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At least 667 records · Page 37Linked to original sources
PubMed1978

Convenient synthesis of (RS)-4-amino-3-hydroxybutyric acid.

A new three-step synthesis of 4-amino-3-hydroxybutyric acid from an inexpensive starting material and under mild reaction conditions is described. Crotonic acid was brominated by the Wohl-Ziegler reaction to 4-bromocrotonic acid, which, in turn, was converted with ammonium hydroxide into 4-aminocrotonic acid. This compound, refluxed in water in the presence of a strong acid resin, afforded 4 amino-3-hydroxybutyric acid in good yields.

Aminobutyrates↗
PubMed1990

New potent topical anti-inflammatory steroids with reduced side effects: derivatives of steroid-16-carboxy esters.

Therapeutic use of anti-inflammatory steroids is limited due to their potential suppressive effects on pituitary-adrenal function and the immune system. Based on the antedrug concept, a new class of potent locally active compounds with reduced risk of side effects has been synthesized from prednisolone by introducing a metabolically labile methoxycarbonyl substituent at C-16. Results of topical application of the lead compound, methyl 11 beta,17 alpha,21-trihydroxy-3,20-dioxo-pregna-1,4-diene-16 alpha-carboxylate (P16CM;1), showed that it was 14 times more potent than prednisolone and that it had a greatly reduced tendency to cause systemic side effects. In the present investigations, we have demonstrated that chemical modifications such as 17- and/or 21-esterifications and 17,21-acetonidation of 1 further enhance topical activity in the croton oil ear edema model in rats. Following multiple topical ID50 applications of 1 or its derivatives, no thymolysis was noted. In the carrageenan-soaked sponge model of acute inflammation, all derivatives were potent inhibitors of leukocyte migration, generation of PGE2, and release of elastase. Taken together, these results indicate that esterification or acetonidation of hydroxyl groups at the 17 and/or 21 position, in combination with a labile C-16 methoxycarbonyl group, increases topical activity without concomitantly increasing the risk of side effects.

Adrenal Glands↗
PubMed1994

Synthesis of 6-(methoxycarbonyl)prednisolone and its derivatives as new antiinflammatory steroidal antedrugs.

The synthesis and pharmacological evaluation of 6-(methoxycarbonyl)prednisolone (11) (a 3:1 mixture of 6 alpha-isomer 11a and 6 beta-isomer 11b), its 21-ol acetates 13a (6 alpha-isomer) and 13b (6 beta-isomer), and 17,21-diol acetonide 14 (a 6:1 mixture of 6 alpha-isomer 14a and 6 beta-isomer 14b) as local antiinflammatory steroidal antedrugs are described. The lead compound 11 was prepared via 12 steps from hydrocortisone (1). In the croton oil-induced ear edema assay, the topical antiinflammatory activity of 13a was higher than that of its epimer 13b. Except for 13a, the compounds (11, 13b, and 14) showed less activity than prednisolone. The systemic activities were assessed after 5 days of consecutive administration of these compounds at equiactive doses. Neither 11 nor 14 depressed plasma corticosteroid levels or significantly altered adrenal weights. Thymic involution was absent for 14, 15% for 11, and 47% for prednisolone at the equiactive doses. Both 13a and 13b showed significant reduction of adverse systemic effects assessed as the increase of body weight and the decreases of adrenal and thymus weights. The putative metabolite, carboxylic acid 12, showed 26 times less topical antiinflammatory activity than prednisolone. These results suggest that introduction of a labile methoxycarbonyl group at the C-6 position of prednisolone results in retention of antiinflammatory activity while reducing systemic effects noted following topical application of the parent compound prednisolone.

Administration, Topical↗
PubMed2006

Alternative medicine remedies might stimulate viability of leukemic cells.

OBJECTIVE: Ex vivo activity of three products of alternative therapy against leukemic and normal cells was analyzed. MATERIAL AND METHODS: Extracts of Viscum album, Uncaria tomentosa, and Croton lechleri were used for the study. Leukemic cells of 53 children with acute leukemias and four cell lines, Jurkat, CCRF-CEM, HL-60, and K-562 were tested for sensitivity to alternative medicine remedies by the MTT assay, cell-cycle analysis and annexin-V binding assay. RESULTS: Leukemic cells showed high resistance to tested three compounds of alternative medicine in all performed assays. Additionally, tested remedies stimulated survival of leukemic cells in 45%, 96%, and 83% cases, respectively; while no effect was observed in normal lymphocytes. In combination studies, Viscum album extract did not increase prednisolone and cytarabine cytotoxicity in leukemic cells. CONCLUSION: We conclude that some alternative medicine remedies might stimulate the viability of childhood leukemic cells.

