Water Mediated One-Pot, Stepwise Green Synthesis, Anti-Inflammatory and Analgesic Activities of (3-Amino-1-Phenyl-1H-Benzo[f]Chromen-2-yl) (1H-Indol-3-yl) Methanone Catalysed by L-Proline

Aim: The reactions were carried out by one pot three-component synthesis, 3-cyanoacetylindole (1) on reaction with aromatic aldehydes (2) and β-naphthol (3) in an aqueous medium in presence of L-proline as a catalyst under reflux for 30 min, resulted (3-amino-1-phenyl-1H-benzo[f]chromen-2-yl) (1H-indol-3-yl)methanone (4). The method has many advantages like short reaction times, good yields and simple workup procedure besides being green in nature. Pharmacological evaluation of title compounds was done for anti-inflammatory and analgesic activities. Anti-inflammatory activity was carried carrageenan-induced paw edema model in which indomethacin was used as standard and analgesic activity was evaluated by eddy's hot plate method using diclofenac as standard drug. Background: Benzopyrans or chromenes are an important class of heterocyclic compounds due to their broad spectrum of biological activity and a wide range of applications in medicinal chemistry. The chromene moiety is found in various natural products with interesting biological properties. Chromenes constitute the basic backbone of various types of polyphenols and are widely found in alkaloids, tocopherols, flavonoids and anthocyanins. Indoles are omnipresent in various bioactive compounds like alkaloids, agrochemicals and pharmaceuticals. Objective: To synthesize one-pot stepwise Green synthesis, anti-inflammatory and analgesic activities of 3-amino-1-phenyl-1H-benzo[f]chromen-2-yl) (1H-indol-3-yl)methanones Methods: The acute anti-inflammatory effect was evaluated by carrageenan-induced mice paw edema (Ma Rachchh et al., 2011). Edema was induced by injecting carrageenan (1% w/v, 0.1 ml) in the right hind paw of mice. The test compounds 1-12, indomethacin (10 mg/kg) and the vehicle were administered orally one hour before injection of carrageenan. Paw volume was measured with digital plethysmometer at 0, 30, 60, 90, 120 min after injection. Percentage increase =A-B/ A *100 Results: Carrageenan Induced paw edema model was used for Anti-inflammatory activity in which animals treated with standard (indomethacin) and test compounds showed a significant decrease in the paw edema. Analgesic activity was estimated by using Eddy’s hot plate method; animals were treated with standard (diclofenac) and test compounds showed a significant increase in the reaction time. Conclusion: A green, One-pot, step-wise and three-component synthesis of 3-amino-1-phenyl-1H-benzo[f]chromen-2-yl) (1H-indol-3-yl) methanone was achieved by using water as a solvent, L-proline as catalyst under reflux conditions. The reactions were carried out in eco-friendly conditions with shorter reaction times, easier workup and high yields. Anti-inflammatory activity was evaluated by carrageenan-induced paw edema model where significant anti-inflammatory activity is shown by all the test compounds (4a-l) when compared to standard drug. Analgesic activity was studied by Eddy’s Hot plate method and Test compounds 4e, 4f, 4h, 4i, 4j, 4k, 4l showed significant activities when compared to the reference drug.

Dual-modal Assessment for in Vivo Investigation of Neurovascular Characteristic of Cerebral Edema Induced by Lipopolysaccharide

The pathological features of cerebral edema are complicated, but usually only intracranial pressure (ICP) is regarded as the most important indicator for monitoring cerebral edema. The research focused on investigating the neurovascular characteristic of the lipopolysaccharide (LPS)-induced cerebral edema model in rats by using simultaneous electrophysical and hemodynamic recording. The results showed that neurophysiology (firing rate (FR), interval histogram index (ISI), and the power spectrum of local field potential (LFPs power)) and hemodynamic response (oxygenated hemoglobin (HbO2), deoxyhemoglobin (HbR) and relative cerebral blood flow (CBF)) were linearly related, and the Pearson’s correlation coefficient was determined by the BBB integrity after LPS injection. Furtherly, the improvement of treatment after two agents were observed successfully through these neurophysiological and hemodynamic parameters. The optical-electrical joint method provided a technical solution for cerebral edema functional monitoring and anti-edema drug efficacy evaluation. Our findings revealed the neurovascular and BBB impact of cerebral edema and improved the limitation of in vivo pathological diagnosis of cerebral edema.

EVALUATION OF ANTI-INFLAMMATORY (IN VIVO) ACTIVITY OF ARIFLEX LINIMENT IN COMPARISON WITH DICLOFENAC GEL IN CARRAGEENAN INDUCED RAT PAW EDEMA MODEL

Objective: The present study was conducted to evaluate anti-inflammatory activity of Ariflex liniment (conceptualized and developed by Ari Healthcare Pvt. Ltd) in comparison with Diclofenac gel in carrageenan induced rat paw edema model. Methods: Wistar rats of either sex weighing 150-180 g were taken and divided into 3 groups with 6 animals in each group i.e. Group 1 (Controlled Group), Group 2 (Diclofenac gel) and Group 3 (Ariflex liniment). The study drugs were topically applied 30 min prior to carrageenan injection. After 30 min 1% w/v of 0.05 ml carrageenan was injected subcutaneously in the paw. The paw was marked with ink at the level of lateral malleolus and immersed in mercury up to the lateral malleolus mark. The paw volume was measured plethysmographically, immediately after injection i.e. on 0 min, and then on 30 min,1h, 2h,3h, 4h and 5hr after injection. Results: Diclofenac gel sodium treated group showed significant inhibition (p<0.01) of paw edema at 30 min, 1, 2, 3, 4 and 5th hrs as compared to control group. Ariflex Liniment showed significant inhibition (p<0.05) of paw edema at 30 min, 1, 2, 3, and 4th hrs as compared to the control group. Group treated with Ariflex Liniment did not show any significant decrease in paw edema volume at 5th hrs when compared to the control group. Conclusion: Ariflex Liniment possesses anti-inflammatory activity.

