Biosynthesis of copper oxide nanoparticles using Enicostemma axillare (Lam.) leaf extract

In the present study copper oxide nanoparticles (CuONPs) were synthesized via simple and eco-friendly green route using leaf extract of Enicostemma axillare (Lam.). Characterization of synthesized nanoparticles (NPs) was undertaken. The characteristic absorption peak of CuONPs was in range 264nm in UV–Vis spectrum. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) studies revealed the morphological and structural character of green NPs. The mean particle size was calculated to 30nm. Energy dispersive spectroscopy (EDS) showed high intense metallic peak of copper (Cu), oxygen (O) and low intense peaks of carbon (C), sulfur (S), phosphorus (P) elements due to the capping action of biomolecules of plant extract in CuONPs formation. The X-ray diffraction (XRD) pattern showed distinctive peaks corresponding to (200), (211) and (310) planes revealing the high crystalline nature of synthesized CuONPs with a primitive phase. Zeta potential and size distribution of synthesized green NPs was concluded by Dynamic light scattering (DLS) studies.     

The anti-inflammatory activity of Enicostemma littorale and Mollugo cerviana

The anti-inflammatory activity of E. littorale and M. cerviana was assessed by carrageenan-induced inflammation and cotton pellet granuloma method in rats. E. littorale and M. cerviana exerted 54 and 26% anti-inflammatory activity for a dose of 100 mg/100 g body wt, respectively, in carrageenan-induced acute inflammation. In chronic inflammation of cotton pellet granuloma, E. littorale and M. cerviana exerted 30 and 46% anti-inflammatory activity at the above dosage, respectively. The optimal dose for these drugs was determined in carrageenan inflammation. The effect of the alcoholic extract of these drugs on human erythrocyte membrane stabilization and inhibition of cobra venom phospholipase A2 was studied in vitro and the drugs were found to be effective. Further, these drugs were found to inhibit the levels of lipid peroxides, acid phosphatase, and gamma-glutamyl transpeptidase activity in the exudate of cotton pellet granuloma. The effects were compared with those of standard anti-inflammatory drug, hydrocortisone. A possible mode of action of these drugs is suggested.     

Antioxidant and hepatoprotective effect of the ethyl acetate extract of Enicostemma axillare (Lam). Raynal against CCL4-induced liver injury in rats

Enicostemma axillare is used in Indian traditional medicine as a liver tonic. Its ethyl acetate extract has shown potent in vitro antioxidant activity and found to contain 7.26% of a bitter secoiridoid glycoside, swertiamarin. Hence, in the present study the ethyl acetate extract was screened for hepatoprotective and antioxidant properties against CCl4 induced hepatic injury in rats. The hepatoprotection was assessed in terms of reduction in histological damage and changes in serum enzymes and metabolites. The pretreatment with the extract at 100 and 200 mg/kg body weight doses given orally for eight days prior to CCl4 caused significant restoration of altered biochemical changes due to CCl4 towards the normal in serum, liver and kidney. The extract treatment at 200 mg/kg body weight was found to be more potent than the standard silymarin at 100 mg/kg body weight in reversing most of the biochemical parameters. Histopathological studies complemented the results of biochemical estimations in providing a proof of hepatoprotective and antioxidant actions of the extract. The study provides a support to the ethnomedical use of E. axillare in India.     

Antinociceptive activity of the natural piperidine alkaloid hydrochlorides from Syphocampylus verticellatus

In addition to 3'-methoxyluteolin and mixtures of sterols and triterpenes, the leaves of Syphocampylus Verticellatus yielded two piperidine alkaloid hydrochlorides, one of them has a novel structure. The alkaloids exhibit antinociceptive activity.     

Antinociceptive properties of morusin, a prenylflavonoid isolated from Morus nigra root bark

The antinociceptive effects of morusin (1), the main prenylflavonoid present in the Morus nigra root barks have been investigated in classical models of pain in mice. The results showed that 1 exhibits a promising antinociceptive or analgesic profile by the intraperitoneal route, being more potent than some standard drugs used as reference. The mechanism by which the morusin exerts antinociceptive activity still remains undetermined, but our results strongly suggest that it involves the participation of the opioid system.     

