Anti-Oxidant in China: A Thirty-Year Journey.

Anti-oxidant refers to such a kind of endogenous or exogenous compound that is able to retard or even prohibit in vivo or in vitro oxidation with only small amount being used. The study of anti-oxidants starts nearly 30 years ago, and the research on this topic in China almost begins simultaneously with that in the world. Gratifyingly, contributions on anti-oxidants from China researchers have rapidly increased in the recent decade as anti-oxidants have become a hot topic in biochemistry, pharmacology, food science, chemistry as well as other related disciplines. Anti-oxidants provide a specific viewpoint for clarifying pharmacological effects of Chinese medicinal herbs. For example, as a traditional Chinese medicinal herb, Panax ginseng C. A. Meyer is found to be a natural anti-oxidant resource. Meanwhile, some signaling pathways such as nuclear factor-κB (NF-κB), nuclear factor erythroid 2 related factor 2 (Nrf2), and Kelch-like ECH associated protein 1 (Keap1) are regarded to play an important role in anti-oxidant responses. These findings provide a substantial basis for understanding the pharmacological behaviors of Chinese medicinal herbs in view of regulating the aforementioned signaling pathways. Moreover, inhibition of reactive oxygen species (ROS) by supplementation of anti-oxidant becomes a popularly accepted idea in keeping health and treating diseases. Isolations of antio-xidative ingredients from medicinal herbs and foods lead to set up a large range of anti-oxidative compound libraries, and intake of anti-oxidants from foods may be the most efficient way for supplementing exogenous anti-oxidants. On the other hand, designing anti-oxidants with novel structures motivates organic and medicinal chemists to explore the structure-activity relationship, and then, to find novel structural features with anti-oxidative properties. Therefore, it is reasonable to believe that China researchers will donate more endeavors to obtain more achievements on anti-oxidants in the future.

[Natural bioactive agents in liver therapy]. / Természetes hatóanyagok a májterápiában.

Medical science alongside with other sciences, aiming to preserve health and combat diseases, has evolved significantly since the late 1930s. It has reached incredible results and opened up unpredicted perspectives for future generations to come. From the 1980s significant results also emerged from researching natural plant active ingredients for the prevention of damage from free radicals which were discovered in different symptoms. One of the important areas of research is the recognition of significant bioactive molecules from the aspects of food consumption, alongside the detection of their effect in the context of their structure. It is also important that by possessing these data it is possible to develop correct food consumption habits, especially for people who are suffering from diseases. Through the decades we came a long way from folk medicine observations to molecular, biological justification of effect mechanisms.

[History of electric colloidal metals in therapy : the case of selenium]. / Histoire des métaux colloïdaux électriques en thérapeutique: l'exemple du selenium.

At the beginning of the 1910's period, several scientists and pharmaceutical companies are working actively on colloids, which were discovered in 1845. The pharmaceutical use of"electrical colloids" was the subject of publications and researches for a therapeutic usage, mainly in infectology and oncology. One hun- dred years later, it is under the name ofnanoparticles that the same subject comes to light-and is the source of new works for a potential use for cancer treatment. The example of selenium, which was introduced under a colloidal form in medicine in 1912, is studied here, but other metals could have given the same result: metallic nanoparticles evaluation in pharmacy is not new!

Redox pioneer: professor Roland Stocker.

Dr. Roland Stocker (Ph.D. 1985) is recognized here as a Redox Pioneer, because he has published one article on antioxidant/redox biology as first author that has been cited over 1000 times and has published another 32 articles, each cited over 100 times. Dr. Stocker received his undergraduate education at the Federal Institute of Technology Zürich, Switzerland (1975-1981), followed by postgraduate training at the Australian National University Canberra, Australia (1982-1985) and postdoctoral training at the University of California, Berkeley (1986-1987), and the University of Berne, Switzerland (1987-1988). Dr. Stocker's top scientific contributions are in the following areas: (i) molecular action and interaction of nonproteinaceous antioxidants, particularly bilirubin, α-tocopherol, and ubiquinol-10; (ii) lipoprotein lipid oxidation and its inhibition, with a particular focus on how α-tocopherol affects these processes; (iii) the role of arterial lipoprotein lipid oxidation in atherosclerosis and related diseases; (iv) modes of antiatherosclerotic action of probucol and the involvement of heme oxygenase-1 in vascular protection; and (v) the regulation of indoleamine 2,3-dioxygenase and its contribution to vascular tone and blood pressure in inflammatory diseases.

