Search

Colorectal cancer is a significant cause of morbidity and represents a serious public health issue in many countries. The development of a breakthrough preventive method for colorectal cancer is urgently needed. Aspirin has recently been attracting attention as a cancer preventive drug, and its inhibitory effects on the development of various cancers have been reported in several large prospective studies. However, the underlying molecular mechanisms have not yet been elucidated in detail. In the present study, we attempted to identify the target proteins of aspirin using a chemical biology technique with salicylic acid, the main metabolite of aspirin. We generated salicylic acid-presenting FG beads and purified salicylic acid-binding proteins from human colorectal cancer HT-29 cells. The results obtained showed the potential of ribosomal protein S3 (RPS3) as one of the target proteins of salicylic acid. The depletion of RPS3 by siRNA reduced CDK4 expression and induced G1 phase arrest in human colorectal cancer cells. These results were consistent with the effects induced by the treatment with sodium salicylate, suggesting that salicylic acid negatively regulates the function of RPS3. Collectively, the present results show the potential of RPS3 as a novel target for salicylic acid in the protective effects of aspirin against colorectal cancer, thereby supporting RPS3 as a target molecule for cancer prevention.

Complete aqueous dissolution of starch requires the use of temperatures exceeding 100 °C. During and after cooling of the resultant aqueous solutions, starch polymers precipitate by aggregation and crystallization. Low-temperature gelatinization and dissolution of maize starch (MS) is induced, and the stability of the resultant solutions is enhanced when they contain the hydrotrope sodium salicylate (NaSal). Differential scanning calorimetry and optical microscopy evidence showed that MS gelatinization shifts to lower temperatures and that the associated enthalpy decreases with increasing NaSal concentrations. The enhanced gelatinization and dissolution are probably brought about by the association of NaSal with the more hydrophobic MS structural moieties. The minimum NaSal content of aqueous mixtures allowing full gelatinization of MS at room temperature, that is, about 11 wt %, was found to be independent of MS content (in the range 10-66.7 wt % MS). ispartof: BIOMACROMOLECULES vol:23 issue:7 ispartof: location:United States status: published

Pogostemon cablin (Patchouli) is an aromatic herb cultivated for its high-value essential oil. It is majorly used as a base oil in fragrance formulation due to its characteristics sesquiterpenoid alcohols. Patchoulol is an imperative and bioactive sesquiterpenoid in the patchouli essential oil, which is primarily isolated from the aerial part of the plant. The patchoulol was enriched in this essential oil by ultrasonic-assisted extraction techniques using different hydrotropes viz., sodium p-toluene sulphonate, resorcinol, sodium cumene sulphonate and sodium salicylate. The effect of various parameters such as extraction time (min), ultrasonic amplitude (%) and pulse interval (s) with 2 M concentration of hydrotropes was studied. Ultrasonic assisted-techniques has improved the percentage of patchoulol in patchouli essential oil. The highest composition of patchoulol i.e., 70.06 % was obtained for 5 min extraction time, 40 % ultrasonic amplitude, 30:30 s pulse interval for sodium salicylate at 2 M concentration.

This article provides information about biostimulants, trace elements and other additives used in the growth and development of poultry in farms.

Hydrogels based on hyaluronic acid (HA) and agarose-carbomer (AC) raised an increasing interest as drug delivery systems. The complex architecture of the polymer network, such as mesh size, HA molecular weight and drug-polymer non covalent interactions across the 3D polymer matrix strongly influence the release capability/profile of these materials. In this study, AC-HA hydrogels with different mesh sizes have been prepared and characterised. High Resolution Magic Angle Spinning (HR-MAS) NMR spectroscopy has been used to investigate the motion of two drugs, such as ethosuximide (neutral molecule) and sodium salicylate (net negative charge) within the AC and AC-HA hydrogel networks. Analysis of the experimental data provides evidence of superdiffusive motion for all formulations containing sodium salicylate, while ethosuximide molecules undergo unrestricted diffusion within the gel matrix. We further speculate that the superdiffusive motion, observed at the nanoscale, can be responsible for the faster release of sodium salicylate from all hydrogel formulations.

Previous studies have demonstrated nonsteroidal antiinflammatory drug treatment in early lactation had a positive impact on whole-lactation milk production in older cows. The objective of this study was to evaluate proliferative, transcriptional, and epigenetic changes in the mammary gland that could explain increased production responses due to nonsteroidal antiinflammatory drug treatment. Sodium salicylate (SAL; 125 g/d) or water (CON) were administered via oral drench to multiparous Holstein cows (n = 8/treatment) once daily for 3 d beginning approximately 24 h after parturition, and mammary tissue was collected on d 1, 4, and 45 postpartum. Day 1 tissue was collected immediately preceding the initial drench, and d 4 tissue was collected 24 h following the final drench. Blood was collected twice weekly and analyzed for plasma glucose, insulin, β-hydroxybutyrate, free fatty acids, and prolactin. Cows were milked twice daily until d 7 of lactation, and thrice daily for the remainder of the study. Total RNA extracted from tissue was deep-sequenced and analyzed for differential gene expression using DESeq2. We detected no treatment effect on milk yield or plasma metabolites through 45 d of lactation; additionally, no change in mammary epithelial cell proliferation was detected when assessed by Ki67 labeling. Comparison of SAL versus CON revealed that only 16 of 18,286 genes were differentially expressed (false discovery rate

The treatment of acne presents a major clinical and dermatological challenge. Investigating the nanomechanical properties of the microcomedone precursor lesions using atomic force microscopy (AFM) may prove beneficial in understanding their softening, dissolution and prevention. Although the exact biochemical mechanism of NaSal on microcomedones is not fully understood at present, it appears to exhibit a significant exfoliation effect on the skin via corneodesmosome dissolution.Therefore, to support this exploration, sodium salicylate (NaSal), a common ingredient employed in skin care products, is applied ex vivo to microcomedones,collected by nose strip adhesive tape, and their nanomechanical properties are assessed using AFM. Although the exact biochemical mechanism of NaSal on microcomedones is not fully understood at present, it appears to exhibit a significant exfoliation effect on the skin via corneodesmosome dissolution.Herein, our findings demonstrate that when microcomedones are treated with 2% NaSal, samples appeared significantly more compliant ('softer') ((1.3 ± 0.62) MPa) when compared to their pre-treated measurements ((7.2 ± 3.6) MPa; p = 0.038). Furthermore, elastic modulus maps showed that after 2% NaSal treatment, areas in the microcomedone appeared softer and swollen in some, but not in all areas, further proving the valuable impact of 2% NaSal solution in altering the biomechanical properties and morphologies in microcomedones.Our results are the first of their kind to provide qualitative and quantitative mechanobiological evidence that 2% NaSal decreases the elastic modulus of microcomedones. Therefore, this study provides evidence that NaSal can be beneficial as an active ingredient in topical treatments aimed at targeting microcomedones.Le traitement de l'acné présente un défi clinique et dermatologique majeur. L'étude des propriétés nanomécaniques des lésions précurseurs en tant que microcomédons à l'aide de la microscopie à force atomique (AFM) peut s'avérer bénéfique pour comprendre leur ramollissement, leur dissolution et leur prévention. MÉTHODES: Par conséquent, pour soutenir cette exploration, le salicylate de sodium (NaSal), un ingrédient couramment utilisé dans les produits de soins de la peau, est appliqué ex vivo aux microcomédons et leurs propriétés nanomécaniques sont évaluées à l'aide de l'AFM. Bien que le mécanisme biochimique exact du NaSal sur les microcomédons ne soit pas entièrement compris à l'heure actuelle, il semble présenter un effet exfoliant significatif sur la peau via la dissolution des cornéodesmosomes. RÉSULTATS: Ici, nos résultats démontrent que lorsque les microcomédons sont traités avec 2% de NaSal, les échantillons semblaient significativement plus conformes ("plus doux") ((1.3 ± 0.62) MPa) par rapport à leurs mesures pré-traitées ((7.2 ± 3.6) MPa ; P = 0,03826). De plus, les cartes du module d'élasticité ont montré qu'après un traitement à 2 % de NaSal, les zones du microcomédon semblaient plus molles et gonflées dans certaines zones, mais pas dans toutes, prouvant ainsi l'impact précieux d'une solution de NaSal à 2 % dans la modification des propriétés biomécaniques et de la morphologie des microcomédons.Nos résultats sont les premiers du genre à fournir des preuves mécanobiologiques qualitatives et quantitatives que 2% de NaSal diminue le module d'élasticité des microcomédons. Par conséquent, cette étude fournit des preuves que NaSal peut être bénéfique en tant qu'ingrédient actif dans les traitements topiques visant à cibler les microcomédons.

