Of Cholesterol Gallstone Formation

The Gallstone Elimination Report

Gallstone Natural Solutions by David Smith

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Hussain and Chandrasekhara studied the efficacy of curcumin in reducing the incidence of cholesterol gallstones induced by feeding a lithogenic diet in young male mice (83). Feeding a lithogenic diet supplemented with 0.5% curcumin for 10 weeks reduced the incidence of gallstone formation to 26%, as compared to 100% incidence in the group fed with the lithogenic diet alone. Biliary cholesterol concentration was also significantly reduced by curcumin feeding. The lithogenic index, which was 1.09 in the cholesterol-fed group, was reduced to 0.43 in the 0.5% curcumin-supplemented group. Further, the cholesterol:phospholipid ratio of bile was also reduced significantly when 0.5% curcumin-supplemented diet was fed. A dose-response study with 0.2%, 0.5%, and 1% curcumin-supplemented lithogenic diets showed that 0.5% curcumin was more effective than a diet with 0.2% or 1% curcumin. How curcumin mediates antilithogenic effects in mice was further investigated by this group (84). For this purpose, the hepatic bile of rats was fractionated by gel filtration chromatography, and the low-molecular-weight (LMW) protein fractions were tested for their ability to influence cholesterol crystal growth in model bile. The LMW protein fraction from the lithogenic-agent-fed control group's bile shortened the nucleation time and increased the crystal growth rate and final crystal concentration. But with the LMW protein fractions from the bile of rats given curcumin, the nucleation times were prolonged and the crystal growth rates and final crystal concentrations were decreased. The LMW fractions were further purified into three different sugar-specific proteins by affinity chromatography. A higher proportion of LMW proteins from the control group bile was bound to Con-A, whereas higher proportions of LMW proteins from the groups fed with curcumin were bound to wheat germ agglutinin and Helix pomatia lectin. The Con-A-bound fraction obtained from the control group showed a pronucleating effect. In contrast, the WGA-bound fraction obtained from curcumin group showed a potent antinucleating activity.

IX. CURCUMIN MODULATES MULTIPLE SCLEROSIS

Multiple sclerosis (MS) is an inflammatory disease of the central nervous system (CNS) that afflicts more than 1 million people worldwide. The destruction of oligodendrocytes and myelin sheath in the CNS is the pathological hallmark of MS. MS is an inflammatory autoimmune disease of the CNS resulting from myelin antigen-sensitized T cells in the CNS. Experimental allergic encephalomyelitis (EAE), a CD4 + Th1-cell-mediated inflammatory demyelinating autoimmune disease of the CNS, serves as an animal model for MS. IL-12 plays a crucial proinflammatory role in the induction of neural-antigen-specific Th1 differentiation and pathogenesis of CNS demyelination in EAE and MS.

Natarajan and Bright investigated the effect of curcumin on the pathogenesis of CNS demyelination in EAE (109). In vivo treatment of SJL/J mice with curcumin significantly reduced the duration and clinical severity of active immunization and adoptive transfer EAE (109). Curcumin inhibited EAE in association with a decrease in IL-12 production from macrophage/microglial cells and differentiation of neural-antigen-specific Th1 cells. In vitro treatment of activated T cells with curcumin inhibited IL-12-induced tyrosine phosphorylation of Janus kinase 2, tyrosine kinase 2, and STAT3 and STAT4 transcription factors. The inhibition of Janus kinase-STAT pathway by curcumin resulted in a decrease in IL-12-induced T-cell proliferation and Th1 differentiation. These findings show that curcumin inhibits EAE by blocking IL-12 signaling in T cells and suggest its use in the treatment of MS and other Th1-cell-mediated inflammatory diseases.

X. CURCUMIN BLOCKS THE REPLICATION OF HIV

Transcription of type 1 human immunodeficiency virus (HIV-1) provirus is governed by the viral long terminal repeat (LTR). Drugs can block HIV-1 replication by inhibiting the activity of its LTR. Li et al. examined the effect of curcumin on HIV-1 LTR-directed gene expression and virus replication

(110). Curcumin was found to be a potent and selective inhibitor of HIV-1 LTR-directed gene expression, at concentrations that have minor effects on cells. At the studied concentrations, curcumin inhibited p24 antigen production in cells either acutely or chronically infected with HIV-1 through transcriptional repression of the LTR. Sui et al. examined the effect of the HIV-1 and HIV-2 proteases by curcumin and curcumin boron complexes

(111). Curcumin is a modest inhibitor of the HIV-1 (IC50 = 100 ||M) and

HIV-2 (IC50 = 250 am) proteases. Simple modifications of the curcumin structure raise the IC50 value, but complexes of the central dihydroxy groups of curcumin with boron lower the IC50 to a value as low as 6 am. The boron complexes are also time-dependent inactivators of the HIV proteases. The increased affinity of the boron complexes may reflect binding of the orthogonal domains of the inhibitor in interesecting sites within the substrate-binding cavity of the enzyme, while activation of the a,h-unsaturated carbonyl group of curcumin by chelation to boron probably accounts for time-dependent inhibition of the enzyme.

Mazumder et al. examined the effect of curcumin analogs with altered potencies against HIV-1 integrase (112). They reported the inhibitory activity of curcumin against HIV-1 integrase. They also synthesized and tested analogs of curcumin to explore the structure-activity relationships and mechanism of action of this family of compounds in more detail. They found that two curcumin analogs, dicaffeoylmethane and rosmarinic acid, inhibited both activities of integrase with IC50 values below 10 am. They demonstrated that lysine 136 may play a role in viral DNA binding. They showed equivalent potencies of the two curcumin analogs against both this integrase mutant and wild-type integrase, suggesting that the curcumin-binding site and the substrate-binding site may not overlap. Combining one curcumin analog with the recently described integrase inhibitor NSC 158393 resulted in integrase inhibition that was synergistic, again suggesting that drug-binding sites may not overlap. These authors also determined that these analogs could inhibit binding ofthe enzyme to the viral DNA but that this inhibition is independent of divalent metal ion. Furthermore, kinetic studies of these analogs suggest that they bind to the enzyme at a slow rate. These studies can provide mechanistic and structural information to guide the future design of integrase inhibitors.

The transcription of HIV-1 provirus is regulated by both cellular and viral factors. Various pieces of evidence suggest that Tat protein secreted by HIV1-infected cells may have additional activity in the pathogenesis of AIDS because of its ability to also be taken up by noninfected cells. Barthelemy et al. showed that curcumin used at 10-100 nM inhibited Tat transactivation of HIV1-LTR lacZ by 70-80% in HeLa cells (113). To develop more efficient curcumin derivatives, they synthesized and tested in the same experimental system the inhibitory activity of reduced curcumin (C1), which lacks the spatial structure of curcumin; allyl-curcumin (C2), which possesses a condensed allyl derivative on curcumin that plays the role of metal chelator; and tocopheryl-curcumin (C3), which enhances the antioxidant activity of the molecule. Results obtained with the C1, C2, and C3 curcumin derivatives showed a significant inhibition (70-85%) of Tat transactivation. Despite the fact that tocopheryl-curcumin (C3) failed to scavenge O2, this curcumin derivative exhibited the most activity; 70% inhibition was obtained at 1 nM, while only 35% inhibition was obtained with the curcumin.

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Get Rid of Gallstones Naturally

Get Rid of Gallstones Naturally

One of the main home remedies that you need to follow to prevent gallstones is a healthy lifestyle. You need to maintain a healthy body weight to prevent gallstones. The following are the best home remedies that will help you to treat and prevent gallstones.

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