The effect of turmeric extracts on inflammatory mediator production.

Major compounds of several commonly used botanicals, including turmeric, have been purported to have anti-inflammatory actions. In order to test the anti-inflammatory activity of compounds isolated from rhizomes of Curcuma longa L. (Zingiberaceae), we have established an in vitro test system. HL-60 cells were differentiated and exposed to lipopolysaccharide (LPS) from Escherichia coli (1 microg/ml) in the presence or absence of botanical compounds for 24 h. Supernatants were collected and analyzed for the production of tumor necrosis factor alpha (TNF-alpha) and prostaglandin E2 (PGE2) using standard ELISA assays. Water-soluble extracts were not cytotoxic and did not exhibit biological activity. Organic extracts of turmeric were cytotoxic only at concentrations above 50 microg/ml. Crude organic extracts of turmeric were capable of inhibiting LPS-induced TNF-alpha (IC50 value = 15.2 microg/ml) and PGE2 (IC50 value = 0.92 microg/ml) production. Purified curcumin was more active than either demethoxy- or bisdemethoxycurcumin. Fractions and subfractions of turmeric extracts collected via preparative HPLC had differing biological activity, ranging from no activity to IC50 values of < 1 microg/ml. For some fractions, subfractionation resulted in a loss of activity, indicating interaction of the compounds within the fraction to produce an anti-inflammatory effect. A combination of several of the fractions that contain the turmeric oils was more effective than the curcuminoids at inhibiting PGE2. While curcumin inhibited COX-2 expression, turmeric oils had no effect on levels of COX-2 mRNA.     

Anti-inflammatory and anti-arthritic effects of new synthetic 3-(4-hydroxyphenyl)-4-(4-thiomethoxyphenyl)-1H-pyrrole-2,5-dione

We previously reported that 3-(4-hydroxyphenyl)-4-(4-thiomethoxyphenyl)-1H-pyrrole-2,5-dione (1, HMP) has a strong inhibitory effect on prostaglandin E(2) (PGE(2)) production. In this study, the anti-inflammatory and anti-arthritic effects of HMP were evaluated on LPS-induced RAW 264.7 macrophages and rats with carrageenan-induced paw edema and adjuvant-induced arthritis (AIA). The attenuation of PGE(2) production by HMP was found to be caused by the inhibition of cyclooxygenase-2 (COX-2) activity, but not COX-1 activity. However, HMP did not affect COX-2 at the protein or mRNA levels, whereas it suppressed the releases and expressions of inflammatory cytokines, such as, interleukin-1β (IL-1β) and IL-6 in LPS-induced macrophages. Furthermore, HMP suppressed LPS-induced nitric oxide (NO) production by down regulating the protein and mRNA expressions of inducible nitric oxide synthase (iNOS). In rats with carrageenan-injected acute inflammation, oral administration of HMP (25 or 50mg/kg, po) reduced paw swelling, and PGE(2) release and myeloperoxidase (MPO) activity in tissue. Furthermore, HMP (25 or 50mg/kg, po) significantly reduced paw swelling, arthritic indices and plasma PGE(2) concentrations in rat with AIA. These results show that HMP reduces swelling in a model acute inflammation and inhibits arthritic responses in a model of chronic inflammation via the inhibition of PGE(2) production. These results suggest that HMP is a potential therapeutic agent for the treatment of arthritis and associated disorders.     

Curcumin activates AMPK and suppresses gluconeogenic gene expression in hepatoma cells

