Nitricycle

Recent Nobel Prize winning research has led to a deeper understanding of the important role played by an exceedingly simple molecule: nitric oxide (NO). Three of the pioneers in working out the biological roles of NO shared a Nobel Prize in 1998 for their discoveries. The award to one of them, Ferid Murad, honored his discovery that nitroglycerine works by releasing NO. This seems particularly appropriate because Alfred Nobel's fortune came from his invention of making dynamite from nitroglycerine!

The combination of nitrogen and oxygen, nitric oxide has now been shown to play a critical role in many diseases such as diabetes, cancer, sunburn, anorexia and male impotence. Nitric oxide has also been shown to influence many of our most basic health processes, including even speed and ease by which we learn. In our bodies nitric oxide functions as a "signaling molecule." For example, it can tell the body to make blood vessels relax and widen.

Nitric oxide (NO) protects the heart, stimulates the brain and kills many pathogenic microbes (bacteria etc.)

It was a sensation that this simple, common air pollutant, which is formed when nitrogen burns, for instance in automobile exhaust fumes, could exert important functions in the organism. It was particularly surprising since NO is totally different from any other known signal molecule and so unstable that it is converted to nitrate and nitrite within 10 seconds. NO was known to be produced in bacteria but this simple molecule was not expected to be important in higher animals such as mammals.

Further research results rapidly confirmed that NO is a signal molecule of key importance for the cardiovascular system and it was also found to exert a series of other functions. We know today that NO acts as a signal molecule in the nervous system, as a weapon against infections, as a regulator of blood pressure and as a gate keeper of blood flow to different organs. NO is present in most living creatures and made by many different types of cells.

When NO is produced by the innermost cell layer of the arteries, the endothelium, it rapidly spreads through the cell membranes to the underlying muscle cells. Their contraction is turned off by NO, resulting in a dilatation of the arteries.  In this way, NO controls the blood pressure and its distribution. It also prevents the formation of thrombi. When NO is formed in nerve cells, it spreads rapidly in all directions, activating all cells in the vicinity. This can modulate many functions, from behaviour to gastrointestinal motility. When NO is produced in white blood cells (such as macrophages), huge quantities are achieved and become toxic to invading bacteria and parasites.

Functions known to be influenced by nitric oxide include:

• Behavioral studies offer further evidence that nitric oxide may play a role in learning. Drugs that interfere with the nitric oxide signaling pathway also interfere with some types of learning tasks (e.g. spatial learning tasks) that require longterm memory formation.
• Nitric oxide controls blood pressure and prevents formation of blood clots by signaling the muscles that control relaxation and expansion of blood vessels. There is some evidence that the night time urination many people find so disturbing to their sleep may be the result of nocturnal variations in blood pressure that are the result of the fluctuations in nitric oxide activity.
• When arteries become clogged, they produce less nitric oxide than normal. Treatment with nitroglycerin can increase nitric oxide, widening blood vessels and increasing blood flow.  Nitric oxide also interacts with blood platelets to decrease platelet aggregation, thus lowering the risk of blood clots.
• Huge quantities of nitric oxide are produced in white blood cells to kill invading bacteria and parasites. White blood cells use nitric oxide to defend the body against tumors. Scientists are investigating whether it can be used to stop the growth of tumors.
• Nitric oxide is synthesized in neurons of the central nervous system, where it acts as a mediator with many physiological functions, including the formation of memory, coordination between neuronal activity and blood flow, and modulation of pain.
• Although most anyone can benefit from healthy modulation of nitric oxide metabolism, there is some evidence that those individuals who possess the gene for the blood group B antigen (blood groups B and AB) may be more at risk for health problems associated imbalances in nitric oxide metabolism.

A recent letter to the editor in the journal Lancet had an interesting letter on differences between ABO groups and the responsiveness of respiratory patients to nitric oxide (NO) therapy. Apparently, those types with a B antigen (B and AB) have less success with this therapy.  The authors speculate that this must be the result of a lack of "anti-B antibody" which perhaps assists the NO in working. They speculate that this might result from "some putative, unknown gene associated with the ABO locus on chromosome 9Q34."

Actually, we do know what gene would "putatively" assist in NO function and would be influenced by ABO genetics. It codes for an enzyme unfortunately abbreviated "ASS." ASS stands for argininosuccinate synthetase, an enzyme which recycles arginine from citrulline in the production of NO. The ABO locus is so closely positioned to the ASS locus, they literally sit on top of the other!

L-Arginine and L-Citulline. Are essential amino acids (protein building block). Arginine is used to make nitric oxide, which reduces blood vessel stiffness, increases blood flow, and improves blood vessel function. Used to recycle nitric oxide in the nervous system), known as the ‘endothelium-derived relaxing factor’, or ‘EDRF’, is biosynthesised from arginine and oxygen by various nitric oxide synthase (NOS) enzymes and by reduction of inorganic nitrate.