This work is concerned with the drag reduction using cationic surfactants. (quaternary ammonium amine-sodium salicylate)dissolved in water. Drag reduction measurements were carried out in 6.17 and 2.69 mm diameter tubes, for Reynolds numbers from 101 to 106 and for temperature range of 30o to 120o C. The influence of surfactant composition. Temperature, mechanical shear, concentration and sodium salicylate concentration on the dragreduction were investigated. Trimethyl amine salts are most effective drag reducing agents. While alkyl dimethyl ammonium amine salts are not affective. Length of alkyl group has a major affect on the upper temperature limit for drag reduction. Appreciable amount of shorter chain reduces the maximum temperature. Concentrations of 1500 ppm of quaternary ammonium amine and 1500ppm of sodium salicylate are needed for affective drag reduction for Czz amines. Cationic surfactants of this type was found to produce higher drag reduction values in the larger tube than that for non-ionic surfactants or for high polymer solutions.

Implant associated infections (IAIs) place stress on patients and burden the healthcare system, and Staphylococcus epidermidis is a common pathogen involved. This study analyzed the effects of aqueous garlic extract (AGE) and sodium salicylate (SOD SAL) on the inhibition and eradication of S. epidermidis biofilms grown on titanium to find a potential remedy for IAIs. In the inhibition assay, bacterial suspensions were incubated with titanium discs and either AGE, SOD SAL, or both. In the eradication assay, bacteria cultured on titanium were treated with the treatments. The absorbance in optical density (OD) of each sample after treatment was analyzed using a spectrophotometer. AGE inhibited >40% of biofilm growth, whereas AGE and the combination treatment eradicated 17% of bacteria. It was concluded that AGE is better at inhibiting biofilm growth, but all treatments showed the same efficacy in eradicating pre-grown biofilm. Therefore, AGE could be used to treat and prevent IAIs.

Sodium salicylate is an anti-inflammatory medication with a side-effect of tinnitus. Here, we used mouse cochlear cultures to explore the effects of salicylate treatment on cochlear inner hair cells (IHCs). We found that IHCs showed significant damage after exposure to a high concentration of salicylate. Whole-cell patch clamp recordings showed that 1–5 mmol/L salicylate did not affect the exocytosis of IHCs, indicating that IHCs are not involved in tinnitus generation by enhancing their neuronal input. Instead, salicylate induced a larger peak amplitude, a more negative half-activation voltage, and a steeper slope factor of Ca(2+) current. Using noise analysis of Ca(2+) tail currents and qRT-PCR, we further found that salicylate increased the number of Ca(2+) channels along with Ca(V)1.3 expression. All these changes could act synergistically to enhance the Ca(2+) influx into IHCs. Inhibition of intracellular Ca(2+) overload significantly attenuated IHC death after 10 mmol/L salicylate treatment. These results implicate a cellular mechanism for tinnitus generation in the peripheral auditory system.

A potential bioactive compound limonin is found in citrus fruits, especially tremendous extent in seeds. In this study, an attempt has been made to develop a novel and proficient extraction method ...

Cyclooxygenase (COX) plays a critical role in synaptic plasticity. Therefore, long-term administration of acetylsalicylic acid (ASA) and its main metabolite, salicylate, as a COX inhibitor may impair synaptic plasticity and subsequently memory formation. Although different studies have tried to explain the effects of ASA and sodium salicylate (SS) on learning and memory, the results are contradictory and the mechanisms are not exactly known. The present study was designed to investigate the effects of long-term low-dose (equivalent to prophylactic dose) and short-term high-dose (equivalent to analgesic dose) administration of ASA and SS respectively, on spatial learning and memory and hippocampal synaptic plasticity. Animals were treated with a low dose of ASA (2 mg/ml solvated in drinking water, 6 weeks) or a high dose of SS, a metabolite of ASA, (300 mg/kg, 3 days, twice-daily, i.p). Spatial memory and synaptic plasticity were assessed by water maze performance and in vivo field potential recording from CA1, respectively. Animals treated with ASA but not SS showed a significant increase in escape latency and distance moved. Furthermore, in the probe test, animals treated with both drugs spent less time in the target quadrant zone. The paired-pulse ratio (PPR) at 20-ms inter-pulse intervals (IPI) as an index of short-term plasticity in both treated groups was significantly higher than of the control group. Interestingly, none of the administered drugs affected long-term potentiation (LTP). These data suggested that long-term inhibition of COX disrupted memory acquisition and retrieval. Interestingly, cognitive impairments happened along with short-term but not long-term synaptic plasticity disturbance.

Interactions among the oppositely charged polymer and surfactant are significantly complex in comparison to the interaction between an ionic surfactant and nonionic polymer vis-a-vis the physicochemical properties of the resulting polymer–surfactant solutions. In this work, we have deliberated upon the interactions taking place in between a water-soluble anionic polymer, sodium alginate (SA), with a cationic amphiphile, hexadecylbenzyldimethylammonium chloride (C16BzCl), in absence and in presence of sodiumchloride (NaCl) and sodium salicylate (NaSl) employing tensiometric, conductometric, and rheometric measurements. The system was characterized by evaluating physicochemical properties like viscosity curves, critical aggregation concentration (cac), and critical micelle concentration (cmc) as a function of C16BzCl concentration. The results show significant differences between the ions furnished by NaCl and NaS1 which could be justified on the basis of effect of solubilization, differential binding of NaSl to polymeric backbone, electrolyte effect, and the solvent modifying tendencies in contrast to the only salt effect of NaCl.

Sodium salicylate, one of the non-steroidal anti-inflammatory drugs, is widely prescribed in the clinic, but a high dose of usage can cause hyperactivity in the central nervous system, including the hippocampus. At present, the neural mechanism underlying the induced hyperactivity is not fully understood, in particular, in the hippocampus under an in vivo condition. In this study, we found that systemic administration of sodium salicylate increased the field excitatory postsynaptic potential slope and the population spike amplitude in a dose-dependent manner in the hippocampal dentate gyrus area of rats with in vivo field potential extracellular recordings, which indicates that sodium salicylate enhances basal synaptic transmission and neural excitation. In the presence of picrotoxin, a GABA-A receptor antagonist, sodium salicylate failed to increase the initial slope of the field excitatory postsynaptic potential and the amplitude of the population spike in vivo. To further explore how sodium salicylate enhances the neural excitation, we made whole-cell patch-clamp recordings from hippocampal slices. We found that perfusion of the slice with sodium salicylate decreased electrically evoked GABA receptor-mediated currents, increased paired-pulse ratio, and lowered frequency and amplitude of miniature inhibitory postsynaptic currents. Together, these results demonstrate that sodium salicylate enhances the neural excitation through suppressing GABAergic synaptic transmission in presynaptic and postsynaptic mechanisms in the hippocampal dentate gyrus area. Our findings may help understand the side effects caused by sodium salicylate in the central nervous system.

