Tetraazamacrocyclic derivatives and their metal complexes as antileishmanial leads.

A total of 44 bis-aryl-monocyclic polyamines, monoaryl-monocyclic polyamines and their transition metal complexes were prepared, chemically characterized, and screened in vitro against the Leishmania donovani promastigotes, axenic amastigotes and intracellular amastigotes in THP1 cells. The IC50 and/or IC90 values showed that 10 compounds were similarly active at about 2-fold less potent than known drug pentamidine against promastigotes. The most potent compound had an IC50 of 2.82 µM (compared to 2.93 µM for pentamidine). Nine compounds were 1.1-13.6-fold more potent than pentamidine against axenic amastigotes, the most potent one being about 2-fold less potent than amphotericin B. Fourteen compounds were about 2-10 fold more potent than pentamidine, the most potent one is about 2-fold less potent than amphotericin B against intracellular amastigotes in THP1 cells. The 2 most promising compounds (FeL7Cl2 and MnL7Cl2), with strong activity against both promastigotes and amastigotes and no observable toxicity against the THP1 cells are the Fe2+- and Mn2+- complexes of a dibenzyl cyclen derivative. Only 2 of the 44 compounds showed observable cytotoxicity against THP1 cells. Tetraazamacrocyclic monocyclic polyamines represent a new class of antileishmanial lead structures that warrant follow up studies.

Formation patterns of water clusters in CMK-3 and CMK-5 mesoporous carbons: a computational recognition study.

Grand canonical Monte Carlo simulations are performed to study the adsorption of water in realistic CMK-3 and CMK-5 models at 300 K. The adsorption isotherms are characterized by negligible uptake at lower chemical potentials and complete pore filling once the threshold chemical potential is increased. Results for the isosteric heat of adsorption, radial distribution function (O-O and O-H), hydrogen bond statistics and the cluster size distribution of water molecules are presented. The snapshots of GCMC simulations in CMK-3 and CMK-5 models show that the adsorption happens via the formation of water clusters. For the CMK-3 model, it was found that the pore filling occurred via the formation of a single water cluster and a few very small clusters. The water cluster size increased with an increase in pore size of the CMK-3 model. For the CMK-5 model, it was found that the adsorption first occurred in the inner porosity (via cluster formation). There was no adsorption of water in the outer porosity during the filling of the inner porosity. After the inner porosity was completely filled, the water begins to fill the outer porosity. Snapshots from GCMC simulations of the CMK-5 model clearly show that the water adsorption in the outer porosity occurs via the formation and growth of clusters and there was no formation of layers of water in the porosity as seen for nonpolar fluids like nitrogen.

Molecular Modeling and Adsorption Properties of Ordered Silica-Templated CMK Mesoporous Carbons.

Realistic molecular models of silica-templated CMK-1, CMK-3, and CMK-5 carbon materials have been developed by using carbon rods and carbon pipes that were obtained by adsorbing carbon in a model MCM-41 pore. The interactions between the carbon atoms with the silica matrix were described using the PN-Traz potential, and the interaction between the carbon atoms was calculated by the reactive empirical bond order (REBO) potential. Carbon rods and pipes with different thicknesses were obtained by changing the silica-carbon interaction strength, the temperature, and the chemical potential of carbon vapor adsorption. These equilibrium structures were further used to obtain the atomic models of CMK-1, CMK-3, and CMK-5 materials using the same symmetry as found in TEM pictures. These models are further refined and made more realistic by adding interconnections between the carbon rods and carbon pipes. We calculated the geometric pore size distribution of the different models of CMK-5 and found that the presence of interconnections results in some new features in the pore size distribution. Argon adsorption properties were investigated using GCMC simulations to characterize these materials at 77 K. We found that the presence of interconnection results greatly improves the agreement with available experimental data by shifting the capillary condensation to lower pressures. Adding interconnections also induces smoother adsorption/condensation isotherms, and desorption/evaporation curves show a sharp jump. These features reflex the complexity of the nanovoids in CMKs in terms of their pore morphology and topology.

