Turmeric group10 final
- 1. Tradition to Science: Benefits and Risks of Turmeric in Anti-Inflammatory Therapy Anna Donnis, Kathy Nguyen, Jennifer Rowland, Rajani Ranga, Brian Schmitz, and Laura Swatzyna VCU School of Pharmacy 410 North 12th Street Richmond, Virginia 23298 Abstract Introduction 2,3 Marketing and Regulation 9 Major Activities 6 Side Effects/ Toxicity 6 Pharmacology 5,8,10 Acknowledgements Pharmacokinetics/ Pharmacodynamics 1,4,7 Resources The turmeric plant grows as an herb to around 1 meter tall. Turmeric belongs to the ginger family Zingiberaceae . Its botanical name is Curcuma longa . Turmeric was arisen by selection and vegetative propagation of a hybrid between the wild turmeric ( Curcuma aromatic ) and other species, native to India, Sri Lanka and the eastern Himalayas. Turmeric contains yellow pigments called curcuminoids, which mainly include curcumin (diferuloyl methane). The rhizome (underground stem) is boiled, dried and ground to make turmeric powder, which is widely available as capsules, tea extracts, or pastes for topical application.  It has a long history of medicinal use. Turmeric has been thought to have originated from India, around 3000 BC. Turmeric was introduced to China in 700 AD, East Africa in 800 AD, West Africa in 1200 AD, and Jamaica in the 18 th  century. Susruta’s Ayurvedic Compendium dates back to 250 BC and recommends using turmeric ointment to relieve effects of poisoned food. It is used as an anti-inflammatory in ancient medicine to heal/reduce pain on burned skin, to prevent infections in wounds, prevent inflammation of eye, reduce menstrual/digestive cramping, treat atherosclerosis, inflammation during hemorrhoids/anal fissures, treat skin conditions (eczema, acne, etc), relieve arthritis pain, anticancer and liver detoxification.  It is believed that turmeric has numerous benefits including anti-inflammatory activity. NIH studies have revealed that turmeric does show anti-inflammatory activity in laboratory and animal studies, however there is no reliable data for humans. Many studies have been performed on turmeric which may suggest anti-inflammatory activity however there is unclear scientific evidence for this use. Turmeric has been demonstrated to be a safe product to use in adults however the NIH does not have any proven or safe medicinal dose for children.  Curcumin expresses an anti-oxidant action neutralizing free radicals by enhancing the activity of an important detoxifying enzyme. The exact mechanism is unknown, but is thought to have an aspirin-like effect on the pain production cascade by inhibiting 5-lipo-oxygenase and cyclooxygenase-2, thereby inhibiting the conversion of arachidonic acid to prostaglandin E-2, Thromboxane B2, and 12-HHT. The inhibition of cyclooxygenase-2 is carried out through deacylation of phospholipids in arachidonic acid. The nature of inhibition, however, has been found to be reversible. Inhibition of phospholipid deacylation may not be specific for platelets and may be common to other cell types.   Inhibition of arachidonic acid release in other cells, such as polymorphonuclear leukocytes may explain anti-inflammatory activity. Multiple pathway inhibition (Figure 2) redirects arachidonic acid to the 12-LOX pathway, leading to increased production of 12-HPETE. Platelet aggregation is inhibited, and at higher concentrations of 12-HPETE, platelet thromboxane formation is inhibited. Although evidence is uncertain, leukotriene inhibition is also possible. Curcumin has been proposed to inactivate and down regulate nuclear factor-kappa B, a powerful transcription factor that promotes the inflammatory response necessary for some cancers to spread and are destructive to joints.  The hypothesis of down regulating NF-kB promotes traditional anti-cancer and anti-inflammatory actions of curcumin and possibly other turmeric compounds. Thanks to VCU School of Pharmacy for the supplies and resources available to complete this project. For any questions or comments, please contact Group 10 at swatzynala@vcu.edu Major activities include: Anti- inflammatory Anti- tumor Antioxidant Liver Support Tumeric is a natural herb with a long history of use beginning as early as 3000 BC. Despite the fact that it is natural, turmeric should not be assumed to be safe and its marketing claims should be noted with caution, as natural products are not regulated by the Food and Drug Administration. The active ingredient in turmeric is curcumin, and its medicinal benefit claims include namely anti-inflammatory, anti-tumor, and antioxidant. There are studies that show curcumin effective as an anti-inflammatory, inhibiting COX 2 and leukotrienes. General side effects include nausea, diarrhea, and altered plasma drug concentrations due to enzyme inhibition of P450, glutathione-S-transferase, and UDP-glucuronosyltransferase enzymes. Some studies with rats have shown some concern that curcumin may actually increase ones risk of cancer. No human trials to date have tested curcumin in large doses. When taken orally, curcumin reaches Tmax at approximately one hour, and exhibits poor bioavailability and high first pass metabolism, leaving possible benefits questionable. Figure 2. Curcumin inhibits the incorporation of arachidonic acid into platelet phospholipids and also inhibits the deacylation of phospholipids. Both inhibitions result in reduced amounts of free arachidonic acid. Curcumin exhibits its effects at several steps in the arachidonic acid cascade in platelets. The U.S. Food and Drug Administration does not strictly regulate herbs and supplements. From the lack of regulations there is no guarantee of the strength, purity or safety of products, and the effects may vary. Always read product labels. If you have a medical condition, or