Tinnitus is deemed as the result of abnormal neural activities in the brain, and Homer proteins are expressed in the brain that convey nociception. The expression of Homer in tinnitus has not been studied. We hypothesized that expression of Homer in the auditory cortex was altered after tinnitus treatment. Mice were injected with sodium salicylate to induce tinnitus. Expression of Homer was detected by quantitative real-time polymerase chain reaction, western blotting, and immunohistochemistry assays. We found that Homer1 expression was upregulated in the auditory cortex of mice with tinnitus, while expression of Homer2 or Homer3 exhibited no significant alteration. Effects of two inhibitors of metabolic glutamate receptor 5 (mGluR5), noncompetitive 2-Methyl-6-(phenylethynyl)-pyridine (MPEP) and competitive α-methyl-4-carboxyphenylglycine (MCPG), on the tinnitus scores of the mice and on Homer1 expression were detected. MPEP significantly reduced tinnitus scores and suppressed Homer1 expression in a concentration dependent manner. MCPG had no significant effects on tinnitus scores or Homer1 expression. In conclusion, Homer1 expression was upregulated in the auditory cortex of mice after tinnitus, and was suppressed by noncompetitive mGluR5 inhibitor MPEP, but not competitive mGluR5 inhibitor MCPG.

The roles of ethylene, jasmonic acid, and salicylic acid and their interactions in frankincense resin production in Boswellia sacra trees growing in the drylands of Oman were studied. On March 18 (Experiment 1) and September 17 (Experiment 2), 2018, 32-year-old B. sacra trees with multiple trunks were selected at the Agricultural Experiment Station, Sultan Qaboos University, Oman. Various lanolin pastes containing Ethrel, an ethylene-releasing compound; methyl jasmonate; sodium salicylate; and combinations of these compounds were applied to debarked wounds 15 mm in diameter on the trunks. After a certain period, the frankincense resin secreted from each wound was harvested and weighed. The anatomical characteristics of the resin ducts were also studied in the bark tissue near the upper end of each wound. The combination of Ethrel and methyl jasmonate greatly enhanced frankincense resin production within 7 days in both seasons. The application of methyl jasmonate alone, sodium salicylate alone or a combination of both did not affect resin production. These findings suggest a high possibility of artificial enhancement of frankincense resin production by the combined application of Ethrel and methyl jasmonate to B. sacra trees.

Urchin-like porous silica nanoparticles (UPSNs) with hierarchical dual-pore structure and tunable particle size have been synthesized by utilizing sodium salicylate (NaSal) and cetyltrimethylammoni...

Tinnitus is a common auditory disease worldwide; it is estimated that more than 10% of all individuals experience this hearing disorder during their lifetime. Tinnitus is sometimes accompanied by hearing loss. However, hearing loss is not acquired in some other tinnitus generations. In this study, we injected adult rats with salicylate sodium (SS) (200 mg/kg/day for 10 days) and found no significant hearing threshold changes at 2, 4, 8, 12, 14, 16, 20, or 24 kHz (all p>0.05). Tinnitus was confirmed in the treated rats via Behaviour Testing of Acoustic Startle Response (ASR) and Gap Prepulse Inhibition Test of Acoustic Startle Reflex (GPIAS). A immunostaining study showed that there is significant loss of anti-CtBP2 puncta (a marker of cochlear inner hair cell (HC) ribbon synapses) in treated animals in apical, middle, and basal turns (all p<0.05). The ABR wave I amplitudes were significantly reduced at 4, 8, 12, 14, 16, and 20 kHz (all p<0.05). No significant losses of outer HCs, inner HCs, or HC cilia were observed (all p>0.05). Thus, our study suggests that loss of cochlear inner HC ribbon synapse after SS exposure is a contributor to the development of tinnitus without changing hearing threshold.

We prepared two types of multidimensional gradient hydrogels by simple electrophoresis using spherical graphite electrode. To explore their application in controlled drug release, rhodamine B (RB) and sodium salicylate (SS) were used as oppositely charged drug models respectively to in situ loading into the hydrogels by electrostatic interaction with the charged components accordingly. In both cases, the model drugs and the charged components of the hydrogels were gradiently distributed with the drug concentration increased from the gel surface to the gel core. For the crosslinking gradient hydrogel prepared at 2 V, the network size near the gel surface is about 3 times that of the gel core, and the release rate is 0.85 times of that of the non-gradient hydrogel. For the polymer chain gradient hydrogel prepared at 2.5 V, the relative content of polymer chain near the core of the gel is 2.5 times that of the gel surface, and the release rate is 0.71 times of the non-gradient hydrogel.

Objective: To describe the preparation and characterization of nanoemulsion of sodium salicylate loaded butane tetracarboxylic acid (Bt-Sc-NPs). It also investigates the possible protective effects of Bt-Sc-NPs and\or medicinal plant ginger to evaluate the changes of liver functions, oxidative stress and histopathological investigations against cisplatin-induced hepatotoxicity. Methods: Serum was used to determine alanine aminotransferase (ALT), aspartate aminotransferase (AST), δ-glutamyl transferase (δGT), serum human laminin (LN) and tissue inhibitors of metalloproteinase1 (TIMP1). Liver tissue samples collected from the rats were used for the measurement of malondialdehyde (MDA), nitric oxide (NO) and paraoxonase 1 (PON1). Results: The beneficial effects of Bt-Sc-NPs with its anti-inflammatory effect and the medicinal ginger with its antioxidant effect were observed. Injection of rats with cisplatin significantly increased serum ALT, AST, ɤGT, TIMP1 and LN. It also increased cisplatin-induced oxidative stress by a significant elevation in liver MDA, NO content; however, a significant decrease of PON1 content. While protection with Bt-Sc-NPs or ginger significantly improved these parameters. In addition, combination of both Bt-Sc-NPs and ginger significantly induced a decrease in serum ALT, AST, ɤGT, TIMP1 and LN. It also reduced cisplatin-induced oxidative stress by the significant reduction in liver MDA, NO content and elevation of PON1 content much more than protection with Bt-Sc-NPs or ginger alone. Conclusion: Bt-Sc-NPs were synthesized using nanoemulsion with the help of homogenization and ultra-sonication waves. Combination with both of Bt-Sc-NPs and ginger showed a hepatoprotective role in ameliorating cisplatin‑induced hepatotoxicity due to their anti-inflammatory and antioxidant effects.

Oral squamous cell carcinoma (OSCC) is an extremely aggressive neoplasm, which is usually diagnosed in the advanced stage of the disease. Extensive studies have shown a link between chronic inflammation and various types of cancer, including OSCC. Salicylate is a biotransformation product of aspirin, with similar anti-inflammatory ability to aspirin but lacks aspirin's inhibitory effect on the isolated cyclooxygenase activity. Our study indicates that salicylate sensitizes OSCC to anti-cancer drugs, but the mechanisms of its action are unclear. Here, OSCC cells were used to evaluate the cytotoxicity of salicylate alone or in combination with cisplatin (CDDP). RPPA proteomic array and Western blotting were employed to determine the signaling pathways affected by salicylate. Salicylate decreased cell survival rate and induced cell apoptosis in OSCC cells but not human normal oral mucosal epithelial cells (hTERT-OME). The use of sodium salicylate (SS) dramatically sensitized OSCC cells to CDDP. RPPA array showed that SS reduced many oncogenes such as PI3K/mTOR signaling and cancer stem cell (CSC)-related genes versus control. Western and transcriptional analyses substantiated that salicylate down-regulated these CSC-associated genes and the mTOR pathway dose dependently. Salicylate preferentially repressed the ability of sorted ALDH1+ cells to form tumor spheres. Finally, salicylate suppressed tumor growth in vivo, and the combination of salicylate and CDDP further synergistically reduced the growth of tumors. Salicylate hinders OSCC cell growth and sensitizes OSCC cells to CDDP through targeting CSCs and the mTOR signaling pathway. We propose that salicylate is beneficial for OSCC patients, and salicylate may be combined with chemotherapies to effectively treat OSCC patients.