Understanding adsorption of CO2, N2, CH4 and their mixtures in functionalized carbon nanopipe arrays.

The selective adsorption behaviours of carbon dioxide, methane and nitrogen on bundles of functionalized CMK-5 are investigated at 303 K using grand-canonical Monte Carlo simulations. Functional groups (-OH, -COOH) cause a significant enhancement in CO2 uptake (up to 19.5% at a pressure of 38.13 bar for -COOH). On the other hand, the adsorption amount of methane decreases with respect to bare CMK-5 by ∼13% (at 38.13 bar) upon functionalization. Furthermore, functionalized CMK-5 with different pore sizes (4 nm, 6 nm, 8 nm) and inter-tube distances (d = 0 to 1.5 nm) are used to investigate the adsorption behaviour of flue gases. While the pore diameter is seen to reduce the isosteric heat of adsorption, the inter-tube distance of 0.25 nm shows the highest uptake of CO2 at p ≤ 18 bar, followed by 0.5 nm for the pressure range of 18 < p ≤ 30 bar, whereas for p > 30 bar, d = 1.0 nm shows the maximum uptake. For methane and nitrogen, the maximum adsorption is obtained at d = 0.25 nm in the studied pressure range. The selective adsorption of CO2 in binary mixtures is investigated using ideal adsorption solution theory. CO2-N2 selectivity is found to increase significantly by surface functionalization of CMK-5 compared to pure CMK-5. The maximum selectivity of CO2-CH4 using -COOH functionalized CMK-5 is found to be ∼10 for an equimolar CO2-CH4 mixture at a pressure of 38.13 bar.

Screening North American plant extracts in vitro against Trypanosoma brucei for discovery of new antitrypanosomal drug leads.

BACKGROUND: Human African Trypanosomiasis (HAT) is a protozoan parasitic disease caused by Trypanosoma brucei. The disease is endemic in regions of sub-Saharan Africa, covering 36 countries and more than 60 million people at the risk. Only few drugs are available for the treatment of HAT. Current drugs suffer from severe toxicities and require intramuscular or intravenous administrations. The situation is further aggravated due to the emergence of drug resistance. There is an urgent need of new drugs that are effective orally against both stages of HAT. Natural products offer an unmatched source for bioactive molecules with new chemotypes. METHODS: The extracts prepared from 522 plants collected from various parts of the North America were screened in vitro against blood stage trypamastigote forms of T. brucei. Active extracts were further screened at concentrations ranging from 10 to 0.4 µg/mL. Active extracts were also investigated for toxicity in Differentiated THP1 cells at 10 µg/mL concentration. The results were computed for dose-response analysis and determination of IC50/IC90 values. RESULTS: A significant number (150) of extracts showed >90 % inhibition of growth of trypomastigote blood forms of T. brucei in primary screening at 20 µg/mL concentration. The active extracts were further investigated for dose-response inhibition of T. brucei growth. The antitrypansomal activity of 125 plant extracts was confirmed with IC50 < 10 µg/mL. None of these active extracts showed toxicity against differentiated THP1 cells. Eight plants extracts namely, Alnus rubra, Hoita macrostachya, Sabal minor, Syzygium aqueum, Hamamelis virginiana, Coccoloba pubescens, Rhus integrifolia and Nuphar luteum were identified as highly potent antitrypanosomal extracts with IC50 values <1 µg/mL. CONCLUSIONS: Limited phytochemical and pharmacological reports are available for the lead plant extracts with potent antitrypanosomal activity. Follow up evaluation of these plant extracts is likely to yield new antitrypanosomal drug-leads or alternate medicines for treatment of HAT.

Enantioselective pharmacokinetics of primaquine in healthy human volunteers.