Curcumin, the bioactive component of curry spice turmeric, and its related structures possess potent anti-oxidant and anti-inflammatory properties. Several lines of evidence suggest that curcumin may play a beneficial role in animal models of diabetes, both by lowering blood glucose levels and by ameliorating the long-term complications of diabetes. However, current understanding of the mechanism of curcumin action is rudimentary and is limited to its anti-oxidant and anti-inflammatory effects. In this study we examine potential anti-diabetic mechanisms of curcumin, curcumin C3 complex^®, and tetrahydrocurcuminoids (THC). Curcuminoids did not exert a direct effect on receptor tyrosine kinase activity, 2-deoxy glucose uptake in L6-GLUT4myc cells, or intestinal glucose metabolism measured by DPP4/α-glucosidase inhibitory activity. We demonstrate that curcuminoids effectively suppressed dexamethasone-induced phosphoenol pyruvate carboxy kinase (PEPCK) and glucose6-phosphatase (G6Pase) in H4IIE rat hepatoma and Hep3B human hepatoma cells. Furthermore, curcuminoids increased the phosphorylation of AMP-activated protein kinase (AMPK) and its downstream target acetyl-CoA carboxylase (ACC) in H4IIE and Hep3B cells with 400 times (curcumin) to 100,000 times (THC) the potency of metformin. These results suggest that AMPK mediated suppression of hepatic gluconeogenesis may be a potential mechanism mediating glucose-lowering effects of curcuminoids.     

Genetic diversity and biological activity of Curcuma longa ecotypes from Rapa Nui using molecular markers

Curcuma Longa (CL) has been used for hundreds of years by native people from Rapa Nui for the treatment of different illness. Despite this plant was introduced from Polynesia or India, there is still scarce information about its origin. The objective of this study was to analyze the genetic variation of three CL ecotypes based on molecular phylogenetic and genotypification using internal transcribed spacer 2 (ITS2) and simple sequence repeats (SSR). Antioxidant and anti-inflammatory properties of rhizomes and leaves extracts of three CL plants were analyzed by spectrophotometric methods and cyclooxygenase 2 (COX-2) inhibition assay. Complementarily, we predicted the potential binding mode and binding energy of curcuminoids and nonsteroidals anti-inflammatory drugs (NSAIDs) into COX-2 via molecular docking. The ITS2 sequence shows two major clusters (I and II), group I consisted of Curcuma haritha and group II consisted of different species of Curcuma and Rapa Nui samples (MR-1, MR-2 and RK-2). Results of SSR markers show that genotype MR-2 was similar to MR-1 and RK-2 with 70.8 and 42.9% similarity, whereas genotype was similar to RK-2, MR-1 and MR-2 with 63.9, 43.2 and 42.9% similarity, respectively. MR-1 have better antioxidant and autoinflammatory activity than rest of CL samples due to its high concentration of polyphenols (33.68 mg/g) and curcumin (29.69 mg/g). Furthermore, docking results show that three curcuminoids of CL and selective NAIDs, as celecoxib, etodolac and meloxicam, share the same binding pocket into COX-2. However, three curcuminoids have a lower ΔG_binding than other COX-2 selective NAIDs as etodolac and meloxicam, except for Coxib family as valdecoxib, celecoxib and rofecoxib. Our findings suggest MR-1, MR-2 and MK-2 from Germplasm Bank (Mataveri Otai of CONAF) are closely related to Curcuma amada and Curcuma montana even though they have genetic variability.     

Occurrence of orally administered curcuminoid as glucuronide and glucuronide/sulfate conjugates in rat plasma

Curcuminoids, curcumin and its structurally related compounds, constitute the phenolic yellowish pigment of turmeric. We investigated the absorption and metabolism of orally administered curcuminoids (curcumin, demethoxycurcumin and bisdemethoxycurcumin) in rats. HPLC and LC-MS analyses after enzymatic hydrolyses showed that the predominant metabolites in plasma following administration were glucuronides and glucuronide/sulfates (conjugates with both glucuronide and sulfate) of curcuminoids. The plasma concentrations of conjugated curcuminoids reached a maximum one hour after administration. The conjugative enzyme activities for glucuronidation and sulfation of curcumin were found in liver, kidney and intestinal mucosa. These results indicate that orally administered curcuminoids are absorbed from the alimentary tract and present in the general blood circulation after largely being metabolized to the form of glucuronide and glucuronide/sulfate conjugates.     

