Synthesis and pharmacological evaluation of novel derivatives of anti‐inflammatory drugs with increased antioxidant and anti‐inflammatory activities

The role of reactive oxygen species in inflammatory processes has been well documented, while several antioxidant compounds have been shown to exhibit anti‐inflammatory activity. We designed novel compounds as potential agents that combine enhanced antioxidant and anti‐inflammatory activities. Derivatives of indomethacin, diclofenac, tolfenamic acid, and ibuprofen, four widely used nonsteroidal anti‐inflammatory drugs, with cysteamine, a polar antioxidant molecule, were synthesized. The compounds were evaluated for their effect on free radical processes (protection against rat hepatic microsomal lipid‐peroxidation and interaction with the stable free radical 1,1‐diphenyl‐2‐picrylhydrazyl), as well as on carrageenan‐induced inflammation (mouse paw edema inhibition). Furthermore, ulcerogenicity tests in rats were performed in order to evaluate the gastrointestinal irritation of the novel indomentacin derivative. It was found that all compounds were very potent antioxidants in vitro; they could inhibit lipid peroxidation very significantly, having IC₅₀ values ranging from 55 to 510 μM, while they could also interact ∼90% with DPPH at equimolar concentrations. We attribute these activities to their sulfhydryl group, as well as to their increased lipophilicity compared to cysteamine. Furthermore, the derivatives demonstrated significant anti‐inflammatory activity, comparable to that of the parent molecules, while they showed significantly reduced ulcerogenic potency. Our results indicate that the combined pharmacological properties of these new derivatives may prove useful for the design and development of novel cytoprotective/anti‐inflammatory molecules with potentially important therapeutic applications. Drug Dev. Res. 47:9–16, 1999. © 1999 Wiley‐Liss, Inc.     

Free radicals irreversibly decrease Ca2+ currents in isolated guinea-pig ventricular myocytes

The effects of free radicals on voltage-gates Ca²⁺ currents (I_Ca) were investigated in single guinea-pig ventricular myocytes using the whole-cell clamp technique. I_Ca was measured in the baseline state and after the application of free radicals from cumene hydroperoxide or generated from the addition of purine to xanthine oxidase. I_Ca decreased from 846 ± 533 (S.D.) pA to 688 ± 444 pA (n = 7, P < 0.05) in the presence of 100 μM cumene hydroperoxide and from 708 ± 157 pA to 457 ± 163 pA(n = 5, P < 0.0001) in the presence of 500 μM cumene hydroperoxide. I_Ca also decreased from 1303 ± 560 pA to 965 ± 360 pA in the presence of the free radical generating system (2.3 mM purine plus 20 U/l xanthine oxidase). The reduced I_Ca could not be restored by washing for up to 5 min using normal recording solution. We conclude that I_Ca is decreased in the presence of cumene hydroperoxide and an oxygen-derived free radical generating system in single guinea-pig ventricular myocytes. The cellular Ca²⁺ overload observed in free radical mediated reperfusion injury is therefore unlikely to result from an increase in sacrolemmal Ca²⁺ entry via voltage-gated Ca²⁺ channels.     

Assessment of isorhamnetin 3‐O‐neohesperidoside from Acacia salicina: protective effects toward oxidation damage and genotoxicity induced by aflatoxin B1 and nifuroxazide

Antioxidant activity of isorhamnetin 3‐O‐neohesperidoside, isolated from the leaves of Acacia salicina, was determined by the ability of this compound to inhibit xanthine oxidase activity and to scavenge the free radical 2,2′‐azino‐bis (3‐ethylbenzthiazoline‐6‐sulfonic acid) (ABTS^.?) diammonium salt. Antigenotoxic activity was assessed using the SOS chromotest assay. This compound has the ability to scavenge the ABTS^.+ radical by a hydrogen donating mechanism. We also envisaged the study of the antioxidant effect of this compound by the enzymatic xanthine/xanthine oxidase (X/XOD) assay. Results indicated that isorhamnetin 3‐O‐neohesperidoside was a potent inhibitor of xanthine oxidase and superoxide anion scavengers. Moreover, this compound induced an inhibitory activity against nifuroxazide and aflatoxine B1 (AFB1) induced genotoxicity. Taken together, these observations provide evidence that isorhamnetin 3‐O‐neohesperidoside isolated from the leaves of A. salicina is able to protect cells against the consequences of oxidative stress. Copyright © 2010 John Wiley & Sons, Ltd.     