Primaquine (PQ), a racemic drug, is the only treatment available for radical cure of relapsing Plasmodium vivax malaria and blocking transmission of P. falciparum malaria. Recent studies have shown differential pharmacologic and toxicologic profiles of individual PQ enantiomers in rodent, dog, and primate animal models. This study was conducted in six healthy adult human volunteers to determine the plasma pharmacokinetic profile of enantiomers of PQ and carboxyprimaquine (cPQ), the major plasma metabolite. The individuals were orally administered PQ diphosphate, equivalent to 45-mg base, 30 minutes after a normal breakfast. Blood samples were collected at different time intervals, and plasma samples were analyzed for enantiomers of PQ and cPQ. Plasma PQ concentrations were low and variable for both parent enantiomers and peaked around 2-4 hours. Peak (-)-(R)-PQ concentrations ranged from 121 ng/ml to 221 ng/ml, and peak (+)-(S)-PQ concentrations ranged from 168 ng/ml to 299 ng/ml. The cPQ concentrations were much higher and were surprisingly consistent from subject to subject. Essentially all the cPQ detected in plasma was (-)-cPQ. The peak concentrations of (-)-cPQ were observed at 8 hours (range: 1104-1756 ng/ml); however, very high concentrations were sustained through 24 hours. (+)-cPQ was two orders of magnitude lower than (-)-cPQ, and in a few subjects it was detected but only under the limit of quantification. In vitro studies with primary human hepatocytes also suggested more rapid metabolism of (-)-PQ compared with (+)-PQ. The results suggest more rapid metabolism of (-)-PQ to (-) cPQ compared with (+)-PQ. Alternatively, (+)-PQ or (+)-cPQ could be rapidly converted to another metabolite(s) or distributed to tissues. This is the first clinical report on enantioselective pharmacokinetic profiles of PQ and cPQ and supports further clinical evaluation of individual PQ enantiomers.

The antileishmanial activity of isoforms 6- and 8-selective histone deacetylase inhibitors.

Histone deacetylase inhibitors (HDACi) pleiotropy is largely due to their nonselective inhibition of various cellular HDAC isoforms. Connecting inhibition of a specific isoform to biological responses and/or phenotypes is essential toward deconvoluting HDACi pleiotropy. The contribution of classes I and II HDACs to the antileishmanial activity of HDACi was investigated using the amastigote and promastigote forms of Leishmania donovani. We observed that the antileishmanial activities of HDACi are largely due to the inhibition of HDAC6-like activity. This observation could facilitate the development of HDACi as antileishmanial agents.

Synthesis, antileishmanial and antitrypanosomal activities of N-substituted tetrahydro-ß-carbolines.

A series of N-substituted tetrahydro-ß-carbolines were synthesized and screened for antileishmanial activity through an in vitro assay that involves promastigotes and axenic amastigotes of Leishmania donovani, the causative agent for visceral leishmaniasis. The thiophen-2-yl analogs 9b and 11f and naphthyl analog 11h were found to show significant activity against promastigotes with IC50 values of 12.7, 9.1 and 22.1 µM, respectively. Analogs 9b and 11h were also effective against axenic amastigotes with IC50 values of 62.8 and 87.6 µM, respectively. The antileishmanial activity of analogs was then tested in human macrophage cell line infected with L. donovani amastigotes and 2-naphthyl linked analog 11h was found to be effective with IC50 value of 28.3 µM. Several analogs also displayed antitrypanosomal activity against Trypanosoma brucei, the causative agent for human African trypanosomiasis. Compounds 11e, 11f and 11h were more effective than others with IC50 values of 1.0, 8.9 and 10.2 µM, respectively. All synthesized analogs were not cytotoxic towards mammalian cell lines including Vero (monkey kidney fibroblasts), HEPG2 (human hepatoma cells), LLC-PK1 (pig kidney epithelial cells) and THP-1 (human macrophages).

Pharmacological activities of cilantro's aliphatic aldehydes against Leishmania donovani.