The aim of this study was to evaluate the analgesic and anti-inflammatory effects of the hydroalcoholic extracts of Malva sylvestris flowers or Carum carvi and Medicago sativa seeds, alone and in combination, which have been used in traditional Iranian medicine.Male Wistar rats were divided into 6 treatment groups: distilled water, sodium salicylate (SS), M. sylvestris extract (600 mg/kg), C. carvi extract (600 mg/kg), M. sativa extract (300 mg/kg) and combined extract (including 300 mg/kg M. sylvestris and C. carvi extracts, and 150 mg/kg M. sativa extract). The formalin pain model was used to evaluate the antinociceptive effects of the treatments. For anti-inflammatory effect, acute (one hour after injection) and chronic (during a week after injection) paw inflammation was measured after subcutaneous injection of 2.5% formalin in the hindpaw. Finally, tissue samples from all groups were prepared for histopathological studies.The combined extract significantly inhibited the nociception in the acute phase of the formalin test (P 0.001). In the chronic phase, all the extracts and SS had significant analgesic effect (P 0.001). Analgesic activity of the combined extract was significantly stronger than SS (P 0.01). In the acute inflammation model, M. sylvestris, C. carvi and the combined drug had significant inhibitory effects against paw edema (P 0.05). All extracts, individually and in combination, significantly alleviated chronic paw inflammation (P 0.01). The combined extract had much more anti-inflammatory activity than SS (P 0.05). Histopathological results indicated improvement and reduction of inflammatory factors in the treatment groups.M. sylvestris, C. carvi and M. sativa have analgesic and anti-inflammatory properties. Potentially, each of these extracts or a mixture of them might be a valuable alternative drug to control pain and inflammation.

Browning, a white to brown-like (beige) adipocyte conversion, offers a promising therapeutic strategy for the treatment of human obesity. In the present study, the effects of sodium salicylate, a nonsteroidal anti-inflammatory drug, on adipocyte browning were investigated. We found sodium salicylate altered the macrophage phenotype to M2 in RAW264.7 cells, mediated by up-regulation of heme oxygenase-1 (HO-1), and sodium salicylate-treated conditioned medium from macrophages (Sal-M2 CM) induced browning of fully differentiated 3T3-L1 adipocytes. Conversely, the conditioned medium obtained from macrophages when treated with sodium salicylate in the presence of either ZnPP (a HO-1 inhibitor) or HO-1 siRNA did not induce browning. In association with macrophage HO-1 induction by sodium salicylate, iron production also increased, and deferoxamine (an iron chelator) blunted the browning effects of Sal-M2 CM, suggesting that iron may play a role in the Sal-M2 CM-induced browning. The in vivo browning effects of sodium salicylate were confirmed in ob/ob mice, whereas in vivo macrophage depletion by clodronate as well as HO-1 blockade by either ZnPP or adeno-associated virus carrying HO-1 shRNA (AAV-HO-1 shRNA) attenuated the browning effects of sodium salicylate. These results reveal sodium salicylate induces browning in vitro and in vivo by up-regulating HO-1 thus promoting M2 polarization.

This study aimed to investigate the effectiveness of curcumin (CCM) against gentamicin (GEN) and sodium salicylates (NaS)-induced ototoxic effects in rats. For 15 consecutive days, seven rat groups were given 1 mL/rat physiological saline orally, 1 mL/rat olive oil orally, 50 mg/kg bwt CCM orally, 120 mg/kg bwt GEN intraperitoneally, 300 mg/kg bwt NaS intraperitoneally, CCM+GEN, or CCM+NaS. The distortion product otoacoustic emission measurements were conducted. The rats' hearing function and balance have been behaviorally assessed using auditory startle response, Preyer reflex, and beam balance scale tests. The serum lipid peroxidation and oxidative stress biomarkers have been measured. Immunohistochemical investigations of the apoptotic marker caspase-3 and the inflammatory indicator nuclear factor kappa (NF-κB) in cochlear tissues were conducted. GEN and NaS exposure resulted in deficit hearing and impaired ability to retain balance. GEN and NaS exposure significantly decreased the reduced glutathione level and catalase activity but increased malondialdehyde content. GEN and NaS exposure evoked pathological alterations in cochlear and vestibular tissues and increased caspase-3 and NF-κB immunoexpression. CCM significantly counteracted the GEN and NaS injurious effects. These outcomes concluded that CCM could be a naturally efficient therapeutic agent against GEN and NaS-associated ototoxic side effects.

Introduction High-fat diet (HFD)-induced obesity impairs clearance of cholesterol through the Reverse Cholesterol Transport (RCT) pathway, with downregulation in hepatic expression of cholesterol and bile acid transporters, namely ABCG5/8 and ABCB11, and reduced high-density lipoprotein (HDL) cholesterol efflux capacity (CEC). In the current study, we hypothesized that the development of hepatosteatosis, secondary to adipose-tissue dysfunction, contributes to obesity-impaired RCT and that such effects could be mitigated using the anti-inflammatory drug sodium salicylate (NaS). Materials and methods C57BL/6J mice, fed HFD ± NaS or low-fat diet (LFD) for 24 weeks, underwent glucose and insulin tolerance testing. The 3H-cholesterol movement from macrophage-to-feces was assessed in vivo. HDL-CEC was determined ex vivo. Cytokine secretion from adipose-derived stromal vascular fraction (SVF) cells was measured ex vivo. Liver and HDL proteins were determined by mass spectrometry and analyzed using Ingenuity Pathway Analysis. Results NaS delayed HFD-induced weight gain, abrogated priming of pro-IL-1β in SVFs, attenuated insulin resistance, and prevented steatohepatitis (ectopic fat accumulation in the liver). Prevention of hepatosteatosis coincided with increased expression of PPAR-alpha/beta-oxidation proteins with NaS and reduced expression of LXR/RXR-induced proteins including apolipoproteins. The latter effects were mirrored within the HDL proteome in circulation. Despite remarkable protection shown against steatosis, HFD-induced hypercholesterolemia and repression of the liver-to-bile cholesterol transporter, ABCG5/8, could not be rescued with NaS. Discussions and conclusions The cardiometabolic health benefits of NaS may be attributed to the reprogramming of hepatic metabolic pathways to increase fatty acid utilization in the settings of nutritional overabundance. Reduced hepatic cholesterol levels, coupled with reduced LXR/RXR-induced proteins, may underlie the lack of rescue of ABCG5/8 expression with NaS. This remarkable protection against HFD-induced hepatosteatosis did not translate to improvements in cholesterol homeostasis., Graphical abstract Image 1, Highlights • Sodium salicylate (NaS) initially delays weight-gain in mice fed high-fat diet (HFD) - catch-up evident in weeks 12–24. • NaS prevents HFD-induced insulin resistance, hepatosteatosis and pro-IL-1β priming in adipose tissue even upon weight-gain. • Hepatic expression of proteins involved in beta oxidation, oxidative phosphorylation and TCA cycle upregulated with NaS. • Hepatic expression of LXR/RXR proteins eg. apolipoproteins reduced with NaS; these effects were mirrored in HDL proteome. • NaS failed to improve HFD-impaired Reverse Cholesterol Transport or hypercholesterolemia despite preventing hepatosteatosis.

Ketoprofen used as a Non-steroidal anti-inflammatory drug selected as a poorly water-soluble model drug. Due to the poorly soluble nature of Ketoprofen liberate reduced bioavailability. Hydrotropic solubilization technique is a promising technique used to improve the solubility of water-insoluble drugs. In this investigation, 2M sodium salicylate has been employed in the titrimetric estimation of Ketoprofen and shows synergistic enhancement in the solubility of Ketoprofen by many folds as compared to the distilled water. It excluded the use of various organic solvent like ethanol; methanol and chloroform widely utilized in the titrimetric estimation of various poorly soluble drugs but due to the higher cost, volatility, toxicities lead to environmental pollution hence are the cons of it. The proposed method is new, simple, precise, and inexpensive. The results of the analysis have been validated statistically. The mean % recoveries were found to be close to 100, indicating the accuracy of the proposed method. Low values of standard deviation, % coefficient of variation, and standard error further proved the reproducibility and precision of the proposed method.