Adolescent↗
PubMed2003

Anti-inflammatory effect of Solanum lycocarpum fruits.

The croton oil-induced mouse ear oedema test, acetic acid-induced abdominal writhing, and carrageenan-induced peritonitis were used to study the anti-inflammatory effects of the crude ethanol extract and its alkaloid fraction from Solanum lycocarpum fruits. The alkaloid fraction induced a dose-dependent reduction in ear oedema formation and leukocyte migration, suggesting that S. lycocarpum fruits may contain steroidal alkaloids accounting for the anti-inflammatory effect of the crude ethanol extract.

Acetic Acid↗
PubMed2005

Evaluation of chemopreventive action and antimutagenic effect of the standardized Panax ginseng extract, EFLA400, in Swiss albino mice.

In the present investigation the chemopreventive action and antimutagenic effects of a standardized Panax Ginseng extract (EFLA400, processed Panax ginseng extract containing a high titre of ginsenoside Rg3 (>3.0% w/w) known as Phoenix ginseng) in Swiss albino mice have been evaluated. The oral administration of EFLA400 at 1, 3 and 10 mg/kg body weight at pre, peri and post-initiational phases, showed significant reductions in the number, size and weight of the papillomas. A significant reduction in tumour incidence (71.41 +/- 6.73%, 72.19 +/- 4.54% and 70.46 +/- 0.38% at 1, 3 and 10 mg/kg body weight, respectively) was observed in animals in the EFLA400 treated group compared with 100% tumour incidence in the control group. The cumulative number of papillomas during an observation period of 16 weeks was significantly reduced in the EFLA400 treated group (24 +/- 0.94, 16 +/- 1.41 and 11 +/- 1.41 at 1, 3 and 10 mg/kg body weight, respectively). However, the average latent period was significantly increased from 10.81 +/- 0.1 weeks in the control group to 12.39 +/- 0.28 weeks in the treated group (10 mg/kg body weight). The average tumour weight was recorded as 128.55 +/- 8.48, 116.00 +/- 8.48 and 57.5 +/- 3.29 mg in 1, 3 and 10 mg/kg body weight EFLA400 treated groups respectively. Chromosomal aberrations and micronuclei induction was also evaluated in bone marrow cells. These genotoxicity end-points were compared with papilloma occurrence at the same dose levels of carcinogen and ginseng. In the EFLA400 treated groups significantly reduced frequencies of chromosomal aberrations and micronuclei induced by DMBA and croton oil were observed. However, the maximum decrease in the frequencies of chromosomal aberrations and micronuclei were recorded in the 10 mg/kg body weight EFLA400 treated group than that of the 1 and 3 mg/kg body weight EFLA400 treated animals. The results from the present study suggest the dose dependent effectiveness of EFLA400 in chemoprevention and antimutagenicity in Swiss albino mice.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed2004

Antiinflammatory activity of Synurus deltoides.

Synurus deltoides Aiton, Nakai, is an edible plant that has been used as a folk medicine for treating inflammatory disorders. This investigation was carried out to establish the antiinflammatory activity of this plant material using a 75% ethanol extract from the aerial part of S. deltoides. Against the acute inflammatory animal model of mouse croton oil-induced ear oedema assay, the extract did not show significant inhibition at 100-800 mg/kg by oral administration. On the other hand, the extract showed considerable inhibition against the chronic inflammatory animal model of rat adjuvant-induced arthritis (25% inhibition at 100 mg/kg/day) while prednisolone exerted 40% inhibition at 10 mg/kg/day. In addition, S. deltoides possessed strong analgesic activity (IC50 = 50 mg/kg) in the acetic acid-induced writhing test. From the extract, ursolic acid and scopoletin were successfully isolated and their contents were found to be 0.31% and 0.37% (w/w), respectively, based on the dried extract by HPLC analysis. All the results obtained indicate that this plant material may be used beneficially as an antiinflammatory agent having analgesic action.

