We have investigated the antinociceptive activity of zerumbone (1), a natural cyclic sesquiterpene isolated from Zingiber zerumbet Smith, in acetic acid-induced abdominal writhing test and hot plate test in mice. 1 given by intraperitoneal route produced significant dose-dependent antinociceptive effect in all the test models used. In addition, the antinociceptive effect of 1 in the hot plate test was reversed by the non-selective opioid receptor antagonist naloxone, suggesting that the opioid system is involved in its analgesic mechanism of action.
The anti-inflammatory activity of zerumbone (1), a natural cyclic sesquiterpene isolated from Zingiber zerumbet Smith was investigated using carrageenan-induced paw edema and cotton pellet-induced granuloma tissue formation test in mice. It was demonstrated that intraperitoneal administration of 1 at a dose of 5, 10, 50 and 100 mg/kg produced significant dose-dependent inhibition of paw edema induced by carrageenan. It was also demonstrated that 1 at similar doses significantly suppressed granulomatous tissue formation in cotton pellet-induced granuloma test.
The present study examined the potential antinociceptive activity of flavokawin B (6'-hydroxy-2',4'-dimethoxychalcone), a synthetic chalcone using chemical- and thermal-induced nociception models in mice. It was demonstrated that flavokawin B (FKB; 0.3, 1, 3 and 10 mg/kg) administered via both oral (p.o.) and intraperitoneal (i.p.) routes produced significant and dose-dependent inhibition in the abdominal constrictions induced by acetic acid, with the i.p. route producing antinociception of approximately 7-fold more potent than the p.o. route. It was also demonstrated that FKB produced significant inhibition in the two phases of the formalin-induced paw licking test. In addition, the same treatment of flavokawin B (FKB) exhibited significant inhibition of the neurogenic nociceptive induced by intraplantar injections of glutamate and capsaicin. Likewise, this compound also induced a significant increase in the response latency period to thermal stimuli in the hot plate test and its antinociceptive effect was not related to muscle relaxant or sedative action. Moreover, the antinociception effect of the FKB in the formalin-induced paw licking test and the hot plate test was not affected by pretreatment of non-selective opioid receptor antagonist, naloxone. The present results indicate that FKB produced pronounced antinociception effect against both chemical and thermal models of pain in mice that exhibited both peripheral and central analgesic activity.
Phytochemical investigations on the methanolic extract of Melicope ptelefolia Champ ex Benth. resulted in the isolation of three new compounds, identified as 3beta-stigmast-5-en-3-ol butyl tridecanedioate (melicoester) (1), (2Z, 6Z, 10Z, 14Z, 18Z, 22Z, 26E)-3', 7', 11', 15', 19', 23', 27', 31'-octamethyldotriaconta-2, 6, 10, 14, 18, 22, 26, 30-octadecanoate (melicopeprenoate) (2) and p-O-geranyl-7"-acetoxy coumaric acid (3). The compounds were isolated along with twenty-one other known compounds, lupeol (4), oleanolic acid (5), kokusaginine (6) genistein (7), p-O-geranyl coumaric acid (8), 4-stigmasten-3-one (9), 3beta-hydroxystigma-5-en-7-one (10) cis-phytyl palmitate (11), dodecane, dodecan-1-ol, ceryl alcohol, hentriacontanoic acid, eicosane, n-amyl alcohol, caprylic alcohol, octatriacontane, nonatriacontane, hexatriencontan-1-ol, methyl octacosanoate, beta-sitosterol, beta-sitosterol glucoside. Structures of all the compounds were established on the basis of MS and 1D and 2D NMR spectral data, as well as comparison with reported data.