In vitro and intracellular antioxidant capacity of thymyl methyl ether as a major component in Blumea lanceolaria (Roxb.) Druce leaf oil

Thymyl methyl ether is a major component of Blumea lanceolaria (Roxb.) Druce leaves. In this study, the antioxidant capacity of thymyl methyl ether and its better known hydroxylated form thymol was examined using oxygen radical absorption capacity and intracellular antioxidant capacity assays. Thymol displayed stronger peroxyl radical and hydroxyl radical-scavenging capacity, as well as reducing capacity than those of thymyl methyl ether, which can be explained by its hydrogen or electron donating capacity. However, thymyl methyl ether exhibited potent protection against peroxyl radical and Cu²⁺-induced oxidative stress when compared to thymol in the intracellular antioxidant capacity and lipid peroxidation assays using HepG2 cells. These results illustrate the higher cell membrane permeability of thymyl methyl ether to thymol and its transformation to thymol, which results in potent intracellular antioxidant capacity contributing to protection against lipid peroxidation.     

白芍总苷体外抗氧化活性研究

目的研究白芍总苷体外对不同化学体系和生物体系的抗氧化活性。方法通过Fenton反应生成·OH自由基,采用DPPH·自由基,观察不同质量浓度的白芍总苷溶液对化学体系自由基的清除作用。利用邻二氮菲-Fe2+-H2O2产生的·OH自由基造成红细胞膜破裂,以及肝、脑细胞脂质的过氧化,观察不同质量浓度的白芍总苷溶液对生物体系自由基的清除作用。结果白芍总苷对·OH有一定的清除作用,其IC50为0.62 g/L。白芍总苷对DPPH·自由基有较强的清除作用,IC50为6.6 mg/L;对·OH自由基引发的红细胞膜破裂有一定的抑制作用,其IC50为30.17 mg/L,对肝、脑匀浆脂质过氧化有一定的抑制作用,其IC50分别为6.9、16.3 mg/L。结论白芍总苷具有清除自由基作用,在不同体外实验体系中抗氧化量效关系存在差异。     

Antioxidant activity and total phenolic content of methanol extracts of Ixora coccinea

Objective: To investigate the in vitro antioxidant activity of methanol extracts of Ixora coccinea L. (Rubiaceae) flower, leaf and stem.

Materials and methods: The 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity, total antioxidant capacity (TAC) and xanthine oxidase inhibition assay were carried out to evaluate the antioxidant potential of the extract. The IC₅₀ values were calculated for the DPPH and xanthine oxidase assays in order to evaluate the antioxidant efficiency of each of the I. coccinea extracts. The phenol contents were also determined.

Results: I. coccinea flowers revealed the best antioxidant property, presenting much lower IC₅₀ value (6.6?mg/mL for DPPH assay). The flower extract showed a significantly higher antioxidant capacity compared to the other extracts. Furthermore, the highest phenolic content (polyphenols) was found in the flower extract (210.55?±?6.31 µg GAE/mg extract). Moreover, I. coccinea extracts scavenged the superoxide radical generated by the xanthine/xanthine oxidase system. The xanthine oxidase inhibition activity was in the order of allopurinol > leaf > flower > stem with the percentage of inhibition ranged from 39.7% to 77.3% for the plant parts investigated. The highest phenolic contents (polyphenols) were found in the flower extracts (210.55?±?6.31 µg GAE/mg extract).

Conclusions: I. coccinea could be considered as a potential source of natural antioxidant.     

