Pretreatment of curcumin attenuates coagulopathy and renal injury in LPS-induced endotoxemia.
ABSTRACT Disseminated intravascular coagulation (DIC) is a lethal situation in severe infections, characterized by the systemic formation of microthrombi complicated with bleeding tendency and organ dysfunction. Current clinical trials are not promising. In this study, we investigated the protective effect of curcumin in a lipopolysaccharide (LPS)-induced DIC model in rats. Experimental DIC was induced by sustained infusion of LPS (10 mg/kg body weight) for 4 h through the tail vein. Curcumin (60 mg/kg body weight) was given intraperitoneally 3 h before LPS infusion. Results showed that, in vivo, curcumin reduced the mortality rate of LPS-infused rats by decreasing the circulating TNF-alpha levels and the consumption of peripheral platelets and plasma fibrinogen. Furthermore, in vivo curcumin also has the effect of preventing the formation of fibrin deposition in the glomeruli of kidney. These results reveal the therapeutic potential of curcumin in infection-related coagulopathy of DIC.
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ABSTRACT: 1. Curcumin is the active ingredient of the dietary spice turmeric and has been consumed for medicinal purposes for thousands of years. Modern science has shown that curcumin modulates various signalling molecules, including inflammatory molecules, transcription factors, enzymes, protein kinases, protein reductases, carrier proteins, cell survival proteins, drug resistance proteins, adhesion molecules, growth factors, receptors, cell cycle regulatory proteins, chemokines, DNA, RNA and metal ions. 2. Because of this polyphenol's potential to modulate multiple signalling molecules, it has been reported to possess pleiotropic activities. First demonstrated to have antibacterial activity in 1949, curcumin has since been shown to have anti-inflammatory, anti-oxidant, pro-apoptotic, chemopreventive, chemotherapeutic, antiproliferative, wound healing, antinociceptive, antiparasitic and antimalarial properties as well. Animal studies have suggested that curcumin may be active against a wide range of human diseases, including diabetes, obesity, neurological and psychiatric disorders and cancer, as well as chronic illnesses affecting the eyes, lungs, liver, kidneys and gastrointestinal and cardiovascular systems. 3. Although many clinical trials evaluating the safety and efficacy of curcumin against human ailments have already been completed, others are still ongoing. Moreover, curcumin is used as a supplement in several countries, including India, Japan, the US, Thailand, China, Korea, Turkey, South Africa, Nepal and Pakistan. Although inexpensive, apparently well tolerated and potentially active, curcumin has not been approved for the treatment of any human disease. 4. In the present article, we discuss the discovery and key biological activities of curcumin, with a particular emphasis on its activities at the molecular and cellular levels, as well as in animals and humans.Clinical and Experimental Pharmacology and Physiology 11/2011; 39(3):283-99. · 2.41 Impact Factor
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ABSTRACT: Because tumor necrosis factors (TNFs) are major mediators of inflammation and inflammation-related diseases, the United States Food and Drug Administration (FDA) has approved blockers of the cytokine, TNF-α, which include chimeric TNF antibody (Infliximab), humanized TNF-α antibody (Humira), and soluble TNF receptor-II (Enbrel). TNF blockers are now being used for the treatment of osteoarthritis, inflammatory bowel disease, psoriasis, and ankylosis at a total cumulative market value of more than $20 billion/year. Besides being expensive ($15,000-20,000/person/year), these drugs must be injected and have enough adverse effects to be given a black label warning by the FDA. In the current report, we describe an alternative, curcumin (diferuloylmethane), a component of turmeric (Curcuma longa) that is very inexpensive, orally bioavailable, and highly safe in humans, yet can block TNF-α action and production in in vitro models, in animal models, and in humans. In addition, we provide evidence for curcumin's activities against all of the diseases for which TNF blockers are being used. Mechanisms by which curcumin inhibits the production and the cell signaling pathways activated by this cytokine are also discussed. With health care costs and safety being major issues today, this golden spice may help provide the solution.British Journal of Pharmacology 02/2013; · 5.07 Impact Factor
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ABSTRACT: The human intestinal tract comprises a rich and complex microbial ecosystem. This intestinal microbota provides a large reservoir of potentially toxic molecules, including bacterial endotoxin (ie, lipopolysaccharide [LPS]). This potent inflammatory molecule is detectable in the circulation of healthy individuals, and levels transiently increase following ingestion of energy-rich meals. Chronic exposure to circulating endotoxin has been associated with obesity, diabetes, and cardiovascular disease. Western-style meals augment LPS translocation and by this mechanism may contribute to the pathogenesis of these diseases. By contrast, the gut and other organs have evolved mechanisms to detoxify endotoxin and neutralize the potentially inflammatory qualities of circulating endotoxin. Of specific interest to clinicians is evidence that acute postprandial elevation of circulating endotoxin is dependent on meal composition. In this review, the authors present an overview of the biochemical and cellular mechanisms that lead to endotoxemia, with emphasis on the interplay between microbial and nutrition determinants of this condition. The link between endotoxemia, diet, and changes in the intestinal microbiota raise the possibility that dietary interventions can, at least in part, ameliorate the detrimental outcomes of endotoxemia.Nutrition in Clinical Practice 02/2012; 27(2):215-25. · 1.58 Impact Factor