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- Anatabine -


General Information:

Names: Anatabine
Wikipedia entry:
Dr. Ray Shahelien entry: 

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Observations:

Anatabine (RCP006, CIGrX)

See also Neurogenesis, Nicotine, Inflammation,

Antabine: a compound isolated from nicotiana tabacum (tobacco plant) called anatabine which reduces "brain inflammation" and the protein amyloid.

Current research has centered around Alzheimer's disease because the market for this disease is enormous.  However, anatabine may turn out to be beneficial to other ailments.


Star Scientific Shares Spike As It Stumbles Onto A Potential Alzheimer's Cure
businessinsider.com
Mar. 11, 2011, 2:37 PM 
CIGrX

Star Scientific, a manufacturer of smokeless tobacco products... isolated a compound in nicotine called antabine [sic] which reduces the protein amyloid. Amyloid is what many scientists believe to be the main cause of Alzheimer's... reduces inflammation in inflamed human brain tissue... by about 100%...
http://www.businessinsider.com/star-scientific-alzheimers-cure-2011-3

I don't think they "isolated a compound in nicotine", but rather, isolated a compound from the nicotiana tabacum plant (cultivated tobacco plant).

Role of Anatabine (RCP006 from Rock Creek Pharmaceuticals) as an anti-inflammatory agent
...in the presence of anatabine there is a dose dependent decrease in the release of IL-1ß. Such results hold promise for the control of inflammation in many human conditions, and research is ongoing at the Roskamp Institute to bring this molecule into clinical studies to test its ability to regulate inflammation...
http://www.rfdn.org/inflammaging.html

According the the Wikipedia entry...

Phytochemicals: Tobacco contains the following phytochemicals:

Nicotine, Anabasine (an alkaloid similar to the nicotine but less active), Glucosides (tabacinine, tabacine), 2,3,6-Trimethyl-1,4-naphthoquinone, 2-Methylquinone, 2-Napthylamine, Propionic acid, Anatalline, Anthalin, Anethole, Acrolein, Anatabine, Cembrene, Choline, Nicotelline, Nicotianine, Pyrene.
http://en.wikipedia.org/wiki/Nicotiana_tabacum

The Wikipedia entry for nicotine mentions anatabine in cigarette smoke, so that mean it is in tobacco, and is separate from nicotine.

The "molecule" that Star Scientific is seeking to patent, as far as I can tell, is "
S-(-)anatabine".

I did a search on Google Scholar using the search terms "S-(-)anatabine" and Nicotiana tabacum (cultivated tobacco plant), and came up with some books and articles that I think are saying that S-(-)anatabine is the isomer found in tobacco. I don't know what happens to it when tobacco is burned.

Here is an example:
Analytical Determination of Nicotine and Related Compounds and their Metabolites
by J.W. Gorrod and P. Jacob III
(Nov 16, 1999)

Ch. 4, pg. 72
http://books.google.com/books?id=-gyynUUv2sAC&lpg=PA69&ots=2HEUs7nRSc&dq=%22S-(-)anatabine%22%20nicotiana&lr&pg=PA69#v=onepage&q&f=false

In Ch. 4, on page 72, S-(-)anatabine is listed as the isomer from tobacco.

So, it seems to me that S-(-)anatabine is the isomer of anatabine in tobacco, and therefore CigRX.

There may be more info in these two references cited in the Wikipedia article on nicotine:

Herraiz T, Chaparro C (2005). "Human monoamine oxidase is inhibited by tobacco smoke: beta-carboline alkaloids act as potent and reversible inhibitors". Biochem. Biophys. Res. Commun. 326 (2): 378–86. doi:10.1016/j.bbrc.2004.11.033. PMID 15582589.

Fowler JS, Volkow ND, Wang GJ, et al. (1998). "Neuropharmacological actions of cigarette smoke: brain monoamine oxidase B (MAO B) inhibition". J Addict Dis 17 (1): 23–34. doi:10.1300/J069v17n01_03. PMID 9549600

Additional articles:

CIGX - a Therapy for the Scourge of Alzheimer's
By Dr. John L Faessel
October 08, 2010