Separation and free radical-scavenging activity of major curcuminoids of Curcuma longa using HPTLC-DPPH method

A direct HPTLC assay was developed for the determination of total curcuminoids and three individual curcuminoids, curcumin, demethoxycurcumin and bisdemethoxycurcumin. In addition, a new procedure was developed to separate and quantitative the free radical-scavenging activity of individual compounds from the rhizome of Curcuma longa L. (Zingiberaceae) based on the combination of HPTLC with a diode array detector (DAD) and post chromatographic DPPH(*) radical derivatisation. It was established that both individual curcuminoids and the extract of C. longa were capable of scavenging DPPH(*) radicals. From the estimated ID(50) values, it can be seen that the order of activity was curcumin > demethoxycurcumin > bisdemethoxycurcumin > ascorbic acid. However, the ID(50) values of curcuminoids were not significantly different. The data indicates the presence of a synergistic mechanism of antiradical activity of curcuminoids.     

Anti-inflammatory effects of novel curcumin analogs in experimental acute lung injury

Background

Acute lung injury (ALI) and its most severe form acute respiratory distress syndrome (ARDS) have been the leading cause of morbidity and mortality in intensive care units (ICU). Currently, there is no effective pharmacological treatment for acute lung injury. Curcumin, extracted from turmeric, exhibits broad anti-inflammatory properties through down-regulating inflammatory cytokines. However, the instability of curcumin limits its clinical application.

Methods

A series of new curcumin analogs were synthesized and screened for their inhibitory effects on the production of TNF-α and IL-6 in mouse peritoneal macrophages by ELISA. The evaluation of stability and mechanism of active compounds was determined using UV-assay and Western Blot, respectively. In vivo, SD rats were pretreatment with c26 for seven days and then intratracheally injected with LPS to induce ALI. Pulmonary edema, protein concentration in BALF, injury of lung tissue, inflammatory cytokines in serum and BALF, inflammatory cell infiltration, inflammatory cytokines mRNA expression, and MAPKs phosphorylation were analyzed. We also measured the inflammatory gene expression in human pulmonary epithelial cells.

Results

In the study, we synthesized 30 curcumin analogs. The bioscreeening assay showed that most compounds inhibited LPS-induced production of TNF-α and IL-6. The active compounds, a17, a18, c9 and c26, exhibited their anti-inflammatory activity in a dose-dependent manner and exhibited greater stability than curcumin in vitro. Furthermore, the active compound c26 dose-dependently inhibited ERK phosphorylation. In vivo, LPS significantly increased protein concentration and number of inflammatory cells in BALF, pulmonary edema, pathological changes of lung tissue, inflammatory cytokines in serum and BALF, macrophage infiltration, inflammatory gene expression, and MAPKs phosphorylation . However, pretreatment with c26 attenuated the LPS induced increase through ERK pathway in vivo. Meanwhile, compound c26 reduced the LPS-induced inflammatory gene expression in human pulmonary epithelial cells.

Conclusions

These results suggest that the novel curcumin analog c26 has remarkable protective effects on LPS-induced ALI in rat. These effects may be related to its ability to suppress production of inflammatory cytokines through ERK pathway. Compound c26, with improved chemical stability and bioactivity, may have the potential to be further developed into an anti-inflammatory candidate for the prevention and treatment of ALI.

Electronic supplementary material

The online version of this article (doi:10.1186/s12931-015-0199-1) contains supplementary material, which is available to authorized users.     