Where are we with probucol: a new life for an old drug?

Probucol has a long history of clinical application with established efficacy and safety profiles. Probucol is a potent anti-oxidant drug that has been in clinical use during the past few decades for the treatment and prevention of cardiovascular diseases. Here we review the current status of knowledge on the pharmacology, clinical benefits, and the mechanism of actions of this unique drug. Probucol has diverse pharmacological properties with therapeutic effects on the cardiovascular systems. Its mechanism of pharmacologic actions at the molecular level has recently been elucidated with the new concept of HDL metabolism associated with cholesteryl ester transfer protein (CETP) or scavenger receptor class B type I (SR-BI). HDL-C reduction may not be a "side effect" but it most likely might reflect a mechanism of action of probucol. Probucol could be reconsidered as an option at least in case statins, which are known to be effective in lowering low-density lipoproteins (LDL) and coronary artery disease (CAD) risk, are not effective. In particular, a marked CAD risk reduction has been recently reported in long-term probucol treatment of patients with heterozygous familial hypercholesterolemia (FH) in Japan. Therefore, probucol could be a more common therapeutic drug for the treatment of patients with FH as well. There is more than enough reason to believe that this old drug has much more to offer than hitherto known.

Thirty four years since the discovery of gastrointestinal melatonin.

After the discovery of melatonin in the pineal gland by Lerner and co-workers in 1958, melatonin was also detected in the retina and the human appendix. Later, melatonin was confirmed immunohistologically in all segments of the gastrointestinal tract (GIT), in the guts of bovine embryos and in the GIT of low vertebrates. Melatonin was also confirmed in the pancreas and the hepatobiliary system. Melatonin is produced in the enteroendocrine cells of the GIT mucosa. The concentrations of melatonin in the GIT are 10-100x higher than in the plasma and the total amount of melatonin in the GIT is around 400x higher than the amount of melatonin in the pineal gland. Similar to pineal melatonin, GIT melatonin is a multifunctional compound which exhibits some general as well as some specific effects, depending on the organ and the location of GIT tissue. In the GIT, melatonin exhibits endocrine, paracrine, autocrine and luminal actions. Generally, the episodic secretion of melatonin from the GIT is related to the intake and digestion of food and to the prevention of tissue damage caused by hydrochloric acid and digestive enzymes. Some actions, such as the scavenging of hydroxyl free radicals, immunoenhancement and antioxidant effects are of general nature, whereas others, such as an increase of mucosal blood flow, the reduction of peristalsis and the regulation of fecal water content, are specific to the tubular GIT. Generally, melatonin actions oppose those of serotonin. Laboratory and clinical studies indicate that the utilization of melatonin can prevent or treat pathological conditions such as esophageal and gastric ulcers, pancreatitis, colitis, irritable bowel disease, and colon cancer.

Health benefits of herbs and spices: the past, the present, the future.

