NIH CARBON Program:
Botanicals and Metabolic Resiliency: 2005-2020

Results in NIHReporter  

2005-2010

Metabolic Syndrome

Director: William T. Cefalu, M.D.
Institution: Pennington Botanical Research Center, Baton Rouge, LA
Website:  http://www.botanical.pbrc.eduexternal link disclaimer
Partner: Rutgers University Center of Agriculture and the Environment, The State University of New Jersey, New Brunswick, NJ

Researchers conducted basic and clinical studies to determine how selected botanicals may influence molecular, cellular and physiological mechanisms by which they may prevent or reverse the development of insulin resistance, a key pathophysiologic feature of the metabolic syndrome. The metabolic syndrome, which consists of obesity, insulin resistance, development of type 2 diabetes, and accelerated cardiovascular disease has reached epidemic proportions worldwide. Research projects included: Actions of Russian tarragon (Artemisia dracunculus) on Insulin Action, Anti-obesity Potential of Shilianhua (Sinocrassula indica), and Grape Anthocyanins and Insulin Sensitivity. 

Highlighted Publications

 

Ribnicky DM, Poulev A, Watford M, Cefalu WT, Raskin I. Antihyperglycemic activity of Tarralin, an ethanolic extract of Artemisia dracunculus L. Phytomedicine. 2006;13(8):550-557. doi:10.1016/j.phymed.2005.09.007external link disclaimer
This was the first is a series of papers showing PMI-5011 (then called Taralin) has anti-hyperglycemic effects in an animal model of diabetes.

Dey M, Ribnicky D, Kurmukov AG, Raskin I. In vitro and in vivo anti-inflammatory activity of a seed preparation containing phenethylisothiocyanate. J Pharmacol Exp Ther. 2006;317(1):326-333. doi:10.1124/jpet.105.096511 external link disclaimer
This study revealed that seed extract preparations from Barbarea verna (winter cress) are rich in phenethylisothiocyanates (PEITC) that have potent anti-inflammatory properties.

 

2010-2015

Botanicals and Metabolic Syndrome

Director: William T. Cefalu, M.D.
Institution: Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, LA
Website: http://www.botanical.pbrc.eduexternal link disclaimer
Partners: Biotechnology Center for Agriculture and the Environment, Rutgers, New Brunswick, NJ; Louisiana State University, Baton Rouge, LA

This center had been supported for 5 years and in this 5-year period aimed to provide a comprehensive evaluation of specific, compelling hypotheses about the molecular, cellular and physiological mechanisms by which botanicals can modulate the development of the underlying pathophysiologic mechanisms of, and attenuate the development to, metabolic syndrome. Research projects included:  Artemisia species and Insulin Action, Adipocytes and Botanicals, and Pregnane Glycosides and Obesity.

Highlighted Publications

 
Richard AJ, Fuller S, Fedorcenco V, et al. Artemisia scoparia enhances adipocyte development and endocrine function in vitro and enhances insulin action in vivo. PLoS One. 2014;9(6):e98897. Published 2014 Jun 10. doi:10.1371/journal.pone.0098897external link disclaimer
It is well known that the best place to store lipids is in adipose tissue. Limiting the formation of new adipocytes results in ectopic lipid storage that promotes system metabolic dysfunction in mice and man. A screen of over 400 different botanical extracts from around the globe revealed that Artemisia scoparia could promote adipocyte development and have metabolically favorable effects on adipocytes in vivo. These were first studies to demonstrate that Artemisia scoparia could promote adipogenesis in vivo and improve the health of mice with metabolic syndrome

Wang ZQ, Ribnicky D, Zhang XH, et al. An extract of Artemisia dracunculus L. enhances insulin receptor signaling and modulates gene expression in skeletal muscle in KK-A(y) mice. J Nutr Biochem. 2011;22(1):71-78. doi:10.1016/j.jnutbio.2009.11.015external link disclaimer
This study demonstrated that the anti-hyperglycemic properties of PMI-5011 are associated with enhanced insulin signaling in skeletal muscle, pointing to a specific target organ for PMI-5011’s bioactivity. 
 