The interaction between sodium salicylate (NaSal) and the two macrocycles 5,11,17,23-tetrakissulfonatomethylene-2,8,14,20-tetra(ethyl)resorcinarene (Na4EtRA) and β-cyclodextrin (β-CD) has been studied by the determination of ternary mutual diffusion coefficients, and spectroscopic and computational techniques. The results obtained by the Job method suggest that the complex formation is given in a 1:1 ratio for all systems. The mutual diffusion coefficients and the computational experiments have shown that the β-CD-NaSal system presents an inclusion process, whereas the Na4EtRA-NaSal system forms an outer-side complex. This fact is also in line with the results obtained from the computational experiments, where the calculated solvation free energy has been found to be more negative for the Na4EtRA-NaSal complex because of the partial entry of the drug inside the Na4EtRA cavity.

To meet the current demand of assisted reproduction and animal breeding via superovulation and reduce the impact of hormone drugs, it is necessary to develop new superovulation drugs. This study examined the role of inflammation and steroids in ovulation. Sodium salicylate can regulate inflammation and steroids. However, the effect of sodium salicylate on ovulation has not been studied. In this study, mice were intraperitoneally injected with different concentrations of sodium salicylate for four consecutive days. The effects of sodium salicylate on oocyte quality and on the number of ovulations were examined, and these effects were compared with those of pregnant horse serum gonadotropin (PMSG)/follicle-stimulating hormone (FSH) treatment. We found that low-dose sodium salicylate increased the levels of ovulation hormones and inflammation by promoting the expression of CYP17A1. Sodium salicylate had the same effect as the commonly used superovulation drug PMSG/FSH and reduced the histone methylation level. Sodium salicylate can promote ovulation in mice and Awang sheep. It can greatly decrease the use of hormone drugs, reduce breeding costs and physical impacts, and can thus be used for livestock breeding.

A natural compound of marine herbal origin has been used in Persian Traditional Medicine to relieve some symptoms of multiple sclerosis. The present study investigated the anti-inflammatory effects of a patented extracts of the traditional receipt (MS14). In this preliminary experiment, we used seven groups of six rats: the control group received vehicle, the two positive control groups were treated with either sodium salicylate (300 mg/kg) intraperitoneal (i.p.) or methyl prednisolon (MPN 10 mg/kg) i.p., while the test groups were treated with a solution centrifuged MS14 (SANT 100 mg/kg) and suspension of MS14 (SUSP 100, 150, 300 mg/kg) i.p. After thirty minutes, paw volume was measured by plethysmometer and immediately formalin solution was injected subcutaneously into the hind paw and after an hour, inflamed paw volume was measured. In days 2-8, the inflamed paw volume was measured and immediately drugs were injected i.p. The anti-inflammatory effect of MPN was significant only on days 5 and 6. The anti-inflammatory effect of SS was significant only on the 6th day, while the anti-inflammatory effect of SANT MS14 (100 mg/kg) was also significant only on the 6th day. SUSP MS14 (150 mg/kg) significantly reduced edema from second to 6th day. Intra-peritoneal injection of SUSP MS14 with 300 mg/kg was toxic, so excluded from the study. This research indicates that the MS14 possesses an anti-inflammatory effect after intra-peritoneal administration. Comparative anti-inflammatory effects of MS14 with Glucocorticoids in this study, may justify a possible mechanism for its action in multiple sclerosis, if further studies will provid strong statistically confirmatory effects in animals and safety human trials.

A study on the hydrotropic solubility and linearity profile of Apixaban was carried out by using Sodium Salicylate as the solubilizing agent as Apixaban is poorly soluble in water. Apixaban was freely soluble in water when 1.5M Sodium Salicylate was used as a solubilizing agent. Apixaban shows an absorption maximum at 318nm in First derivative mode of measurement using Shimadzu UV Spectrophotometer 1800 Spectronic model. At this absorption maximum of 318nm, Apixaban shows a linear response in the range of 2μg/ml to 14μg/ml concentration. The present study is useful for the aqueous solubilization and quantitative determination of Apixaban in bulk drug and in pharmaceutical formulations thus avoiding toxic solvents.

White root rot caused by Dematophora necatrix Hartig is one of the most devastating soil borne diseases attacking apple plants worldwide. In the present investigation, a pot experiment was conducted during 2016 at Model research Farm of Dr. YS Parmar university of Horticulture and Forestry Solan (H.P.) to evaluate the effect of induced resistance (IR) chemicals viz., salicylic acid, benzothiadiazole-s-methyl ester, potassium oxalate, β-amino butyric acid, calcium carbonate, sodium salicylate and di-potassium hydrogen orthophosphate against white root rot pathogen. These inducers were assayed at 0, 7, 14 and 21 days of pathogen inoculation. The results revealed that the salicylic acid treated apple seedlings developed highest amount of total phenol (493.13μg/g) which was followed by benzothiadiazole-s-methyl ester (451.80μg/g) and β-aminobutyric acid (422.60μg/g) respectively. While the lowest amount of total phenol was recorded in calcium carbonate (296.27μg/g). However, the maximum increase in polyphenol activity in terms of change in absorbance min-1 g-1 fresh weight of leaf (0.601) was recorded in salicylic acid treated apple seedlings followed by benzothiadiazole-s-methyl ester (0.551) and β-aminobutyric acid (0.505). The study likewise in polyphenol oxidase also revealed the effectiveness of salicylic acid in enhancing the peroxidase activity being highest in salicylic acid (0.703) followed by benzothiadiazole-s-methyl ester (0.643) and β-aminobutyric acid (0.609) respectively. However, the least activity was registered in calcium carbonate (0.366). In similar trends, highest PAL activity in terms of change in absorbance min-1 g-1 fresh weight of leaf was registered in salicylic acid treated seedlings (0.942) followed by benzothiadiazole-s-methyl ester (0.880) and β-aminobutyric acid (0.820). While least PAL activity was observed in treatment with (0.450). The salicylic acid estimation was also conducted and was found higher in benzothiadiazole-s-methyl ester (57.07μg/g) followed by β-aminobutyric acid (51.87 μg/g) respectively. Interestingly, it was found that irrespective of sampling intervals, maximum content of above tested biochemical parameters was noticed at 7th days followed by 14th days of pathogen inoculation. Our findings suggest that enhancing resistance in apple seedlings before infection could be an innovative, safe and alternative control method against white root rot of apple.

The focus of the current research is to evaluate the adsorption mechanisms of sodium salicylate and metronidazole on the polyaniline (PANi) using density functional theory (DFT) at B3LYP/6-31G(d) level of theory. The molecular electrostatic potentials of sodium salicylate, metronidazole and PANi were calculated. The theoretical data show that the oxygenated functional groups of adsorbates and amino groups of PANi are the nucleophilic and electrophilic attack sites, respectively. The structural, electronic and energetic properties of PANi complexed with sodium salicylate and metronidazole were investigated. The adsorption mechanism is due to the formation of hydrogen bond between polymer and adsorbate molecules. The low intermolecular electron transfer at solute/solid interface reveals that the sodium salicylate and metronidazole are physisorbed onto the PANi. In addition, the interaction energies between PANi and adsorbate molecules suggest the stability of the formed complexes, indicating a good adsorbate-adsorbent affinity. All quantum chemical data are in good agreement with the experimental observations.

