The significance of Curcuma longa Linn. (turmeric) in health and nutrition has changed considerably since the discovery of the antioxidant properties of naturally occurring phenolic compounds. The dried rhizome of Curcuma longa, which has been used for centuries as a spice, food preservative and a coloring agent, has been found to be a rich source of beneficial phenolic compounds known as the curcuminoids¹. Turmeric exemplifies a herb for which clinical applications have evolved over time. The long established image of turmeric as a commercial dyestuff and component of curry ² was partly responsible for overshadowing its importance as a medicinal herb, although traditional cultures have long recognized its medicinal properties.

Curcuminoids refers to a group of phenolics present in turmeric, which are chemically related to its principal ingredient, curcumin. Three main curcuminoids were isolated from turmeric: curcumin (C), demethoxycurcumin (DMC) and bisdemethoxycurcumin (BDMC) . All three impart the hallmark yellow pigmentation to Curcuma longa plant, and particularly to its rhizome. Tetrahydrocurcuminoids (THC) are derived from curcuminoids by hydrogenation. This product is colorless and therefore finds use in achromatic food and cosmetic applications.

Although the chemical structure of curcumin was determined by Lampe in 1910, it was only in the seventies and eighties that the potential uses of curcuminoid compounds in medicine have been extensively studied. The ongoing laboratory and clinical research indicates that turmeric and its phenolics have unique antioxidant and anti-inflammatory properties^3,4,5,6,7,8 . Their potential use in prevention of cancer and in the treatment of infection with human immunodeficiency virus (HIV) are also subjects of intensive laboratory and clinical research ^9,10,11. These interesting findings on curcuminoids, as well as concerns over toxicity of synthetic phenolic antioxidants such as butylated hydroxytoluene (BHT) and butylated hydroxyanisole (BHA), have further stimulated interest in natural phenolics for medicinal and food applications.

The primary pharmacological actions of curcuminoids which have been researched extensively include:

• Antioxidant action
• Anti-inflammatory action
• Anti-carcinogenic
• Anti-mutagenic
• Anti- thrombotic action
• Hepatoprotectective action
• Antimicrobial action
• Antiviral action
• Antiparasitic action

These actions are attributed the unique molecular structure of the curcuminoids (Figure 1).

Figure 1 : Molecular Structures and Biological Activity

Curcuminoids protect the integrity of biological systems

The antioxidant properties of curcuminoids can best be summarized as protective properties. This protective quality of turmeric which has been exploited in the traditional role of turmeric as a food preservative, translates into the results of current research which validate the fact that turmeric (more appropriately the antioxidant curcuminoids) protects the integrity of biomolecules in the body. Interestingly, preventing deterioration of food and preventing deterioration of tissue integrated nutrients, appear to be closely related to each other. The property of turmeric that prevents rancidity of meat, for example, helps to provide edible meat containing less oxidized fat or free radicals. On ingestion, this meat supplies nutrients, rather than damaging nutrient-radicals.

Importantly, curcuminoids have been found both safe and effective antioxidants. Efficient antioxidants, like curcuminoids, scavenge free radicals at the cost of becoming weak free radicals themselves. These "second hand" free radicals are unreactive products, and do not pose a health hazard. Also the curcuminoid free radicals, unlike those of synthetic phenolics e.g. BHT or BHA, are short-lived - a feature that further adds to their safety.

It seems likely that the same quality of turmeric that preserves the freshness of food that we eat, may also exert its role in the body by protecting living tissue from being exposed to degenerative processes. Clinical and laboratory research indicate that diets supplemented with turmeric or curcuminoids stabilize and protect biomolecules in the body at the molecular level ^12,13. This stabilizing effect can be illustrated by the antioxidant, anti-mutagenic and anti-carcinogenic action of curcuminoids, both under in vitro and in vivo conditions¹⁴

Pharmacological effects : Overview of laboratory and clinical studies

The properties of curcuminoids in preventing build-up of tissue-injuring free radicals, particularly those responsible for the cardiovascular disease lipid peroxides, are among better known antioxidant properties of these compounds. As biological oxidation is a free radical mediated chain reaction, the efficacy of an antioxidant is linked to its role in preventing the formation of free radicals and quenching the already existing free radicals.

Curcuminoids were shown to prevent lipid peroxides formation in a significantly higher degree than the pine bark extract, grape seed extract or the commonly used synthetic antioxidant BHT, in an in vitro study.¹⁵ This study employed a conventional test procedure called the "Rancimat Method". The test measures the conductivity changes caused by the formation of small free fatty acid molecules, when fats and oils undergo experimentally induced accelerated rancidity or oxidative changes. Pure lard is used for the preparation of test samples containing 0.02% by weight of the antioxidant being tested. The results of these experiments are indicated in the Figure 2. The particular blend of curcuminoids (2) used in the above experiment is known as C³ -Complex which has been shown to be more effective as an antioxidant than each of the components curcumin, demethoxy curcumin or bisdemethoxy curcumin used alone.¹⁵

Figure 2 : Prevention of rancidity by various antioxidants

Curcuminoids were also shown to intervene in free radical propogation by quenching pre-formed free radicals. The capacities of the individual curcuminoids in this regard were measured using the DPPH radical scavenging method.