A comparative study of PNIPAM nanoparticles of curcumin, demethoxycurcumin, and bisdemethoxycurcumin and their effects on oxidative stress markers in experimental stroke

Oxidative stress and inflammatory damage play an important role in cerebral ischemic pathogenesis and may represent a target for treatment. The development of new strategies for enhancing drug delivery to the brain is of great importance in diagnostics and therapeutics of central nervous diseases. The present study examined the hypothesis that intranasal delivery of nanoformulation of curcuminoids would reduce oxidative stress-associated brain injury after middle cerebral artery occlusion (MCAO). The rats were subjected to 2 h of MCAO followed by 22 h reperfusion, after which the grip strength, locomotor activity was performed. The effects of treatment in the rats were assessed by grip strength, locomotor activity and biochemical studies (glutathione peroxidase, glutathione reductase, lipid peroxidation, superoxide dismutase, and catalase) in the brain. Pretreatment with polymeric N-isopropyl acryl amide (PNIPAM) nanoparticles formulation of all three curcuminoids (curcumin (Cur), demethoxycurcumin (DMC), and bisdemethoxycurcumin (BDMC)) at doses (100 μg/kg body weight) given intranasally was effective in bringing significant changes on all the parameters. While nanoformulation of curcumin at a dose of 100 μg/kg body weight was most active in the treatment of cerebral ischemia as compared to others nanoformulation of curcuminoids. The potency of antioxidant activity significantly decreased in the order of PNIPAM nanoformulation of Cur > DMC >> BDMC, thus suggesting the critical role of methoxy groups on the phenyl ring.     

Synthesis and tubulin-binding properties of non-symmetrical click C5-curcuminoids

A click-type entry into shortened curcuminoids of the diarylpentanoid type has been developed. The reaction is ideally suited to generate non-symmetrical analogues of curcumin, a class of natural products difficult to access but of growing biomedical relevance and special mechanistic interest to investigate the unique binding mode of curcumin to tubulin. Investigation of a series of click diarylpentane curcuminoids and their pyrazole adducts in various cellular tubulin functional assays validated this class of compounds as a novel type of anti-mitotic agents, evidencing structure–activity relationships, and identifying the pyrazole adduct 4k as a promising lead.     

Anti-allergic principles from Thai zedoary: structural requirements of curcuminoids for inhibition of degranulation and effect on the release of TNF-alpha and IL-4 in RBL-2H3 cells

The 80% aqueous acetone extract of the rhizomes of Curcuma zedoaria cultivated in Thailand (Thai zedoary) was found to inhibit release of beta-hexosaminidase, as a marker of antigen-IgE-mediated degranulation, in RBL-2H3 cells and passive cutaneous anaphylaxis reaction in mice. From the active fraction, four curcuminoids (curcumin, dihydrocurcumin, tetrahydrodemethoxycurcumin, and tetrahydrobisdemethoxycurcumin) were isolated together with two bisabolane-type sesquiterpenes, and the effects of four curcuminoids from Thai zedoary and several related compounds on the degranulation were examined. Among them, curcumin showed the highest activity against beta-hexosaminidase release with IC(50) of 5.3 microM, followed by bisdemethoxycurcumin (IC(50) = 11 microM). With regard to the structural requirements of curcuminoids for the activity, the conjugated olefins at the 1-7 positions and the 4'- or 4'-hydroxyl groups of curcuminoids were suggested to be essential for the strong activity, whereas the 3'- or 3'-methoxyl group only enhanced the activity. Furthermore, effects of curcumin and bisdemethoxycurcumin on calcium ionophores (A23187 and ionomycin)-induced degranulation and antigen-induced release of TNF-alpha and IL-4 were examined.     

姜黄素类化合物生物合成研究进展

姜黄素类化合物是植物中一类稀少的二酮类化合物,存在于姜科、天南星科植物的块根或根茎中,是姜黄等植物中主要活性成分,因具有抗氧化、抗癌等诸多药理活性而被广泛应用于食品领域和新药研发中.因其苯环侧链取代基不同,姜黄素类化合物可进一步分为姜黄素、去甲氧基姜黄素、双去甲氧基姜黄素等.目前,姜黄素类化合物主要是通过植物提取法获得...     