Antinociceptive activity of filenadol on inflammatory pain

The novel analgesic filenadol (d,1-erythro-1-(3′,4′-methylenedioxyphenyl)-1-morpholinopropan-2-ol) inhibited phenyl-p-benzoquinone-induced writhing in mice with ID₅₀ values of 68.8 (p.o.), 1.67 (i.v.) and 0.48 (i.c.v.) mg/kg. Hyperalgesia induced by arachidonic acid, PGE₂ or LTB₄ in this test was also decreased by filenadol (ID₅₀ = 24.4, 3.7 and 50.1 mg/kg p.o., respectively). This compound was effective on PGE₂, LTB₄, bradykinin, PAF or IL-1μ-induced decrease in pain threshold in the rat paw pressure model and almost totally suppressed the writhing induced by zymosan in mice, while peritoneal production of 6-ketoPGF_1α was inhibited by 48.5–62 % and only at 100 mg/kg significant inhibition of LTC₄ was achieved. The late phase of formalin-induced pain response in mice was prevented by filenadol, without affecting the oedema. Filenadol is an antinociceptive agent that reduces the hyperalgesic effects of inflammatory mediators besides inhibiting partially the synthesis of eicosanoids.     

Antinociceptive activity of a novel buprenorphine analogue

HS-599 is a didehydroderivative of buprenorphine that displays high affinity and good selectivity for mu-opioid receptors. We studied its antinociceptive properties after s.c. injection in mice with the tail-flick and hot-plate tests. In the tail-flick test HS-599 (AD50 = 0.2801 micromol/kg s.c.) behaved as a full agonist and was twice as potent as buprenorphine (AD50=0.4569 micromol/kg s.c.) and 50 times more potent than morphine (AD50 = 13.3012 micromol/kg s.c.). Whereas the mu-opioid receptor antagonists naloxone (1-10 mg/kg s.c.) and naltrexone (5-15 mg/kg s.c.) antagonized HS-599 induced analgesia, the delta-opioid receptor antagonist naltrindole (20 mg/kg s.c.) and the kappa-opioid receptor antagonist nor-binaltorphimine (20 mg/kg s.c.) did not. With the hot-plate test at 50 degrees C, HS-599 (AD50 = 0.0359 micromol/kg s.c.) was a full agonist about 130 times more potent than morphine (AD50 = 4.8553 micromol/kg s.c.). With a high intensity nociceptive stimulus (55 degrees C) HS-599 (AD50 = 1.0382 micromol/kg s.c.) remained 7 times more potent than morphine (AD50 = 7.0210 micromol/kg s.c.) but never exceeded the 55% of the maximum possible effect, behaving as a partial agonist able to antagonize morphine antinociception in a dose-dependent manner. HS-599 promises to be a potent and safe new analgesic, preferentially acting at spinal level.     

Antinociceptive activity and chemical composition of constituents from Caragana microphylla seeds

This investigation was undertaken to ascertain the antinociceptive activity of Caragana microphylla Lam. seeds and isolate and characterize the constituents. Antinociceptive activity was screened using acetic acid-induced abdominal constriction in ICR mice. The 75% ethanol extract and some fractions showed analgesic activity, but the antinociceptive activity of chloroform fraction was the strongest and was more productive than other fractions. Seven compounds were isolated from it and identified as: (1) machaeric acid, (2) beta-sitosterol, (3) stigmasterol, (4) pratol, (5) dehydrocavidine, (6) formononetin and (7) sucrose. Caragana microphylla Lam. seeds showed analgesic activity, with the chloroform fraction showing the strongest analgesic activity among the fractions.     