Acetic Acid↗
PubMed2006

Fatty acids profile and antiinflammatory activity of Nonea setosa R. et S.

In order to verify the antiinflammatory properties of Nonea setosa R. et S. (Fam. Boraginaceae) and to identify the relevant active principles, aerial parts of this plant were extracted with increasing polarity solvents. The antiinflammatory activity was investigated by a bioassay-oriented fractionation using the inhibition of the croton oil-induced ear oedema in mice as an experimental model of inflammation. GC-MS analysis of the most active fraction revealed the presence of high amounts of polyunsaturated fatty acids.

Animals↗
PubMed2006

Effect of Rosmarinus officinalis in modulating 7,12-dimethylbenz(a)anthracene induced skin tumorigenesis in mice.

The chemopreventive potential of rosemary (Rosmarinus officinalis) on 7,12-dimethlybenz(a)anthracene (DMBA) initiated and croton oil promoted mouse skin tumorigenesis was assessed. The modulatory effects of R. officinalis was monitored on the basis of the average latency period, tumor incidence, tumor burden, tumor yield, tumor weight and diameter as well as lipid peroxidation and glutathione level. The results indicate that R. officinalis leaves extract could prolong the latency period of tumor occurrence, decrease the tumor incidence, tumor burden and tumor yield. The average weight and diameter of tumors recorded were comparatively lower in the rosemary extract treated mouse groups. The level of lipid peroxidation was significantly reduced in blood serum and liver. Furthermore, depleted levels of glutathione were restored in RE-administered animal groups. Thus, at a dose rate of 500 mg/kg body wt/mouse, the oral administration of rosemary extract was found to be significantly protective against two-stage skin tumorigenesis.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed2001

Effects of antiinflammatory triterpenes isolated from Leptadenia hastata latex on keratinocyte proliferation.

Several triterpenes isolated from Leptadenia hastata latex were tested for their anti-inflammatory activity. Lupeol (1), its acetate (2) and palmitate (3) esters were found to be the main antiinflammatory constituents in the croton oil-induced ear oedema test. Furthermore, lupeol hemisuccinate (4), synthesized from lupeol, exhibited a higher activity than lupeol in the test. These results prove that the triterpenes play a pivotal role in the topical antiinflammatory effect of this latex. In addition, an in vitro model of human skin keratinocytes (epidermal explants) cultured at an air-liquid interface on a de-epidermized human dermis (DED) was used to investigate the effects of lupeol esters on skin repair in vitro. Compared with the control, compounds 2 and 3 improved keratinocyte proliferation at a concentration of 5 microM in the culture medium; however, they remained less active than compounds 1 and 4. In contrast to compound 1, all the lupeol esters (2-4), and particularly compound 4, induced a good differentiation of keratinocytes with a well-formed stratum corneum without parakeratosis. These results substantiate the topical use of Leptadenia hastata latex in traditional medicine and showed that both antiinflammatory activity and the effect on keratinocyte proliferation of compound 1 could be improved by its hemisuccinylation; on the contrary, esterification by acetylation or palmitoylation decreased these activities.

Adult↗
PubMed2000

Restraint-induced modulation of allergic and irritant contact dermatitis in male and female B6.129 mice.

Recent studies in rats have indicated that acute restraint enhances cutaneous hypersensitivity. We hypothesized that acute restraint would also modulate the development of allergic and irritant dermatitis in mice and that these restraint-induced changes would be reflected in the cutaneous cytokine profile and be gender-specific. For these studies, male and female B6.129 mice were sensitized and challenged with the contact sensitizer dinitrofluorobenzene or challenged with the irritant croton oil. Two-hour restraint was applied prior to chemical challenge. Restraint combined with chemical increased ear swelling in both genders in ACD, a change that was blocked by administration of RU-486 prior to restraint. Neither restraint nor RU-486 administration modulated development of ICD; however, IL-1beta was decreased by restraint in females only. TNF-alpha and IFN-gamma production were modified in ACD; TNF-alpha in both genders and IFN-gamma in female mice only. Our data demonstrate that acute restraint increases serum corticosterone in B6.129 male and female mice to comparable levels. Restraint modulated the murine ear swelling in ACD, but not ICD, in both genders, and the change in the ear swelling response and cytokine production were, at least in part, corticosterone-dependent.

Animals↗
PubMed1997

Fibrous tissue and angiotensin II.