The objective of this research was to interpret the drying behaviour of hydrated hydroxypropyl cellulose (HPC) types HF, MF, LF and their blends (1:1 w/w) composed of drugs with low solubility as salicylic acid and high solubility as sodium salicylate. Polysaccharides differed significantly in their molecular mass and viscosity. The evaporation measurements were carried out using differential scanning calorimetry. The dry mass normalized dependency of vaporization enthalpy (ΔH) and respective contents of water Wc (water fraction in the dry mass of sample) ΔH = f(Wc) were linear. The sought values of water associated with the evaporation process (Nev) were calculated after extrapolation ΔH to 0. The obtained data confirmed earlier results that Nev values are not directly related to molecular weight of the polymer, because they were equal to 0.11 g g−1 for all raw types of HPC. Poorly soluble salicylic acid slightly increased the Nev content to 0.11–0.15 g g−1. A higher increase in the Nev content was observed for matrices composed of sodium salicylate and was ranging from 0.16 to 0.27 g g−1. For all types of raw HPC, it was concluded that beside the non-freezing water bound to sorption sites, there is a part of water restricted in temporary pores. In the case of studied mixtures, the non-freezing water consists mostly of water molecules interacting with sorption sites not trapped in pores. A slightly higher content of Nev calculated for HPC and sodium salicylate mixtures could be explained by the fact of stronger interaction between the dissociated ion pair of sodium salicylate and water molecules.

Fusarium head blight caused by the hemibiotrophic fungus Fusarium graminearum is one of the most devastating diseases of wheat which reduces both grain yield and quality. To better understand mechanism underlying wheat resistance to this pathogen, the expressions of five candidate genes encoding phenylalanine ammonia-lyase (PAL), glucanase-2 (Gl 2), class IV chitinase (Cht-4), cytochrome P450 (CYP), and pleiotropic drug resistance (PDR) following spike inoculation with F. graminearum was compared in susceptible cv. Falat and resistant cv. Sumai3 at three time points (48, 96, 144 h after inoculation). Real-time quantitative PCR analysis indicated earlier and greater inductions of PAL, Glu-2, and Cht-4 in spikes of 'Sumai3' as compared to 'Falat' in response to F. graminearum inoculation. The expression of CYP in the resistant 'Sumai3' was about three times higher than in 'Falat' at 144 h after pathogen inoculation. Moreover, soil drench application of sodium salicylate (SA) one day before pathogen inoculation drastically curtailed pathogen infection in both the cultivars. Furthermore, SA treatment caused an induction of these genes in spikes of the susceptible cultivar to show a similar pattern as in the resistant one when inoculated with F. graminearum. Proteomics analysis of F. graminearum treated spikes 96 h after inoculation confirmed an increase of Glu and Cht spot volume in 'Sumai3' whereas a decrease in 'Falat'. The SA treatment also caused significant increases in Glu and Cht spot volumes in both the cultivars. Our findings show an association between SA improvement of wheat defense against F. graminearum infection and induction of genes encoding proteins involved in pathogen response (Glu-2, Cht-4), secondary metabolite biosyntheses (PAL), and xenobiotic detoxification (CYP and PDR).

Background Aspirin-exacerbated respiratory disease (AERD) is characterized by severe, sometimes life-threatening reactions to nonsteroidal anti-inflammatory drugs (NSAIDs). Mechanisms driving the disease include overproduction of leukotrienes and loss of anti-inflammatory prostaglandin E2 (PGE2) production. Many cell types contribute to the disease; however, eosinophils are markedly elevated and are important drivers of pathologic findings. Objective To investigate the capacity of aspirin and NSAIDs to drive eosinophil activation and the ability of PGE2 to inhibit this activation. Methods Eosinophils were purified from blood of healthy individuals without AERD and stimulated with lysine aspirin, ketorolac, or sodium salicylate. The role of PGE2 in altering activation was determined by incubating eosinophils with increasing doses of PGE2 before lysine aspirin stimulation. Specific PGE2 receptor use was determined by incubating eosinophils with receptor agonists and antagonists before aspirin stimulation. Cysteinyl leukotrienes (CysLTs), leukotriene B4 (LTB4), and eosinophil-derived neurotoxin (EDN) were quantified by enzyme-linked immunosorbent assay. Results Stimulation of eosinophils with lysine aspirin, ketorolac, or sodium salicylate resulted in secretion of CysLTs and LTB4 in the absence of EDN release. Low doses of PGE2 inhibited LTB4 and CysLT release, an effect lost at higher PGE2 concentrations. Use of butaprost, an EP2 receptor agonist, suppressed lysine aspirin stimulation. This mechanism was supported by blocking activity of the EP1 and EP3 receptors. Conclusion Eosinophils can be directly activated by NSAIDs via cyclooxygenase-independent pathways to produce CysLTs and LTB4. This effect can be inhibited by PGE2 acting through the EP2 receptor. The recognized loss of EP2 receptor expression combined with low PGE2 levels explains in part the sensitivity to NSAIDs.

Taylor dispersion is used to measure the binary mutual diffusion coefficient (D) of aqueous solutions of sodium salicylate (NaSal), a non-steroidal anti-inflammatory drug (NSAID). The D° value estimated by extrapolation to zero NaSal concentration is used to calculate the limiting mobility of the Sal− ion for comparison with the value determined previously from conductivity data. Salt effects on NSAID diffusion are studied by measuring the ternary mutual diffusion coefficients (Dik) of aqueous NaSal(C1) + NaCl(C2) solutions, including results for the diffusion of NaSal in physiological saline solutions with C2 = 0.15 mol dm−3. As the NaCl:NaSal ratio increases, NaSal diffusion coefficient D11 changes from the binary diffusion coefficient of aqueous NaSal (a weighted average of the Na+ and Sal− diffusion coefficients) to the tracer diffusion coefficient of the Sal− ion in NaCl solutions. Coupled diffusion in the solutions is analysed by using Nernst-Planck equations to calculate the fluxes of ions migrating in the electric field (diffusion potential) generated by NaSal and NaCl concentration gradients.

Objectives Sodium salicylate (SS) is well known for its ototoxic properties that induce functional and morphological changes in the cochlea and brain. Ginkgo biloba extract (GBE) has been widely used for treatment of various neurodegenerative diseases; however, its effects on salicylate-induced ototoxicity remain unclear. Herein, we examined the effects of EGb 761 (EGb), a standard form of GBE, on the plasticity of the N-methyl-D-aspartate receptor subunit 2B (GluN2B) in the inferior colliculus (IC) following SS administration. Methods Seven-week-old Sprague Dawley rats (n=24) were randomly allocated to control, SS, EGb, and EGb+SS groups. The SS group received a single intraperitoneal SS injection (350 mg/kg), the EGb group received EGb orally for 5 consecutive days (40 mg/kg), and the EGb+SS group received EGb for 5 consecutive days, followed by an SS injection. The auditory brainstem responses (ABRs) were assessed at baseline and 2 hours after SS administration. GluN2B expression was examined by Western blot and immunohistochemistry. Results There were no significant differences in ABR threshold shifts among the groups. The expression of the GluN2B protein normalized by which of glyceraldehyde 3-phosphate dehydrogenase (GAPDH) was significantly lower in the EGb+SS group, as compared to the SS group (P=0.012). Weak and diffused GluN2B immunoreactivity was detected in the IC neural cells of the EGb+SS group, while those of the SS group exhibited strong and diffused GluN2B positivity. Conclusion EGb may play a role in regulating the GluN2B expression in the IC of salicylate-induced ototoxicity model.

The present study was examined the antioxidant effect of tamoxifen, a synthetic non-steroidal antiestrogen, on cromakalim or nicorandil (ATP-sensitive K+ (KATP) channels opener)-enhanced hydroxyl radical ( OH) generation induced by 1-methyl-4-phenylpyridinium ion (MPP+) in extracellular fluid of rat striatum. Rats were anesthetized, and sodium salicylate in Ringer's solution (0.5 mM or 0.5 nmol/µl/min) was infused through a microdialysis probe to detect the generation of OH as reflected by the non-enzymatic formation of 2,3-dihydroxybenzoic acid (DHBA) in the striatum. Cromakalim (100 µM) or nicorandil (1 mM) enhanced the formation of OH trapped as DHBA induced by MPP+ (5 mM). Concomitantly, these drugs enhanced dopamine (DA) efflux induced by MPP+. Tamoxifen (30 µM) significantly decreased the level of DA enhanced by cromakalim or nicorandil. Tamoxifen suppressed DHBA formation induced by MPP+ and cromakalim or nicorandil. When iron(II) was administered to cromakalim treated animals, a marked elevation of DHBA was observed, compared with the tamoxifen-treated rats These results indicated that the effects of tamoxifen on opening of KATP channels enhances OH generation in the extracellular space of striatum during of DA release by MPP+. These results indicated that estrogen protects against neuronal degeneration by as an anti-oxidant.