Antinociceptive substances from Incarvillea delavayi

Antinociceptive activities of an Incarvillea delavayi extract, as well as its constituents, 8-epideoxyloganic acid and delavayine A, were evaluated in the acetic acid induced writhing test in mice. An oral administration of the delavayi extract weakly decreased the number of writhings and stretchings in this test, in a dose-dependent manner. Furthermore, orally administered 8-epideoxyloganic acid showed weak antinociceptive activity, whereas administration by subcutaneous injection did not. However, subcutaneous injection of delavayine A, a novel monoterpene alkaloid, showed a more significant level of antinociceptive activity.     

Antinociceptive activity of furan-containing congeners of improgan and ranitidine

Furan-containing congeners of the histamine H(2) receptor antagonist ranitidine were synthesized and tested for improgan-like antinociceptive activity. The most potent ligand of the series, VUF5498, is the most potent improgan-like agent described to date (ED(50)=25 nmol, icv). This compound is approximately equal in potency with morphine. These non-imidazole, improgan-like pain relievers further define the structural requirements for analgesics of this class and are important tools for ongoing mechanism-based studies.     

Antinociceptive activity of atranorin in mice orofacial nociception tests

Physicochemical characterization and antinociceptive and anti-inflammatory activities of atranorin (AT) extracted from Cladina kalbii Ahti in formalin- and capsaicin-induced orofacial pain and anti-inflammatory tests in rodents were studied. Physicochemical characterization showed that AT has the general formula C19H18O8. Male Swiss mice were pretreated with AT (100, 200, and 400 mg/kg, i.p.), morphine (3 mg/kg, i.p.), or vehicle (0.9% saline with two drops of 0.2% Tween 80) before formalin (20 microl, 2%) or capsaicin (20 microl, 2.5 microg) were injected into the right vibrissa. Our results showed that i.p. treatment with AT displayed marked inhibitory effects in different orofacial pain tests in mice. AT (400 mg/kg, i.p.) was effective in reducing the nociceptive face-rubbing behavioural response in both phases of the formalin test, which was also naloxone-sensitive. Additionally, AT produced a significant antinociceptive effect at all doses in the capsaicin test. Such results were unlikely to be provoked by motor abnormality, since AT-treated mice exhibited no performance alteration on the rota rod apparatus. AT exhibited significant anti-inflammatory activity in the acute model of inflammation (leukocyte migration to the peritoneal cavity), carrageenan- and arachidonic acid-induced hind paw edema in rats. Additionally, AT exhibited a dose-dependent antioxidant activity in vitro, as assessed by total radical-trapping antioxidant parameter and total antioxidant reactivity assays. All these findings suggest that AT might represent an important tool for the management of orofacial pain and/or inflammatory disorders.     

Fungicidal activity of yeast isolated from chal

A Kluyveromyces strain secreting a fungicidal proteinaceous toxin has been isolated. Its maximal activity is observed at pH 5.0 and an increased osmotic pressure. This agent has been identified as a mycocin; it is active towards species belonging to the genus Kluyveromyces and some representatives of taxonomically related taxa.     

Antifungal activity of lactobacilli isolated from salami

Sixty-five strains of lactobacilli isolated from salami were tested for their antifungal activity in early and late phases of growth. Ten strains showed inhibitory activity in the early phase of growth towards moulds such as Aspergillus and Penicillium. The active compounds identified were phenyl-lactate and hydroxy-phenyl-lactate. All strains tested had activity in the late phase, after autolysis. The compounds released were peptidic and showed antifungal activity.     

Antinociceptive properties of the methanolic extract and two triterpenes isolated from Epidendrum Mosenii stems (Orchidaceae)