are taking other drugs, herbs, or supplements, you should speak with a qualified healthcare provider before taking a new therapy. Consult a healthcare provider immediately if you experience any side effects. Marketing Claims: “ Antioxidants help fight cell damaging free radicals in the body, free radicals contribute to oxidative stress, which in turn can lead to the premature aging of cells”. (Nature’s Bounty Brand claim)  “ Immune Defense”. (Spring Valley Brand)  “ Antioxidant”. (Finest Natural) Each brand can make a different health claim on the benefit of taking a product such as turmeric. It is important to read the claim and take it just for what it is saying and not make any assumptions from that. Again, this is why it is important to discuss all new therapies with your healthcare provider. It has been found that with oral dosing, much of the active ingredient, curcumin, is excreted via feces (50-55%) while the majority of the remaining 45-50% that is absorbed 1 is metabolized via first-pass metabolism 7 . Only about 7-10% of total amount of curcumin that is absorbed reaches the blood and other organs 1 . The remaining amount of curcumin is eventually converted to highly water soluble metabolites and then excreted through the kidneys or back to the large intestine 1 . Standard curcumin when taken orally reaches a Tmax at about 1 hr but is then excreted rapidly thus reducing its therapeutic effect and AUC, while the majority of curcumin is eliminated within 72 hours after ceasing dosing regimen. Due to its high level of first-pass metabolism, poor bioavailability, and rapid metabolism, the ability for curcumin to exhibit some sustained therapeutic effect is still questionable 4 . General guidelines for turmeric intake range from 0.9 to 3.6 g day, where the most common side effects include nausea and diarrhea. To date, high dose levels have not been tested in humans. A number of non-human reports, eight from the past twenty years, suggest toxicity of turmeric. Data suggested that the active ingredient in turmeric, curcumin, caused DNA damage to mitochondria and genomes and alterations in chromosomes at therapeutic concentrations of 2.5 ug/mL and 5 ug/mL. This data is concerning for the average consumer as a risk for cancer. Furthermore, a two-year feeding study with rats and mice supported the carcinogenic concerns for turmeric, with ingestion causing increased cases of ulcers, hyperplasia, inflammation of the digestive tract, and anemia. Other experiments related ingestion of turmeric to increased reactive oxygen, a known carcinogen. Turmeric’s active ingredient, curcumin, has also been shown to inhibit several enzymes, including P450, glutathione-S-transferase, and UDP-glucuronosyltransferase, which could cause changes in plasma concentrations of other drugs. Anand, P., Ajaikumar, B., Newman, R.A., and Aggarwal, B.B. 2007. Bioavailability of Curcumin: Problems and Promises. Mol. Pharmaceutics. 4(6): 807-818. Bengmark, M.D. Mesa and A. Gil. 2009. Plant-derived health - the effects of turmeric and curcuminoids. Nutr. Hosp. 24(3): 273-281. (3) Dori, Jonathon. 2005. Turmeric: Plant Cultures, Exploring Plants and People. Accessed March 14 from --http://www.plantcultures.org/plants/turmeric_landing.html (4) Gota, VS. GB Maru, TG Soni, TR Gandhi, N Kochar, MG Agarwal. 2010. “Safety and pharmacokinetics of a solid lipid curcumin particle formulation in osteosarcoma patients and healthy volunteers.” Journal of Agriculture and Food Chemistry. 58(4): 2095-2099. (5) Herbal COX-2 Inhibitors: A Natural Alternative. Gene Bruno, B.S., M.H.S., R.H.(AHG). (6) Shankar, S. and Srivastava, R.K. 2007. Bax and Bak genes are essential for maximum apoptotic response by curcumin, a polyphenolic compound and cancer chemopreventive agent derived from turmeric, Curcuma longa. Carcinogenesis 2007 28(6):1277-1286. (7) Sharma, Ricky. William Steward. Andreas Gesher. 2007. Pharmacokinetics and pharmacodynamics of curcumin” Kluwer Academic Publishers. (8) Srivastava KC, Bordia A, Verma SK. 1995. Curcumin, a major component of food spice turmeric (Curcuma longa) inhibits aggregation and alters eicosanoid metabolism in human blood platelets. Prostaglandins Leukot Essent Fatty Acids. 52(4):223-227. (9) Turmeric (Curcuma longa Linn.) and Curcumin. 2009. Medline. Accessed March 13, 2010 from http://www.nlm.nih.gov/medlineplus/druginfo/natural/patient-turmeric.html (10) Turmeric: Integrative Medicine. Louis V. Gerstner, Jr. Graduate School of Biomedical Sciences, Memorial Sloan-Kettering Cancer Center 2008. Active Ingredient 6 Figure 1. Structure of curcumin, the active ingredient in turmeric, constituting 3% to 5% of turmeric Image from: http://www.nutritionandmetabolism.com/content/figures/1743-7075-4-8-1-l.jpg Wound healing Anti-infective Anti-amloidogenic (memory) Images from: http://www.aggressivehealthshop.co.uk/ http://www.1stchineseherbs.com/resvertrol_and_Turmeric_bonus.html http://www.vitadiscount.com/vitasprings/turmeric-extract-planetary.jpg Images from http://grisshammer.blogspot.com/2008/08/turmeric-curcuma-is-one-of-natures-most.html, http://josuediaz.files.wordpress.com/2010/02/post_turmeric_.jpg Pharmacology Continued Conclusion The use of turmeric has been popular for thousands of years. Cucurmin is the active ingredient in turmeric. Though evidence shows turmeric as an effective anti-inflammatory agent, the exact mechanism is unknown, and more data is needed to determine if the benefits of using turmeric as an anti-inflammatory agent outweigh the risks. Turmeric has little bioavailability, adding further question to its benefits. As it stands, the data do not allow turmeric to be recommended to patients with confidence, and in fact patients should approach nearly all natural products with caution.