Potential beneficial effects of goldenseal on the digestive tract. Digestion of food begins in the mouth. In fact the process begins before food ever reaches your mouth as just the anticipation of eating stimulates the flow of gastric fluid alerting the entire digestive system that food is on the way. The first place food touches is the tongue. This is important because the tongue contains hundreds of receptors which form the basis of not only taste such as sweet, salty, sour, or bitter, but also stimulate enzyme and other gastric secretions which facilitate proper digestion. Bitters in particular, have been generally removed in most Western diets resulting in unbalanced stimulation and subsequent digestive inefficiencies. Bitter herbs have been used by humans to stimulate these receptors and improve digestion for thousands of years. These herbs stimulate salivation and act to keep the entire digestive system in balance. An unbalanced digestive system manifests itself in a number of ways including acid reflux, poor or painful digestion, ulcers, uninhibited cell growth (cancer), hemorrhoids, constipation and diarrhea. Hydrastis canadensis, goldenseal, is one of those bitter herbs whose beneficial effects on digestion were first shown to European Settlers by the Native Americans. Modern science has discovered these effects can be attributed to a number of compounds found in the plant called alkaloids, the primary one being berberine. Besides the active compounds in goldenseal, the plant contains other constituents which act synergistically with the alkaloids to increase their potency and/or reduce any potential adverse effects. Potential effects on digestive function include: Maintenance of a balanced microbial population, Inhibition of abnormal cell growth, Regulation of inflammatory responses. POTENTIAL EFFECT ON MICROBIAL POPULATIONS Microbes play an important role in the digestive process primarily through the breakdown of food into a form usable by the body. Many types of microbes live in the gut including beneficial bacteria such as Lactobacillus acidophilus plus pathogens such as Helicobactor pylori and Escherichia coli. Others include yeasts such as Candida sp. and parasitic protozoa such as Giardia lamblia. In a balanced digestive system, beneficial bacteria far outnumber the pathogens and in fact play a large role in keeping the pathogens in check. Imbalances can be induced through diet, stress, infection from an outside source or as a result of conventional antibiotic treatment. One potential beneficial effect of goldenseal on the digestive tract is selective microbial inhibition. Berberine is considered a natural broad spectrum antibacterial agent. Unlike prescription antibiotics which utilize the “shotgun” approach to pathogen control, i.e., kill everything just to make sure we just the ones we want, goldenseal uses a more “laser guided” approach, inhibiting the growth of pathogenic organisms with little effect on or even enhancing the growth of several beneficial bacteria. Our own research has indicated that Goldenseal Advanced Digestive Support exhibited no inhibition of L. acidophilus at eight times the concentration required to inhibit Staphylococcus aureus. Therefore goldenseal could support digestive function by promoting beneficial gut microbial populations while inhibiting the growth of pathogens. In addition to inhibiting the growth of pathogenic bacteria, goldenseal may mitigate the effects of those bacteria that do survive through induction of a process called “quorum quenching”. In many cases, the adverse effects of pathogenic bacteria are caused by the release of toxins from the bacteria into the host organism. A few pathogens scattered through the digestive tract do cause problems because their numbers are too low. Uncannily, the bacteria know this and so do not release their toxins until a sufficient number (a quorum) are present to cause significant harm. The obvious question is how do the bacteria know when enough are present? Though it seems far out, bacteria have developed a form of communication through the release of identifying chemical markers. Each cell has receptors, antennae if you will, which monitor the concentration of those markers in its surrounding environment. When the concentration reaches a certain level, all of the bacteria release their toxins at once in an attempt to overwhelm the host. Iin laboratory studies, Goldenseal was shown to interrupt this communication system and thus “quenche” the quorum thereby inhibiting the release of the toxins even though sufficient numbers of bacteria may be present to cause an infection. Another beneficial aspect of goldenseal is that it does not contribute to the emergence of drug resistant bacteria. This is accomplished through two pathways. First, antibiotics only kill bacteria that are not resistant to them. This is natural selection in reverse and allows the resistant strains to rapidly multiply eventually rendering the antibiotic treatment ineffective due to elimination of all susceptible strains. Goldenseal leaf contains compounds that act to disable microbial