Biosynthesized nanosilver as anti-oxidant,anti-apoptotic and anti-inflammatory agent against Plasmodium chabaudi infection in the mouse liver

In recent years, the use of plant-mediated nanoparticle synthesis to combat infectious diseases has become increasingly significant. Malaria is one of the world's most infectious diseases caused by Plasmodium species. The antioxidant, anti-apoptotic, and anti-inflammatory properties of nanosilver biosynthesized from Indigofera oblongifolia leaf extracts (NS) against Plasmodium chabaudi infection of the mouse liver were investigated in this research. Male mice were infected with P. chabaudi infected erythrocytes then treated with NS for 7 days. The parasitemia was suppressed by approximately 24, 28, 47 and 75% on days 4, 5, 6 and 7 postinfection, respectively after treatment of mice with NS. Also, NS was able to regulate the leucocytes count and the IL1β and TNF-α-mRNA expression in mice. Ns could increase the antioxidant activity in liver of mice and was able to regulate the apoptotic genes, Bcl2 and Casp3. We showed that NS has antioxidant, anti-apoptotic, and anti-inflammatory properties when it was used to treat the livers of mice infected with P. chabaudi.     

Curcumin as an anti-inflammatory agent: Implications to radiotherapy and chemotherapy

Cancer is the second cause of death worldwide. Chemotherapy and radiotherapy are the most common modalities for the treatment of cancer. Experimental studies have shown that inflammation plays a central role in tumor resistance and the incidence of several side effects following both chemotherapy and radiotherapy. Inflammation resulting from radiotherapy and chemotherapy is responsible for adverse events such as dermatitis, mucositis, pneumonitis, fibrosis, and bone marrow toxicity. Chronic inflammation may also lead to the development of second cancer during years after treatment. A number of anti-inflammatory drugs such as nonsteroidal anti-inflammatory agents have been proposed to alleviate chronic inflammatory reactions after radiotherapy or chemotherapy. Curcumin is a well-documented herbal anti-inflammatory agents. Studies have proposed that curcumin can help management of inflammation during and after radiotherapy and chemotherapy. Curcumin targets various inflammatory mediators such as cyclooxygenase-2, inducible nitric oxide synthase, and nuclear factor κB (NF-κB), thereby attenuating the release of proinflammatory and profibrotic cytokines, and suppressing chronic production of free radicals, which culminates in the amelioration of tissue toxicity. Through modulation of NF-κB and its downstream signaling cascade, curcumin can also reduce angiogenesis, tumor growth, and metastasis. Low toxicity of curcumin is linked to its cytoprotective effects in normal tissues. This protective action along with the capacity of this phytochemical to sensitize tumor cells to radiotherapy and chemotherapy makes it a potential candidate for use as an adjuvant in cancer therapy. There is also evidence from clinical trials suggesting the potential utility of curcumin for acute inflammatory reactions during radiotherapy such as dermatitis and mucositis.     

Morroniside cinnamic acid conjugate as an anti-inflammatory agent

A morroniside cinnamic acid conjugate was prepared and evaluated on E-selectin mediated cell–cell adhesion as an important role in inflammatory processes. 7-O-Cinnamoylmorroniside exhibited excellent anti-inflammatory activity (IC₅₀ = 49.3 μM) by inhibiting the expression of E-selectin; further, it was more active than another cinnamic-acid-conjugated iridoid glycoside (harpagoside; IC₅₀ = 88.2 μM), 7-O-methylmorroniside, and morroniside itself. As a result, 7-O-cinnamoylmorroniside was observed to be a potent inhibitor of TNF-α-induced E-selectin expression.     

Copper salicylate as an anti-inflammatory and analgesic agent in arthritic rats

Recent research indicates that endogenous copper is involved in anti-inflammatory and tissue repair processes. Of interest also is the analgesic efficacy of Cu complexes, since rheumatoid arthritis and similar inflammatory conditions are extremely painful. In pilot experiments, arthritic rats failed to increase voluntarily their rate of drinking a 5 mg/ml solution of copper salicylate (Cu Sal). The data from the experiment reported here showed that a forced oral dose of Cu Sal calculated at 200 mg/kg body weight significantly reduced sensitivity to mechanical pressure in less than 30 minutes but more than 15 minutes. The analgesic effect of the Cu Sal was greater for arthritic than for non-arthritic rats, suggesting that two types of analgesia are involved. First, it produces a direct analgesic effect which works irrespective of the presence of inflammation. Second, it appears to have an indirect analgesic effect due to reduction of inflammatory hyperalgesia. It was also found that Cu Sal administered orally reduces inflammation in rats with adjuvant arthritis. In summary, the results from this experiment demonstrate that Cu Sal has specific and general analgesic properties and anti-inflammatory potential.     

