Bioavailability of Curcumin: Problems and Promises
P r e e t h a A n a n d , † A j a i k u m a r B . K u n n u m a k k a r a , † R o b e r t A . N e w m a n , ‡ a n Bharat B. Aggarwal* d ,†
Cytokine Research Laboratory and Pharmaceutical DeVelopment Center, Department of Experimental Therapeutics, The UniVersity of Texas M. D. Anderson Cancer Center, Houston, Texas 77030
Received August 19, 2007; Revised Manuscript Received September 27, 2007; Accepted September 28, 2007
Abstract: Curcumin, a polyphenolic compound derived from dietary spice turmeric, possesses diverse pharmacologic effects including anti-inflammatory, antioxidant, antiproliferative and antian- giogenic activities. Phase I clinical trials have shown that curcumin is safe even at high doses (12 g/day) in humans but exhibit poor bioavailability. Major reasons contributing to the low plasma and tissue levels of curcumin appear to be due to poor absorption, rapid metabolism, and rapid systemic elimination. To improve the bioavailability of curcumin, numerous approaches have been undertaken. These approaches involve, first, the use of adjuvant like piperine that interferes with glucuronidation; second, the use of liposomal curcumin; third, curcumin nanoparticles; fourth, the use of curcumin phospholipid complex; and fifth, the use of structural analogues of curcumin (e.g., EF-24). The latter has been reported to have a rapid absorption with a peak plasma half-life. Despite the lower bioavailability, therapeutic efficacy of curcumin against various human diseases, including cancer, cardiovascular diseases, diabetes, arthritis, neurological diseases and Crohn’s disease, has been documented. Enhanced bioavailability of curcumin in the near future is likely to bring this promising natural product to the forefront of therapeutic agents for treatment of human disease.
Keywords: Curcumin; bioavailability; absorption; metabolism; formulations; adjuvants; nano- particles; biocurcumax
Curcumin, a hydrophobic polyphenol derived from the rhizome of the herb Curcuma longa has a wide spectrum of biological and pharmacological activities. Chemically, cur- cumin is a bis-R,-unsaturated -diketone (commonly called diferuloylmethane, Figure 1), which exhibits keto–enol tautomerism having a predominant keto form in acidic and neutral solutions and stable enol form in alkaline medium. Commercial curcumin contains approximately 77% diferu- loylmethane, 17% demethoxycurcumin, and 6% bisdemethoxy- curcumin. Traditionally, turmeric has been used for many ailments, particularly as an anti-inflammatory agent, and
To whom correspondence should be addressed. Mailing address: Department of Experimental Therapeutics, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd, Box 143, Houston, TX 77030. Phone: 713-792-3503. E-mail: firstname.lastname@example.org
Cytokine Research Laboratory.
Pharmaceutical Development Center.
curcumin has been identified as the active principle of turmeric.1 Curcumin has been shown to exhibit antioxidant, anti-inflammatory,2–5 antimicrobial, and anticarcinogenic activities. Additionally, the hepato- and nephro-protective, thrombosis supressing,14 myocardial infarction protective, 6–10 11–13 15–17
Aggarwal, B. B.; Kumar, A; Bharti, A. C. Anticancer potential of curcumin: preclinical and clinical studies. Anticancer Res. 2003, 23 (1A), 363–98.
Sharma, O. P. Antioxidant activity of curcumin and related compounds. Biochem. Pharmacol. 1976, 25 (15), 1811–1812.
Ruby, A. J.; Kuttan, G; Babu, K. D.; Rajasekharan, K. N.; Kuttan,
Anti-tumour and antioxidant activity of natural curcuminoids. Cancer Lett. 1995, 94 (1), 79–83.
Sugiyama, Y; Kawakishi, S; Osawa, T. Involvement of the
diketone moiety in the antioxidative mechanism of tetrahy- drocurcumin. Biochem. Pharmacol. 1996, 52 (4), 519–25.
Srimal, R. C.; Dhawan, B. N. Pharmacology of diferuloyl methane (curcumin), a non-steroidal anti-inflammatory agent. J. Pharm. Pharmacol. 1973, 25 (6), 447–52.
Jordan, W. C.; Drew, C. R. Curcumin––a natural herb with anti- HIV activity. J. Natl. Med. Assoc. 1996, 88 (6), 333.
10.1021/mp700113r CCC: $37.00 2007 American Chemical Society Published on Web 11/14/2007
VOL. 4, NO. 6, 807–818 MOLECULAR PHARMACEUTICS 807