Naturally Occurring ◽

Ziziphus Jujuba

Plants have been used as drugs to treat human disease for centuries. Ursonic acid (UNA) is a naturally occurring pentacyclic triterpenoid extracted from certain medicinal herbs such as Ziziphus jujuba. Since the pharmacological effects and associated mechanisms of UNA are not well-known, in this work, we attempt to introduce the therapeutic potential of UNA with a comparison to ursolic acid (ULA), a well-known secondary metabolite, for beneficial effects. UNA has a keto group at the C-3 position, which may provide a critical difference for the varied biological activities between UNA and ULA. Several studies previously showed that UNA exerts pharmaceutical effects similar to, or stronger than, ULA, with UNA significantly decreasing the survival and proliferation of various types of cancer cells. UNA has potential to exert inhibitory effects in parasitic protozoa that cause several tropical diseases. UNA also exerts other potential effects, including antihyperglycemic, anti-inflammatory, antiviral, and antioxidant activities. Of note, a recent study highlighted the suppressive potential of UNA against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Molecular modifications of UNA may enhance bioavailability, which is crucial for in vivo and clinical studies. In conclusion, UNA has promising potential to be developed in anticancer and antiprotozoan pharmaceuticals. In-depth investigations may increase the possibility of UNA being developed as a novel reagent for chemotherapy.

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