Antioxidative and cardiovascular-protective activities of metabolite usnic acid and psoromic acid produced by lichen species Usnea complanata under submerged fermentation

Context: Lichens have been used for various purposes such as dyes, perfumes and remedies in folk medicine indicating the pharmaceutical potential of lichens.

Objective: Lichen growth in nature is very slow. To overcome this major drawback, we standardized the culture media to culture the lichen Usnea complanata (Müll.Arg.) Motyka (Parmeliaceae) for (1) in vitro synthesis of natural lichen substances, and (2) determination of antioxidative and cardiovascular-protective activity of usnic acid and psoromic acid.

Materials and methods: Lichen U. complanata has been cultured in fermentor under submerged condition. Antioxidative and cardiovascular-protective activity of the extract and the purified lichen substances usnic and psoromic acid have been determined.

Results: Except methanol, all other extracts exhibited antioxidative action in terms of free radical scavenging activity (FRSA) with a half-inhibiting concentration (IC₅₀) value of 22.86 to 25.0 µg/mL, nitric oxide radical scavenging activity (NORSA) 141.3 to 149.1 µg/mL and for lipid peroxidation inhibition (LPI) 125 to 157.9 µg/mL. Usnic acid or psoromic acid showed antioxidative action with IC₅₀ values ranging from 0.174 to 0.271?mg/mL. Methanol and ethyl acetate extract showed hydroxy-3-methyl-glutaryl-CoA reductase (HMGR) inhibition of 65.18 to 74.81%. Only 43.47% inhibition of angiotensin converting enzyme (ACE) was shown by methanol extract. Usnic acid showed noncompetitive type of HMGR inhibition and uncompetitive type of ACE inhibition. Psoromic acid exhibited competitive type of HMGR inhibition and mixed type of ACE inhibition.

Discussion: U. complanata showed both cardiovascular-protective and antioxidant properties.

The lichen species U. complanata may be a natural bioresource for possible pharmaceutical applications.     

In Vitro Evaluation of Selected Benzimidazole Derivatives as an Antioxidant and Xanthine Oxidase Inhibitors

2‐Aryl‐1‐arylmethyl‐1H‐benzimidazole derivatives having different side chains on the structure were examined in vitro for their antioxidant abilities by 2,2‐diphenyl‐1‐picryl hydrazine radical scavenging activity, reducing ability, OH radical scavenging activity, inhibition of polyphenol oxidase and xanthine oxidase. Overall, with few exceptions, all the 2‐aryl‐1‐arylmethyl‐1H‐benzimidazoles showed moderate biological activity with all parameters examined. The 2‐aryl‐1‐arylmethyl‐1H‐benzimidazoles were found to be reactive toward 2,2‐diphenyl‐1‐picryl hydrazine radical and had considerable reducing ability, with significant xanthine oxidase inhibition. With few exceptions, all the compounds under study were found to possess moderate‐to‐poor OH radical scavenging activity and inhibited polyphenol oxidase significantly. These findings suggest that these 2‐aryl‐1‐arylmethyl‐1H‐benzimidazoles can be considered as potential antioxidant and xanthine oxidase inhibitory agents, those might be further, explored for the design of lead antioxidant and antigout drug candidates using in vivo trials.     