Aluminum substituted yttrium iron garnet nano particles with compositional variation of Y(3.0-x) A1(x)Fe5O12, where x = 0.0, 0.5, 1.0, 1.5, 2.0, 2.5 and 3.0 were prepared using sol gel technique. The X-ray diffraction results showed that the best garnet phase appeared when the sintering temperature was 800 degrees C. Nano-crystalline particles with high purity and sizes ranging from 20 to 100 nm were obtained. It was found that the aluminum substitution had resulted in a sharp fall of the d-spacing when x = 2, which we speculated is due to the preference of the aluminum atoms to the smaller tetrahedron and octahedron sites instead of the much larger dodecahedron site. High resolution transmission electron microscope (HRTEM) and electron diffraction (ED) patterns showed single crystal nanoparticles were obtained from this method. The magnetic measurement gave moderate values of initial permeability; the highest value of 5.3 was shown by sample Y3Fe5O12 at more than 100 MHz which was attributed to the morphology of the microstructure which appeared to be homogeneous. This had resulted in an easy movement of domain walls. The substitution of aluminum for yttrium is speculated to cause a cubic to rhombodedral structural change and had weakened the super-exchange interactions thus a fall of real permeability was observed. This might have created a strain in the sub-lattices and had subsequently caused a shift of resonance frequencies to more than 1.8 GHz when x > 0.5.
This is our initial response towards preparation of nano-inductors garnet for high operating frequencies strontium iron garnet (Sr3Fe5O12) denoted as SrIG and yttrium iron garnet (Y3Fe5O12) denoted as YIG. The garnet nano crystals were prepared by novel sol-gel technique. The phase and crystal structure of the prepared samples were identified by using X-ray diffraction analysis. SEM images were done to reveal the surface morphology of the samples. Raman spectra was taken for yttrium iron garnet (Y3Fe5O12). The magnetic properties of the samples namely initial permeability (micro), relative loss factor (RLF) and quality factor (Q-Factor) were done by using LCR meter. From the XRD profile, both of the Y3Fe5O12 and Sr3Fe5O12 samples showed single phase garnet and crystallization had completely occurred at 900 degrees C for the SrIG and 950 degrees C for the YIG samples. The YIG sample showed extremely low RLF value (0.0082) and high density 4.623 g/cm3. Interesting however is the high Q factor (20-60) shown by the Sr3Fe5O12 sample from 20-100 MHz. This high performance magnetic property is attributed to the homogenous and cubical-like microstructure. The YIG particles were used as magnetic feeder for EM transmitter. It was observed that YIG magnetic feeder with the EM transmitter gave 39% higher magnetic field than without YIG magnetic feeder.
This study investigated the antinociceptive effects of zerumbone in chemical behavioural models of nociception in mice. Zerumbone given through intraperitoneal route (i.p.) produced dose-related antinociception when assessed on acetic acid-induced abdominal writhing test in mice. In addition, the i.p. administration of zerumbone exhibited significant inhibition of the neurogenic pain induced by intraplantar (i.pl.) injection of capsaicin and bradykinin. Likewise, zerumbone given by i.p. route reduced the nociception produced by i.pl. injection of glutamate and phorbol myristate acetate (PMA). The antinociception caused by zerumbone in the acetic acid test was significantly attenuated by i.p. pre-treatment of mice with l-arginine (nitric oxide precursor) and glibenclamide (ATP-sensitive K(+) channel inhibitor). However, the antinociception of zerumbone was enhanced by methylene blue (non-specific gyanylyl cyclase inhibitor). Together, these results indicate that zerumbone produces pronounced antinociception against chemical models of nociception in mice. It also strongly suggests that the l-arginine-nitric oxide-cGMP-PKC-K(+) ATP channel pathways, the TRPV1 and kinin B2 receptors play an important role in the zerumbone-induced antinociception.
The possible mechanisms of action in the antinociceptive activity induced by systemic administration (intraperitoneal, i.p.) of flavokawin B (FKB) were analysed using chemical models of nociception in mice. It was demonstrated that i.p. administration of FKB to the mice at 0.3, 1.0, 3.0 and 10 mg/kg produced significant dose-related reduction in the number of abdominal constrictions. The antinociception induced by FKB in the acetic acid test was significantly attenuated by i.p. pre-treatment of mice with L-arginine, the substrate for nitric oxide synthase or glibenclamide, the ATP-sensitive K(+) channel inhibitor, but was enhanced by methylene blue, the non-specific guanylyl cyclase inhibitor. FKB also produced dose-dependent inhibition of licking response caused by intraplantar injection of phorbol 12-myristate 13-acetate, a protein kinase C activator (PKC). Together, these data indicate that the NO/cyclic guanosine monophosphate/PKC/ATP-sensitive K(+) channel pathway possibly participated in the antinociceptive action induced by FKB.
