Naturally occurring Batatasins and their derivatives as α-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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Flavonoids as Human Intestinal α-Glucosidase Inhibitors

Foods ◽

10.3390/foods10081939 ◽

2021 ◽

Vol 10 (8) ◽

pp. 1939

Author(s):

Elizabeth Barber ◽

Michael J. Houghton ◽

Gary Williamson

Keyword(s):

Glucose Absorption ◽

Inhibitory Effects ◽

Antidiabetic Drug ◽

Glucosidase Inhibitors ◽

Acarbose Treatment ◽

Ic50 Values ◽

Intestinal Glucose Absorption ◽

Inhibition Pattern ◽

Carbohydrate Digestion ◽

Enzyme Source

Certain flavonoids can influence glucose metabolism by inhibiting enzymes involved in carbohydrate digestion and suppressing intestinal glucose absorption. In this study, four structurally-related flavonols (quercetin, kaempferol, quercetagetin and galangin) were evaluated individually for their ability to inhibit human α-glucosidases (sucrase, maltase and isomaltase), and were compared with the antidiabetic drug acarbose and the flavan-3-ol(−)-epigallocatechin-3-gallate (EGCG). Cell-free extracts from human intestinal Caco-2/TC7 cells were used as the enzyme source and products were quantified chromatographically with high accuracy, precision and sensitivity. Acarbose inhibited sucrase, maltase and isomaltase with IC50 values of 1.65, 13.9 and 39.1 µM, respectively. A similar inhibition pattern, but with comparatively higher values, was observed with EGCG. Of the flavonols, quercetagetin was the strongest inhibitor of α-glucosidases, with inhibition constants approaching those of acarbose, followed by galangin and kaempferol, while the weakest were quercetin and EGCG. The varied inhibitory effects of flavonols against human α-glucosidases depend on their structures, the enzyme source and substrates employed. The flavonols were more effective than EGCG, but less so than acarbose, and so may be useful in regulating sugar digestion and postprandial glycaemia without the side effects associated with acarbose treatment.

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Fusarisolins A–E, Polyketides from the Marine-Derived Fungus Fusarium solani H918

Marine Drugs ◽

10.3390/md17020125 ◽

2019 ◽

Vol 17 (2) ◽

pp. 125 ◽

Cited By ~ 6

Author(s):

Siwen Niu ◽

Xi-Xiang Tang ◽

Zuowang Fan ◽

Jin-Mei Xia ◽

Chun-Lan Xie ◽

...

Keyword(s):

Gene Expression ◽

Antifungal Activity ◽

Fusarium Solani ◽

Spectroscopic Data ◽

Coenzyme A ◽

Pathogenic Fungus ◽

Chemical Conversion ◽

Inhibitory Effects ◽

Data Analyses ◽

Naturally Occurring

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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Clinical, Pathological, and Ethical Considerations for the Conduct of Clinical Trials in Dogs with Naturally Occurring Cancer: A Comparative Approach to Accelerate Translational Drug Development

ILAR Journal ◽

10.1093/ilar/ily019 ◽

2018 ◽

Vol 59 (1) ◽

pp. 99-110 ◽

Cited By ~ 5

Author(s):

Daniel Regan ◽

Kelly Garcia ◽

Douglas Thamm

Keyword(s):

Clinical Trials ◽

Drug Development ◽

Translational Research ◽

Cancer Biology ◽

Comparative Approach ◽

Cancer Drug ◽

Comparative Oncology ◽

Pet Dogs ◽

Naturally Occurring

Abstract The role of comparative oncology in translational research is receiving increasing attention from drug developers and the greater biomedical research community. Pet dogs with spontaneous cancer are important and underutilized translational models, owing to dogs’ large size and relative outbreeding, combined with their high incidence of certain tumor histotypes with significant biological, genetic, and histological similarities to their human tumor counterparts. Dogs with spontaneous tumors naturally develop therapy resistance and spontaneous metastasis, all in the context of an intact immune system. These fundamental features of cancer biology are often lacking in induced or genetically engineered preclinical tumor models and likely contribute to their poor predictive value and the associated overall high failure rate in oncology drug development. Thus, the conduct of clinical trials in pet dogs with naturally occurring cancer represents a viable surrogate and valuable intermediary step that should be increasingly incorporated into the cancer drug discovery and development pipeline. The development of molecular-targeted therapies has resulted in an expanded role of the pathologist in human oncology trials, and similarly the expertise of veterinary pathologists will be increasingly valuable to all phases of comparative oncology trial design and conduct. In this review, we provide a framework of clinical, ethical, and pathology-focused considerations for the increasing integration of translational research investigations in dogs with spontaneous cancer as a means to accelerate clinical cancer discovery and drug development.

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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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