Anti-Inflammatory and Antimicrobial Activities of Compounds Isolated from Distichochlamys benenica

Distichochlamys benenica is a native black ginger that grows in Vietnam. In point of fact, there is limitation of available information in the literature making mention of the chemical constituents and bioactive properties of this plant. This study is aimed at isolating trans-o-coumaric acid (1), trans-cinnamic acid (2), and borneol (3) from the rhizomes of D. benenica Q.B.Nguyen & Škorničk and evaluate the anti-inflammatory and antimicrobial activities of 1-3 using the carrageenan paw edema model and the dilution broth method, respectively. This revealed that 1 was as effective as diclofenac in reducing the intensity of the edema development. The in silico research showed that the activity of 1 might be derived from inhibiting COX-2 by generating h-bonds at the positions of Arg 120, Tyr 355, and Arg 513 residues. The antimicrobial activities against Gram-positive strains (Staphylococcus aureus and Bacillus subtilis) were comparable, with the minimum inhibitory concentrations ranging from 1.52 to 3.37 mM. This is the first study of the bioactivity of compounds isolated from D. benenica Q.B.Nguyen & Škorničk. Our results suggest that 1 may be a nature-derived compound which demonstrates the anti-inflammatory properties and inhibit the proliferation of several Gram-positive bacteria.

Identification, Molecular Profiling, Docking Studies and determination of In-vivo Anti-Inflammatory Potential of Teucrium Stocksianum Bioss Fixed Oil (FO)

Background: Considering the positive and valuable upshots of the naturally occurring ingredients as the complementary treatment for many ailments, this study investigates the Teucrium Stocksianum Bioss Fixed Oil (FO) for the treatment of inflammation.Methods: Different plants of the Teucrium genera have been employed occasionally for the management of different disorders. Teucrium stocksianum (Lamiaceae) is traditionally use as antipyretic along with remedy of inflammation, diabetes and tumors. It also occupies the capacity to purify the blood. The aim of this study is to determine the chemical constituents and anti-inflammatory potentials of Teucrium stocksianum fixed oil (FO). Qualitative and quantitative analysis of fixed oil were performed via GC-MS (Gas Chromatography coupled with Mass Spectrometer). Preliminary inflammation antagonistic activity was calculated in mice using the carrageenan-induced paw edema model while the mechanism behind this inflammatory antagonistic effect was determined by employing various inflammogens including arachidonic acid, prostaglandins E2 and leukotriene via paw edema model.Results: The acute toxicity of fixed oil was determined at 3, 6 and 10 ml/kg body weight of the mouse. The GC-MS analysis documented 21 various unsaturated and saturated fatty acids elements. The methyl esters of octadecadienoic and linoleic acids were found predominantly at 22.60% and 23.84% respectively. In preliminary screening, FO demonstrated substantial anti-inflammatory capacity (67.87%, **P ˂ 0.01) in carrageenan induced paw edema model at 3 ml/kg body weight. The activity reached a peak value at the 3rd hour and continued persistent until the 5th hour of sample administration. FO displayed dose-dependent inhibition against all inflammogens at 3 ml/kg at 3rd h of the FO administration. These have shown marvelous protection i.e. 64.92%, 68.75%and 58.3% against arachidonic acid, prostaglandin E2 and leukotriene accordingly, at 3 ml/kg. The arachidonic acid antagonist (Caffeic acid) demonstrated 69.43% activity at 100 mg/kg after 3rd h of its administration while in the acute toxicity test, FO has shown no grass lethality at 10 ml/kg dose.Conclusion: According to our findings, the FO of T. stocksianum exhibits inflammation antagonistic potential through both lipoxygenase (LOX) and cyclooxygenase (COX) enzyme inhibition strategies that intensely sustenance the traditional practice of T. stocksianum in the management of multiple pathological inflammatory situations. The computed binding energies of the molecules exposed have synergistic potential to avert inflammation.

Preparation and Evaluation of Amino Acid Conjugates of Celecoxib as Prodrugs to Improve the Pharmacokinetic and Therapeutic Properties of Celecoxib

Although celecoxib is quite effective in the management of inflammation-related diseases, especially arthritis, its use is limited by concerns including low bioavailability (BA), non-linear pharmacokinetic (PK) profile, and peak concentration-related toxicity. To overcome these issues, we designed and prepared hydrophilic celecoxib prodrugs, namely N-glycyl-aspart-1yl celecoxib (N-GA1C), glutam-1-yl celecoxib (G1C), and aspart-1yl celecoxib (A1C), for the sustained release of celecoxib in the intestine with limited systemic absorption. The celecoxib derivatives were converted to celecoxib in the intestinal contents. The conversion rates were in order of N-GA1C > G1C > A1C. Oral administration of the celecoxib derivatives (oral celecoxib derivatives) sustained the plasma concentration of celecoxib for 24 h, improving the BA and linearity of the PK profile of celecoxib. The peak concentrations (Cmax) of celecoxib after oral celecoxib derivatives were lower than that after oral celecoxib. In a carrageenan-induced rat paw edema model, oral N-GA1C exhibited greater anti-inflammatory activity for a longer duration compared with oral celecoxib. The order of efficacy of the celecoxib derivatives was N-GA1C > G1C > A1C. Taken together, the prodrug approach is a feasible strategy to improve the PK and therapeutic properties of celecoxib, and among the celecoxib derivatives, N-GA1C may be the most promising prodrug of celecoxib.