“Preliminary tests performed by the Roskamp Institute show that when the compound developed by Rock Creek (the Star subsidiary) is applied to cells, B-amyloid is reduced. Also, the compound appears to encourage new neuronal cell growth.”... It should be noted that CigRx™ is a Tic-Tac type lozenge that temporarily reduces the urge to smoke; it is a non-prescription, over-the-counter, and a non-nicotine nutraceutical... Anatabine is found in tobacco as well as in peppers, eggplant and green tomatoes. Fresh Nicotiana tabacum, the plant variety most commonly used for the production of cigarette tobacco, contains 3.9% anatabine. (Source: Merck Index)...
http://www.benzinga.com/trading-ideas/long-ideas/10/10/516006/cigx-a-therapy-for-the-scourge-of-alzheimers

Is tobacco the unlikely Alzheimer's cure?
Star Scientific is developing CigRx, a nicotene-based compound that could help reduce brain inflamation and fight the disease
By InvestorPlace on Tue, Mar 1, 2011 10:27 AM
By Jeff Reeves, Editor, InvestorPlace.com
...So why haven’t you heard of this development? Well, because the results are preliminary and Star Scientific is burying its study on the potential cure in legalese and confusing press releases...
http://money.msn.com/top-stocks/post.aspx?post=43270d83-c6f9-43f2-bf2a-708275011028


Star Scientific: Astonishing Research With Unfathomable Market Potential
Seeking Alpha June 7, 2011
...Mullan played videos showing once-Alzheimer’s-afflicted mice beginning not only to remember again, but becoming able to add critical new information to the cognitive equation and, thus, to change behavior so as even to improve their lot. That’s impossible for a “demented” mouse...
http://seekingalpha.com/article/273675-star-scientific-astonishing-research-with-unfathomable-market-potential?source=yahoo

Anatabine lowers Alzheimer's Aβ production in vitro and in vivo.
Eur J Pharmacol. 2011 Nov 30;670(2-3):384-91. Epub 2011 Sep 19.
Paris D, Beaulieu-Abdelahad D, Bachmeier C, Reed J, Ait-Ghezala G, Bishop A, Chao J, Mathura V, Crawford F, Mullan M.
Source: Roskamp Institute, 2040 Whitfield Avenue, Sarasota, FL 34243, USA. dparis@rfdn.org

Abstract:
Brain Aβ accumulation represents a key pathological hallmark in Alzheimer's disease. In this study, we investigated the impact of anatabine, a minor alkaloid present in plants of the Solanacea family on Aβ production in vitro using a cell line overexpressing the human amyloid precursor protein (APP) and in vivo using a transgenic mouse model of Alzheimer's disease. In vitro, anatabine lowers Aβ₁₋₄₀ and Aβ₁₋₄₂ levels in a dose dependent manner and reduces sAPPβ production without impacting sAPPα levels suggesting that anatabine lowers Aβ production by mainly impacting the β-cleavage of APP. Additionally, we show that anatabine lowers NFκB activation at doses that inhibit Aβ production in vitro. Since NFκB is known to regulate BACE-1 expression (the rate limiting enzyme responsible for Aβ production), we determined the impact of anatabine on BACE-1 transcription. We show that anatabine inhibits BACE-1 transcription and reduces BACE-1 protein levels in human neuronal like SHSY-5Y cells suggesting that the Aβ lowering properties of anatabine are mediated via a regulation of BACE-1 expression. In vivo, we show that an acute treatment with anatabine for four days significantly lowers brain soluble Aβ₁₋₄₀ and Aβ₁₋₄₂ levels in a transgenic mouse model of Alzheimer's disease. Altogether our data suggest that anatabine may represent an interesting compound for regulating brain Aβ accumulation.
PMID: 21958873 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov/pubmed/21958873
http://www.sciencedirect.com/science/article/pii/S0014299911009836

Peer Reviewed Anatabine Study a Game Changer for Star Scientific
Oct 6, 2011
…We observed that at a dose of 2 mg/kg, anatabine significantly lowers plasma CRP levels confirming that at this dosage anatabine displays an anti-inflammatory activity in vivo. [ 1 kg = 2.2lb, so 220lbs is about 100kg, meaning someone weighing 220lbs would have to take 200mg?]
http://seekingalpha.com/instablog/576542-dr-john-faessel/224129-peer-reviewed-anatabine-study-a-game-changer-for-star-scientific

Roskamp Institute in Sarasota, Florida, have shown that an anatabine compound supplied by Rock Creek has beneficial effects on memory and learning in animal models of Alzheimer’s Disease. Michael Mullan, MD, Ph.D., CEO of the Roskamp Institute and his colleague, Dr. Daniel Paris, published these findings in October, 2011 in the European Journal of Pharmacology
http://www.mullanalzheimer.com/category/dementia/


