Capsaicin for Postherpetic neuralgia....

About Capsaicin :

Capsaicin,(8-methyl-N-vanillyl-6-nonenamide, (CH₃)₂CHCH=CH(CH₂)₄CONHCH₂C₆H₃-4-(OH)-3-(OCH₃)) is the active component of chili peppers, which are plants belonging to the genus Capsicum. It is an irritant for mammals, including humans, and produces a sensation of burning in any tissue with which it comes into contact. Capsaicin and several related compounds are called capsaicinoids and are produced as a secondary metabolite by chili peppers, probably as deterrents against certain herbivores and fungi. Pure capsaicin is a hydrophobic, colorless, odorless, crystalline to waxy compound.

We know that many pain killer gels are using this and even some companies are trying to establish the anti cancer activity (prostate cancer).

Mode of action :

The burning and painful sensations associated with capsaicin result from its chemical interaction with sensory neurons. Capsaicin, as a member of the vanilloid family, binds to a receptor called the vanilloid receptor subtype 1 (VR1). The resulting depolarization of the neuron stimulates it to signal the brain. By binding to the VR1 receptor, the capsaicin molecule produces the same sensation that excessive heat or abrasive damage would cause, explaining why the spiciness of capsaicin is described as a burning sensation.

Now FDA has approved the Qutenza(TM) (capsaicin) 8% patch, the first and only product containing prescription strength capsaicin, for the management of neuropathic pain due to postherpetic neuralgia (PHN). As per the claim by the company, Qutenza works by targeting certain pain nerves in the area of skin where pain is being experienced. The Qutenza patch is applied by a physician or a healthcare professional. Clinical studies have shown that PHN pain can be reduced for up to 12 weeks following a single one-hour treatment. Up to four patches may be used and patches may be cut to conform to the size and shape of the painful area.

Source : http://ngsx.client.shareholder.com/releasedetail.cfm?ReleaseID=424559

Active ingredient of pungent substances slows growth of breast cancer cells

Capsaicin, an active ingredient of pungent substances such as chilli or pepper, inhibits the growth of breast cancer cells. This was reported by a team headed by the Bochum-based scent researcher Prof Dr Dr Dr habil Hanns Hatt and Dr Lea Weber, following experiments in cultivated tumour cells. In the journal "Breast Cancer - Targets and Therapy", the researchers from Ruhr-Universität Bochum presented their findings together with colleagues from the Augusta clinics in Bochum, the hospital Herz-Jesu-Krankenhaus Dernbach and the Centre of Genomics in Cologne.

The experiments were carried out with the SUM149PT cell culture, a model system for a particularly aggressive type of breast cancer, i.e. the triple-negative type. Chemotherapy is currently the only available treatment for this type of cancer. 

Frequently occurring receptor

In the cultivated cells, the team detected a number of typical olfactory receptors. One receptor occurred very frequently; it is usually found in the fifth cranial nerve, i.e. the trigeminal nerve. It belongs to the so-called Transient Receptor Potential Channels and is named TRPV1. That receptor is activated by the spicy molecule capsaicin as well as by helional - a scent of fresh sea breeze.

 (helional)  Capsaicin

In collaboration with Dr Gabriele Bonatz from the Augusta clinics in Bochum (Brustzentrum), Hatt's team confirmed the existence of TRPV1 in tumour cells in nine different samples from patients suffering from breast cancer.

Cancer cells die

The researchers activated the TRPV1 receptor in the cell culture with capsaicin or helional, by adding the substances to the culture for a period of several hours or days. As a result, the cancer cells divided more slowly. Moreover, the treatment caused tumour cells to die in larger numbers. The surviving cells were no longer able to move as quickly as heretofore; this implies that their ability to form metastases in the body was impeded.

"If we could switch on the TRPV1 receptor with specific drugs, this might constitute a new treatment approach for this type of cancer," says Hanns Hatt. An intake via food or inhalation is insufficient for this purpose.

Effective in mice

Earlier studies had demonstrated that the chemical arvanil - with a chemical make-up similar to that of the spicy molecule capsaicin - was effective against brain tumours in mice; it reduces tumour growth in the animals. Due to its side effects, however, this substance is not approved for humans. In addition to capsaicin and helional, the endovanilloids, produced naturally in the body, also activate the TRPV1 receptor.

