curcumin and Colonic-Diseases

Curcumin, a natural polyphenolic compound present in turmeric, exhibited multiple pharmacological activities. Extensive studies in last two decade suggested that curcumin possesses anti-inflammatory, anticancer, antiviral, anti-amyloid, antiarthritic and antioxidant properties. The mechanism for these effects involves modulation of several signaling transduction pathways. Various clinical studies have suggested that curcumin might be a potential candidate for the prevention and/or treatment of a variety of colonic diseases such as ulcerative colitis, Crohn's disease and colonic cancer. However, several evidences suggested the role of curcumin in multiple diseases, but the major challenge is to obtain optimum therapeutic levels of curcumin due to its low solubility and poor bioavailability. Improved absorption and cellular uptake of curcumin can be achieved through alteration in formulation properties and novel approaches in delivery systems. This review presents an overview of the background of curcumin, pharmacology, pharmacokinetics, clinical evidence in chemoprevention of bowel diseases and recent approaches to deliver curcumin for improved cellular uptake and bioavailability.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Antineoplastic Agents; Antioxidants; Biological Availability; Chemistry, Pharmaceutical; Colonic Diseases; Curcumin; Drug Delivery Systems; Humans; Signal Transduction

Inducible nitric oxide synthase (iNOS) is overexpressed in colonic tumors of humans and also in rats treated with a colon carcinogen. iNOS appear to regulate cyclooxygenase-2 (COX-2) expression and production of proinflammatory prostaglandins, which are known to play a key role in colon tumor development. Experiments were designed to study the inhibitory effects of S,S'-1,4-phenylene-bis(1,2-ethanediyl)bis-isothiourea (PBIT) a selective iNOS-specific inhibitor, measured against formation of azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF). Beginning at 5 weeks of age, male F344 rats were fed experimental diets containing 0 or 50 p.p.m. of PBIT, or 2000 p.p.m. of curcumin (non-specific iNOS inhibitor). One week later, rats were injected s.c. with AOM (15 mg/kg body wt, once weekly for 2 weeks). At 17 weeks of age, all rats were killed, colons were evaluated for ACF formation and colonic mucosa was assayed for isoforms of COX and NOS activities. Both COX and iNOS activities in colonic mucosa of the AOM-treated rats were significantly induced. Importantly, 50 p.p.m. PBIT suppressed AOM-induced colonic ACF formation to 58% (P < 0.0001) and crypt multiplicity containing four or more crypts per focus to 78% (P < 0.0001); it also suppressed AOM-induced iNOS activity. Curcumin inhibited colonic ACF formation by 45% (P < 0.001). These observations suggest that iNOS may play a key regulatory role in colon carcinogenesis. Developing iNOS-specific inhibitors may provide a selective and safe chemopreventive strategy for colon cancer treatment.

Topics: Animals; Anticarcinogenic Agents; Azoxymethane; Carcinogens; Colonic Diseases; Colonic Neoplasms; Curcumin; Cyclooxygenase 2; Enzyme Inhibitors; Intestinal Mucosa; Isoenzymes; Male; Nitric Oxide Synthase; Nitric Oxide Synthase Type II; Precancerous Conditions; Prostaglandin-Endoperoxide Synthases; Prostaglandins; Rats; Rats, Inbred F344; Thiourea