Human Cancer Virology: An Historical Review

Two isoprenylated flavonoids from Dorstenia psilurus activate AMPK, stimulate glucose uptake, inhibit glucose production and lower glycemia

Biochemical Journal ◽

10.1042/bcj20190326 ◽

2019 ◽

Vol 476 (24) ◽

pp. 3687-3704 ◽

Cited By ~ 2

Author(s):

Aphrodite T. Choumessi ◽

Manuel Johanns ◽

Claire Beaufay ◽

Marie-France Herent ◽

Vincent Stroobant ◽

...

Keyword(s):

Glucose Uptake ◽

Human Cancer ◽

Glucose Production ◽

Liver Mitochondria ◽

New Drugs ◽

Structural Isomer ◽

Rat Liver Mitochondria ◽

Ionization Mass ◽

Ampk Activation ◽

Starting Point

Root extracts of a Cameroon medicinal plant, Dorstenia psilurus, were purified by screening for AMP-activated protein kinase (AMPK) activation in incubated mouse embryo fibroblasts (MEFs). Two isoprenylated flavones that activated AMPK were isolated. Compound 1 was identified as artelasticin by high-resolution electrospray ionization mass spectrometry and 2D-NMR while its structural isomer, compound 2, was isolated for the first time and differed only by the position of one double bond on one isoprenyl substituent. Treatment of MEFs with purified compound 1 or compound 2 led to rapid and robust AMPK activation at low micromolar concentrations and increased the intracellular AMP:ATP ratio. In oxygen consumption experiments on isolated rat liver mitochondria, compound 1 and compound 2 inhibited complex II of the electron transport chain and in freeze–thawed mitochondria succinate dehydrogenase was inhibited. In incubated rat skeletal muscles, both compounds activated AMPK and stimulated glucose uptake. Moreover, these effects were lost in muscles pre-incubated with AMPK inhibitor SBI-0206965, suggesting AMPK dependency. Incubation of mouse hepatocytes with compound 1 or compound 2 led to AMPK activation, but glucose production was decreased in hepatocytes from both wild-type and AMPKβ1−/− mice, suggesting that this effect was not AMPK-dependent. However, when administered intraperitoneally to high-fat diet-induced insulin-resistant mice, compound 1 and compound 2 had blood glucose-lowering effects. In addition, compound 1 and compound 2 reduced the viability of several human cancer cells in culture. The flavonoids we have identified could be a starting point for the development of new drugs to treat type 2 diabetes.

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A Historical Review of Complex Regional Pain Syndrome in the “Guides Library”

Guides Newsletter ◽

10.1001/amaguidesnewsletters.2009.novdec01 ◽

2009 ◽

Vol 14 (6) ◽

pp. 1-9

Author(s):

Robert J. Barth

Keyword(s):

Differential Diagnosis ◽

Complex Regional Pain Syndrome ◽

Reflex Sympathetic Dystrophy ◽

International Association ◽

Historical Review ◽

Pain Syndrome ◽

Sixth Edition

Abstract Complex regional pain syndrome (CRPS) is a controversial, ambiguous, unreliable, and unvalidated concept that, for these very reasons, has been justifiably ignored in the “AMA Guides Library” that includes the AMAGuides to the Evaluation of Permanent Impairment (AMA Guides), the AMA Guides Newsletter, and other publications in this suite. But because of the surge of CRPS-related medicolegal claims and the mission of the AMA Guides to assist those who adjudicate such claims, a discussion of CRPS is warranted, especially because of what some believe to be confusing recommendations regarding causation. In 1994, the International Association for the Study of Pain (IASP) introduced a newly invented concept, CRPS, to replace the concepts of reflex sympathetic dystrophy (replaced by CRPS I) and causalgia (replaced by CRPS II). An article in the November/December 1997 issue of The Guides Newsletter introduced CRPS and presciently recommended that evaluators avoid the IASP protocol in favor of extensive differential diagnosis based on objective findings. A series of articles in The Guides Newsletter in 2006 extensively discussed the shortcomings of CRPS. The AMA Guides, Sixth Edition, notes that the inherent lack of injury-relatedness for the nonvalidated concept of CRPS creates a dilemma for impairment evaluators. Focusing on impairment evaluation and not on injury-relatedness would greatly simplify use of the AMA Guides.

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