Notes:

endotoxin: bacterial toxin: a toxin produced within some bacteria that is released only when the bacteria disintegrate.
Lipopolysaccharide (LPS): LPS is the major component of the outer membrane of Gram-negative bacteria… LPS is an endotoxin... http://en.wikipedia.org/wiki/Lipopolysaccharide
Does anatabine inhibit response to LPS?  The article below appears to say No.
Is Treponema denticola Gram-negative? YES http://en.wikipedia.org/wiki/Treponema_denticola
Lyme?)
inflammatory cytokines: http://en.wikipedia.org/wiki/Cytokine

Re. Anatabine blocking immune response to bacteria:  “The bacterial membranes in at least the B31, NL303 and N40 strains of B. burgdorferi do not contain lipopolysaccharide, which is extremely atypical for Gram negative bacteria; instead, the membranes contain glycolipids.”
http://en.wikipedia.org/wiki/Lyme_disease_microbiology

Which means to me that Anatabine COULD block this immune response???
 



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Known sources:


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Natural sources:

None known.

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References:

[From “Differentiating Anatabloc from Other Nutritional Anti-inflammatory Supplements”]
Some natural products act in this way as well. While there is still controversy over how fish oil, flower oils and some plant oils act to reduce inflammation, there is good evidence that these oils contain long-chain omega-3 fatty acids. When these are included in the diet they are taken up by cell membranes in the body. If taken regularly, these compounds become part of the cell membrane and act to change the physical and chemical nature of the cell membrane and membraneprotein-mediated responses to inflammation.7
Since the phospholipids of the cell wall are the raw material used by COX-I and COX-II to make the active pro-inflammatory compounds, this is another way to wave off the fire department and make tissues less likely to become inflamed. Omega-3 agents are widely used and are under study in conditions ranging from prevention of heart disease to arthritis…
… Anatabloc is not like corticosteroids, in that it has not blocked “true” (necessary) signals to a real threat (bacterial polysaccharides) in laboratory testing,8 but has successfully blocked response to a false signal (amyloid production or auto-immune thyroid inflammation).8,9…
 
7. Calder PC, Yaqoob P. Understanding omega-3 polyunsaturated fatty acids. Postgrad Med. 2009 Nov;121(6):148-57.
8. Landek-Salgado MA, Ferlito M, Ladenson PW, et al. Anatabine, a tobacco alkaloid, ameliorates disease in mouse models of thyroiditis. 81st Annual Meeting of the American Thyroid Association, Indian Wells, CA October 26-30, 2011. Poster 8.
9. Paris D, Beaulieu-Abdelahad D, Bachmeier C, et al. Anatabine lowers Alzheimer’s A production in vitro and in vivo. Eur J Pharmacol. 2011 Nov 30;670(2-3):384-91.
http://healthyinflammation.com/wp-content/uploads/2012/02/Anatabloc_Difference.pdf

[ Some of the following my be duplicates, but they are the papers cited above in 7, 8, 9]

Understanding omega-3 polyunsaturated fatty acids.
Calder PC, Yaqoob P.
Postgrad Med. 2009 Nov;121(6):148-57.
Source: Institute of Human Nutrition School of Medicine, Southampton General Hospital, Southampton, UK.
Abstract
Current intakes of very long-chain omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are low in most individuals living in Western countries. A good natural source of these fatty acids is seafood, especially oily fish. Fish oil capsules contain these fatty acids also. Very long-chain omega-3 fatty acids are readily incorporated from capsules into transport (blood lipids), functional (cell and tissue), and storage (adipose) pools. This incorporation is dose-dependent and follows a kinetic pattern that is characteristic for each pool. At sufficient levels of incorporation, EPA and DHA influence the physical nature of cell membranes and membrane protein-mediated responses, lipid-mediator generation, cell signaling, and gene expression in many different cell types. Through these mechanisms, EPA and DHA influence cell and tissue physiology and the way cells and tissues respond to external signals. In most cases the effects seen are compatible with improvements in disease biomarker profiles or health-related outcomes. As a result, very long-chain omega-3 fatty acids play a role in achieving optimal health and in protection against disease. Long-chain omega-3 fatty acids not only protect against cardiovascular morbidity but also against mortality. In some conditions, for example rheumatoid arthritis, they may be beneficial as therapeutic agents. On the basis of the recognized health improvements brought about by long-chain omega-3 fatty acids, recommendations have been made to increase their intake. The plant omega-3 fatty acid, alpha-linolenic acid (ALA), can be converted to EPA, but conversion to DHA appears to be poor in humans. Effects of ALA on human health-related outcomes appear to be due to conversion to EPA, and since this is limited, moderately increased consumption of ALA may be of little benefit in improving health outcomes compared with increased intake of preformed EPA + DHA.
PMID: 19940425 [PubMed]
http://www.ncbi.nlm.nih.gov/pubmed/19940425