UNLABELLED: Herbs and spices have a traditional history of use, with strong roles in cultural heritage, and in the appreciation of food and its links to health. Demonstrating the benefits of foods by scientific means remains a challenge, particularly when compared with standards applied for assessing pharmaceutical agents. Pharmaceuticals are small-molecular-weight compounds consumed in a purified and concentrated form. Food is eaten in combinations, in relatively large, unmeasured quantities under highly socialised conditions. The real challenge lies not in proving whether foods, such as herbs and spices, have health benefits, but in defining what these benefits are and developing the methods to expose them by scientific means. CULTURAL ASPECTS: The place of herbs and spices in the diet needs to be considered in reviewing health benefits. This includes definitions of the food category and the way in which benefits might be viewed, and therefore researched. Research may focus on identifying bioactive substances in herbs and spices, or on their properties as a whole food, and/or be set in the context of a dietary cuisine. THE ROLE OF HERBS AND SPICES IN HEALTH: The antioxidant properties of herbs and spices are of particular interest in view of the impact of oxidative modification of low-density lipoprotein cholesterol in the development of atherosclerosis. There is level III-3 evidence (National Health and Medical Research Council [NHMRC] levels of evidence) that consuming a half to one clove of garlic (or equivalent) daily may have a cholesterol-lowering effect of up to 9%. There is level III-1 evidence that 7.2 g of aged garlic extract has been associated with anticlotting (in-vivo studies), as well as modest reductions in blood pressure (an approximate 5.5% decrease in systolic blood pressure). A range of bioactive compounds in herbs and spices have been studied for anticarcinogenic properties in animals, but the challenge lies in integrating this knowledge to ascertain whether any effects can be observed in humans, and within defined cuisines. Research on the effects of herbs and spices on mental health should distinguish between cognitive decline associated with ageing and the acute effects of psychological and cognitive function. There is level I and II evidence for the effect of some herbal supplements on psychological and cognitive function. There is very limited scientific evidence for the effects of herbs and spices on type 2 diabetes mellitus, with the best evidence being available for the effect of ginseng on glycaemia, albeit based on four studies. More research is required, particularly examining the effects of chronic consumption patterns. With increasing interest in alternatives to non-steroidal anti-inflammatory agents in the management of chronic inflammation, research is emerging on the use of food extracts. There is level II evidence for the use of ginger in ameliorating arthritic knee pain; however, the improvement is modest and the efficacy of ginger treatment is ranked below that of ibuprofen. More definitive research is required. PUBLIC HEALTH AND DIETARY IMPLICATIONS: Recommendations for intakes of food in the Australian guide to healthy eating do not yet include suggested intakes of herbs and spices. Future consideration should be given to including more explicit recommendations about their place in a healthy diet. In addition to delivering antioxidant and other properties, herbs and spices can be used in recipes to partially or wholly replace less desirable ingredients such as salt, sugar and added saturated fat in, for example, marinades and dressings, stir-fry dishes, casseroles, soups, curries and Mediterranean-style cooking. Vegetable dishes and vegetarian options may be more appetising when prepared with herbs and spices. FUTURE DIRECTIONS: As several metabolic diseases and age-related degenerative disorders are closely associated with oxidative processes in the body, the use of herbs and spices as a source of antioxidants to combat oxidation warrants further attention. Immediate studies should focus on validating the antioxidant capacity of herbs and spices after harvest, as well as testing their effects on markers of oxidation. This will work in parallel with clinical trials that are aiming to establish antioxidants as mediators of disease prevention. From a dietary perspective, the functionality of herbs and spices will be exposed through consideration of their properties as foods. As with most foods, the real benefits of including them in the diet are likely to emerge with a better understanding of the attributes of health that are best supported by food, and in methodological developments addressing the evidence base for their effects. These developments are well underway through evidence-based frameworks for substantiating health claims related to foods. At present, recommendations are warranted to support the consumption of foods rich in bioactive components, such as herbs and spices. With time, we can expect to see a greater body of scientific evidence supporting the benefits of herbs and spices in the overall maintenance of health and protection from disease.

The history of beta-carotene and cancers: from observational to intervention studies. What lessons can be drawn for future research on polyphenols?

An important question being raised by nutritionists today is whether available scientific data support an important role for polyphenols in the prevention of pathologic conditions that represent an important public health burden, such as cardiovascular diseases, cancers, and osteoporosis. More broadly, when can we consider scientific knowledge sufficient to allow specific public health implications and recommendations? The history of the relationship between beta-carotene and cancer illustrates the complexity of the research process leading to the demonstration of a causal relationship between nutritional factors and the prevention of disease. The beta-carotene story, which has developed in the past 30 y, is particularly significant and illustrative because of apparent controversies that are far from resolved. This is an extremely interesting example from which many lessons can be learned. For beta-carotene, we need to collect sufficient information from experimental, clinical, and epidemiologic research before we support any specific public health recommendations. The same principles must be applied to recommendations regarding polyphenols (in particular, which polyphenols, at which doses, to achieve which benefits for which populations). If these questions are not answered, then we run the risk of needing to renounce recommendations regarding polyphenols in the future, damaging the credibility of nutritional recommendations for public health.

[The roots of Cha and Gambir].