Effect of MK‐886 on Ca2+ Level and Viability in PC3 Human Prostate Cancer Cells

Abstract: 3‐[1‐(p‐chlorobenzyl)‐5‐(isopropyl)‐3‐tert‐butylthioindol‐2‐yl]‐2, 2‐dimethylpropanoic acid (MK‐886) is widely used for inhibition of leucotriene synthesis in in vitro studies, however, many of its other effects have been reported. The present study investigated the effect of MK‐886 on cytosolic‐free Ca²⁺ concentrations ([Ca²⁺]_i) and viability in human PC3 prostate cancer cells. [Ca²⁺]_i in suspended cells was measured by using fura‐2. MK‐886 at concentrations of 1 µM and above increased [Ca²⁺]_i in a concentration‐dependent manner with an EC₅₀ value of 20 µM. The Ca²⁺ signal was reduced partly by removing extracellular Ca²⁺. MK‐886 evoked Mn²⁺ quenching of fura‐2 fluorescence, implicating Ca²⁺ entry. MK‐886‐induced Ca²⁺ influx was inhibited by store‐operated Ca²⁺ entry inhibitors nifedipine, econazole and SKF96365. In Ca²⁺‐free medium, after pre‐treatment with 10 µM MK‐886, 1 µM thapsigargin (an endoplasmic reticulum Ca²⁺ pump inhibitor)‐induced [Ca²⁺]_i rises were abolished; and conversely, thapsigargin pre‐treatment abolished MK‐886‐induced [Ca²⁺]_i rises. Inhibition of phospholipase C with U73122 did not alter MK‐886‐induced [Ca²⁺]_i rises. MK‐886 at concentrations of 1–100 µM concentration‐dependently decreased cell viability with an IC₅₀ value of 60 µM. The cytotoxic effect of MK‐886 was not inhibited by pre‐chelating cytosolic Ca²⁺ with BAPTA/AM. Together, in PC3 cells, MK‐886 induced [Ca²⁺]_i rises by causing phospholipase C‐independent Ca²⁺ release from the endoplasmic reticulum; and Ca²⁺ influx via store‐operated Ca²⁺ channels. Independently, MK‐886 was cytotoxic to cells in a Ca²⁺‐independent manner.     

Free radical scavenging and antioxidant activities of Glinus oppositifolius (carpet weed) using different in vitro assay systems

Glinus oppositifolius (L.) Aug. DC. (Aizoceae), commonly called slender carpet weed, is a prostrate or diffuse herb which acts as stomachic, uterine stimulant, aperient and lochia. It is used traditionally in the treatment of earache, itch and skin diseases. Glinus oppositifolius was extracted with ethanol (70%) and used for the evaluation of various in vitro antioxidant assays which includes H-donor activity, nitric oxide scavenging, superoxide anion scavenging, reducing ability, hydroxyl radical, hydrogen peroxide scavenging, total phenolic content, total flavonoid content, total antioxidant activity by thiocyanate and phosphomolybdenum method, metal chelating, β-carotene bleaching, total peroxy radical assays. The pro-oxidant activity was measured using bleomycin-dependent DNA damage. Ex vivo models such as lipid peroxidation were used to study the antioxidant property of the extract. The various antioxidant activities were compared with suitable standard antioxidants such as ascorbic acid, butylated hydroxyl toluene (BHT), α-tocopherol, curcumin, quercetin and Trolox. The generation of free radicals, viz., O₂^·?, OH^·, H₂O₂, NO^· and peroxyl radicals, were effectively scavenged by the ethanol extract of Glinus oppositifolius. The antioxidant activity depends on concentration and increases with increasing amounts of the extract. The total phenolic content, flavonoid content and total antioxidant activity in Glinus oppositifolius were determined as microgram (μg) pyrocatechol, quercetin and α-tocopherol equivalent/mg, respectively. The extract did not exhibit any pro-oxidant activity when compared with ascorbic acid. The results obtained in this study indicate that Glinus oppositifolius scavenges free radicals and reduces lipid peroxidation, ameliorating the damage imposed by oxidative stress in different disease conditions and serve as a potential source of natural antioxidant.     