Curcumin‐galactomannosides mitigate alcohol‐induced liver damage by inhibiting oxidative stress,hepatic inflammation,and enhance bioavailability on TLR4/MMP events compared to curcumin

Alcoholic liver diseases are classified as one of the major reasons for worldwide morbidity and mortality. Curcuminoids exhibit a wide range of pharmacological activities that are beneficial for health, including hepatoprotective effects, but its clinical significance is limited due to poor oral bioavailability. In the present study, a novel formulation of curcumin as curcumin‐galactomannosides (CGM) with enhanced oral bioavailability alleviated alcohol‐induced liver damage in wistar rats with an increased potency compared to the unformulated natural curcuminoids (CM). Ethanol administration significantly elevated liver toxicity markers, lipid peroxidation and inflammatory markers with a simultaneous reduction in antioxidant defenses. Supplementation of CGM reversed all of the pathological effects of alcohol administration, almost close to the normal level, when compared with CM. Histopathology of liver tissue also confirmed the better protective effect of CGM, indicating the enhancement in antioxidant and anti‐inflammatory effects as a function of bioavailability.     

Pro-oxidant, anti-oxidant and cleavage activities on DNA of curcumin and its derivatives demethoxycurcumin and bisdemethoxycurcumin.

Curcumin, a naturally occurring phytochemical responsible for the colour of turmeric shows a wide range of pharmacological properties including antioxidant, anti-inflammatory and anti-cancer effects. We have earlier shown that curcumin in the presence of Cu(II) causes strand cleavage in DNA through generation of reactive oxygen species, particularly the hydroxyl radical. Thus, curcumin shows both antioxidant as well as pro-oxidant effects. In order to understand the chemical basis of various biological properties of curcumin, we have studied the structure-activity relationship between curcumin and its two naturally occurring derivatives namely demethoxycurcumin (dmC) and bisdemethoxycurcumin (bdmC). Curcumin was found to be the most effective in the DNA cleavage reaction and a reducer of Cu(II) followed by dmC and bdmC. The rate of formation of hydroxyl radicals by the three curcuminoids also showed a similar pattern. The relative antioxidant activity was examined by studying the effect of these curcuminoids on cleavage of plasmid DNA by Fe(II)-EDTA system (hydroxyl radicals) and the generation of singlet oxygen by riboflavin. The results indicate that curcumin is considerably more active both as an antioxidant as well as an oxidative DNA cleaving agent. The DNA cleavage activity is the consequence of binding of Cu(II) to various sites on the curcumin molecule. Based on the present results, we propose three binding sites for Cu(II). Two of the sites are provided by the phenolic and methoxy groups on the two benzene rings and the third site is due to the presence of 1,3-diketone system between the rings. Furthermore, both the antioxidant as well as pro-oxidant effects of curcuminoids are determined by the same structural moieties.     

Diarylidene-N-Methyl-4-Piperidones and Spirobibenzopyrans as Antioxidant and Anti-Inflammatory Agents

Curcumin has antioxidant properties resulting from its radical scavenging ability and inhibition of inflammation-associated factors. However, its lack of solubility, instability, and poor bioavailability are impediments to its therapeutic use. As potential alternatives, we synthesized and performed chemical analysis of thirty diarylidene-N-methyl-4-piperidone (DANMP), diheteroarylidene-N-methyl-4-piperidone (DHANMP), and spirobibenzopyran (SBP) derivatives, one of which was also characterized by single crystal X-ray diffraction. All compounds were evaluated for antioxidant activity via 2,2-Diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay and for drug-like properties in silico. A subset of five compounds was investigated in terms of aqueous solubilities, which were significantly improved compared to that of curcumin. In vitro assessments of cellular and anti-inflammatory effects were conducted via real time polymerase chain reaction (RT-PCR) and Griess assays to evaluate the presence of inflammatory/activated (M1) markers and production of nitric oxide (NO) species, which are associated with inflammation. The five compounds reduced levels of markers and NO to extents similar to or better than curcumin in inflamed cells, and showed no adverse effects on cell viability. We show that these compounds possess anti-inflammatory properties and may be used as curcumin-substitutes with improved characteristics.     