This article attempts to trace the origin of tea. The author believes the ancient Chinese tea, "chia", is either Jicha (water extract from the pith of Acacia catechu that grows naturally in the mountainous border between the Yunnan province of China and southern Asian countries) or Jicha-Kagikazura (water extract from the young branches and leaves of Uncaris gambir, originally found in India/Sri Lanka). Both were pulverized after being kiln-dried and then mixed with water to produce a thick suspension, or tea. Although the drink is bitter and has an astringent property, it has a particular flavor with a refreshing after-taste. Its components with medicinal properties include tannin, catechin, and various flavonoids, making us believe it was worthwhile for the people at the time to consume the drink regularly. Generally speaking, tea cultivation in China flourished south of the Yangzi Jiang River including the present Zhejiang and Anhui provinces. Depending on the regions, there were words for tea in various languages, including the names of places where particular teas were grown. In addition to the names that appear in the famous Chajing book, it is interesting to note Da Fang pronounced tea as "TAH". Because the area south of the Yangzi Jiang has traditionally been active in foreign trade since the ancient and middle ages. People in this region consumed various foreign originated teas as well. This included Gambir, which was introduced to southern Asia (including present Malaysia and Indonesia) and was consumed as an herbal tea under names such as Guo Luo or Ju Luo teas. Paan, from India, also uses Gambir paste and was a popular chewing refreshment to prevent diseases caused by miasma as well as to keep one's mouth clean. The name A-sen-yaku used in Japan was taken from the plant name Acasia, and Gambir was used to dye Buddhist monks' Ke-Ra bags to a blackish yellow color. The Daikanwa dictionary states the Ra in the name, which means thin silk, was later replaced with "A". The official name for Ji-cha [Er Cha] in modern China is "Gaiji-cha", [Hal-Er Cha], which comes from the name of a variety of tea made by the Ai-Ni tribal subgroup of the ethnic Ha-Ni in Yunnan province. The [see character in text] character is pronounced "ni", which is a homophony of [character in text]. Based on these facts, "Ai-Ni" should be considered the same as "Hai-Ni". Because the ethnic groups in Yunnan province used primitive and tough tea leaves, which were eaten instead of being infused in water, the leaves were first fermented by being buried in the ground. Even today, people of these ethnic groups prefer fungus-fermented black tea with a particular flavor. In contrast, the ethnic Hans used and still use improved and softer young shoots of tea leaves to prepare mainly green tea. It has recently been discovered that Acapsia, as well as Gambir, has anti-oxidant properties, and that consumption over time is effective against many lifestyle-related adult diseases. It may be well worthwhile to cast fresh light upon ancient tea drinking customs.

The 80th anniversary of vitamin E: beyond its antioxidant properties.

Molecules provided with an antioxidant function may have additional properties, the latter being sometimes of greater importance than the former. In the last ten years, alpha-tocopherol has revealed precise cellular functions, some of which are independent of its antioxidant/radical scavenging ability. At the posttranslational level, alpha-tocopherol inhibits protein kinase C and 5-lipoxygenase and activates protein phosphatase 2A and diacylglycerol kinase. Some genes (CD36, alpha-TTP, alpha-tropomyosin, and collagenase) are affected by alpha-tocopherol at the transcriptional level. alpha-Tocopherol also induces inhibition of cell proliferation, platelet aggregation and monocyte adhesion. These effects are unrelated to the antioxidant activity of vitamin E, but rather are believed to be a result of specific interactions of vitamin E with components of the cell, e. g. proteins, enzymes and membranes. This review focuses on novel non-antioxidant functions of alpha-tocopherol and discusses the possibility that many of the effects previously attributed to the antioxidant functions can also be explained by non-antioxidant mechanisms.

Free radicals in the 1900's: from in vitro to in vivo.

Remarkable progress has been achieved in the past 100 years in the field of free radical chemistry, biology and medicine since the discovery of free radicals in 1900. Free radical-mediated processes play a major role in the present industrial chemistry, but they also cause deleterious effects on rubber, plastics, oil products and foods. The importance of free radicals in vivo has been recognized increasingly from both positive and negative sides. Free radicals play an important role in phagocytosis, the production of some biologically essential compounds and possibly cell signaling. At the same time, they may cause oxidative modification of biological molecules, which leads to oxidative damage and eventually to various diseases, cancer and aging. The role and beneficial effects of antioxidants against such oxidative stress support this view. Furthermore, novel issues have been continuously found in this fascinating and yet controversial field of free radicals in biology. In this short article, the past work, present problems and future perspectives of free radicals in life science will be briefly discussed.