In the DPPH radical scavenging method, the ability of an antioxidant to bind the 1.1 diphenyl-2-picrylhydrazyl -radical (a very stable free radical species) is measured, using various concentrations of the selected antioxidants. A compound with high antioxidant potential effectively traps this radical thereby preventing its propogation and the resultant chain reaction. Figure 3 compares the free radical scavenging ability of curcuminoids.

Figure 3 : Free radical scavenging ability of curcuminoids

This experiment reveals the superior antioxidant properties of Tetrahydrocurcuminoids in intervening with free radical propogation.

The effect of curcumin supplementation on serum lipid peroxides was studied in ten healthy volunteers, to evaluate the antioxidant property of curcumin in preventing serum lipid peroxidation¹⁶. Administration of curcumin resulted in a statistically significant reduction of serum lipid peroxides formation and decrease in the levels of total cholesterol. These results clearly illustrate the potential role for curcuminoids in the prevention and treatment of cardiovascular disease.

The other major biological property of turmeric and curcuminoids is their anti-inflammatory activity, comparable in strength to steroidal drugs and non-steroidal drugs like indomethacin and phenylbutazone^17,18,19,20. Curcuminoids inhibit enzymes which participate in the synthesis of inflammatory substances in the body derived from arachidonic acid. For example, curcuminoids prevent the synthesis of several inflammatory prostaglandins and prostacyclines^21,22,23. The overall anti-inflammatory action of curcuminoids is also related to their well-known antioxidant properties. For example, curcumin has been shown to inhibit lipid peroxidation, a phenomenon associated with antioxidant as well as anti-inflammatory activities^24,25. The anti-inflammatory properties of curcumin were tested in a double-blind clinical trial in patients with rheumatoid arthritis²⁰. Curcumin produced a significant improvement in all patients, and the therapeutic effects were comparable to those obtained with phenylbutazone²⁰.

The nutritional role of turmeric extract and curcuminoids as anticarcinogens (preventing the development of cancer) and antimutagens (preventing damage to genetic material) has been the subject of recent research ^26,27,28,29. Both the turmeric extract and curcuminoids have been shown to inhibit carcinogenesis and mutagenesis in laboratory animals.

Curcumin was tested in patients with oral cancer³⁰. Some patients responded with dramatic clinical improvement within days, while others responded gradually to the treatment. When administered to a group of chronic smokers, curcumin significantly reduced the urinary excretion of tobacco mutagens, and also enhanced enzymatic efficacy to detoxify cigarette smoke mutagens and carcinogens ^28,29.

Curcuminoids have also been shown to exhibit antimicrobial properties. Extracts from turmeric as well as the active principles, the curcuminoids, were found to inhibit the growth of numerous gram positive and gram negative bacteria, fungi and the intestinal parasite Entamoeba histolytica¹⁴. Curcumin also inhibits in vitro production of aflatoxins - toxins produced by the mold Aspergillus parasiticus, which may grow and contaminate the poorly preserved foods ³¹. Aflatoxin is a potent biological agent causing injury to the liver, often resulting in liver cancer. An interesting property of curcuminoids is their anti-HIV effect which has been demonstrated during in vitro and in vivo experiments, including a limited number of human studies^9,10.

Platelet aggregation plays a vital role in initiation of thrombosis. In a comparative study on the protective effects of curcumin and aspirin in mice subjected to induced thrombotic challenge, curcumin was found to exhibit dose-related antithrombotic effect³². Curcumin, like aspirin, was found to inhibit cyclooxygenase activity of platelets and platelet thromboxane B₂ (TXB₂ )levels. However, curcumin did not affect vascular prostacyclin (PGI₂) synthesis. The protective effect of curcumin was directly proportional to the dose upto a level of 200 mg/kg as an intraperitoneal administration, whereas the same was inversely proportional in the case of aspirin administration.

Significance of the biological properties of curcuminoids

The unique composition of curcuminoids and their demonstrated capabilities to not only scavenge and neutralize harmful existing free radicals, but also to prevent their formation merits their description as "bioprotectant". This bioprotective action of curcuminoids validates their potential role as antioxidants for oral administration as well as for topical application to retard the progression of free radical mediated disease processes.

Curcuminoids thus represent a class of valuable phytonutrients with unique bioprotective properties. If regularly administered as nutritional supplement, these natural compounds would potentially help in maintaining good health and in slowing down the progression of various disease conditions. Topical application would help in neutralizing damaging free radicals on the surface of the skin, thereby retarding aging and damage due to ultraviolet radiation.

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