The antinociceptive effect of the methanolic extract (ME) and two triterpenes isolated from E. mosenii (Orchidaceae) has been investigated in chemical and thermal models of nociception in mice. The ME of E. mosenii (0.3-30 mg kg(-1), i.p. or 50-400 mg kg(-1), p.o.) produced dose-related, significant and long-lasting (4 to 6 h) inhibition of acetic acid-induced abdominal constriction, with ID50 values of 3.9 and 137.0 mg kg(-1), respectively. Pholidotin and 24-methylenecycloartenol isolated from E. mosenii (0.1-3.0 mg kg(-1), i.p.) also produced marked and dose-related inhibition of acetic acid-induced pain, with ID50 values of 0.9 and 1.1 mg kg(-1). However, these compounds and the ME were about 3- to 13-fold more potent at the level of ID50 than diclofenac when assessed in acetic acid-induced abdominal constriction. The ME of E. mosenii in the same range of doses produced dose-related inhibition of both phases of formalin-induced licking, with mean ID50 values for the first and the second phases of 0.9, 122.0 mg kg(-1) and 0.7, 258.0 mg kg(-1), respectively by i.p. or p.o. routes. In addition, the ME (0.3-30 mg kg(-1), i.p., or 50-400 mg kg(-1), p.o.) also caused dose-related inhibition of capsaicin-induced neurogenic pain with mean ID50 values of 5.2 and 130.0 mg kg(-1), respectively. Treatment of animals with naloxone (5 mg kg(-1), i.p.) completely reversed the antinociceptive effect caused by morphine (5 mg kg(-1), s.c.) and that caused by ME of E. mosenii (1 mg kg(-1), i.p.) when assessed against either phase of the formalin-induced pain. Furthermore, when assessed in the hot-plate test, ME (100 mg kg(-1), i.p.) and morphine (10 mg kg(-1), s.c.) caused significant increase in response latency. However, ME given daily for to 7 consecutive days did not develop tolerance to itself nor did it induce cross-tolerance to morphine. Taken together these data demonstrate that the ME of E. mosenii elicited pronounced antinociception, when assessed by i.p. or p.o. routes, against several models of pain. Its actions involve, at least in part, an interaction with opioid system, seeming no to be related with a non-specific peripheral or central depressant actions. Finally, the active principle(s) responsible for the antinociceptive action of E. mosenii is likely related to the presence of the triterpenes.     

Antinociceptive activity of structural analogues of rotundifolone: structure-activity relationship

Rotundifolone, a monoterpene isolated from the essential oil of the leaves of Mentha x villosa, is a constituent of several essential oils and known to have antinociceptive activity. Our recent study demonstrated that the analogues of rotundifolone showed also a significant antinociceptive effect. In the present report, to investigate the correlation between the structure and antinociceptive activity, rotundifolone and its analogues were evaluated in the acetic acid-induced writhing test in mice. All compounds showed to be more antinociceptive than rotundifolone against the pain response induced by acetic acid. Comparing the antinociceptive effect of rotundifolone with limonene oxide and (+)-pulegone, the results demonstrated that the epoxide group contributes as much as the ketone group to the antinociceptive activity of rotundifolone. Similarly, pulegone oxide and carvone epoxide were more antinociceptive than rotundifolone, thereby suggesting that the position of the functional group on the ring also influences the antinociceptive activity. (-)-Carvone produced maximal inhibition of the writhing response and was slightly more active than (+)-carvone. The study showed that by appropriate structural modification it may be possible to develop novel antinociceptive agents.     

Antinociceptive activity of the S1P-receptor agonist FTY720

FTY720 is a novel immunosuppressive drug that inhibits the egress of lymphocytes from secondary lymphoid tissues and thymus. In its phosphorylated form FTY720 is a potent S1P receptor agonist. Recently it was also shown that FTY720 can reduce prostaglandin synthesis through the direct inhibition of the cytosolic phospholipase A2 (cPLA2). Since prostaglandins are important mediators of nociception, we studied the effects of FTY720 in different models of nociception. We found that intraperitoneal administration of FTY720 reduced dose-dependently the nociceptive behaviour of rats in the formalin assay. Although the antinociceptive doses of FTY720 were too low to alter the lymphocyte count, prostanoid concentrations in the plasma were dramatically reduced. Surprisingly, intrathecally administered FTY720 reduced the nociceptive behaviour in the formalin assay without altering spinal prostaglandin synthesis, indicating that additional antinociceptive mechanisms beside the inhibition of prostaglandin synthesis are involved. Accordingly, FTY720 reduced also the nociceptive behaviour in the spared nerve injury model for neuropathic pain which does not depend on prostaglandin synthesis. In this model the antinociceptive effect of FTY720 was similar to gabapentin, a commonly used drug to treat neuropathic pain. Taken together we show for the first time that FTY720 possesses antinociceptive properties and that FTY720 reduces nociceptive behaviour during neuropathic pain.     