resistance mechanisms thereby allowing the active compounds to enter and destroy the cell. This results in a relatively equal kill rate across all pathogenic strains and the maintenance of normal bacterial populations without promoting the development of resistant strains. Secondly, almost paradoxically, berberine has been shown to upregulate DNA repair systems in pathogenic bacteria. Many antibacterials, including berberine, induce bacterial death through some type of DNA damage. However, there are instances where a particular cell may only be “wounded” and not die. When this cell reproduces, it will reproduce the damaged DNA section resulting in a mutation and the potential emergence of resistant organisms. By switching on DNA repair systems in wounded cells that don’t die, damaged DNA is repaired thereby avoiding a mutation and the emergence of resistant bacteria. INHIBITION of ABNORMAL CELL GROWTH Under balanced conditions digestive tract cells go through a natural cycle which includes cell death and replacement. In fact, every cell in the body is replaced about every three weeks. In some instances, this cycle is disrupted and instead of dying at the preprogrammed time, the cell just keeps multiplying. Similar to drug resistant bacteria discussed above, the mutation is reproduced in subsequent generations leading to the development of an uncontrolled mass of cells referred to as a cyst, tumor, and/or cancer. Goldenseal could help to maintain normal cell life cycles in a number of ways. First, numerous articles have indicated berberine to be selective in its inhibition of cell growth meaning that as long as the cell is functioning as designed, the compound has little or no effect. However, in abnormal cells, berberine induces the preprogrammed cell death signal thereby retarding the growth of the mass. This characteristic of Goldenseal Advanced Digestive Support is confirmed in every production batch through quality control assays which demonstrate the product is more inhibitory to colon and stomach cancer cell types than to normal intestinal lining cell types. Uncontrolled growth requires a massive amount of energy to sustain itself. This requires the cell mass to reach out to surrounding blood vessels for additional nourishment similar to a tree expanding its root system in search of water. This process is called angiogenesis. Berberine has also been shown to inhibit the formation of feeder blood vessels to the mass. Researchers from Texas A & M University recently tested berberine for its preventive potential in colon cancer (SW480) cells. Berberine inhibited the growth of colon cancer cells in a dose- and time-dependent manner. The group also reported that berberine exhibited minimal toxicity in normal cells at the highest concentration tested. It was demonstrated that berberine arrested the colon cancer cell cycle at G2/M phase. Berberine then induced a series of biochemical events including loss of mitochondrial membrane potential, release of cytochrome-c, and other pathways leading to cell death. In addition, berberine also inhibited inflammation and angiogenesis in the colon cancer cells. The Authors concluded that berberine has the ability to cause cell cycle arrest, induce pre-programmed cell death, and inhibit inflammation in colon cancer cells. They further state that the magnitude of the effects observed suggests that berberine should be considered for further studies of its use either as a preventative and/or treatment for colon cancer. Our research indicates that Goldenseal Advanced Digestive Support exhibits these same characteristics as isolated berberine with less effect on normal cells making it an ideal dietary supplement to support intestinal lining integrity. REGULATION of INFLAMMATORY RESPONSES Inflammatory responses are manifestations of immune system stimulation. The immune system senses a problem somewhere in the body, such as an infection, then dispatches a whole host of specialized cells and chemicals to both fight the infection and attempt to repair any damage. A classic example of this is diarrhea. Lipopolysaccharide (LPS) is the major component of the outer membrane of Gram-negative bacteria such as Escherichia coli (E. coli), Salmonella, Shigella, and many other pathogens. LPS is toxic to the digestive system and induces a strong response from normal human immune systems. Intestinal linings become swollen and inflamed while body temperature begins to rise as white blood cells rush to the scene in order to fight off the intruders. As the battle progress down the intestinal tract, very quickly at times, large quantities of fluid are called into the colon in order to quickly flush out the left over debris and toxins released by the dying bacteria resulting in the experience we have all endured, severe cramping, nausea, and diarrhea. One of the most often reported historical uses for goldenseal is for cases of bacterial induced diarrhea. We now know that there are multiple paths through which could goldenseal both protect against damage from LPS exposure and restore balance to battle ravaged intestinal linings.