Bioassay-guided extraction of the stem bark of Knema laurina showed the acetylcholinesterase (AChE) inhibitory activity of DCM and hexane fractions. Further repeated column chromatography of hexane and DCM fractions resulted in the isolation and purification of five alkenyl phenol and salicylic acid derivatives. New compounds, (+)-2-hydroxy-6-(10'-hydroxypentadec-8'(E)-enyl)benzoic acid (1) and 3-pentadec-10'(Z)-enylphenol (2), along with known 3-heptadec-10'(Z)-enylphenol (3), 2-hydroxy-6-(pentadec-10'(Z)-enyl)benzoic acid (4), and 2-hydroxy-6-(10'(Z)-heptadecenyl)benzoic acid (5) were isolated from the stem bark of this plant. Compounds (1-5) were tested for their acetylcholinesterase inhibitory activity. The structures of these compounds were elucidated by the 1D and 2D NMR spectroscopy, mass spectrometry and chemical derivatizations. Compound 5 showed strong acetylcholinesterase inhibitory activity with IC(50) of 0.573 ± 0.0260 μM. Docking studies of compound 5 indicated that the phenolic compound with an elongated side chain could possibly penetrate deep into the active site of the enzyme and arrange itself through π-π interaction, H-bonding, and hydrophobic contacts with some critical residues along the complex geometry of the active gorge.
Zingiber zerumbet (L.) Smith, a wild edible ginger species or locally known as "lempoyang", commonly used in the Malays traditional medicine as an appetizer or to treat stomachache, toothache, muscle sprain and as a cure for swelling sores and cuts.
A series of 1,3,5-triaryl-2-pyrazolines was synthesized by dissolving the corresponding 4-alkoxychalcones in glacial acetic acid containing a few drops of concentrated hydrochloric acid. This step was followed by the addition of (3,4-dimethylphenyl) hydrazaine hydrochloride. Finally the target compounds were precipitated by pouring the reaction mixture onto crushed ice. The structures of the synthesized compounds were established by physicochemical and spectroscopic methods. The 1,3,5-triaryl-2-pyrazolines bearing homologous alkoxy groups were found to possess fluorescence properties in the blue region of the visible spectrum when irradiated with ultraviolet radiation. The fluorescent behavior of these compounds was studied by UV-Vis and emission spectroscopy, performed at room temperature.
Asthma is associated with increased pulmonary inflammation and airway hyperresponsiveness. The current use of corticosteroids in the management of asthma has recently raised issues regarding safety and lack of responsiveness in 5-10% of asthmatic individuals. The aim of the present study was to investigate the therapeutic effect of a non-steroidal small molecule that has cysteinyl leukotriene (cysLT) inhibitory activity, upon attenuation of allergic lung inflammation in an acute murine model. Mice were sensitized with ovalbumin (OVA) and treated with several intraperitoneal doses (100, 20, 2 and 0.2mg/kg) of 2,4,6,-trihydroxy-3-geranylacetophenone (tHGA). Bronchoalveolar lavage was performed, blood and lung samples were obtained and respiratory function was measured. OVA sensitization increased pulmonary inflammation and pulmonary allergic inflammation was significantly reduced at doses of 100, 20 and 2mg/kg with no effect at the lowest dose of 0.2mg/kg. The beneficial effects in the lung were associated with reduced eosinophilic infiltration and reduced secretion of Th2 cytokines and cysLTs. Peripheral blood reduction of total IgE was also a prominent feature. Treatment with tHGA significantly attenuated altered airway hyperresponsiveness as measured by the enhanced pause (Penh) response to incremental doses of methacholine. These data demonstrate that tHGA, a synthetic non-steroidal small molecule, can prevent acute allergic inflammation. This proof of concept opens further avenues of research and development of tHGA as an additional option to the current armamentarium of anti-asthma therapeutics.