New evidence that chili pepper ingredient fights fat..

In continuation of my update on Capsaicin may cause weight loss....

In an effort to find out, the scientists lead by Jong Won Yun of of Daegu University, Kyungsan, Korea,  fed high-fat diets with or without capsaicin to lab rats used to study obesity. The capsaicin-treated rats lost 8 percent of their body weight and showed changes in levels of at least 20 key proteins found in fat. The altered proteins work to break down fats.

"These changes provide valuable new molecular insights into the mechanism of the antiobesity effects of capsaicin the scientists say"...

Through secretion of adipokines into the blood, adipose tissue plays a central role in development of these syndromes. In particular, white adipose tissue (WAT) functions as an energy storage organ through formation of triacylglycerol and release of fatty acids into the bloodstream during a shortage of energy. In association with overnutrition, excess WAT play a major role in obesity and obesity-related disorders through dysregulation of adipokine secretion from WAT. Therefore, inhibition of excess WAT can be an efficient strategy for prevention of obesity and metabolic disorders.

Researchers concludes that, thermogenesis and lipid metabolism related proteins were markedly altered upon capsaicin treatment in WAT, suggesting that capsaicin may be a useful phytochemical for attenuation of obesity....

Ref:http://pubs.acs.org/stoken/presspac/presspac/full/10.1021/pr901175w

Hyperthermia-free TRPV1 antagonists - new category of pain killers?

The transient receptor potential cation channel, subfamily V, member 1 (TRPV1), also known as the capsaicin receptor is a protein which in humans is encoded by the TRPV1 gene. This protein is a member of the TRPV group of transient receptor potential family of ion channels. TRPV1 is a nonselective cation channel that may be activated by a wide variety of exogenous and endogenous physical and chemical stimuli. The best known activators of TRPV1 are heat greater than 43°C,  pepper like chemicals  (capsaicin - most of us might have used gel containing capsaicin) and proton. The same channel is responsible for pain caused by these diverse stimuli. For a number of years scientists have focused on the development of TRPV1 antagonists, but have been stymied by the dangerous hyperthermia side effect.

Now researchers lead by  Dr. Andrej A. Romanovsky,  have come up with an explanation for the side effect and how one can avoid the side effect. 

Researchers found that the hyperthermic effect has the highest sensitivity to the extent of TRPV1 blockade in the proton mode (0.43 to 0.65) with no to moderate sensitivity in the capsaicin mode (–0.01 to 0.34) and no sensitivity in the heat mode (0.00 to 0.01). Hence they conclude that hyperthermia-free TRPV1 antagonists do not block TRPV1 activation by protons, even if they are potent blockers of the heat mode, and that decreasing the potency to block the capsaicin mode may further decrease the potency to cause hyperthermia. Researchers suggests that the  drugs that are being developed should be designed not to block the proton activation of TRPV1.

Scientists believe that this new generation of painkillers will be effective in treating pain related to a number of conditions including cancer, AIDS, migraines and diabetes. Let us hope some good news from these class of compounds....

Ref : Abstract of the paper

Peppers may increase energy expenditure in people tying to lose weight....

We know that, Capsinoids, which include capsiate, dihydrocapsiate,  and nordihydrocapsiate, are substances naturally present in chili peppers. Although they are structurally similar to capsaicin, the substance that causes pungency in hot peppers, they largely lack that characteristic. Capsinoids have an estimated “hot taste threshold” which is about 1000 times lower than of that of capsaicin. Many health effects have been ascribed to capsaicin and capsinoids, both anecdotally and through scientific study, including anticancer, anti-inflammatory, analgesic activity, and weight management.

Now researchers form UCLA's Center for Human Nutrition in Los Angeles, CA, lead by Dr. David Heber have come up with more interesting findings, i.e., "peppers may increase energy expenditure in people tying to lose weight". 


In a study designed to test the weight-loss potential of this DCT containing, non-spicy cousin of hot peppers, researchers at the UCLA Center for Human Nutrition set out to document its ability to increase heat production in human subjects consuming a weight-loss diet.

