Natural Product Nitric Oxide Chemistry: New Activity of Old Medicines

The use of complementary and alternative medicine (CAM) as a therapy and preventative care measure for cardiovascular diseases (CVD) may prove to be beneficial when used in conjunction with or in place of conventional medicine. However, the lack of understanding of a mechanism of action of many CAMs limits their use and acceptance in western medicine. We have recently recognized and characterized specific nitric oxide (NO) activity of select alternative and herbal medicines that may account for many of their reported health benefits. The ability of certain CAM to restore NO homeostasis both through enhancing endothelial production of NO and by providing a system for reducing nitrate and nitrite to NO as a compensatory pathway for repleting NO bioavailability may prove to be a safe and cost-effective strategy for combating CVD. We will review the current state of science behind NO activity of herbal medicines and their effects on CVD

Valorizing the 'Irulas' traditional knowledge of medicinal plants in the Kodiakkarai Reserve Forest, India

A mounting body of critical research is raising the credibility of Traditional Knowledge (TK) in scientific studies. These studies have gained credibility because their claims are supported by methods that are repeatable and provide data for quantitative analyses that can be used to assess confidence in the results. The theoretical importance of our study is to test consensus (reliability/replicable) of TK within one ancient culture; the Irulas of the Kodiakkarai Reserve Forest (KRF), India. We calculated relative frequency (RF) and consensus factor (Fic) of TK from 120 Irulas informants knowledgeable of medicinal plants. Our research indicates a high consensus of the Irulas TK concerning medicinal plants. The Irulas revealed a diversity of plants that have medicinal and nutritional utility in their culture and specific ethnotaxa used to treat a variety of illnesses and promote general good health in their communities. Throughout history aboriginal people have been the custodians of bio-diversity and have sustained healthy life-styles in an environmentally sustainable manner. However this knowledge has not been transferred to modern society. We suggest this may be due to the asymmetry between scientific and TK, which demands a new approach that considers the assemblage of TK and scientific knowledge. A greater understanding of TK is beginning to emerge based on our research with both the Irulas and Malasars; they believe that a healthy lifestyle is founded on a healthy environment. These aboriginal groups chose to share this knowledge with society-at-large in order to promote a global lifestyle of health and environmental sustainability

Metagenomic Analysis of Nitrate-Reducing Bacteria in the Oral Cavity: Implications for Nitric Oxide Homeostasis

<div><p>The microbiota of the human lower intestinal tract helps maintain healthy host physiology, for example through nutrient acquisition and bile acid recycling, but specific positive contributions of the oral microbiota to host health are not well established. Nitric oxide (NO) homeostasis is crucial to mammalian physiology. The recently described entero-salivary nitrate-nitrite-nitric oxide pathway has been shown to provide bioactive NO from dietary nitrate sources. Interestingly, this pathway is dependent upon oral nitrate-reducing bacteria, since humans lack this enzyme activity. This pathway appears to represent a newly recognized symbiosis between oral nitrate-reducing bacteria and their human hosts in which the bacteria provide nitrite and nitric oxide from nitrate reduction. Here we measure the nitrate-reducing capacity of tongue-scraping samples from six healthy human volunteers, and analyze metagenomes of the bacterial communities to identify bacteria contributing to nitrate reduction. We identified 14 candidate species, seven of which were not previously believed to contribute to nitrate reduction. We cultivated isolates of four candidate species in single- and mixed-species biofilms, revealing that they have substantial nitrate- and nitrite-reduction capabilities. Colonization by specific oral bacteria may thus contribute to host NO homeostasis by providing nitrite and nitric oxide. Conversely, the lack of specific nitrate-reducing communities may disrupt the nitrate-nitrite-nitric oxide pathway and lead to a state of NO insufficiency. These findings may also provide mechanistic evidence for the oral systemic link. Our results provide a possible new therapeutic target and paradigm for NO restoration in humans by specific oral bacteria.</p></div

The nitrate- and nitrite-reducing capacity of four candidate species grown individually and as a consortium.

<p>Each bar represents the concentration of nitrate and nitrite remaining in the spent medium after 24(<i>A. odontolyticus</i>, <i>V. dispar</i>, <i>F. nucleatum</i>, and <i>S. mutans</i>) or a consortium of all four species at 24 hours after biofilm inoculation. The nitrate concentration, orange; nitrite concentration, green. The data are the average ± SEM of three individual experiments.</p

Unweighted UniFrac-based PCoA analysis reveals a gradient of samples as nitrate reduction capacity decreases with specific taxa associated with different groups.

<p><b>A</b>) Unweighted UniFrac-based PCoA illustrates samples based on community similarity. Red dots = Best nitrate reducing samples, blue dots = intermediate nitrate reducing samples, green dots = worst nitrate reducing samples, and orange dots = inocula (original tongue scrapings). <b>B</b>) Bi Plot superimposing taxonomic information onto an unweighted UniFrac-based PCoA illustrating how similar the microbial communities of the samples are to one another. Red dots = Best nitrate-reducing samples, blue dots = intermediate nitrate-reducing samples, orange dots = worst nitrate-reducing samples, and gray dots = taxa.</p

Flow diagram for study design and subject recruitment.

<p>Flow diagram for study design and subject recruitment.</p

The mean relative abundance of genera present in each group of nitrate reducers.

<p>Bar charts with insets depict the mean relative abundance of genera present <b>A</b>) in the best (n = 9), <b>B</b>) intermediate (n = 10), and <b>C</b>) worst (n = 5) nitrate-reduction groups. Inset bars depict all genera detected in each group except <i>Streptococcus</i>, which was the most abundant genus detected in all groups and is depicted in the main bars. The percent abundance and taxonomic classification of the most abundance taxa are noted on the graphs.</p

Top Ten Genera Present in Individual Tongue Scrapings.

<p>Top Ten Genera Present in Individual Tongue Scrapings.</p

The 14 candidate species detected through WGS sequencing and analysis of one representative sample from each group are listed.

<p>The percent abundance of the species in the all three nitrate-reducing groups is listed.</p