This study investigated the potential antinociceptive efficacy of a novel synthetic curcuminoid analogue, 2,6-bis-(4-hydroxy-3-methoxybenzylidene)cyclohexanone (BHMC), using chemical- and thermal-induced nociception test models in mice. BHMC (0.03, 0.1, 0.3 and 1.0 mg/kg) administered via intraperitoneal route (i.p.) produced significant dose-related inhibition in the acetic acid-induced abdominal constriction test in mice with an ID(50) of 0.15 (0.13-0.18) mg/kg. It was also demonstrated that BHMC produced significant inhibition in both neurogenic (first phase) and inflammatory phases (second phase) of the formalin-induced paw licking test with an ID(50) of 0.35 (0.27-0.46) mg/kg and 0.07 (0.06-0.08) mg/kg, respectively. Similarly, BHMC also exerted significant increase in the response latency period in the hot-plate test. Moreover, the antinociceptive effect of the BHMC in the formalin-induced paw licking test and the hot-plate test was antagonized by pre-treatment with the non-selective opioid receptor antagonist, naloxone. Together, these results indicate that the compound acts both centrally and peripherally. In addition, administration of BHMC exhibited significant inhibition of the neurogenic nociception induced by intraplantar injections of glutamate and capsaicin with ID(50) of 0.66 (0.41-1.07) mg/kg and 0.42 (0.38-0.51) mg/kg, respectively. Finally, it was also shown that BHMC-induced antinociception was devoid of toxic effects and its antinociceptive effect was associated with neither muscle relaxant nor sedative action. In conclusion, BHMC at all doses investigated did not cause any toxic and sedative effects and produced pronounced central and peripheral antinociceptive activities. The central antinociceptive activity of BHMC was possibly mediated through activation of the opioid system as well as inhibition of the glutamatergic system and TRPV1 receptors, while the peripheral antinociceptive activity was perhaps mediated through inhibition of various inflammatory mediators.
The increasing prevalence of neurodegenerative diseases has prompted investigation into innovative therapeutics over the last two decades. Non-steroidal anti-inflammatory drugs (NSAIDs) are among the therapeutic choices to control and suppress the symptoms of neurodegenerative diseases. However, NSAIDs-associated gastropathy has hampered their long term usage despite their clinical advancement. On the natural end of the treatment spectrum, our group has shown that cardamonin (2',4'-dihydroxy-6'-methoxychalcone) isolated from Alpinia rafflesiana exerts potential anti-inflammatory activity in activated macrophages. Therefore, we further explored the anti-inflammatory property of cardamonin as well as its underlying mechanism of action in IFN-γ/LPS-stimulated microglial cells. In this investigation, cardamonin shows promising anti-inflammatory activity in microglial cell line BV2 by inhibiting the secretion of pro-inflammatory mediators including nitric oxide (NO), prostaglandin E(2) (PGE(2)), tumour necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6). The inhibition of NO and PGE(2) by cardamonin are resulted from the reduced expression of inducible nitric oxide synthase (iNOS) and cycloxygenase-2 (COX-2), respectively. Meanwhile the suppressive effects of cardamonin on TNF-α, IL-1β and IL-6 were demonstrated at both protein and mRNA levels, thus indicating the interference of upstream signal transduction pathway. Our results also validate that cardamonin interrupts nuclear factor-kappa B (NF-κB) signalling pathway via attenuation of NF-κB DNA binding activity. Interestingly, cardamonin also showed a consistent suppressive effect on the cell surface expression of CD14. Taken together, our experimental data provide mechanistic insights for the anti-inflammatory actions of cardamonin in BV2 and thus suggest a possible therapeutic application of cardamonin for targeting neuroinflammatory disorders.