Curcumin attenuates ovalbumin-induced airway inflammation by regulating nitric oxide

Curcumin has been strongly implicated as an anti-inflammatory agent, but the precise mechanisms of its action are largely unknown. In this study, we show that curcumin contributes to anti-inflammatory activity in the murine asthma model and lung epithelial cell A549 through suppression of nitric oxide (NO). To address this problem, curcumin was injected into the peritoneum of ovalbumin (OVA)-sensitized mice before the last allergen challenge. OVA challenge resulted in activation of the production of inducible nitric oxide (iNOS) in lung tissue, inflammatory cytokines, recruitment of eosinophils to lung airways, and airway hyper-responsiveness to inhaled methacholine. These effects of ovalbumin challenge were all inhibited by pretreatment of mice with curcumin. Furthermore, supplementation with curcumin in the A549 human airway epithelial cells decreased iNOS and NO production induced by IFN-γ. These findings show that curcumin may be useful as an adjuvant therapy for airway inflammation through suppression of iNOS and NO.     

Capsaicin exhibits anti-inflammatory property by inhibiting IkB-a degradation in LPS-stimulated peritoneal macrophages

Capsaicin, a major ingredient of hot pepper, was considered to exhibit an anti-inflammatory property. In order to clarify the signalling mechanism underlying the anti-inflammatory action of capsaicin, we investigated the effect of capsaicin on the production of inflammatory molecules in lipopolysaccharide (LPS)-stimulated murine peritoneal macrophages. The level of PGE2 was measured by EIA. The expression levels of COX-2, iNOS, IkB-a, and vanilloid receptor-1 (VR-1) were determined at the protein and mRNA levels. Significant inhibition of the production of LPS-induced PGE2 by capsaicin was observed in a dose-dependent manner. Capsaicin did not affect the COX-2 expression at either the protein or mRNA level, but inhibited the enzyme activity of COX-2 and the expression of the iNOS protein. Capsaicin completely blocked LPS-induced disappearance of IkB-a and therefore inactivated NF-kB. The inhibitory action of capsaicin on PGE2 production was not abolished by capsazepine, a specific antagonist to VR-1. A high expression level of the VR-1 like protein (VRL-1) was observed in peritoneal macrophages, while the expression of VR-1 was not detected. These findings suggest that the anti-inflammatory action of capsaicin may occur through a novel mechanism, not by a VR-1 receptor-mediated one. Both capsaicin and capsazepine may be a promising drug candidates for ameliorating inflammatory diseases and cancer.     

Attenuation of high-glucose-induced inflammatory response by a novel curcumin derivative B06 contributes to its protection from diabetic pathogenic changes in rat kidney and heart

There is increasing evidence indicating that inflammatory processes are involved in the development and progression of diabetic complications. However, effective anti-inflammatory treatments for patients who have diabetic complications have yet been practically identified. Curcumin is a main component of Curcuma longa with numerous pharmacological activities. Previously, we synthesized a novel curcumin analogue (B06) that exhibited an improved pharmacokinetic and enhanced anti-inflammatory activity compared to curcumin. The present study aimed to test the hypothesis that B06 may reduce high-glucose-induced inflammation and inflammation-mediated diabetic complications. In vitro, pretreatment with B06 at a concentration of 5 μM significantly reduced the high-glucose-induced overexpression of inflammatory cytokines in macrophages. This anti-inflammatory activity of B06 is associated with its inhibition of c-Jun N-terminal kinase/nuclear factor κB activation. In vivo, despite that B06 administration at 0.2 mg·kg^? 1·d^? 1 for 6 weeks did not affect the blood glucose profile of diabetic rats, the B06-treated animals displayed significant decreases in inflammatory mediators in the serum, kidney, and heart and renal macrophage infiltration. This was accompanied with an attenuation of diabetes-induced structural and functional abnormalities in the kidney and heart. Taken together, these data suggest that the novel derivative B06 might be a potential therapeutic agent for diabetic complications via an anti-inflammatory mechanism and support the potential application in diabetic complication therapy via anti-inflammatory strategy.     