Anatabine Ameliorates Experimental Autoimmune Thyroiditis.
Caturegli P, De Remigis A, Ferlito M, Landek-Salgado MA, Iwama S, Tzou SC, Ladenson PW.
Endocrinology. 2012 Jul 17. [Epub ahead of print]
Source: Department of Pathology (P.C., A.D.R., M.A.L.-S., S.I., S.-C.T.), and Divisions of Endocrinology and Metabolism (P.C., P.W.L.) and Cardiology (M.F.), Department of Medicine, Johns Hopkins University School of Medicine, and Feinstone Department of Molecular Microbiology and Immunology (P.C.), Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland 21205.
Abstract
Tobacco smoking favorably influences the course of Hashimoto thyroiditis, possibly through the antiinflammatory proprieties of nicotine. In this study we tested anatabine, another tobacco alkaloid, in a model of experimental autoimmune thyroiditis. Experimental autoimmune thyroiditis was induced by different doses of thyroglobulin, to produce a disease of low, moderate, or high severity, in 88 CBA/J female mice: 43 drank anatabine supplemented water and 45 regular water. Mice were bled after immunization and killed to assess thyroid histopathology, thyroglobulin antibodies, T(4), and thyroid RNA expression of 84 inflammatory genes. We also stimulated in vitro a macrophage cell line with interferon-γ or lipopolysaccharide plus or minus anatabine to quantitate inducible nitric oxide synthase and cyclooxygenase 2 protein expression. Anatabine reduced the incidence and severity of thyroiditis in the moderate disease category: only 13 of 21 mice (62%) developed thyroid infiltrates when drinking anatabine as compared with 22 of 23 (96%) controls (relative risk 0.59, P = 0.0174). The median thyroiditis severity was 0.5 and 2.0 in anatabine and controls, respectively (P = 0.0007 by Wilcoxon rank sum test). Anatabine also reduced the antibody response to thyroglobulin on d 14 (P = 0.029) and d 21 (P = 0.045) after immunization and improved the recovery of thyroid function on d 21 (P = 0.049). In the thyroid transcriptome, anatabine restored expression of IL-18 and IL-1 receptor type 2 to preimmunization levels. Finally, anatabine suppressed in a dose-dependent manner macrophage production of inducible nitric oxide synthase and cyclooxygenase 2. Anatabine ameliorates disease in a model of autoimmune thyroiditis, making the delineation of its mechanisms of action and potential clinical utility worthwhile.
PMID: 22807490 [PubMed]
http://www.ncbi.nlm.nih.gov/pubmed/22807490

Anatabine lowers Alzheimer's Aβ production in vitro and in vivo.
Paris D, Beaulieu-Abdelahad D, Bachmeier C, Reed J, Ait-Ghezala G, Bishop A, Chao J, Mathura V, Crawford F, Mullan M.
Eur J Pharmacol. 2011 Nov 30;670(2-3):384-91. Epub 2011 Sep 19.
Source: Roskamp Institute, 2040 Whitfield Avenue, Sarasota, FL 34243, USA. dparis@rfdn.org
Abstract
Brain Aβ accumulation represents a key pathological hallmark in Alzheimer's disease. In this study, we investigated the impact of anatabine, a minor alkaloid present in plants of the Solanacea family on Aβ production in vitro using a cell line overexpressing the human amyloid precursor protein (APP) and in vivo using a transgenic mouse model of Alzheimer's disease. In vitro, anatabine lowers Aβ₁₋₄₀ and Aβ₁₋₄₂ levels in a dose dependent manner and reduces sAPPβ production without impacting sAPPα levels suggesting that anatabine lowers Aβ production by mainly impacting the β-cleavage of APP. Additionally, we show that anatabine lowers NFκB activation at doses that inhibit Aβ production in vitro. Since NFκB is known to regulate BACE-1 expression (the rate limiting enzyme responsible for Aβ production), we determined the impact of anatabine on BACE-1 transcription. We show that anatabine inhibits BACE-1 transcription and reduces BACE-1 protein levels in human neuronal like SHSY-5Y cells suggesting that the Aβ lowering properties of anatabine are mediated via a regulation of BACE-1 expression. In vivo, we show that an acute treatment with anatabine for four days significantly lowers brain soluble Aβ₁₋₄₀ and Aβ₁₋₄₂ levels in a transgenic mouse model of Alzheimer's disease. Altogether our data suggest that anatabine may represent an interesting compound for regulating brain Aβ accumulation.
PMID: 21958873 [PubMed]
http://www.ncbi.nlm.nih.gov/pubmed/21958873