Magnetic nanoparticles in the hollow region of carbon nanotubes have attraction due to their changing physical electrical and magnetic properties. Nickel zinc ferrite plays an important role in many applications due to its superior magnetic properties. Ni0.8Zn0.2Fe2O4 single crystals were encapsulated in multiwall carbon nanotubes (MWCNTs). The magnetic nano crystals were prepared using a sol-gel self combustion method at the sintering temperature of 750 degrees C and were characterized by XRD, FESEM, TEM and VSM. Initial permeability, Q-factor and relative loss factor were measured by impedance vector network analyzer. XRD patterns were used for the phase identification. FESEM images show morphology and dimensions of the grains of Ni0.8Zn0.2Fe2O4 single crystals and Ni0.8Zn0.2Fe2O4 single crystals in MWCNTs. TEM images were used to investigate single crystal and encapsulation of Ni0.8Zn0.2Fe2O4 single crystals in the MWCNTs. VSM results confirmed super paramagnetic behaviour of encapsulated Ni0.8Zn0.2Fe2O4 single crystals. It was also attributed that encapsulated Ni0.8Zn0.2Fe2O4 single crystals in MWCNTs showed a higher initial permeability (51.608), Q-factor (67.069), and low loss factor (0.0002) as compared to Ni0.8Zn0.2Fe2O4 single crystals. The new encapsulated Ni0.8Zn0.2Fe2O4 single crystals in the MWCNTs may have potential applications in electronic and medical industries.
In seabed logging the magnitude of electromagnetic (EM) waves for the detection of a hydrocarbon reservoir in the marine environment is very important. Having a strong EM source for exploration target 4000 m below the sea floor is a very challenging task. A new carbon nanotubes (CNT) fibres/aluminium based EM transmitter is developed and NiZn ferrite as magnetic feeders was used in a scaled tank to evaluate the presence of oil. Resistive scaled tank experiments with a scale factor of 2000 were carried out. X-ray Diffraction (XRD), Raman Spectroscopy and Field Emission Scanning Electron Microscope (FESEM) were done to characterize the synthesized magnetic feeders. Single phase Ni0.76Mg0.04Zn0.2Fe2O4, obtained by the sol-gel method and sintered at 700 degrees C in air, has a  major peak. FESEM results show nanoparticles with average diameters of 17-45 nm. Samples which have a high Q-factor (approximately 50) was used as magnetic feeders for the EM transmitter. The magnitude of the EM waves of this new EM transmitter increases up to 400%. A curve fitting method using MATLAB software was done to evaluate the performance of the new EM transmitter. The correlation value with CNT fibres/aluminium-NiZnFe2O4 base transmitter shows a 152.5% increase of the magnetic field strength in the presence of oil. Modelling of the scale tank which replicates the marine environment was done using the Finite Element Method (FEM). In conclusion, FEM was able to delineate the presence of oil with greater magnitude of E-field (16.89%) and the B field (4.20%) due to the new EM transmitter.
Previous studies have shown that systemic administration of 6'-hydroxy-2',4'-dimethoxychalcone (flavokawin B, FKB) exerts significant peripheral and central antinociceptive effects in laboratory animals. However, the mechanisms underlying these peripheral and central antinociceptive effects have yet to be elucidated. Therefore, the objective of the present study was to evaluate the participation of nitric oxide (NO)/cyclic guanosine monophosphate (cGMP)/potassium (K+) channels pathway in the peripheral antinociception induced by FKB. It was demonstrated that intraplantar (i.pl.) administration of FKB (150, 250, 375 and 500 µg/paw) resulted in dose-dependent peripheral antinociception against mechanical hyperalgesia in carrageenan-induced hyperalgesia test model in rats. The possibility of FKB having either a central or a systemic effect was excluded since administration of FKB into the right paw did not elicit antinociception in the contralateral paw. Furthermore, peripheral antinociception induced by FKB (500 µg/paw) was significantly reduced when L-arginine (25 µg/paw, i.pl.), Oxadiazolo[4,3-a]quinoxalin-1-one (ODQ; 50 µg/paw, i.pl.), glibenclamide (300 µg/paw, i.pl.), tetraethylammonium (300 µg/paw, i.pl.) and charybdotoxin (3 µg/paw, i.pl.) were injected before treatment. Taken together, our present data suggest that FKB elicits peripheral antinociception when assessed in the mechanical hyperalgesia induced by carrageenan. In addition, it was also demonstrated that this effect was mediated through interaction of the NO/cGMP/K+ channels signaling pathway.