Under the direction of Dr. David Heber (Professor of Medicine and Public Health), they recruited 34 men and women who were willing to consume a very low-calorie liquid meal replacement product for 28 days. The researchers then randomized the subjects to take either placebo pills or supplements containing the non-burning DCT pepper analog. Two dosage levels of dihydrocapsiate DCT (see above structure ) were tested. At the beginning and end of the study, body weight and body fat were assessed, and the researchers determined energy expenditure (heat production) in each subject after he or she consumed one serving of the test meal.

The data provided convincing evidence that, at least for several hours after the test meal was consumed, energy expenditure was significantly increased in the group consuming the highest amount of DCT. In fact, it was almost double that of the placebo group. This suggests that eating this pepper-derived substance that doesn't burn can have the same potential benefit as hot peppers at least in part by increasing food-induced heat production. They were also able to show that DCT significantly increased fat oxidation, pushing the body to use more fat as fuel. This may help people lose weight when they consume a low-calorie diet by increasing metabolism. 


However, that a limitation to this study was that, the researchers only tested the effect of DCT on the thermic response to a single meal. Heber and colleagues also point out that that there might be a different effect in lean vs. obese subjects. But to their credit, this was the first study ever conducted to examine the potential health benefits of DCT consumed together with a very low calorie diet....

Ref : Dr. David Heber et. al., FASEB Journal 

Heat in Chili Peppers Can Ease Sinus Problems, Research Shows

In continuation of my update on the usefulness of   Casaicin...

We know that, Capsicum annum contains capsaicin, which is the main component of chili peppers and produces a hot sensation. Capsaicin is also the active ingredient in several topical medications used for temporary pain relief. It is approved for use by the U.S. Food and Drug Administration and is available over the counter.

Now researchers lead by  Jonathan A. Bernstein of University of Cincinnati College of Medicine, Cincinnati, Ohio, have come up with an interesting finding about Capsicum annum.  As per the claim by the researchers a nasal spray containing an ingredient derived from hot chili peppers (Capsicum annum) may help people "clear up" certain types of sinus inflammation. Researchers add that, study which showed that participants who used a nasal spray with Capsicum reported a faster onset of action or relief, on average within a minute of using the spray, than the control group and the spray is safe  and effective on non-allergic rhinitis.

Interestingly, this is the first controlled trial where capsaicin was able to be used on a continuous basis to control symptoms. It is considered a significant advance, because of the fact  that in  the previous trials the ingredient was too hot to administer without anesthesia.

Ref : http://www.annallergy.org/article/S1081-1206%2811%2900383-8/abstract

Chili peppers for a healthy gut: Spicy chemical may inhibit gut tumors

In continuation of my update on capsaicin

Researchers report that dietary capsaicin – the active ingredient in chili peppers – produces chronic activation of a receptor on cells lining the intestines of mice, triggering a reaction that ultimately reduces the risk of colorectal tumors....

Chili peppers for a healthy gut: Spicy chemical may inhibit gut tumors  

Chili peppers may cause weight loss and fight fat buildup, says study

In one of my earlier blog article, titled "Peppers may increase energy expenditure in people tying to lose weight"....have mentioned that researchers form UCLA's Center for Human Nutrition in Los Angeles, CA, lead by Dr. David Heber claimed that "peppers may increase energy expenditure in people tying to lose weight". 

Now interestingly, Steven C. Powell, has come up with new evidence that capsaicin (see below structure), the stuff that gives chili peppers their kick, may cause weight loss and fight fat buildup by triggering certain beneficial protein changes in the body. Their study, which could lead to new treatments for obesity, appears in ACS' monthly Journal of Proteome Research........details ...

Ref : Chili peppers may cause weight loss and fight fat buildup, says study  

Chillies for diabetes: Study

In continuation of my update on diabetes and its treatment,  I find the following study interesting.  In fact, I had a blog article  , where in the authors claim that Capsaicin may cause weight loss and I think these findings are of great significance........