Myofibroblasts (myoFb) are cells responsible for fibrous tissue formation in injured systemic organs such as the heart. Cultured myoFb, obtained from rat cardiac scar tissue, express genes that encode components requisite for angiotensin (Ang) II generation, which in turn regulates myoFb collagen turnover in an autocrine/paracrine manner. In this study, we tested the hypothesis that these wound-healing fibroblast-like cells and locally generated Ang II are involved in other repairing tissue. To test this hypothesis, we used a granuloma pouch model, where a subcutaneous air sac is created followed by injection of croton oil. Pouch tissue was collected at days 4, 7, 14 and 21. The presence of myoFb was determined by immunohistochemical alpha-smooth muscle actin (alpha-SMA) labeling and collagen accumulation by picrosirius red staining. Angiotensin converting enzyme (ACE) and Ang II receptor binding were detected by in vitro quantitative autoradiography using 125I-351A and 125I[Sar1, Ile8]Ang II, respectively, while Ang II receptor subtype was defined by displacement studies using either an AT1 (losartan) or AT2 (PD123177) receptor antagonist. Cells expressing ACE were determined by immunohistochemistry. Ang II content in pouch tissue was measured by radioimmunoassay following HPLC separation while its capacity to generate Ang II was assessed in tissue bath, with and without exogenous Ang I or lisinopril, an ACE inhibitor. Collagen accumulation in pouch tissue was examined by determining hydroxyproline content in response to lisinopril, AT1 or AT2 receptor antagonists (losartan or PD123177). In pouch tissue, we found: (1) myoFb at day 4 which became more extensive at days 7, 14 and 21; (2) morphologic evidence of collagen deposition evident at day 4, which gradually became more extensive thereafter; (3) ACE and Ang II receptor binding was evident at day 4 and remained invariant on days 7, 14 and 21; (4) the predominant Ang II receptor subtype expressed was AT1; (5) myoFb express ACE and AT1 receptors; (6) picogram quantities of Ang II (per g tissue) was evident on days 7, 14 and 21; and (7) Ang II was generated from Ang I substrate. Lisinopril and losartan, but not PD123177, significantly attenuated pouch weight and accumulation of collagen. Thus, in this model of cutaneous repair, the appearance of myoFb is associated with Ang II generation that regulates fibrogenesis by AT1 receptor binding. Signals involved in the appearance of myoFb remain uncertain. Further studies are required to address the regulation of Ang II generation in pouch tissue of the rat.

Actins↗
PubMed1997

Evaluation of the anti-oedematous effects of some H1-receptor antagonists and methysergide in rats.

A combined method was used for a comparative study of some H1 and H2 antagonists and methysergide. In male rats of the Wistar strain weighing 130 +/- 5 g, oedema was induced in the hind paw by the subplantar injection of zymosan, and simultaneously in the ear by the application of croton oil to the inner surface of the ear. Intraperitoneally orally administered H1 antagonists (dimethindene, clemastine, cyproheptadine, astemizole, cetirizine, loratadine and terfenadine) inhibited the oedema to a statistically significant extent, in a dose-dependent manner. Outstanding inhibition was observed after simultaneous administration of the antiserotonin methysergide with dimethindene, clemastine, loratadine or cetirizine.

Animals↗
PubMed1998

An integrated model for the differentiation of chemical-induced allergic and irritant skin reactions.

Contact and photocontact allergic as well as irritant and photoirritant skin reactions represent a major problem in clinical dermatology and during the development of new pharmaceuticals. Furthermore, there is a lack of in vitro and in vivo assays that provide a clear differentiation between allergic and irritant skin reactions. Here, we describe an integrated model to differentiate between chemical-induced allergic and irritant skin reactions by measuring objective and easy-to-determine parameters within both skin and skin-draining lymph nodes. Dose-response studies with standard contact and photocontact allergens as well as irritants and photoirritants revealed that irritants predominantly induced skin inflammation, which in turn stimulated draining lymph node cell proliferation. In contrast, the induction phase of contact or photocontact allergy was characterized by marginal skin inflammation, but a marked activation and proliferation of skin-draining lymph node cells. Therefore, a differentiation index (DI) was defined describing the relation between skin-draining lymph node cell activation (lymph node cell count index) and skin inflammation (ear swelling). A DI > 1 indicates an allergic reaction pattern whereas DI < 1 demonstrates an irritant potential of a chemical. Experiments with the contact allergen oxazolone, the photocontact allergen TCSA + UVA, the irritant croton oil, and the photoirritant 8-methoxypsoralen + UVA confirmed the predictive value of DI. Furthermore, flow cytometric analysis of lymph node-derived T- and B-cell subpopulations revealed that contact sensitizer, but not irritant, induced the expression of CD69 on the surface of I-A+ cells. In conclusion, further studies with a broad range of irritants and allergens will be required to confirm general applicability.