Naturally occurring anthraquinones, damnacanthal (1) and nordamnacanthal (2) were synthesized with modified reaction steps and investigated for their cytotoxicity against the MCF-7 and K-562 cancer cell lines, respectively. Intermediate analogues 2-bromomethyl-1,3-dimethoxyanthraquinone (5, IC50 = 5.70 ± 0.21 and 8.50 ± 1.18 mg/mL), 2-hydroxymethyl-1,3-dimethoxyanthraquinone (6, IC50 = 12.10 ± 0.14 and 14.00 ± 2.13), 2-formyl-1,3-dimethoxyantharquinone (7, IC50 = 13.10 ± 1.02 and 14.80 ± 0.74), 1,3-dimethoxy-2-methylanthraquinone (4, IC50 = 9.40 ± 3.51 and 28.40 ± 2.33), and 1,3-dihydroxy-2-methylanthraquinone (3, IC50 = 25.60 ± 0.42 and 28.40 ± 0.79) also exhibited moderate cytotoxicity against MCF-7 and K-562 cancer cell lines, respectively. Other structurally related compounds like 1,3-dihydroxyanthraquinone (13a, IC50 = 19.70 ± 0.35 and 14.50 ± 1.28), 1,3-dimethoxyanthraquinone (13b, IC50 = 6.50 ± 0.66 and 5.90 ± 0.95) were also showed good cytotoxicity. The target compound damnacanthal (1) was found to be the most cytotoxic against the MCF-7 and K-562 cancer cell lines, with IC50 values of 3.80 ± 0.57 and 5.50 ± 1.26, respectively. The structures of all compounds were elucidated with the help of detailed spectroscopic techniques.
Breast cancer is becoming more prominent in women today. As of now, there are no effective treatments in treating metastatic breast cancer. We have tested the cytotoxic and anti-migration effects of BHAQ, a synthesized anthraquinone, on two breast cancer cell lines, MCF-7 and MDA-MB231. Anthraquinones are an interesting class of molecules that display a wide spectrum of biological applications, including anticancer properties. Cellular inhibition was tested through a MTT assay, double acridine orange/propidium iodide staining and FACS cell cycle analysis. Inhibition of migration was tested by the wound healing method, and migration through a Boyden chamber. BHAQ was cytotoxic towards both cell lines in a dose dependent and possibly cell-dependent manner. Additionally, BHAQ also inhibited the migration of the highly metastatic MDA-MB231 cell line.
The present study investigated the analgesic effect of a novel synthetic cyclohexanone derivative, 2,6-bis-4-(hydroxyl-3-methoxybenzilidine)-cyclohexanone or BHMC in a mouse model of chronic constriction injury-induced neuropathic pain. It was demonstrated that intraperitoneal administration of BHMC (0.03, 0.1, 0.3 and 1.0mg/kg) exhibited dose-dependent inhibition of chronic constriction injury-induced neuropathic pain in mice, when evaluated using Randall-Selitto mechanical analgesiometer. It was also demonstrated that pretreatment of naloxone (non-selective opioid receptor blocker), nor-binaltorphimine (nor-BNI, selective κ-opioid receptor blocker), but not β-funaltrexamine (β-FN, selective μ-opioid receptor blocker) and naltrindole hydrochloride (NTI, selective δ-opioid receptor blocker), reversed the anti-nociceptive effect of BHMC. In addition, the analgesic effect of BHMC was also reverted by pretreatment of 1H-[1,2,4]Oxadiazole[4,3-a]quinoxalin-1-one (ODQ, soluble guanosyl cyclase blocker) and glibenclamide (ATP-sensitive potassium channel blocker) but not Nω-nitro-l-arginine (l-NAME, a nitric oxide synthase blocker). Taken together, the present study demonstrated that the systemic administration of BHMC attenuated chronic constriction, injury-induced neuropathic pain. We also suggested that the possible mechanisms include κ-opioid receptor activation and nitric oxide-independent cyclic guanosine monophosphate activation of ATP-sensitive potassium channel opening.