Monday, February 25, 2013
CURCUMIN: THE INDIAN SOLID GOLD
byBharat B. Aggarwal, Chitra Sundaram, Nikita Malani, and Haruyo Ichikawa
Abstract: Turmeric, derived from the plant Curcuma longa, is a gold-colored spice commonly used in the Indian subcontinent, not only for health care but also for the preservation of food and as a yellow dye for textiles. Curcumin, which gives the yellow color to turmeric, was first isolated almost two centuries ago, and its structure as diferuloylmethane was determined in 1910. Since the time of Ayurveda (1900 bc) numerous therapeutic activities have been assigned to turmeric for a wide variety of diseases and conditions, including those of the skin, pulmonary, and gastrointestinal systems, aches, pains, wounds, sprains, and liver disorders. Extensive research within the last half century has proven that most of these activities, once associated with turmeric, are due to curcumin.
Curcumin has been shown to exhibit antioxidant, anti-inflammatory, antiviral, antibacterial, antifungal, and anticancer activities and thus has a potential against various malignant diseases, diabetes, allergies, arthritis, Alzheimer’s disease, and other chronic illnesses. These effects are mediated through the regulationof various transcription factors, growth factors, inflammatory cytokines,protein kinases, and other enzymes. Curcumin exhibits activities similar to recently discovered tumor necrosis factor blockers (e.g., HUMIRA, REMICADE, and ENBREL), a vascular endothelial cell growth factor blocker (e.g., AVASTIN), human epidermal growth factor receptor blockers (e.g., ERBITUX, ERLOTINIB, and GEFTINIB), and a HER2 blocker (e.g., HERCEPTIN). Considering the recent scientific bandwagon that multitargeted therapy is better than monotargeted therapy for most diseases, curcumin can be considered an ideal “Spice for Life”.
The questions of whether medicines discovered today are safer, more efficacious, and more affordable than generic medicines (whose patents have expired) or medicines that are centuries old could be answered “no” for most of the modern medicines. If so, then it is logical to revisit and revive these age-old medicines for the welfare of mankind. Curcumin is one such medicine. Its history goes back over 5000 years, to the heyday of Ayurveda (which means the science of long life). Turmeric derived from the rhizome of the plant Curcuma longa has been used by the people of the Indian subcontinent for centuries with no known side effects, not only as a component of food but also to treat a wide variety of ailments.
Turmeric is a spice of golden color that is used in cooking in the Indian subcontinent. Because of its color and taste, turmeric was named “Indian saffron” in Europe. Today, India is the primary exporter of turmeric (known as haldi in India). Although its ability to preserve food through its antioxidant mechanism, to give color to food, and to add taste to the food is well known, its health-promoting effects are less well recognized or appreciated. It was once considered a cure for jaundice, an appetite suppressant, and a digestive. In Indian and Chinese medicines, turmeric was used as an anti-inflammatory agents to treat gas, colic, toothaches, chest pains, and menstrual difficulties. This spice was also used to help with stomach and liver problems, to heal wounds and lighten scars, and as a cosmetic.
Turmeric was mentioned in the writings of Marco Polo concerning his 1280 journey to China and India and it was first introduced to Europe in the 13th century by Arab traders. Although Vasco de Gama (a Portugeese sailor) during 15th century, after his visit to India, truly introduced spices to the West, it was during the rule of British in India that turmeric was combined with various other spices and renamed “curry powder,” as it is called in the West. What is there in turmeric that has therapeutic potential, how does this substance mediate its effects, with what types of receptor does it interact, and for what type of diseases is it effective? All of these questions will be addressed in this
2. COMPOSITION OF TURMERIC
Turmeric contains a wide variety of phytochemicals, including curcumin, demethoxycurcumin, bisdemethoxycurcumin, zingiberene, curcumenol, curcumol, eugenol, tetrahydrocurcumin, triethylcurcumin, turmerin, turmerones, and turmeronols. Curcumin, demethoxycurcumin, and bisdemethoxycurcumin have also been isolated from Curcuma mangga, Curcuma zedoaria, Costus speciosus,
Curcuma xanthorrhiza, Curcuma aromatica, Cucruma phaeocaulis, Etlingera elatior, and Zingiber cassumunar. Curcumin is the phytochemical that gives a yellow color to turmeric and is now recognized as being responsible for most of the therapeutic effects. It is estimated that 2–5% of turmeric is curcumin. Curcumin was first isolated from turmeric in 1815, and the structure was delineated in 1910 as diferuloylmethane. Most currently available preparations of curcumin contain approximately 77% diferuloylmethane, 18% demethoxycurcumin, and 5% bisdemethoxycurcumin. Curcumin is hydrophobic in nature and frequently soluble in dimethylsulfoxide, acetone, ethanol, and oils. It has an absorption maxima around 420 nm. When exposed to acidic conditions, the color of turmeric/curcumin turns from yellow to deep red, the form in which it is used routinely for various religious ceremonies.
3. CURCUMIN ANALOGUES
As indicated earlier, turmeric contains three different analogues of curcumin (i.e., diferuloylmethane, also called curcumin, demethoxycurcumin, and bisdemothycurcumin. Whether all three analogues exhibit equal activity is not clear. Although in most systems curcumin was found to be most potent, in some systems bisdemethoxycurcumin was found to exhibit higher activity. There are also suggestions that the mixture of all three is more potent than either one alone. When administered orally, curcumin is metabolized into curcumin glucuronide and curcumin sulfonate.13 However, when administered systemically or intraperitoneally, it is metabolized into tetrahydrocurcumin, hexhyrdrocurcumin, and hexhydrocurcuminol. Tetrahydrocurcumin has been shown to be active in some systems and not in others. Whether other metabolites of curcumin exhibit biological activity is not known.
4. USES OF CURCUMIN
The use of turmeric for health purposes is nothing new. As a folklore medicine, its use has been documented in both Indian and Chinese cultures. The long list of uses include antiseptic, analgesic, anti-inflammatory, antioxidant, antimalarial, insectrepellant, and other activities associated to turmeric. Perhaps one of the most often prescribed uses is for wound-healing. This activity is well known to people from the Indian subcontinent. Modern research has provided considerable evidence, and the mechanism by which turmeric/curcumin could accelerate wound-healing has been described.
It is now well recognized that most chronic diseases are the result of disregulated inflammation. Turmeric has been traditionally described as an anti-inflammatory agent. Recent scientific evidence has indeed demonstrated that turmeric, and curcumin in particular, exhibits potent anti-inflammatory activities as determined by a wide variety of systems. Therefore, it is not too surprising that turmeric displays activities against a variety of diseases. Because curcumin also exhibits potent antioxidant activity, whether the anti-inflammatory activity of curcumin is mediated through its antioxidant mechanism is not clear. Since most well-characterized antioxidants do not exhibit antinflammatory activity, it is unlikely that the anti-inflammatory activity of curcumin is due to its antioxidant activity.