Leishmaniasis is a chronic infectious disease caused by different Leishmania species. Global occurrences of this disease are primarily limited to tropical and subtropical regions. Treatments are available; however, patients complain of side effects. Different species of plants have been screened as a potential source of new drugs against leishmaniasis. In this study, we investigated the antileishmanial activity of cilantro (Coriandrum sativum) essential oil and its main components: (E)-2-undecenal, (E)-2-decenal, (E)-2-dodecenal, decanal, dodecanal, and tetradecanal. The essential oil of C. sativum leaves inhibits growth of Leishmani donovani promastigotes in culture with an IC50 of 26.58 ± 6.11 µg/mL. The aliphatic aldehydes (E)-2-decenal (7.85 ± 0.28 µg/mL), (E)-2-undecenal (2.81 ± 0.21 µg/mL), and (E)-2-dodecenal (4.35 ± 0.15 µg/mL), all isolated from C. sativum essential oil, are effective inhibitors of in vitro cultures of L. donovani promastigotes. Aldehydes (E)-2-decenal, (E)-2-undecenal, and (E)-2-dodecenal were also evaluated against axenic amastigotes and IC50 values were determined to be 2.47 ± 0.25 µg/mL, 1.25 ± 0.11 µg/mL, and 4.78 ± 1.12 µg/mL, respectively. (E)-2-Undecenal and (E)-2-dodecenal demonstrated IC50 values of 5.65 ± 0.19 µg/mL and 9.60 ± 0.89 µg/mL, respectively, against macrophage amastigotes. These cilantro compounds showed no cytotoxicity against THP-1 macrophages.

Novel UV-spectrophotometric method for quantitative estimation of furazolidone using mixed hydrotropic agent.

A novel, eco friendly, accurate, sensitive, economic and safe spectrophotometric method was developed by application of mixed hydrotropy using 2 M sodium acetate, 8 M urea, 2 M niacinamide and 2 M sodium benzoate solution (25:25:25:25% V/V) as hydrotropic agent, for the solubalizing of poorly water-soluble Furazolidone (FZ) (solubility:- 3.64e-01 mg/mL in water). There were more than 32 times enhancements in the solubility of FZ were found in mixed hydrotropic solution as compared to solubilities in distilled water. FZ shows maximum absorbance at 360 nm where sodium acetate, urea, niacinamide, sodium benzoate and other tablets excipients did not show any absorbance above 300 nm, and thus no interference in the estimation was seen. FZ was obeyed Beers law in the concentration range of 10 to 50 µg/ml (r(2)=0.9992) in mixed hydrotropic solvent with mean recovery ranging from 97.32% to 98.9%. Proposed method is new, simple, economic, safe, rapid, accurate and reproducible and was validated according to ICH guidelines and values of accuracy, precision and other statistical analysis were found to be in good accordance with the prescribed values.

Evaluation of Radiological and Neurological Outcomes after Anterior Cervical Corpectomy with Fusion using Expandable Cage Alone and Expandable Cage with Anterior Cervical Plating.

Objective After anterior cervical corpectomy expandable cage were used with or without using anterior cervical plate for structural support are being preferred over autologous bone graft and other types of cages. Nowadays, the preferable type of cages and application of anterior cervical plate remain a debatable topic with studies giving divergent results. The purpose of this study is to evaluate the outcomes of expandable cages used alone or expandable cage used with anterior cervical plate following anterior cervical corpectomy. Materials and Methods This study was conducted on 100 patients from January 2019 to December 2021 and all patients were undergone anterior cervical corpectomy and fusion and divided in two groups with expandable cage only (Group A) and expandable cage with anterior cervical plate (Group B). Various long-term benefits and radiological outcomes were studied in both groups. Statistical Analysis and Results In this study, 100 patients were included and all patients underwent corpectomy followed by insertion of expandable cage alone or with anterior cervical plate. There was an improvement in C2-C7 Cobb's angle in group B was significantly higher than group A ( p < 0.05) and decrease in Nurick's scale score in group B was significantly higher than group A ( p < 0.05). The outcomes were measured with fusion rate (94%), subsidence rate (15%) and change in C2-C7 Cobb's angle was 4 degrees in this study. Conclusion Expandable cage with or without anterior cervical plate was used after anterior cervical corpectomy for various cervical pathological conditions. In this study, we conclude the long-term benefits and radiological outcomes of two groups as expandable cage was used alone or with additional application of anterior cervical plate. In this study, the results were more in favor of additional application of anterior cervical plate as compared with expandable cage alone and more studies were required in future for more established long-term benefits and drawbacks.

