Every day, science is validating and explaining the actions of the great tonic herbs. Most of the researchers are not seeking to validate old theories. Instead they are seeking new discoveries and new paths to healing and to promoting healthy functioning. Many of the scientists are wise enough to be looking into Nature as a source of inspiration and resources. By combining the older wisdom with cutting edge theory and technology, they are discovering that science and Nature can be blissfully blended. Thousands of research projects are under way at any one time around the world, in virtually every university, examining the nature and actions of herbs and their constituents. This is a revolutionary time in the evolution of herbology and in the search for radiant health, well being and longevity, as scientists and clinicians verify and acknowledge the traditional benefits of the tonic herbs and discover the mechanisms and new uses for these miraculous gems of creation.
Protection against cerebral ischemia by TSG, a polyphenol from the Chinese tonic herb He Shou Wu (Polygonum multiflorum)
By Ron Teeguarden
ãDragon Herbs 2009
Ischemic brain injury is one of the leading causes of adult disability and death. A transient or permanent reduction of cerebral blood flow often initiates brain ischemia. Ischemia is a restriction in blood supply, generally due to factors in the blood vessels, with resultant damage or dysfunction of tissue. When this occurs in the brain, it usually leads to neuronal cell death in the brain due to lack of oxygen and nutrients and due to initial inflammatory responses. When blood supply returns to the tissue after a period of ischemia, the damage is actually increased. This damage is called reperfusion injury. The restoration of circulation results in inflammation and oxidative damage through the induction of oxidative stress rather than restoration of normal function. Even transient (temporary) ischemia produces large amounts of free radicals and causes severe neurotoxicity in the brain during reperfusion.
The ischemia-induced free radical expression appear to be mediated by the activation of NF-κB, (nuclear factor kappa B) a key signaling molecule in the cell apoptotic (programmed death) process. NF-κB is at the center of all inflammation in the body, acute and chronic. It is central to the process of inflammaging, by which humans become chronically inflamed as they age, leading to degenerative disease and finally death.
NF-κB has been shown to be activated during brain ischemia by increased oxidative stress. Reactive oxygen species (ROS) such as the hydroxyl radical are considered important mediators of the brain damage after ischemia/reperfusion injury. ROS are a major form of free radical. The intracellular ROS generation during ischemia and reperfusion contributes to a severely disturbed membrane function, triggering various critical cellular signal transduction pathways. This results in a critical intracellular calcium accumulation that leads to cell self destruction (apoptosis – programmed cell death) and, if unchecked, to death.
A molecule known as JNK is activated by oxidative stress and mediates ROS-induced cell apoptosis. Reactive nitrogen species (RNS) such as nitric oxide (NO) are another key factor in the pathophysiological response of the brain after ischemia/reperfusion injury. There is an increase of NO production, along with other free radicals which have been implicated in ischemia-induced apoptotic cell death.
Because intracellular ROS/RNS play such important roles in the cerebral ischemia/reperfusion injury, many antioxidants have been studied for their potential ability to attenuate ROS/RNS formation and protect against ischemia/reperfusion injury.
Ischemia is not only caused by trauma to the head. It may occur on a more limited, chronic basis simply as a result of aging and degenerative diseases. Small brain lesions known as cerebral microbleeds are now recognized to be relatively common among baby boomers. Dutch researchers recently found that nearly 20% of people aged 60-69 had noticeable lesions and 38% of people who have survived to the age 80 had such lesions. Microbleeding results in brain lesions that are marked by iron deposits that result from red blood cells that have leaked out of the small blood vessels in the brain. Research indicates that people who smoke, those with high blood pressure, and those with risk markers for Alzheimer’s disease and amyloid angiopathy are at higher risk to have these lesions due to cerebral microbleeding (April 1 issue of Neurology, 2008).
It has been recently affirmed that men and women suffering from coronary heart disease seem to fare worse on measures of cognitive function. The longer the person had heart disease, the worse their performance in such mental processes as reasoning, vocabulary and verbal fluency, according to a study in the July 23 issue of the European Heart Journal. Men who experienced their first CHD more than a decade prior had even lower scores for reasoning, vocabulary and semantic fluency. The risk of declining performance in the realm of reasoning went down by about 30 percent for every five years after a diagnosis of coronary heart disease. There seems little doubt that blood supply to the brain is involved in mental decline as one ages.