Platelet-activating factor-like activity isolated from Trypanosoma cruzi

Platelet-activating factor is a phospholipid mediator that exhibits a wide variety of physiological and pathophysiological effects, including induction of inflammatory response, chemotaxis and cellular differentiation. Trypanosoma cruzi, the etiological agent of Chagas' disease, is transmitted by triatomine insects and while in the triatomine midgut the parasite differentiates from a non-infective epimastigote stage into the pathogenic trypomastigote metacyclic form. We have previously demonstrated that platelet activating factor triggers in vitro cell differentiation of T. cruzi. Here we show a platelet activating factor-like activity isolated from lipid extract of T. cruzi epimastigotes incubated in the presence of [14C]acetate. Trypanosoma cruzi-platelet activating factor-like lipid induced the aggregation of rabbit platelets, which was prevented by platelet activating factor-acetylhydrolase. Mouse macrophage infection by T. cruzi was stimulated when epimastigotes were kept for 5 days in the presence of T. cruzi-platelet activating factor, before interacting with the macrophages. The differentiation of epimastigotes into metacyclic trypomastigotes was also triggered by T. cruzi-platelet activating factor. These effects were abrogated by a platelet activating factor antagonist, WEB 2086. Polyclonal antibody raised against mouse platelet activating factor receptor showed labelling for T. cruzi epimastigotes using immunoblotting and immunofluorescence assays. These data suggest that T. cruzi contain the components of an autocrine platelet activating factor-like ligand-receptor system that modulates cell differentiation towards the infectious stage.     

Collagenolytic activity from isolated bone cells.

A true collagenase (EC 3.4.24.3) which had been discovered previously in bone culture fluids and extracts of whole bone has now been localized to the cellular component of bone. The cellular enzyme bears the same characteristics as that of bone collagenases described earlier. Moreover, it is directly extractable in relatively large quantities. Attempts to demonstrate the presence of a bone cell procollagease were unsuccessful. It was also observed that the cells secrete significant amounts of collagenase in vitro. With increasing incubation time the extracellular collagenase levels rise and the intracellular collagenase levels drop.     

Immunotropic activity of panaxans--bioglycans isolated from ginseng]

Immunomodulating activity of panaxanes--polysaccharides isolated from the roots and culture of Panax ginseng was studied. Effects of both preparations were analogous. Profilaxy use of panaxanes provided increased resistance to coli-sepsis in mice, increased neutrophiles and macrophages phagocytosis, stimulated humoral and cell immune factors and induced important regulating cytokins--interferone gamma and tumor necrosis factor.     

Transcriptional activity of heterocysts isolated from Anabaena variabilis

Nitrogenase activity, RNA synthesis, and protein synthesis were measured in heterocysts of Anabaena variabilis. Heterocysts labelled in situ for 4 h with [¹⁴C]uracil accumulated label in rRNA and tRNA to the same specific activity as RNA from vegetative cells. With isolated heterocysts, however, assimilation of [³H]uracil into RNa occurred at about 10% the rate in vegetative cells, and ceased 90 min after isolation. Pulse-chase experiments indicated that heterogeneous, high-molecular-weight RNA synthesized during the first 30 min of incubation was turned over during a 2 h chase, howver there was no accumulation of label in rRNA and tRNA as was seen with heterocysts labelled in situ and with vegetative cells. Assimilation of [³H]glycine into protein by isolated heterocysts was linear up to about 60 min, then proceeded at a slower rate for an additional 180 min. Maintenance of protein synsthesis and nitrogen fixation were both blocked by chloramphenicol and rifampicin. The data suggest that differentiated heterocysts continue to synthesize RNA and proteins and that these processes may contribute to the functional lifetime of heterocysts.