Antiparasitic and antimicrobial indolizidines from the leaves of Prosopis glandulosa var. glandulosa.

A new indolizidine alkaloid, named Δ¹,6-juliprosopine (1), together with previously known indolizidine analogs (2- 6), was isolated from the leaves of Prosopis glandulosa var. glandulosa, collected from Nevada, USA; while two other known indolizidines, juliprosopine (6) and juliprosine (7), were isolated from P. glandulosa leaves collected in Texas, USA. The structures of compound 1 and 7 were determined using a combination of NMR and MS techniques. Compound 7 exhibited potent antiplasmodial activity against Plasmodium falciparum D6 and W2 strains with IC (50) values of 170 and 150 ng/mL, respectively, while 1 was found to be less active (IC50 values 560 and 600 ng/mL, respectively). Both compounds were devoid of VERO cells toxicity up to a concentration of 23 800 ng/mL. The antileishmanial activity of indolizidines was evaluated against Leishmania donovani promastigotes, axenic amastigotes, and amastigotes in THP1 macrophage cultures. When tested against macrophage cultures, the tertiary bases (1, 3, 6) were found to be more potent than quaternary salts (2, 5, 7), displaying IC50 values between 0.8-1.7 µg/mL and 3.1-6.0 µg/mL, respectively. In addition, compound 7 showed potent antifungal activity against Cryptococcus neoformans and antibacterial activity against Mycobacterium intracellulare, while 1 was potent only against C. neoformans and weakly active against other organisms.

Osmotically controlled drug delivery system with associated drugs.

Conventional drug delivery systems have slight control over their drug release and almost no control over the effective concentration at the target site. This kind of dosing pattern may result in constantly changing, unpredictable plasma concentrations. Drugs can be delivered in a controlled pattern over a long period of time by the controlled or modified release drug delivery systems. They include dosage forms for oral and transdermal administration as well as injectable and implantable systems. For most of drugs, oral route remains as the most acceptable route of administration. Certain molecules may have low oral bioavailability because of solubility or permeability limitations. Development of an extended release dosage form also requires reasonable absorption throughout the gastro-intestinal tract (GIT). Among the available techniques to improve the bioavailability of these drugs fabrication of osmotic drug delivery system is the most appropriate one. Osmotic drug delivery systems release the drug with the zero order kinetics which does not depend on the initial concentration and the physiological factors of GIT. This review brings out new technologies, fabrication and recent clinical research in osmotic drug delivery.

Simple and rapid RP-HPLC method for simultaneous determination of acyclovir and zidovudine in human plasma.

Combination therapy with acyclovir and zidovudine is used for the treatment of herpes-infected immunocompromised patients. In the view of the optimal drug concentrations (minimum effective concentrations) for viral suppression and avoidance of drug toxicity, monitoring of drug levels has been considered essential to determine drug concentrations in plasma after administration of a dose of acyclovir and zidovudine. A simple, precise, and rapid RP-HPLC method has been developed for this purpose. Chromatographic separation was performed using methanol-water (50 + 50, v/v), pH 2.5 adjusted with orthophosphoric acid, as an isocratic mobile phase at a flow rate of 0.8 mL/min with an Inertsil ODS (C18) column (5 microm particle size, 250 x 4.60 mm id). Detection was carried out using a UV photo diode array detector at 258 nm. The plasma samples were prepared by a protein precipitation method. The retention time for acyclovir and zidovudine was 3.5 +/- 0.2 and 6.2 +/- 0.3 min, respectively. The method was linear in the range of 200-1800 and 400-3600 ng/mL with LOQ of 200 ng (SD = +/-1.4) and 400 ng (SD = +/-0.9) for zidovudine and acyclovir, respectively, in plasma. The mean accuracy was 98.0 and 96.4%, with average extraction recovery of 64.8 +/- 2.1 and 77.5 +/- 1.7% for lower nominal concentrations of acyclovir and zidovudine, respectively.