The authors suggest that people should focus on preventing coronary heart disease by not smoking and avoiding or controlling diabetes, high cholesterol and high blood pressure. And the focus should start early, before it's too late.
TSG - He Shou Wu's potent polyphenol
Polyphenols are a group of plant chemical substances mostly found in plants and are widely consumed by humans as a part of their diet. For example, red wine, green tea, many fruits such as muscadine grapes and pomegranate, and herbs such as turmeric (a main ingredient in curry) contain active polyphenols. Recently, these natural polyphenolic compounds have received a great deal of attention due to their biological properties, including antioxidative, anti-inflammatory and neuroprotective effects. One of the most important properties of polyphenols is their ability to confer potent neuroprotection in several models of ischemic brain injury. Numerous studies suggest that polyphenols have therapeutic potential for the prevention or treatment of ischemic brain injury.
Polygonum multiflorum, a traditional Chinese tonic herb also known as He Shou Wu, has been widely used in the Orient as a tonic and anti-aging agent since ancient times. Recently, the extracts from Polygonum multiflorum have been shown to exhibit a significant antioxidant activity.
TSG (2,3,5,4’tetrahydroxystilbene-2-O-β-D-glucoside) is one of the primary active components extracted from the Polygonum multiflorum. TSG exhibits anti-oxidative and anti-inflammatory effects.
TSG (2,3,5,4’tetrahydroxystilbene-2-O-β-D-glucoside)
Recent studies have shown that TSG improved learning-memory abilities in aged rats and in rats that have been genetically bred to develop learning and memory deficits, and to be disposed to develop amyloid deposits like those of Alzheimer’s patients. This suggests that TSG may have a potent neuroprotective effect in brain injury.
A new study, to be published later in 2009 in Free Radical Biology & Medicine (a journal of the International Society of Free Radical Research) and was obtained in pre-release form, indicates that TSG protects against cerebral ischemia/reperfusion injury through multifunctional cytoprotective pathways.
TSG is a polyphenol. In fact, the polyphenolic structure of TSG is very similar to that of resveratrol. It has been reported that TSG exhibits anti-oxidative and anti-inflammatory effects similar to those of resveratrol.
Resveratrol (3,5,4'-trihydroxystilbene)
An important property of resveratrol is its ability to activate SIRT1, a gene that plays a key role in an organism's response to stresses (such as heat or starvation) and has been clearly shown to be responsible for the lifespan-extending effects of calorie restriction. SIRT1 promotes cell survival, which has been the focus of intense scrutiny by researchers of inflammation, aging and age-related diseases. SIRT1 promotes low LDL cholesterol, low blood glucose, and low insulin levels. SIRT1 also promotes increased numbers and higher efficiency of mitochondria in neurons and other tissues throughout the body.
Professor Ting Wang and his researchers have hypothesized that activation of SIRT1 by polyphenols may be involved in their protective effects against oxidative stress-related cell injury. SIRT1 can increase the expression of SOD (superoxide dismutase), a potent antioxidant enzyme innate in the human body, which in turn can increase the cellular ability to detoxify ROS and inhibit NF-κB signaling, thus preventing, reducing or evening eliminating inflammation.
It is well established that the activation of NF-κB, a transcriptional factor which is now widely believed to play the key roll in inflammation throughout the body, can increase the expression of many genes involved in promoting cell death. Inflammation is a necessity of life and plays a key roll in survival. But over-expression of NF-κB results in excessive inflammation which causes or is connected to almost every disease, including, cardiovascular disease, cancer, diabetes, metabolic syndrome, MS, herpes simplex 1 infection, disk degeneration, degenerative arthritic bone loss, Alzheimer’s disease, and is involved in a core way in an almost unlimited variety of other degenerative and infectious diseases. Inflammation is ultimately lethal. NF-κB is one of the primary roots of aging – and thus the recently coined term inflammaging.