A novel anti-oxidant and anti-cancer strategy: a peptoid anti-inflammatory drug conjugate with SOD mimic activity

Activation of reactive oxygen and nitrogen species (RONS) by redox-active metal ions has been proposed to contribute to oxidative damage in inflamed tissues. Here, we report a dual-function anti-oxidant conjugate comprising an anti-inflammatory agent (5-aminosalicylic acid) and a chelator with potential as a superoxide dismutase mimic. The conjugate ethylenediaminetetraacetic acid bis-(5-aminosalicylic acid methyl ester) [EBAME] chelates Cu(II) ions in a 1:1 ratio, as assessed spectrophotometrically using Job's method. Superoxide dismutase (SOD) activity was determined for the Mn(II)-conjugate as 0.758+/-0.130 U at a concentration of 0.99 microM. In inflamed tissues, peptidase mediated release of active 5-ASA would also release the EDTA chelator which has significant SOD mimic activity when complexed to Cu(II) ions. Thus, EBAME has potential as a dual-function anti-inflammatory agent with reduced gastric irritability.     

Structure and conformation of 1-beta-D-ribo furanosyl pyridin-2-one-5-carboxamide: an anti-inflammatory agent

The pyrimidine nucleoside, 1-beta-D-ribofuranosyl pyridine-2-one-5-carboxamide, is an anti inflammatory agent used in the treatment of adjuvant-induced arthritis. It is the 2-one isomer of 1-beta-D-ribofuranosyl pyridine-4-one 5-carboxamide, an unusual nucleoside isolated from the urine of patients with chronic myelogenic leukemia and an important cancer marker. Crystals of 1-beta-D-ribofuranosyl pyridine-2-one-5-carboxamide are monoclinic, space group C2, with the cell dimensions a = 31.7920(13), b = 4.6872 (3), c = 16.1838(11), beta = 93.071(3) degrees , V = 2408.2(2) A(3), D(calc) = 1.496 mg/m(3) and Z = 8 (two molecules in the asymmetric unit). The structure was obtained by the application of direct methods to diffractometric data and refined to a final R value of 0.050 for 1669 reflections with I >or= 3sigma. The nucleoside exhibits an anti conformation across the glycosidic bond (chi(CN) = -15.5 degrees , -18.9 degrees ), a C3 '-endo C2 '-exo [(3)(2)T] ribose pucker and g(+) across the C(4 ')-C(5 ') exocyclic bond. The amino group of the carboxamide group is distal from the 2-one and lacks the intramolecular hydrogen bonding found in the related 2-one molecule. Nuclear magnetic resonance studies shows also an anti conformation across the glycosidic bond but the solution conformation of the furanose ring is not the same as that found in the solid state.     

Investigation of immunomodulatory and anti-inflammatory effects of eriodictyol through its cellular anti-oxidant activity

Many studies have been performed to assess the potential utility of natural products as immunomodulatory agents to enhance host responses against infection or to ameliorate immune-based pathologies. To determine whether eriodictyol has immunomodulatory effects and clarify which types of immune effector cells are stimulated in vitro, we investigated the stimulatory effect of eriodictyol on spleen cells isolated from BALB/c mice. Eriodictyol significantly stimulated splenocyte proliferation. However, only B lymphocytes (not T lymphocytes) could be stimulated by eriodictyol in a dose-related manner. Studies assessing potential effect of eriodictyol on innate immunity reported that eriodictyol enhanced significantly the killing activity of natural killer (NK) cells, T lymphocytes, and macrophages. We also demonstrated that eriodictyol inhibited nitric oxide (NO) production and lysosomal enzyme activity in murine peritoneal macrophages cultured ex-vivo, suggesting a potential anti-inflammatory effect in situ. Eriodictyol revealed also a cellular anti-oxidant activity in splenocytes and macrophages. Furthermore, eriodictyol increased catalase activity in spleen cells. From this data, it can be concluded that eriodictyol exhibited an immunomodulatory effect that could be ascribed in part to a cytoprotective effect related to its anti-oxidant activity.     

Guangsangons F-J, anti-oxidant and anti-inflammatory Diels-Alder type adducts, from Morus macroura Miq

Five Diels-Alder type adducts, named guangsangons F, G, H, I, and J, along with two known compounds, mulberrofuran J and kuwanon J, were isolated from Morus macroura Miq. Their structures were determined by means of spectroscopic analyses and chemical methods. These compounds were regarded biogenetically as Diels-Alder type adducts of dehydroprenylphenols and chalcone derivatives, and (1)H NMR variable temperature experiments suggested that they all existed as an equilibrium mixture of conformational isomers in solution. Among the isolated new compounds, guangsangons H, I, and J displayed potent antioxidant activities and moderate anti-inflammatory activities.     