Antioxidant potential of Amorphophallus paeoniifolius in relation to their phenolic content

The present study evaluates the antioxidative and radical scavenging potential of the tuber extract of Amorphophallus paeoniifolius (Dennst.) Nicolson, (Araceae). The ethanol extract of A. paeoniifolius (APE) was studied for the inhibition of lipid peroxidation estimated in terms of thiobarbituric acid reactive substances (TBARS) and the levels were reduced by 4.3% to 67.2% in a dose-dependent manner. Further, APE was analyzed for scavenging capacities based on 1,1-diphenyl-2-picrylhydrazyl-2-radical (DPPH) assay and percentage inhibition activity based on 2,2-azinobis-(-3-ethyl) benzo-thiozoline-6-sulfonate (ABTS⁺) and H₂O₂. The A. paeoniifolius extract showed a maximum of 68.6% of DPPH scavenging activity and the maximum inhibition of 74% and 67.2% in the case of ABTS and H₂O₂, respectively. The antioxidant efficiency and inhibition of oxidation of the extract was found to be dose-dependent at the tested concentrations of 1-50?µg/mL. High-performance thin layer liquid chromatography (HPTLC) profile of the extract suggests the presence of polyphenols such as gallic acid, resveratrol, quercetin and two unidentified compounds. The results suggest that the ethanol extract of A. paeoniifolius has a potent antioxidant activity in vitro and can be utilized as an effective and safe source of antioxidants.     

Pharmacological actions of thymol and an analogue at GABAB autoreceptors

GABA_B autoreceptors inhibit release of GABA from GABAergic nerve terminals. Agonists of these receptors (e.g. baclofen) inhibit, whereas antagonists (e.g. (+)‐(S)‐5,5‐dimethylmorpholinyl‐2‐acetic acid; Sch 50911) enhance release of the transmitter. The actions of thymol (2‐isopropyl‐5‐methylphenol) and the structurally related compound 2‐tert‐butyl‐4‐methylphenol, (4MP) on the release of [³H]‐GABA were examined in rat neocortical slices where the GABAergic nerves had been preloaded with [³H]‐GABA and subsequently stimulated electrically on two occasions (S₁ and S₂). Test agents, baclofen and Sch 50911 were added to the superfusion medium prior to the second period of stimulation (S₂). Stimulation‐induced overflow (SIO) of [³H]‐GABA as a consequence of these stimulations (SIO₁ and SIO₂) were calculated and the effects of agents determined by comparing the SIO₂/SIO₁ ratio in the presence of each agent with that in control tissue. Thymol potentiated the release of [³H]‐GABA (EC₅₀ 170 μmol/L), an action reversed by baclofen (2 μmol/L). Baclofen alone had little effect on GABA release. Release of [³H]‐GABA was inhibited by 4MP (IC₅₀ 3 μmol/L) and this effect was blocked by Sch 50911 (10 μmol/L). Alone, Sch 50911 markedly potentiated the release of GABA. These results imply that 4MP is an agonist of GABA_B autoreceptors; however, further studies are needed to confirm that thymol is indeed a GABA_B autoreceptor antagonist. Of interest are structural differences in these agents. Thymol has a propyl group in the ortho position relative to the phenolic hydroxyl, whereas in 4MP this is a butyl group and the methyl group moves from position 5 to 4. Whether one or both of these changes was responsible for the above actions is unknown.     

Novel ketoprofen–antioxidants mutual codrugs as safer nonsteroidal anti‐inflammatory drugs: Synthesis,kinetic and pharmacological evaluation

Ketoprofen belongs to one of the most common nonsteroidal anti‐inflammatory drugs (NSAIDs) but its clinical usefulness has been restricted due to the high incidence of gastrointestinal complications. The release of reactive oxygen species (ROS) in NSAIDs therapy plays a major role in causing gastric complications. Antioxidants not only prevent gastric ulceration and lipid peroxidation but also preserve glutathione‐type peroxidase (GPO) activity. Therefore, the present study investigates the utility of combining anti‐inflammatory and antioxidant properties of two different compounds in a single molecule to form a series of 16 ketoprofen–antioxidant mutual codrugs. The free carboxylic group, which is believed to be one of the reasons for gastric toxicity of ketoprofen, was masked temporarily by simple and double esterification with alcoholic/phenolic–OH of natural antioxidants. In simple esterification, ketoprofen is directly linked to natural antioxidants ( IIa–h ) in the hope to obtain drugs free of gastric side effects. In an attempt to improve the in vivo lability, as well as gastric side effects, the double ester codrugs, that is, ketoprofen–antioxidant through the glycolic acid spacer (–CH₂COO; IIIa–h ), have also been designed and synthesized. The synthesized codrugs were characterized by IR, ¹H NMR, ¹³C NMR, mass spectroscopy and elemental analysis. The in vitro hydrolysis studies showed the lowest hydrolysis (highest stability) in acidic pH 1.2, whereas moderate hydrolysis was seen at pH 7.4 and significant hydrolysis in 80% human blood plasma, as indicated by their t_1/2. The pharmacological evaluation results indicate that these ketoprofen–antioxidant mutual codrugs showed the retention of anti‐inflammatory and analgesic activity with a significant reduction in the ulcer index.     