Curious Case of Atypical Hangman's Fracture: C2-C3 Listhesis without Pars Fracture.

Traumatic spondylolisthesis of axis or hangman's fracture is the second most common C2 vertebra injury. We present a report of a young man presenting with a history of fall from height with C2 to C3 spondylolisthesis without any evidence of injury to pars interarticularis but with associated injury to capsular ligament of facet joint along with posterior spinous ligamentous injury. The patient underwent intraoperative reduction in listhesis with posterior screw fixation. The patient showed uneventful postoperative course with neurological improvement at 6-week follow-up. Hangman's fracture refers to a diverse group of injury in which the soft tissue injury has an equally important part to play as the bone fracture.

Formulation development, in vitro and in vivo evaluation of chitosan engineered nanoparticles for ocular delivery of insulin.

Insulin-dependent diabetic patients have to count on the administration of painful and discomforting insulin injections. However, inadequate insulin absorption and the risk of insulin level escalation in the blood are some disadvantages associated with insulin therapy. Thus, the current study intends to formulate insulin-loaded chitosan nanoparticles for refining the systemic absorption of insulin via the ocular route. Insulin-loaded chitosan nanoparticles were prepared by the ionotropic gelation method and characterized for various parameters. Optimized insulin loaded nanoparticles (C4T4I4) were positively charged with a particle size of 215 ± 2.5 nm and showed 65.89 ± 4.3% entrapment efficiency. The in vitro drug release exhibited sustained release of insulin, where 77.2 ± 2.1% of release was observed after 12 h and leads to an assumption of the non-Fickian diffusion release mechanism. The permeation study discloses good mucoadhesive and better permeation properties of insulin loaded nanoparticles compared to free Insulin. No significant difference was observed in the size of particles after six months of storage, signifying their adequate stability. Nanoparticles were found to be non-irritant to ocular tissues and exhibited prominent blood glucose level reduction in vivo. The outcomes of this study suggested that the chitosan nanoparticulate system could act as a prominent carrier system for insulin with enhanced stability and efficacy.

Salvia ceratophylla L. from South of Jordan: new insights on chemical composition and biological activities.

In Jordan, Salvia ceratophylla L. is traditionally used in the treatment of cancer, microbial infections, and urinary disorders. This study aimed: (1) to chemically characterize S. ceratophylla essential oil (EO) from South Jordan, by gas chromatography (GC) and gas chromatography-mass spectrometry (GC-MS); and (2) to evaluate in vitro the cytotoxic, anti-inflammatory, and antiprotozoal activities of the EO, it's predominant components, and the hexane (A), ethyl acetate (B), methanol (C) and crude-methanol extracts (D). The analysis revealed that the EO has 71 compounds, with linalool (54.8%) as main constituent. Only the hexane extract (A) showed some cytotoxic activity against SK-MEL, KB, BT-549, SK-OV-3, LLC-PK1 and VERO cells lines with IC50 between 60 and > 100 µg/mL. The EO inhibited NO production (IC50 90 µg/mL) and NF-κB activity (IC50 38 µg/mL). The extracts A, B, and D inhibited NO production and NF- κB activity with IC50 between 32 and 150 µg/mL. Linalool considerably inhibited NO production (IC50 18 µg/mL). The extracts tested did not exhibit antileishmanial activity. Regarding antitrypanosomal activity, the EO exhibited significant results with IC50 2.65 µg/mL. In conclusion, Jordan S. ceratophylla EO represents a rich source of linalool and bears a promising therapeutic potential for further antitrypanosomal drug development.