Chillies for diabetes: Study

 

HSS involving resiniferatoxin receives U.S. patent to alleviate intractable pain

We know that, Resiniferatoxin (RTX) is a naturally occurring, ultrapotent capsaicin analog that activates the vanilloid receptor in a subpopulation of primary afferent sensory neurons involved in nociception (the transmission of physiological pain). RTX causes an ion channel in the plasma membrane of sensory neurons — the transient receptor potential vanilloid 1 — to become permeable to cations, most particularly the calcium cation; this evokes a powerful irritant effect followed by desensitization and analgesia. Research is being conducted at the National Institutes of Health and the University of Pennsylvania to design a novel class of analgesics from the latex of resin spurge (Euphorbia resinifera), a cactus-like plant commonly found in Morocco that contains high concentrations of RTX. Resiniferatoxin has a rating of 16,000,000,000 on the Scoville Scale making it one of the highest rated substances known.

Now U. S. Patent and Trademark Office recently issued a patent to the U. S. Department of Health and Human Services involving resiniferatoxin, or RTX, an experimental compound that represents a potential new class of drugs to alleviate the intractable pain that can occur in people with advanced cancer, severe arthritis, and other extremely chronic conditions.

HSS involving resiniferatoxin receives U.S. patent to alleviate intractable pain

Some new insights into the molecular mechanisms of pain perception....

UT Health Science Center researchers,  lead by Dr. Kenneth M. Hargreaves,  found a new family of fatty acids  produced by the body itself, that play an important role in the biology of pain.

Researchers evaluated the hypothesis that,  the heat sensitivity of TRPV1 is regulated by the generation of endogenous ligands and they found that heat-generated linoleic acid metabolites comprise a family of physiologically relevant TRPV1 agonists that contribute to the heat responsiveness of this channel. More interestingly the results also suggest, a previously unknown mechanism by which TRPV1 might mediate biological actions of oxidized linoleic acid metabolites in conditions such as inflammation and hypotension.

Encouraged by the facts that,  heat activation of TRPV1 (mechanistically distinct from capsaicin sensitivity) appears to occur in a membrane-delimited fashion (during short periods), its dependence on C terminus or voltage gating and their  own results, researchers proposed that heating leads to the generation of oxidized linoleic acid products in the plasma membrane that are important for TRPV1 responses to noxious thermal stimuli. It should be noted that in inflammatory diseases, relatively high levels of HODEs are observed even in extracellular compartments.

The data indicate that 9-HODE and 13-HODE substantially contribute to the heat responsiveness of TRPV1 in vitro and in vivo (apart from intrinsic heat sensitivity of TRPV1). Researchers claim that, heat directly activates TRPV1 with a subsequent generation of endogenous ligands that further amplifies the heat response and biological actions occur only in WT neurons and not neurons from TRPV1.

Researchers conclude by their in vitro and in vivo results that, blockade of the endogenous linoleic acid metabolites substantially decreased responses to thermal stimuli and the heat sensitivity of another member of the TRP family, TRPV4, is mediated via generation of a soluble ligand.

Previous studies have demonstrated that leukotrienes activate TRPV1, epoxyeicosatrienoic acids activate TRPV4, and 4-hydroxynonenal and 15d-PGJ₂ activate TRPA1. These results by UT researchers add HODEs as endogenous ligands for TRPV1. It is noteworthy that all these TRP ligands are lipid oxidation products and therefore encouraged the researchers to speculate that, one of the major roles of certain TRP channels in mammals is to act as sensors of membrane lipid oxidation as a surrogate for cellular damage. ..

Ref : http://www.uthscsa.edu/hscnews/singleformat2.asp?newID=3419

FDA Supports Phase 3 Trial for NGX-1998 | News | Drug Discovery and Development Magazine

NeurogesX Inc., a specialty pharmaceutical company focused on developing and commercializing a portfolio of novel non-opioid, pain management therapies, provided an update on its regulatory process for NGX-1998 (see below structure), the company's next generation liquid formulation of prescription-strength capsaicin. NeurogesX has received End-of-Phase 2 guidance from the U.S. Food and Drug Administration (FDA) regarding its previously announced plans for the Phase 3 clinical development of NGX-1998 as a treatment for neuropathic pain conditions, including key elements of its overall development plan related to manufacturing, applicator development, and clinical trial design.

FDA Supports Phase 3 Trial for NGX-1998 | News | Drug Discovery and Development Magazine