Design,synthesis and biological evaluation of glutamic acid derivatives as anti-oxidant and anti-inflammatory agents

A series of glutamic acid derivatives was synthesized and evaluated for their antioxidant activity and stability. We found several potent and stable glutamic acid derivatives. Among them, compound 12b exhibited good in vitro activity, chemical stability and cytotoxicity. A prototype compound 12b showed an anti-inflammatory effect in LPS-stimulated RAW 264.7 cell lines and in a zebrafish model.     

Albumin fusion renders thioredoxin an effective anti-oxidative and anti-inflammatory agent for preventing cisplatin-induced nephrotoxicity

Background

A strategy for preventing cisplatin nephrotoxicity due to enhanced oxidative stress and inflammatory response is highly desirable. Thioredoxin-1 (Trx), an endogenous redox-active protein, has a short retention time in the blood. A long acting form of Trx, human serum albumin-Trx (HSA-Trx), was produced by recombinant HSA fusion and its effectiveness in preventing cisplatin nephrotoxicity was examined.

Methods

HSA-Trx was prepared in Pichia expression system. Cisplatin-induced nephropathy mouse model was established by a single administration of cisplatin.

Results

Compared to saline, Trx or N-acetylcysteine, an intravenous administration of HSA-Trx attenuated the cisplatin-induced elevation in serum creatinine, blood urea nitrogen and urinary N-acetyl-β-d-glucosaminidase along with the decrease in creatinine clearance. HSA-Trx caused a substantial reduction in the histological features of renal tubular injuries and the apoptosis-positive tubular cells. Changes in superoxide, 8-OHdG, glutathione and nitrotyrosine levels indicated that HSA-Trx significantly suppressed renal oxidative stress. HSA-Trx also suppressed the elevation of TNF-α, IL-1β and IL-6. Administered fluorescein isothiocyanate-labeled HSA-Trx was found partially localized in the proximal tubular cells whereas majority remained in the blood circulation. Specific cellular uptake and the scavenging of intracellular reactive oxygen species by HSA-Trx were observed in HK-2 cells.

Conclusion

HSA-Trx could be a novel and effective approach for preventing cisplatin nephrotoxicity due to its prolonged anti-oxidative and anti-inflammatory action not only in extracellular compartment but also inside the proximal tubular cell.

General significance

We report the renoprotective effect of HSA-Trx against cisplatin nephrotoxicity. This work would enhance developing therapeutics against acute kidney injuries including cisplatin nephrotoxicity.     

The use of DPPD (N,N'-diphenyl-P-phenylenediamine) as an anti-inflammatory agent

The anti-oxidant compound, DPPD, was found to be an effctive anti-inflammatory compound by inhibiting carrageenin rat paw edema, adjuvant athritis and serum sickness expression of vascular and renal injury. It is proposed these effects are due to the inhibition of prostaglandin synthesis or fatty acid peroxide formation.     

The therapeutic effects of anti-oxidant and anti-inflammatory drug quercetin on aspiration-induced lung injury in rats

Aspiration pneumonitis refers to acute chemical lung injury caused by aspiration of sterile gastric contents. The aim of this study was to evaluate the role of quercetin (QC) in acid aspiration-induced lung injury in rats. Twenty-eight female Sprague–Dawley rats were used and divided into the following groups (n = 7): sham (aspirated normal saline, S), hydrochloric acid (aspirated HCl), S plus treatment with QC (S + QC), and HCl plus treatment with QC (HCl + QC). After aspiration, the treatment groups received QC 60 mg/kg/day intraperitoneally once a day for 7 days. As a result of acid aspiration, an increase was observed in the levels of serum clara cell protein-16 (CC-16) and advanced oxidation protein products, whereas there was a decrease in serum thiobarbituric acid-reactive substances, superoxide dismutase (SOD), and catalase levels. There was a significant decrease in peribronchial inflammatory cell infiltration, alveolar septal infiltration, alveolar edema, and alveolar exudate scores, except in the alveolar histiocytes in the HCl + QC group. The expression of nitric oxide synthase, which increased after aspiration in the HCl group, showed a statistically significant decrease after the QC treatment. After the treatment with QC, an increase in the serum SOD level was observed, whereas a significant decrease was determined in the serum CC-16 level relative to that of the aspiration group (HCl). The antioxidant QC is effective in the treatment of lung injury following acid aspiration and can be used as a serum CC-16 biomarker in predicting the severity of oxidative lung injury.     