Studies have linked an intracellular increase in ROS production and NF-κB activation. It is now widely accepted that pro-oxidants tend to stimulate NF-κB activation, while certain antioxidants and antioxidant enzymes inhibit the activation of NF-κB by lowering intracellular accumulation of ROS. For example, it has been shown that activation of SIRT1 by resveratrol is associated with the inhibition of NF-κB signaling. Resveratrol is one such antioxidant that has been proven to stimulate SIRT1 activation.
Schizandrin (the most abundant active constituent from the tonic herb Schizandra chinensis berries, gypenoside-49 from Gynostemma pentaphyllum leaf and quercetin from Turmeric are other well known tonic herbs that have recently been discovered to suppress NF-κB and therefore reduce or alleviate acute and chronic inflammation. This may partially explain why these herbs have been considered to be “anti-aging,” “radiant health-promoting” “longevity herbs” since ancient times. It is no coincidence that these herbs have profound broad spectrum health-promoting actions. Some skeptics have said that there is no way for an herb to be a “panacea.” However, with the discovery that the tonic herbs with reputations as panaceas all squelch NF-κB activity and most seem to stimulate SIRT1, it is becoming clear why these herbs are effective in promoting health throughout the body.
TSG attenuates NF-κB activation
TSG is now another polyphenol that that has been found to stop NF-κB from wreaking its havoc in our bodies, and TSG apparently targets the brain, at least as part of its action. TSG attenuates NF-κB activation caused by ischemia/reperfusion in laboratory tests.
Oxidative stress caused by increased intracellular ROS/RNS generation has been implicated in the neurodegeneration after cerebral ischemia/reperfusion-related injury. The Ting group demonstrated that TSG reversed the cell injury induced by ischemia/reperfusion. The injury was characterized by decreased cell viability, nuclear condensation in the neurons, and mitochondrial membrane potential dissipation (loss of energy at the cellular level). TSG dramatically reduced ROS generation and reversed the JNK-related apoptotic signaling pathway, effectively preventing apoptosis (cell death). This was mediated by the activation of SIRT1 and inhibition of NF-κB activation.
And not only was NF-κB suppressed, but the researchers also found that the levels of SIRT1 protein were elevated after the normal cells were incubated for three days with TSG. SIRT1 is widely regarded as the “longevity gene.”
An in vivo study showed that an intraperitoneal application of TSG at the onset of reperfusion is sufficient to provide significant neuroprotection against induced neuronal injury. TSG also had potent neuroprotection against stroke in vivo.
The researchers went on to demonstrate that neural cell damage caused by ischemia/reperfusion and the resulting oxidative stress can be rescued by TSG pretreatment. TSG showed significant protection against cerebral ischemia injury in mice.
Conclusion
These results have not yet been demonstrated in humans and Polygonum multiflorum is not to be used as a drug for the prevention or treatment of ischemia/reperfusion, stroke or any other disease. Nevertheless, these findings indicate that TSG is a potential protective agent against ischemic injury. The implication for us, as students of Chinese herbology, the Way of Radiant Health and anti-aging studies, is that there appears to be a solid biological basis for the age-old belief that certain herbs, known as tonic herbs, may be broadly beneficial, protective and life-enhancing. One of the most important properties of TSG is its ability to confer potent neuroprotection. Perhaps in time scientists will find that consumption of TSG and similar herbal extracts have life-long protective benefits. In the Orient, it is already accepted that by consuming tonics that are protective from an early age, aging itself may be delayed and degenerative disease may be avoided. Centenarians have generally been found to be the ones who have avoided degenerative disease during their middle years. Time will tell if the science supports the use of these tonic herbs, but fortunately we have the freedom to consume these safe herbs at our pleasure.
Reference
This article contains information from the forthcoming article “Protection by Tetrahydroxystilbene glucoside against cerebral ischemia: Involvement of JNK, SIRT1, NF-κB pathways and inhibition of intracellular ROS/RNS generation.” By Ting Wang, Jun Gu, Peng-Fei Wu, Fang Wang, Zhe Xiong, Yuan-Jian Yang, Wen-Ning Wu, Ling-Dan Dong, Jian-Guo Chen. This research paper has been accepted to be published later in 2009 in Free Radical Biology & Medicine, a journal of the International Society of Free Radical Research.
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