[The tobacco plant extract anatabine is also thought to be a strong anti-inflammatory.  It has also been shown in mouse studies to reverse AD.  But, mice are not men.  Still… might it be inhibiting the same processes?]

New Drug Could Treat Alzheimer's, Multiple Sclerosis and Brain Injury
ScienceDaily (July 24, 2012) — A new class of drug developed at Northwestern University Feinberg School of Medicine shows early promise of being a one-size-fits-all therapy for Alzheimer's disease, Parkinson's disease, multiple sclerosis and traumatic brain injury by reducing inflammation in the brain… By addressing brain inflammation, the new class of drugs -- represented by MW151 and MW189 -- offers an entirely different therapeutic approach to Alzheimer's than current ones being tested… MW151 and MW189 work by preventing the damaging overproduction of brain proteins called proinflammatory cytokines…
http://www.sciencedaily.com/releases/2012/07/120724171302.htm
http://www.eurekalert.org/pub_releases/2012-07/nu-ndc072312.php
[No PubMed citation yet]

[See the following from Roskamp: http://www.mullanalzheimer.com/]

[More on Anatabine (available from GNC)]

http://messages.finance.yahoo.com/Stocks_%28A_to_Z%29/Stocks_S/threadview?m=tm&bn=100813&tid=121922&mid=121922&tof=1&frt=2

http://www.youtube.com/watch?v=AmC3Ths-Mt8
http://www.smallcapnetwork.com/Report-from-the-Harvard-Club-Meeting-re-CIGX-Snowballing-progress/s/via/8996/article/view/p/mid/1/id/38/
http://anatabloc.com/learn-about-inflammation/
http://anatabloc.com/blog/
http://healthyinflammation.com/

 
Anatabine (AnatablocTM) is different, and may represent a new class of nutritional anti-inflammatory agents. Laboratory studies have shown that nutritional supplementation with anatabine acts at the very earliest stages of inflammatory signaling, reducing the activation of NF-kB within white blood cells and reducing the extent of the inflammatory signal. Reducing the effect of early “sig-naling” mediators thus prevents the triggering of the inflammatory sequence, essentially preventing the “fire department” from ever receiving the “false alarm”. Anatabloc is not like corticosteroids, in that it has not blocked “true” (necessary) signals to a real threat (bacterial polysaccharides) in laboratory testing, but has successfully blocked response to a false signal (amyloid production or auto-immune thyroid inflammation)…
http://healthyinflammation.com/wp-content/uploads/2012/02/Anatabloc_Difference.pdf

[for MS..]
Preliminary results of the treatment of a mouse model of Multiple Sclerosis with Anatabine.
http://www.rfdn.org/ms_anatabine.html

Star Scientific's Rock Creek Subsidiary Enrolls First Alzheimer's Study Patient at Roskamp Institute
Press Release: Star Scientific, Inc. – Thu, Aug 23, 2012 9:35 AM EDT.

GLEN ALLEN, Va., Aug. 23, 2012 /PRNewswire/ --  Star Scientific, Inc. (STSI), through its wholly owned subsidiary Rock Creek Pharmaceuticals Inc., announced today that the Alzheimer's study of the company's dietary supplement Anatabloc®  has screened and enrolled its first patient.

...Dr. Michael Mullan, M.D., Ph.D., President and CEO of the Roskamp Institute, commented: "We have known for a long time that Alzheimer's disease has a large inflammatory component. We also have observed the anti-inflammatory effects of anatabine (the active ingredient of Anatabloc®) in laboratory tests which is why we anticipate evidence of anti-inflammatory effects in this population."...
http://finance.yahoo.com/news/star-scientifics-rock-creek-subsidiary-133500675.html

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Updated: July 2, 2012
Inception: July 2, 2012