茶多酚清除氧自由基及抑制脑脂质过氧化反应的体外试验

目的研究茶多酚对羟自由基（·ＯＨ）、超氧阴离子自由基（Ｏ·２）的清除作用及其对脂质过氧化的抑制作用。方法茶多酚与自由基发生体系或大鼠脑线粒体共浴后，比色法测定·ＯＨ、Ｏ·２及丙二醛生成量。结果茶多酚对Ｆｅｎｔｏｎ反应生成的·ＯＨ及黄嘌呤－黄嘌呤氧化酶系统产生的Ｏ·２具有较强的清除作用，ＩＣ５０分别为９１９．６ｍｇ·Ｌ－１和８３６ｍｇ·Ｌ－１。茶多酚对·ＯＨ诱导的离体大鼠脑线粒体产生的脂质过氧化有明显的抑制作用。结论茶多酚的抗脂质过氧化作用与其清除氧自由基作用有关     

Oestradiol Protects Against the Harmful Effects of Fluoride More by Increasing Thiol Group Levels than Scavenging Hydroxyl Radicals

Abstract: The aim of the study was to investigate the role of oestrogens in free radical detoxication upon exposure to fluoride. Interactions between xenobiotics and oestrogens need to be investigated, especially as many chemicals interact with the oestrogen receptor. It is still unknown whether free radical‐generating xenobiotics can influence the antioxidative ability of oestradiol (E₂). In an in vitro examination of human placental mitochondria, thiobarbituric active reagent species (TBARS), hydroxyl radical (^?OH) generation and protein thiol (–SH) groups were detected. 17β‐E₂ was examined in physiological (0.15–0.73 nM) and experimental (1–10 µM) concentrations and sodium fluoride (NaF) in concentrations of 6–24 µM. E₂ in all the concentrations significantly decreased lipid peroxidation measured as the TBARS level, in contrast to NaF, which increased lipid peroxidation. Lipid peroxidation induced by NaF was decreased by E₂. The influence of E₂ on ^?OH generation was not very significant and depended on the E₂ concentration. The main mechanism of E₂ protection in NaF exposure appeared to be connected with the influence of E₂ on thiol group levels, not ^?OH scavenging ability. The E₂ in concentrations 0.44–0.73 nM and 1–10 µM significantly increased the levels of –SH groups, in contrast to NaF, which significantly decreased them. E₂ at every concentration reversed the harmful effects of NaF on –SH group levels. No unfavourable interactions in the influence of E₂ and NaF on TBARS production, ^?OH generation, or –SH group levels were observed. The results suggest that postmenopausal women could be more sensitive to NaF‐initiated oxidative stress.     