Selenium as an anti-oxidant and pro-oxidant in ryegrass

Selenium is an essential element for antioxidation reactions in human and animals. In order to study its biological role in higher plants, ryegrass (Lolium perenne) was cultivated in a soil without Se or amended with increasing dosages of H₂SeO₄ (0.1, 1.0, 10.0 and 30.0 mg Se kg⁻¹). Ryegrass was harvested twice and the yields were analyzed for antioxidative systems and growth parameters. Selenium exerted dual effects: At low concentrations it acted as an antioxidant, inhibiting lipid peroxidation, whereas at higher concentrations, it was a pro-oxidant, enhancing the accumulation of lipid peroxidation products. The antioxidative effect was associated with an increase in glutathione peroxidase (GSH-Px) activity, but not with superoxide dismutase (SOD) and αα-tocopherol, which was the only tocopherol detected. In the second yield, the diminished lipid peroxidation due to a proper Se addition coincided with promoted plant growth. The oxidative stress found at the Se addition level ≥ 10 mg kg⁻¹ resulted in drastic yield losses. This result indicates that the toxicity of Se can be attributed, in addition to metabolic disturbances, to its pro-oxidative effects. Neither the growth-promoting nor the toxic effect of Se could be explained by the changes in the total chlorophyll concentration. This revised version was published online in June 2006 with corrections to the Cover Date.     

Spermine regulates N-methyl-D-aspartate receptor desensitization.

The action of the endogenous polyamine spermine on NMDA-induced responses (in the presence of glycine) was evaluated in cultured spinal cord neurons under voltage- and concentration-clamp conditions. Spermine potentiated NMDA-induced responses in a dose-dependent manner. It was more effective in potentiating steady-state currents (i.e., desensitized response) than the peak phase of the response, indicating that the degree of desensitization was reduced in the presence of the polyamine. Kinetic analysis revealed that the desensitization onset rate, but not recovery rate, was affected by spermine. The effect was voltage independent and was seen in thoroughly dialyzed cells, in which desensitization becomes independent of glycine. Spermine potentiation showed fast on-off kinetics, and intracellular spermine, loaded in the recording pipette, did not occlude potentiation by extracellularly applied spermine. These results are consistent with the existence of a modulatory site for polyamines in the extracellular domain of the NMDA receptor, the activation of which potentiates NMDA receptor function by regulating its desensitization kinetics.     

Spermine inhibition of monocyte activation and inflammation.

The innate immune system functions as a defensive front line against pathogenic invasion, but the proinflammatory products of activated monocytes and macrophages (e.g., TNF and NO) can also injure normal cells. Anti-inflammatory mediators restrain the innate immune response and prevent excessive collateral tissue damage. Spermine, a ubiquitous biogenic polyamine, specifically and reversibly suppresses the synthesis of monocyte proinflammatory cytokines. This may provide a counterregulatory mechanism to restrain monocyte activation in injured or infected tissues and in tumors where spermine levels are significantly increased. Here we show that monocyte spermine uptake was significantly increased following lipopolysaccharide stimulation. The polyamine analogue 1, 4-bis(3-aminopropyl)-piperazine (BAP) inhibited LPS-stimulated monocyte spermine uptake via the "nonselective" polyamine transporter. BAP fully restored macrophage TNF synthesis despite the presence of spermine, indicating that the mechanism of monocyte deactivation by spermine is dependent on spermine uptake. Administration of BAP in vivo significantly augmented the development of carrageenan-induced paw edema and nitric oxide release. Thus, endogenous spermine normally inhibits the innate inflammatory response by restraining macrophages.     

2-Chloro-1,4-naphthoquinone derivative of quercetin as an inhibitor of aldose reductase and anti-inflammatory agent

Abstract

The ability of flavonoids to affect multiple key pathways of glucose toxicity, as well as to attenuate inflammation has been well documented. In this study, the inhibition of rat lens aldose reductase by 3,7-di-hydroxy-2-[4-(2-chloro-1,4-naphthoquinone-3-yloxy)-3-hydroxy-phenyl]-5-hydroxy-chromen-4-one (compound 1), was studied in greater detail in comparison with the parent quercetin (compound 2). The inhibition activity of 1, characterized by IC₅₀ in low micromolar range, surpassed that of 2. Selectivity in relation to the closely related rat kidney aldehyde reductase was evaluated. At organ level in isolated rat lenses incubated in the presence of high glucose, compound 1 significantly inhibited accumulation of sorbitol in a concentration-dependent manner, which indicated that 1 was readily taken up by the eye lens cells and interfered with cytosolic aldose reductase. In addition, compound 1 provided macroscopic protection of colonic mucosa in experimental colitis in rats. At pharmacologically active concentrations, compound 1 and one of its potential metabolite 2-chloro-3-hydroxy-[1,4]-naphthoquinone (compound 3) did not affect osmotic fragility of red blood cells.