Design, synthesis, and SAR studies of some 5-aliphatic oximino esters of thiophene as potential anti-inflammatory leads: comparative biological activity profile of aliphatic oximes vs aromatic oximes

A series of novel tetra substituted thiophenes were synthesized, characterized, and evaluated for their anti-inflammatory activity in carrageenin induced rat paw edema model-an acute in vivo model. Compounds V1, V3, V11, V12, V17, and V18 showed good anti-inflammatory activity, indicating the importance of oxime moiety in modulating the activity. The structure-activity relationship studies explore "the aliphatic oxime esters" attached via a ketone bridge to fifth position of the thiophene, and indicate that this feature may enhance the anti-inflammatory activity as compared to aromatic oximes. Since free radicals are implicated in various inflammatory disorders, the free radical scavenging activity of some of the synthesized candidates was assessed using 1,1-diphenyl-2-picryl hydrazyl assay. The oxime containing analogs exhibited weak to moderate activity as free radical scavengers in DPPH assay. A plausible reasoning for its free radical scavenging ability is discussed. All the compounds were also screened in nitro blue tetrazolium model, to assess them as superoxide anion radical scavengers. A direct correlation between anti-inflammatory activity and free radical scavenging activity was not seen. The results disclose a new class of anti-inflammatory agents designed and synthesized for the first time wherein the utility of aliphatic oxime esters in modulating the anti-inflammatory activity profile is apparent. This will give us potential anti-inflammatory leads.     

Reduced exudation and increased tissue proliferation during chronic inflammation in rats deprived of endogenous prostaglandin precursors

Two models of chronic inflammation were studied in rats deprived of endogenous precursors of prostaglandins by feeding the animals on essential fatty acid deficient (EFAD) food. During kaolin-induced pouch-granuloma, exudate production was markedly reduced in EFAD rats, when compared with normal animals. The exudates from normal rats contained large amounts of PGE, but in the exudates from EFAD rats the amount of PGE was very markedly reduced. Similarly, with carrageenan-impregnated polyether sponges, the exudative component of inflammation was reduced in EFAD rats. However, the proliferative component was significantly increased, particularly in relation to the stunted growth of EFAD rats. Sponge exudates from EFAD rats contained fewer leucocytes than those from normal animals but the fall in leucocyte count was much smaller than the very marked reduction in PGE activity. EFAD rats also exhibited a significant increase in adrenal weights.The results are discussed in the light of the ambivalent (pro- or anti-inflammatory) role of endogenous PGs. It appears that, in the proliferative phase of inflammation, the anti-inflammatory role of PGs is more dominant.     

Curcumin protects against thioacetamide-induced hepatic fibrosis by attenuating the inflammatory response and inducing apoptosis of damaged hepatocytes

Inflammation and hepatic stellate cell (HSC) activation are the most crucial steps in the formation of hepatic fibrosis. Hepatocytes damaged by viral or bacterial infection, alcohol or toxic chemicals initiate an inflammatory response that activates collagen production by HSCs. Recent studies indicate curcumin has liver-protective effects due to its anti-inflammatory, antioxidant and anticancer activities; however, the mechanisms are not well understood. In this study, we show that curcumin protected against hepatic fibrosis in BALB/c mice in vivo by inhibiting HSC activation, inflammatory responses and inducing apoptosis of damaged hepatocytes. Using the thioacetamide (TAA)-induced hepatic fibrosis animal model, we found that curcumin treatment up-regulated P53 protein expression and Bax messenger RNA (mRNA) expression and down-regulated Bcl-2 mRNA expression. Together, these responses increased hepatocyte sensitivity to TAA-induced cytotoxicity and forced the damaged cells to undergo apoptosis. Enhancing the tendency of damaged hepatocytes to undergo apoptosis may be the protective mechanism whereby curcumin suppresses inflammatory responses and hepatic fibrogenesis. These results provide a novel insight into the cause of hepatic fibrosis and the cytoprotective effects curcumin has on hepatic fibrosis suppression.