Development of 2‐(Substituted Benzylamino)‐4‐Methyl‐1, 3‐Thiazole‐5‐Carboxylic Acid Derivatives as Xanthine Oxidase Inhibitors and Free Radical Scavengers

A series of 2‐(substituted benzylamino)‐4‐methylthiazole‐5‐carboxylic acid was designed and synthesized as structural analogue of febuxostat. A methylene amine spacer was incorporated between the phenyl ring and thiazole ring in contrast to febuxostat in which the phenyl ring was directly linked with the thiazole moiety. The purpose of incorporating methylene amine was to provide a heteroatom which is expected to favour hydrogen bonding within the active site residues of the enzyme xanthine oxidase. The structure of all the compounds was established by the combined use of FT‐IR, NMR and MS spectral data. All the compounds were screened in vitro for their ability to inhibit the enzyme xanthine oxidase as per the reported procedure along with DPPH free radical scavenging assay. Compounds 5j, 5k and 5l demonstrated satisfactory potent xanthine oxidase inhibitory activities with IC₅₀ values, 3.6, 8.1 and 9.9 μm , respectively, whereas compounds 5k , 5n and 5p demonstrated moderate antioxidant activities having IC₅₀ 15.3, 17.6 and 19.6 μm , respectively, along with xanthine oxidase inhibitory activity. Compound 5k showed moderate xanthine oxidase inhibitory activity as compared with febuxostat along with antioxidant activity. All the compounds were also studied for their binding affinity in active site of enzyme (PDB ID‐1N5X).     

Comparison of xanthine oxidase‐inhibiting and free radical‐scavenging activities between plant adaptogens of Eleutherococcus senticosus and Rhodiola rosea

The present study employed 2,2‐diphenyl‐l‐picrylhydrazyl (DPPH) radical‐scavenging and xanthine–xanthine oxidase (XO) assays to compare the antioxidant capacity between two plant adaptogens, Eleutherococcus senticosus (Araliaceae) and Rhodiola rosea (Crassulaceae). The IC₅₀ value for XO activity for Rhodiola was 355.4 µg/ml, while that for Eleutherococcus was >1,000 µg/ml. Eleutherococcus inhibited DPPH generation by 58.3±2.8% at 1,000 µg/ml, whereas Rhodiola inhibited DPPH radical by 91.1±2.6% at the same concentration. The results suggested that Rhodiola inhibited not only XO but also served as a potent radical scavenger. Rhodiola has potential as a natural source of antioxidants. Drug Dev Res 71:249–252, 2010. © 2010 Wiley‐Liss, Inc.     

五味子酚对大鼠中性粒细胞呼吸爆发的影响

目的　研究五味子酚对大鼠中性粒细胞呼吸爆发时自由基生成和溶酶体酶释放的影响。方法　分别用紫外分光法、荧光分光法和同位素法测定该细胞自由基生成、溶酶体酶释放、胞浆钙离子和环磷酸腺苷(cAMP)含量。结果　五味子酚能抑制中性粒细胞超氧阴离子、过氧化氢、脂质过氧化产物丙二醛（MDA）以及一氧化氮的生成,减少溶菌酶和β-葡糖醛酸苷酶的释放,而且,还能拮抗FMLP引起的细胞胞浆钙离子的增加,进一步增强FMLP引起的胞浆cAMP的增加。结论　五味子酚可能通过降低细胞内钙离子浓度和/或升高胞浆cAMP的含量而抑制中性粒细胞呼吸爆发所导致的上述变化。     

Novel 1,4 Substituted Piperidine Derivatives. Synthesis and Correlation of Antioxidant Activity with Structure and Lipophilicity

A series of novel piperidine derivatives was prepared and their lipophilicity was determined (as R_M values). These compounds as well as two intermediate α-keto-esters were tested for antioxidant activity. It was found that the cysteamine derivatives were efficient antioxidants, i.e. they could inhibit lipid peroxidation, act as hydroxyl radical scavengers and interact with 2,2-diphenyl-l-picrylhydrazyl radicals. This interaction could be attributed to the free SH group and this activity seemed to be favoured by increased lipophilicity. Replacement of SH by NH₂ or OH resulted in a decreased antioxidant activity of the compounds. However, the described activities seem not to be connected with any O^?₂· scavenging ability, at least under the experimental conditions applied. Furthermore, cysteamine derivatives seem to induce O^?₂· generation, a phenomenon often observed with thiol compounds. The antioxidant activity of the intermediate α-keto-esters varied and is probably mediated by different mechanisms.