Nitric oxide, human diseases and the herbal products that affect the nitric oxide signalling pathway

Abstract

SUMMARY Nitric oxide (NO) is formed enzymatically from L -arginine in the presence of nitric oxide synthase (NOS).Nitric oxide is generated constitutively in endothelial cells via sheer stress and blood-borne substances. Nitric oxide is also generated constitutively in neuronal cells and serves as a neurotransmitter and neuromodulator in non-adrenergic, non-cholinergic nerve endings. Furthermore, NO can also be formed via enzyme induction in many tissues in the presence of cytokines.2. The ubiquitous presence of NO in the living body suggests that NO plays an important role in the maintenance of health. Being a free radical with vasodilatory properties, NO exerts dual effects on tissues and cells in various biological systems. At low concentrations, NO can dilate the blood vessels and improve the circulation, but at high concentrations it can cause circulatory shock and induce cell death. Thus, diseases can arise in the presence of the extreme ends of the physiological concentrations of NO.3. The NO signalling pathway has, in recent years, become a target for new drug development. The high level of flavonoids, catechins, tannins and other polyphenolic compounds present in vegetables, fruits, soy, tea and even red wine (from grapes) is believed to contribute to their beneficial health effects. Some of these compounds induce NO formation from the endothelial cells to improve circulation and some suppress the induction of inducible NOS in inflammation and infection.4. Many botanical medicinal herbs and drugs derived from these herbs have been shown to have effects on the NO signalling pathway. For example, the saponins from ginseng, ginsenosides, have been shown to relax blood vessels (probably contributing to the antifatigue and blood pressure-lowering effects of ginseng) and corpus cavernosum (thus, for the treatment of men suffering from erectile dysfunction; however, the legendary aphrodisiac effect of ginseng may be an overstatement). Many plant extracts or purified drugs derived from Chinese medicinal herbs with proposed actions on NO pathways are also reviewed.

Antioxidant and Vascular Protective Activities of Cratoxylum formosum, Syzygium gratum and Limnophila aromatica

“…1,2) Epidemiological studies have shown that dietary intake of polyphenol-rich foods such as fruits and vegetables is inversely associated with the incidence of cardiovascular diseases. [3][4][5][6] Supplementation of antioxidants has been shown to alleviate vascular dysfunction in hemolytic anemia, inflammatory response syndrome, coronary heart disease, hypertension and atherosclerosis. [7][8][9][10] Several population-based studies have suggested that consumption of plants containing bioactive phytochemicals reduces the risk of developing cardiovascular diseases and cancer.…”

Assessment of Eyebright (Euphrasia Officinalis L.) Extract Activity in Relation to Human Corneal Cells Using In Vitro Tests

“…It has been shown that many substances and extracts from botanical sources and medicinal herbs exert an influence on the NO signaling pathway. Among them are saponin, polyphenols, procyanidins, oleic acids, flavonoids, alkaloids and tannins (23,25). A substantial body of evidence supports the view that various herb-derived substances exert significant anti-inflammatory effects.…”

“…It should be also mentioned that the important relationship between ROS and NO is an oxidative reaction forming more active intermediates (RNOS) such as peroxynitrates. These are capable of toxic nitrosylation and/or nitration of some amino acid residues of proteins (23 ), but an important radical like NO should also be evaluated (24).…”

A molecular switch of “Yin and Yang”: S-glutathionylation of eNOS turns off NO synthesis and turns on superoxide generation

“…Importantly, it may also shed new mechanistic light on the action of some antihypertensive herbal extracts that elicit potent antioxidant properties and relax blood vessels in an endothelium-dependent and NO-mediated manner. It can be speculated that herbs with varying degrees of redox potential may exert different, or even opposite, vascular effects by flipping the switch to preferentially cause the formation of NO or ·O 2 [11] , thus lending scientific support for the Yin-Yang temperaments emphasized in the theory of traditional Chinese medicine.…”