The purpose of this study was to observe the regulatory effects of GABAA (γ-aminobutyric acid A) receptor on the N-methyl-D-aspartate (NMDA) receptor during excitotoxicity in spiral ganglion neurons in the rat cochlea induced by sodium salicylate (SS). Western blot illustrated SS decreased the expression of NMDA receptor 2B subunit (NR2B) surface protein through affecting GABAA receptor, but the total protein content did not significantly change. Y1472 and S1480 are important phosphorylation sites in NR2B, SS downregulated the Fyn-dependent phosphorylation of Y1472 in a manner not related to the CK2 (Casein Kinase 2) dependent phosphorylation of S1480, thus regulating the surface distribution and internalization of NMDA receptor through GABAA receptor. These results suggest that the modified pattern of dynamic balance between excitation and inhibition by coactivation of the GABAA receptor can attenuate the excitatory NMDA receptor under the action of SS, via inhibiting the Fyn-dependent phosphorylation of Y1472.

The effect of sodium salicylate (NaSal) on the spherical-to-threadlike micelle shape transition in 3-hexadecyloxy-2-hydroxy-propyl trimethyl ammonium bromide (R16HTAB) solution was studied using mo...

Purpose: Cardamom seeds are widely used for flavoring purposes in food and also as carminative. We aimed to assess the analgesic effect of cardamom seed extract in mice. Methods: In this experimental study, we used hydro-alcoholic extract of cardamom. The effect of extract on acute pain was evaluated by formalin (early phase) and tail flick tests. The effect of extract on chronic pain was studied by formalin (second phase) test. Significant findings: In the formalin test, intra peritoneal injection of cardamom at dose of 300 mg/kg showed significant analgesic effect on early phase (acute pain) in mice. Cardamom 200 and 300 mg/kg exhibited analgesic activity against second phase (chronic pain) of formalin test. Also, cardamom 200 and 300 mg/kg exhibited anti-nociceptive effect on tail flick test. Sodium salicylate (300 mg/kg) only affected on second phase of formalin test that its effect was better than that of cardamom 300 mg/kg. Conclusion: According to our results, cardamom seeds have analgesic effect on acute and chronic pain that may be attributed to tripnoids component in this plant.

Electrophysiological and imaging studies from humans suggest that the phantom sound of tinnitus is associated with abnormal thalamocortical neural oscillations (dysrhythmia) and enhanced gamma band activity in the auditory cortex. However, these models have seldom been tested in animal models where it is possible to simultaneously assess the neural oscillatory activity within and between the thalamus and auditory cortex. To explore this issue, we used multichannel electrodes to examine the oscillatory behavior of local field potentials recorded in the rat medial geniculate body (MBG) and primary auditory cortex (A1) before and after administering a dose of sodium salicylate (SS) that reliably induces tinnitus. In the MGB, SS reduced theta, alpha, and beta oscillations and decreased coherence (synchrony) between electrode pairs in theta, alpha, and beta bands but increased coherence in the gamma band. Within A1, SS significantly increased gamma oscillations, decreased theta power, and decreased coherence between electrode pairs in theta and alpha bands but increased coherence in the gamma band. When coherence was measured between one electrode in the MGB and another in A1, SS decreased coherence in beta, alpha, and theta bands but increased coherence in the gamma band. SS also increased cross-frequency coupling between the phase of theta oscillations in the MGB and amplitude of gamma oscillations in A1. Altogether, our results suggest that SS treatment fundamentally alters the manner in which thalamocortical circuits communicate, leading to excessive cortical gamma power and synchronization, neurophysiological changes implicated in tinnitus. Our data provide support for elements of both the thalamocortical dysrhythmia (TD) and synchronization by loss of inhibition (SLIM) models of tinnitus, demonstrating that increased cortical gamma band activity is associated with both enhanced theta-gamma coupling as well as decreases alpha power/coherence between the MGB and A1. NEW & NOTEWORTHY There are no effective drugs to alleviate the phantom sound of tinnitus because the physiological mechanisms leading to its generation are poorly understood. Neural models of tinnitus suggest that it arises from abnormal thalamocortical oscillations, but these models have not been extensively tested. This article identifies abnormal thalamocortical oscillations in a drug-induced tinnitus model. Our findings open up new avenues of research to investigate whether cellular mechanisms underlying thalamocortical oscillations are causally linked to tinnitus.

The present study analyzed experimental data from volumetric and viscosimetric measurements and computational simulations to understand caffeine hydration and aggregation properties in 0.1 mol∙kg−1 of sodium salicylate aqueous solution. Sodium salicylate reduces the bitter taste and increases the solubility of caffeine in water, which is the main reason for their combination in food products. The results noted in volumetric and viscosimetric measurements indicate that sodium salicylate promotes the self-aggregation of caffeine in water. After self-aggregation, the hydration number of caffeine significantly increases. Molecular simulations have allowed us to hypothesize how salicylate increases caffeine solubility. At the molecular level, relocating salicylate moiety from the parallel stacking (π–π) aromatic complex with caffeine and its hydration could be the main reason for increasing the solubility of caffeine in water. The presented study provides clear guidelines on the choice of additives to increase caffeine’s solubility in aqueous media. The choice of salicylate as an additive to increase the solubility of caffeine is very important because caffeine and salicylate are found in combination in a large number of formulations.

Intra organ of Corti (OC) vibrations differ from those measured at the basilar membrane (BM), with higher amplitudes and a wide-band nonlinearity extending well below a region’s best frequency. The vibrations are boosted by the cochlear amplifier, the active processes within the mammalian hearing organ, and are thus sensitive to metabolic or pharmacological manipulation. We introduced salicylate, a known blocker of outer hair cell (OHC) based electromotility, into the perilymphatic space by applying sodium salicylate onto the round window membrane. Vibration patterns of an area of the OC were mapped with phase sensitive optical coherence tomography before and after treatment; distortion product otoacoustic emissions (DPOAEs) were measured at similar times to assess the cochlear condition. Following treatment, all regions showed a loss of vibration amplitude and tuning while OHC-region vibrations retained their wide-band nonlinearity. OC vibrations, which had been relatively confined in a region including OHCs and extending to the BM at the outer pillar foot, became less confined with structures lateral to the OHCs sometimes exhibiting the highest amplitudes. Vibrations and DPOAEs could recover to baseline levels over approximately three hours post treatment. This article is part of the Special Issue Outer hair cell Edited by Joseph Santos-Sacchi and Kumar Navaratnam

Solubility, extraction and stabilization of curcumin extracted from Curcuma longa are still a challenge. Either the solubility power of the extracting solvent mixture is not at its optimum or non-sustainable solvents are used or the curcumin instability against oxidation is a problem. In order to tackle these problems, we consider here a promising alternative solvent medium, which is a ternary system composed of water/sodium salicylate (an anionic, preservative hydrotrope)/ethyl acetate. The effects of the structuring of the system are also studied. The position of the new critical point and the orientation of tie-lines in the liquid/liquid area were determined and further examined via interfacial tension and diffusion ordered spectroscopy (DOSY NMR) measurements. The critical point between the mono-phasic region and the liquid/liquid area is a classical one, around which no special nano-structuring is found, in contrast to some other ternary mixtures with hydrotropes. The system was investigated in terms of its curcumin solubility and its extraction power thereof. Good extraction yields (~90% of the Soxhlet reference) could be achieved in the area of best solubility. Surprisingly, the hydrophobic curcumin shows a significant solubility in systems that contain a significant amount of water in presence of sodium salicylate. These mixtures are far from the critical point but show significant structuring. The solubility is even higher than in pure ethyl acetate. At the point of highest solubility (water/sodium salicylate/ethyl acetate 7/13/80 w/w/w) 15.48 mg of curcuminoids per g Curcuma longa are successfully extracted. The partition coefficient in the lower liquid/liquid two-phasic region was determined for a subsequent purification of curcumin by precipitation. Surprisingly, curcumin accumulates at the “oil-water” interface in the more polar phase. Sodium salicylate could be removed from the precipitated curcumin by washing it with water (no trace of sodium salicylate has been detected with NMR after the washing process). The preservative effect of salicylate against the oxidative effect of light on curcumin was found to be significant. A better stabilization of curcumin was observed far away from the critical point and was most efficient in the region, where aggregates could be detected. So, extraction, solubilization, and chemical stabilization of a light sensitive substance could be performed using an anti-oxidative hydrotrope.