• Also, the gene for the enzyme dopamine beta hydroxylase and arginine succinate synthase (affecting nitric oxide synthesis), sit right on top of the ABO gene (at 9q34) and there are indications that this may cause psychiatric syndromes to be somewhat related to ABO blood group (gene linkage) connection with blood group B and BUN (urea) blood values, and the haemaglutinin titer. This gene “putatively” assists in NO function and would be influenced by ABO genetics. It codes for an enzyme unfortunately abbreviated “ASS.” ASS stands for argininosuccinate synthetase, an enzyme which recycles arginine from citrulline in the production of NO. The ABO locus is so closely positioned to the ASS locus; they literally sit on top of the other! (8)

Cordyceps sinensis.  In Traditional Chinese Medicine, Cordyceps is used to support healthy liver, kidney, heart, and immune system function. It also appears to act as an antioxidant in the body, protecting it from free radical damage. In animal studies, Cordyceps extract had good anti-aging effects, improving antioxidation and removing free radicals. (7)

Dragon’s Blood Croton (Croton lechleri) Resin, otherwise known as Sangre de Drago, is a South Amaerican tree whose sap has been used for hundreds of years for varies complaints including diarrhea, inflammation, insect bites and wound healing. Croton lechleri has been shown in animal models to act as an anti-oxidant. (13)(14)

Gynostemma (Gynostemma pentaphyllum) or Jiaogulan is a five-leafed, adaptogenic herb. It has a unique ability to restore homeostasis (balance and equilibrium) to all five of the body’s key systems: the cardiovascular, digestive, immune, nervous, and reproductive systems. Gynostemma contains many amino acids, vitamins, and minerals that are essential to optimal human health, including calcium, iron, magnesium, phosphorus, potassium, selenium, zinc, and many other trace minerals. The locals who cultivate & consume Gynostemma call it “miracle tea.”

• The chemical constituents responsible for the adaptogenic characteristic of Gynostemma are saponins (triterpene glycosides or gypenosides). Gynostemma contains the widest range of saponins out of all the plants in nature. There are approximately four times as many saponins in Gynostemma pentaphyllum as there are in Ginseng. The more than 100 different gypenosides in Gynostemma are all very similar to the ginsenosides of Panax ginseng and the eleutherosides of Eleutherococcus senticosus. (9)

Asian Ginseng (Panax ginseng) Root, Is rich in ginsenosides, the active constituents also found in American Ginseng (Panax quinquefolius), Panax ginseng, also known as Asian, Korean, or True Ginseng, is renowned the world over as the supreme warming adaptogen. An adaptogen is a substance that strengthens the body, helping it to return to normal after exposure to prolonged stress. Indeed, the unique combination of its historical reputation and potent actions has elevated Panax to a place above all others in the minds of most professional herbalists.

It appears that Ginseng can actually help the adrenal gland respond to stress, either by actually encouraging growth of the adrenal gland itself (and thereby enabling a more robust response capacity) or decreasing cortisol when it is already too high. Perhaps even more importantly, however, ginseng appears to increase the sensitivity or responsiveness of the body, thereby allowing it to make more cortisol when it is required while enabling a faster normalization of cortisol levels once the stressor is removed. (10)(11)

Chinese Salvia (Salvia miltiorrhiza) Root. The crude drug (dried root) and its preparations are currently used in China to treat patients suffering from heart attack, angina pectoris, stroke and some other conditions. The use of S. miltiorrhiza has been increasing in the management of stroke. Pharmacological examinations showed that the plant and its active ingredients, tanshinones and salvianolic acids, have anticoagulant, vasodilatory, increased blood flow, anti-inflammatory, free radical scavenging, mitochondrial protective and other activities. (12)

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2. Burnett AL. Nitric oxide control of lower genitourinary tract functions: a review. Urology 1995 Jun;45(6):1071-1083.
3. Jung HC, Mun KH, Park TC, Lee YC, Park JM, Huh K, Seong DH, Suh JK.Role of nitric oxide in penile erection. Yonsei Med J 1997 Oct;38(5):261-269
4. Feldman PL et al. The surprising life of nitric oxide. C&EN, 1993;20:26-38.~Kim YM et al. Inhibition of protein synthesis by nitric oxide correlates with cytostatic activity: nitric oxide induces phosphorylation of initiation factor eIF-2 alpha. Mol Med, 1998;4(3):179-90
5. Wascher TC, Graier WF, Dittrich P, Hussain MA, Bahadori B, Wallner S, Toplak H. Effects of low-dose L-arginine on insulin-mediated vasodilatation and insulin sensitivity. Eur J Clin Invest 1997 Aug;27(8):690-695.
6. Baliga MS, Katiyar SK. Chemoprevention of photo carcinogenesis by selected dietary botanicals. Photochem Photobiol Sci. 2006;5(2):243-53.
7. Ammon HPT, Wahl MA. Pharmacology of Curcuma longa. Planta Medica. 1991; 57:1-7.
8. Blumert M, Jialiu L. Jiaogulan: China’s “Immortality” Herb. Badger, CA: Torchlight Publishing. (2003) pp. 66–70 ISBN 1-887089-16-0.
9. Attele AS, Wu JA, Yuan CS. Ginseng pharmacology: multiple constituents and multiple actions. Biochem Pharmacol. 1999; 58(11):1685-1693.
10. Kelly GS. Nutritional and botanical interventions to assist with the adaptation to stress. Alt Med Rev. 1999; 4(4):249-265.
11. Chin Med. 2006 Nov 23;1:3
12. Ran, Y, Wang, R. Dragon’s blood its extracts attenuate radiation-induced oxidative stress in mice. J Radiat Res. 2014 Jul 55(4): 699-706
13. Jones, K. Review of Sangre de Drago (Croton lechleri) – A south American Tree Sap in the Treatment of Diarrhea, Inflammation, Insect Bites, Viral Infections, and Wounds: Traditional Uses to Clinical Research. J of Alternative and Complementary Med. 2004 July 9(6): 877-896