Animals↗
PubMed1989

Evaluation of ATPase-positive Langerhans' cells in skin lesions of lupus erythematosus and experimentally induced inflammations.

We examined the time-dependent dynamics of epidermal Langerhans' cells (LC) in human systemic lupus erythematosus (SLE), in MRL/Mp-lpr/lpr(MRL/lpr) mice, and in various experimental cutaneous inflammations, such as the Arthus reaction, dinitrochlorobenzene allergic dermatitis, and croton oil primary irritant dermatitis, in order to clarify the pathomechanisms of lupus skin lesions. The numbers of LC in untreated SLE patients with newly developed skin lesions decreased in the central lesional sites and increased significantly in the peripheral lesional sites. In MRL/lpr mice, the number of LC increased significantly in the central lesional sites during the initial stage and increased in the peripheral lesional sites and decreased in the central lesional sites 2-4 weeks after the onset of skin lesions. In contrast, with experimental cutaneous inflammations of guinea pigs, the increase in numbers of LC in the peripheral lesional sites was not significant during the time course of the reaction. These results suggest that the increased numbers of LC during the active and early stages of skin lesions in human SLE and MRL/lpr mice are closely related to the specific spontaneous development of skin lesions, unlike the dynamics of LC in experimental cutaneous inflammations.

Adenosine Triphosphatases↗
PubMed1977

New experimental model for the primary evaluation of topical contra-inflammatory agents.

Assays of steroidal and non-steroidal drugs in an experimental model of dermatitis induced in the ear of the rabbit by the application of a solution of croton oil revealed clearly differentiable inhibitory effects on the rise in skin temperature, the oedema and the increase in tissue mass due to the inflammatory process. The results obtained in this test system fairly accurately reflect the relative therapeutic potencies of known dermatocorticoids and, in conjunction with those found by other methods, afford a more exact characterization of the activity profiles of non-steroidal contra-inflammatory agents.

Administration, Topical↗
PubMed1985

Anti-inflammatory activity of orpanoxin administered orally and topically to rodents.

Orpanoxin, a nonsteroidal anti-inflammatory drug (NSAID) lacking gastric ulcerogenic effects in the therapeutic dose range in rats, was compared with six reference NSAIDs for oral activity in the rat paw carrageenin-induced edema assay. Tested NSAIDs were ranked on the basis of oral mg/kg ED50 values: piroxicam, 0.55; orpanoxin, 35.6; diflunisal, 59.6; benoxaprofen, greater than 300; tolmetin sodium, greater than 300; and sulindac, greater than 300. Zomepirac sodium was inactive. Only the three most potent compounds produced greater than 60% inhibition of edema. Inhibition was generally greater at 4 h than at 6 h post carrageenin for all compounds. Oral activity of orpanoxin was also demonstrated in the guinea-pig u.v.-induced erythema model (ED50 = 24.2 mg/kg p.o. when given 1 h before irradiation) and in the mouse ear croton oil induced edema test (ED50 value = 131 mg/kg p.o.). Topical activity of orpanoxin was assessed in both the guinea-pig and mouse models. In the guinea-pig u.v.-induced erythema model, application (1 h after u.v.) of 1, 5, and 10% (w/v) orpanoxin creams (containing 10% urea) significantly inhibited erythema at 2, 3, and 4 h post-irradiation. Orpanoxin, mefenamic acid, and indomethacin as 1% creams inhibited total erythema scores 70, 92 and 74%, respectively. Evidence for topical activity in the mouse ear assay was also obtained for orpanoxin in diethyl ether or 10% urea cream, but not in dimethylsulfoxide. It was concluded that orpanoxin has anti-inflammatory activity comparable to reference NSAIDs in the rat paw edema test, is active orally in rat, mouse, and guinea-pig models, and shows topical activity in the guinea-pig and the mouse.

Administration, Oral↗