2015-2020

Botanicals and Metabolic Resiliency

Principal Investigators: Jacqueline M. Stephens, Ph.D. and Z. Elizabeth Floyd, Ph.D.
Institution: Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA
Website: http://www.botanical.pbrc.eduexternal link disclaimer
Partners: North Carolina State University, Kannapolis, NC; Rutgers, The State University of New Jersey, New Brunswick; NJ

During its first 5 years this Center had focused on the evaluation of botanicals to prevent metabolic syndrome, a group of risk factors for diabetes and heart disease. In its last 5 years the team focused on the ability of botanicals to promote “metabolic resiliency,” the ability to maintain metabolic health in the presence of stressors such as high-fat diet and to study the mechanisms of action of the most promising botanicals in this context. This Center also explored the role of the gastrointestinal microbiome in the biological effects of the products studied, which included bitter melon and fenugreek, as well as Russian tarragon (Artemisia dracunculus), and Artemisia scoparia.

Highlighted Publications

 

Boudreau A, Richard AJ, Burrell JA, et al. An ethanolic extract of Artemisia scoparia inhibits lipolysis in vivo and has antilipolytic effects on murine adipocytes in vitro. Am J Physiol Endocrinol Metab. 2018;315(5):E1053-E1061. doi:10.1152/ajpendo.00177.2018external link disclaimer
These studies revealed a cellular pathway involved in lipid metabolism that is highly regulated by Artemisia scoparia. Lipolysis, or release of glycerol and fatty acids, is critical to provide fuel in times of fasting. However elevated basal lipolysis and inflammation induced lipolysis is associated with poor metabolic health. These studies show that Artemisia scoparia reduces inflammation associated lipolysis in cultured cells as well as in a mouse model of obesity and Type 2 Diabetes. 

Jaja-Chimedza A, Graf BL, Simmler C, et al. Biochemical characterization and anti-inflammatory properties of an isothiocyanate-enriched moringa (Moringa oleifera) seed extract. PLoS One. 2017;12(8):e0182658. Published 2017 Aug 8. doi:10.1371/journal.pone.0182658external link disclaimer
This study demonstrates that the major isothiocyanate (MIC-1) from a moringa seed extract displays strong anti-inflammatory and anti-oxidant properties in vitro and in vivo. This work included a collaboration with another CARBON Center, CENAPT. 

Jaja-Chimedza A, Zhang L, Wolff K, et al. A dietary isothiocyanate-enriched moringa (Moringa oleifera) seed extract improves glucose tolerance in a high-fat-diet mouse model and modulates the gut microbiome. J Funct Foods. 2018;47:376-385. doi:10.1016/j.jff.2018.05.056external link disclaimer
This study provides evidence that a moringa seed extract rich in stable isothiocyanates improves metabolic health by its anti-inflammatory, anti-oxidant and antibiotic-like restructuring of the gut microbiome.

Yu Y, Simmler C, Kuhn P, et al. The DESIGNER approach helps decipher the hypoglycemic bioactive principles of Artemisia dracunculus (Russian tarragon). J Nat Prod. 2019;82(12):3321-3329. doi:10.1021/acs.jnatprod.9b00548external link disclaimer
This paper used an animal model of obesity-induced insulin resistance to demonstrate DMC-2 is the major bioactive present in PMI-5011 that reduces blood glucose levels and enhances insulin signaling in skeletal muscle. Skeletal muscle is shown to be the primary target organ for the effect of DMC-2. Using an analytical approach developed by the CENAPT, this collaborative study demonstrated that other bioactivities in skeletal muscle are revealed in the absence of DMC-2.

 

 Prior CARBON Awards | NIH CARBON Program