Adsorption and Diffusion of Benzene in Mg-MOF-74 with Open Metal Sites.

We performed molecular simulations to investigate the adsorption and diffusion of benzene in metal-organic framework Mg-MOF-74. At 300 K and 20 Pa, the saturated loading of benzene reaches 8.2 mmol/g, almost twice of (12,12) single-walled carbon nanotube with a similar pore size, and 93% of the benzene molecules in Mg-MOF-74 can desorb at 390 K. The energy analysis indicates that the van der Waals contribution still dominates 70-80% of the total fluid-wall interaction energy compared with the Coulombic contribution. We further analyzed the structure of benzene confined in Mg-MOF-74 by the molecular snapshots, pair correlation functions, orientational order parameters, and local density profiles. It is found that low temperature and high pressure make the structure of adsorbed benzene more similar to that of the liquid benzene. Moreover, the benzene molecules in the contact adsorption layer lie flat on the surface of adsorbent, whereas those molecules near the pore center have no particular orientations. Due to the existence of open metal sites, the structures of adsorbed benzene are more compact and ordered than those of bulk liquid benzene. Consequently, the self-diffusion coefficient of saturated benzene in Mg-MOF-74 at 300 K is significantly lower than that of bulk liquid benzene and confined liquid benzene in slit pores and disordered carbons by 4-5 orders of magnitude. We investigated the separation and diffusion of benzene/cyclohexane in the mixture in Mg-MOF-74 and found that the pores almost completely adsorbed benzene, although its self-diffusion coefficient was slightly lower than that of cyclohexane.

Simultaneous estimation of metformin hydrochloride, pioglitazone hydrochloride, and glimepiride by RP-HPLC in tablet formulation.

A simple, precise, rapid, and reproducible reversed-phase high-performance liquid chromatography method is developed for the simultaneous estimation of metformin hydrochloride (MET), pioglitazone hydrochloride (PIO), and glimepiride (GLP) present in multicomponent dosage forms. Chromatography is carried out isocratically at 25 degrees C +/- 0.5 degrees C on an Inertsil-ODS-3 (C-18) Column (250 x 4.60 mm, 5 microm) with a mobile phase composed of methanol-phosphate buffer (pH 4.3) in the ratio of 75:25 v/v at a flow rate of 1 mL/min. Detection is carried out using a UV-PDA detector at 258 nm. Parameters such as linearity, precision, accuracy, recovery, specificity, and ruggedness are studied as reported in the International Conference on Harmonization guidelines. The retention times for MET, PIO, and GLP are 2.66 + 0.5 min, 7.12 + 0.5 min, and 10.17 + 0.5 min, respectively. The linearity range and percentage recoveries for MET, PIO, and GLP are 10-5000, 10-150, and 1-10 microg/mL and 100.4%, 100.06%, and 100.2%, respectively. The correlation coefficients for all components are close to 1. The relative standard deviations for three replicate measurements in three concentrations of samples in tablets are always less than 2%.

Medicinal plants with acetylcholinesterase inhibitory activity.

Alzheimer's disease, a progressive neurodegenerative disease, is characterised by hypofunction of acetylcholine (ACh) neurotransmitter in the distinct region of brain. Acetylcholinesterase (AChE) is an enzyme that metabolises the ACh at synaptic cleft resulting in Alzheimer's disease. Medicinal plants have been used to treat numerous ailments and improve human health from ancient time. A traditional system of medicine is long recognised for its effective management of neurological disorders. The present review confers the scope of some common medicinal plants with a special focus on AChE-mediated central nervous system complications especially Alzheimer's disease. Literature suggests that medicinal plants reduce neuronal dysfunctions by reducing AChE activity in different brain regions. In some instances, activation of AChE activity by medicinal plants also showed therapeutic potential. In conclusion, medicinal plants have a wide scope and possess therapeutic potential to efficiently manage neurological disorders associated with AChE dysregulation.