Does Artemisia dracunculus boost the anabolic effect of insulin?

The plant Artemisia dracunculus contains substances that inhibit muscle breakdown in obese diabetics – and that can aid muscle development, according to animal studies recently published by researchers at Pennington Biomedical Research Center in the US. So might Artemisia dracunculus also be of interest to chemical athletes?

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Artemisia dracunculus

You might have Artemisia dracunculusgrowing in your garden. And if not, you can buy it at any supermarket, dried or fresh. Artemisia dracunculus is tarragon, a common kitchen herb. Athletes know it as Russian Tarragon. Supplement manufacturers sometimes combine extracts of Artemisia dracunculus with creatine.

The extract that the Pennington researchers used for their experiments was PMI 5011. To avoid confusion we say right away that PMI 5011 is not interesting for supplement manufacturers. The human equivalent of the doses that the researchers gave their mice would be somewhere between 10 and 15 g per day.

The active ingredients in PMI 5011 are probably chalcones. If the researchers can work out which chalcones these are, and if reliable supplements containing chalcones appear on the market, then athletes might find that they have a new supplement that’s worth trying. And it’s likely to appeal to athletes who use insulin as a doping agent, we suspect.

Dangerous

If you’re thinking of making your own Artemisia dracunculus extracts, make sure you do your homework first. Artemisia dracunculus contains a few compounds – such as estragol and methyleugenol – which are dangerous in their pure form and in high concentrations. You’ll have to remove these substances from your extract.

Muscles

Diabetics who are also seriously overweight can experience a speeding up of muscle loss in old age. The insulin receptor’s working deteriorates and muscles start to self-destruct. The molecular machinery involved in muscles breaking down their own protein starts to work faster and faster.

Heather Kirk-Ballard recently published a study in Nutrition in which Artemisia dracunculus deactivated the gene for microtubule-associated protein-1 light chain 3 [LC3] in the vastus lateralis of diabetic mice. [Nutrition. 2014 Jul-Aug;30(7-8 Suppl):S21-5.] LC3 plays a key role in muscle breakdown.

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A year ago Kirk-Ballard published an animal study in PLoS One which showed that mice with diabetes do develop larger muscles when their food contains 1 percent PMI 5011.

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Going by the number of studies Pennington has produced in recent years on the anticatabolic effect of Artemisia dracunculus, they are taking PMI 5011 seriously. [Nutrition. 2014 Jul-Aug;30(7-8 Suppl):S43-51.] [Nutrition. 2014 Jul-Aug;30(7-8 Suppl):S59-66.] [Diabetes Obes Metab. 2014 Aug;16(8):728-38.] [J Proteomics. 2012 Jun 18;75(11):3199-210.] [Diabetes. 2012 Mar;61(3):597-605.] [J Nutr Biochem. 2011 Jan;22(1):71-8.] [Phytother Res. 2010 Sep;24(9):1278-84.] [Metabolism. 2008 Jul;57(7 Suppl 1):S58-64.]

Speculation

The figure below, which is from Kirk-Ballard’s PhD thesis [etd.lsu.edu] published in 2012, summarizes how PMI 5011 probably works.

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Mechanism

In doping circles insulin users notice that their gear loses its anabolic effect after a while. Their muscle cells start to lose their sensitivity to insulin, in a way that resembles what happens to muscle tissue in obese diabetics. It may just be that the active ingredients in Artemisia dracunculus can slow this process down. Or prevent it.

An ethanolic extract of Artemisia dracunculus L. regulates gene expression of ubiquitin-proteasome system enzymes in skeletal muscle: potential role in the treatment of sarcopenic obesity.

Abstract

OBJECTIVE:

Obesity is linked to insulin resistance, a primary component of metabolic syndrome and type 2 diabetes. The problem of obesity-related insulin resistance is compounded when age-related skeletal muscle loss, called sarcopenia, occurs with obesity. Skeletal muscle loss results from elevated levels of protein degradation and prevention of obesity-related sarcopenic muscle loss will depend on strategies that target pathways involved in protein degradation. An extract from Artemisia dracunculus, termed PMI 5011, improves insulin signaling and increases skeletal muscle myofiber size in a rodent model of obesity-related insulin resistance. The aim of this study was to examine the effect of PMI 5011 on the ubiquitin-proteasome system, a central regulator of muscle protein degradation.

METHODS:

Gastrocnemius and vastus lateralis skeletal muscle was obtained from KK-A(y) obese diabetic mice fed a control or 1% (w/w) PMI 5011-supplemented diet. Regulation of genes encoding enzymes of the ubiquitin-proteasome system was determined using real-time quantitative reverse transcriptase polymerase chain reaction.

RESULTS:

Although MuRF-1 ubiquitin ligase gene expression is consistently down-regulated in skeletal muscle, atrogin-1, Fbxo40, and Traf6 expression is differentially regulated by PMI 5011. Genes encoding other enzymes of the ubiquitin-proteasome system ranging from ubiquitin to ubiquitin-specific proteases are also regulated by PMI 5011. Additionally, expression of the gene encoding the microtubule-associated protein-1 light chain 3 (LC3), a ubiquitin-like protein pivotal to autophagy-mediated protein degradation, is down-regulated by PMI 5011 in the vastus lateralis.

CONCLUSION:

PMI 5011 alters the gene expression of ubiquitin-proteasome system enzymes that are essential regulators of skeletal muscle mass. This suggests that PMI 5011 has therapeutic potential in the treatment of obesity-linked sarcopenia by regulating ubiquitin-proteasome-mediated protein degradation.

PMID: 24985101 [PubMed - in process] PMCID: PMC4082804 [Available on 2015/7/1]

Source: http://www.ncbi.nlm.nih.gov/pubmed/24985101

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