Background Hua-Zhuo-Jie-Du (HZJD), a Chinese herbal prescription consisting of 11 herbs, is commonly used in China to treat chronic atrophic gastritis (CAG). We aimed to determine the effect of HZJD on the microbiome-associated metabolic changes in CAG rats. Methods The CAG rat models were induced by 1-methyl-3-nitro-1-nitrosoguanidine (MNNG) combined with irregular fasting and 2% sodium salicylate, which was intragastrically administrated in fasted animals for 24 weeks. The CAG rats in the Chinese medicine (CM) group were administered a daily dose of 14.81 g/kg/day HZJD, and the vitacoenzyme (V) group were administered a daily dose of 0.08 g/kg/day vitacoenzyme. All animals were treated for 10 consecutive weeks, consecutively. Hematoxylin and eosin (H&E) staining was used to assess the histopathological changes in the gastric tissues. An integrated approach based on liquid chromatograph mass spectrometer (LC-MS) metabolic profiling combined with 16S rRNA gene sequencing was carried out to assess the effects of HZJD on CAG rats. Spearman analysis was used to calculate the correlation coefficient between the different intestinal microbiota and the metabolites. Results The H&E results indicated that HZJD could improve the pathological condition of CAG rats. The LC–MS results indicated that HZJD could significantly improve 21 gastric mucosal tissue perturbed metabolites in CAG rats; the affected metabolites were found to be involved in multiple metabolic pathways, such as the central carbon metabolism in cancer. The results of 16S rRNA gene sequencing indicated that HZJD could regulate the diversity, microbial composition, and abundance of the intestinal microbiota of CAG rats. Following HZJD treatment, the relative abundance of Turicibacter was increased, and the relative abundance of Desulfococcus and Escherichia were decreased in the CM group when compared with the M group. Spearman analysis revealed that perturbed intestinal microbes had a strong correlation with differential metabolites, Escherichia exhibited a negative correlation with l-Leucine, Turicibacter was negatively correlated with urea, and Desulfococcus exhibited a positive correlation with trimethylamine, and a negative correlation with choline. Conclusions HZJD could protect CAG by regulating intestinal microbiota and its metabolites.

HYPOTHESIS The anterior cingulate cortex (ACC) participates in sodium salicylate (SS)-induced tinnitus through alteration of the disordered neural activity and modulates the neuronal changes in the auditory cortex (AC). BACKGROUND Although the mechanism underlying tinnitus remains unclear, the crucial roles of the auditory center and limbic system in this process have been elucidated. Recent reports suggest that dysfunction of the ACC, an important component of the limbic system that regulates and controls the conduction of multiple sensations, is involved in tinnitus. Although altered functional connectivity between the ACC and the auditory system has been observed in humans with tinnitus, the underlying neuronal mechanism remains unexplored. METHODS SS (350 mg/kg, 10%, i.p.) was used to yield tinnitus model in rats, followed by comparison of the alteration in the spontaneous firing rate (SFR), local field potential (LFP), and extracellular glutamic acid in the ACC. The responses of neurons in the AC to electrical stimulation from the ACC were also observed. RESULTS We determined significant increases in the neuronal SFR and extracellular glutamate level in the ACC after SS injection (p

Diffusion studies using nuclear magnetic resonance (NMR) spectroscopy were conducted on two model surfactant solutions of cetyltrimethylammonium bromide/sodium salicylate (CTAB/NaSal) and cetylpyridinium chloride/sodium salicylate (CPCl/NaSal). By increasing the salt-to-surfactant concentration ratio, these systems display two peaks in the zero-shear viscosity and relaxation time, which are indicative of transitions from linear to branched micellar networks. The goal of this work is to assess the sensitivity of NMR diffusometry to different types of micellar microstructures and identify the mechanism(s) of surfactant self-diffusion in micellar solutions. At low salt-to-surfactant concentration ratios, for which wormlike micelles are linear, the surfactant self-diffusion is best described by a mean squared displacement, Z(2), that varies as Z(2) ∝ T(diff)(0.5), where T(diff) is the diffusion time. As the salt concentration increases to establish branched micelles, Z(2) ∝ T(diff), indicating a Brownian-like self-diffusion of surfactant molecules in branched micelles. This result indicates that NMR diffusometry is capable of differentiating various types of micellar microstructure. In addition, the self-diffusion coefficient of the surfactant molecules in linear and branched micelles are determined, for the first time, by comparing to the existing restricted diffusion models, and shown to be much slower than the diffusion of proton molecules in the bulk. Moreover, in linear and moderately branched wormlike micelles, the dominant mechanism of surfactant self-diffusion is through the curvilinear diffusion of the surfactant molecules along the contour length of the micelles, whereas in the branched micelles, before the second viscosity maxima, the surfactant self-diffusion could arise from a combination of micellar breakage, exchange between micelles and/or the bulk.

Sodium salicylate (SA), a cyclooxygenase inhibitor, has been shown to increase insulin sensitivity and to suppress inflammation in obese patients and animal models. Transient receptor potential vanilloid 1 (TRPV1) is a nonselective cation channel expressed in afferent nerve fibers. Cyclooxygenase-derived prostaglandins are involved in the activation and sensitization of TRPV1. This study tested whether the metabolic and renal effects of SA were mediated by the TRPV1 channel. Wild-type (WT) and TRPV1−/− mice were fed a Western diet (WD) for 4 months and received SA infusion (120mg/kg/day) or vehicle for the last 4 weeks of WD feeding. SA treatment significantly increased blood pressure in WD-fed TRPV1−/− mice (p &lt, 0.05) but not in WD-fed WT mice. Similarly, SA impaired renal blood flow in TRPV1−/− mice (p &lt, 0.05) but not in WT mice. SA improved insulin and glucose tolerance in both WT and TRPV1−/− mice on WD (all p &lt, 0.05). In addition, SA reduced renal p65 and urinary prostaglandin E2, prostaglandin F1α, and interleukin-6 in both WT and TRPV1−/− mice (all p &lt, 0.05). SA decreased urine noradrenaline levels, increased afferent renal nerve activity, and improved baroreflex sensitivity in WT mice (all p &lt, 0.05) but not in TRPV1−/− mice. Importantly, SA increased serum creatinine and urine kidney injury molecule-1 levels and decreased the glomerular filtration rate in obese WT mice (all p &lt, 0.05), and these detrimental effects were significantly exacerbated in obese TRPV1−/− mice (all p &lt, 0.05). Lastly, SA treatment increased urine albumin levels in TRPV1−/− mice (p &lt, 0.05) but not in WT mice. Taken together, SA-elicited metabolic benefits and anti-inflammatory effects are independent of TRPV1, while SA-induced sympathetic suppression is dependent on TRPV1 channels. SA-induced renal dysfunction is dependent on intact TRPV1 channels. These findings suggest that SA needs to be cautiously used in patients with obesity or diabetes, as SA-induced renal dysfunction may be exacerbated due to impaired TRPV1 in obese and diabetic patients.