Effects of Co-composting of Municipal Solid Waste and Pigeon Pea Biochar on Heavy Metal Mobility in Soil and Translocation to Leafy Vegetable Spinach.

An experiment was conducted to study the effects of co-composted products of municipal solid waste (MSW) and pigeon pea biochar (PPB) on heavy metal mobility in soil and its uptake by spinach. Application of municipal solid waste biochar co-compost (MSWBC) significantly (p ≤ 0.05) reduced the heavy metal content in spinach leaves and roots compared to municipal solid waste compost (MSWC) amended soil. The percent decrease in spinach leaf following the application of MSWBC-10% PPB compared to MSWC was 20.62%, 28.95%, 36.02%, 41.88%, 41.50%, and 41.23% for Cu, Cd, Pb, Cr, Ni, and Zn, respectively. The dry matter yield of spinach and soil organic carbon (SOC) content in soil amended with MSWBC-10% PPB was significantly increased by 32.75% and 47.73%; and 17.62% and 27.45% relative to control and MSWC amended soil. The study concludes that co-composted product, MSWBC, stabilized heavy metals in MSW, reduced their uptake by spinach and thus making it a viable option for safe disposal of MSW.

Novel Tetrahydroquinazolinamines as Selective Histamine 3 Receptor Antagonists for the Treatment of Obesity.

The histamine 3 receptor (H3R) is a presynaptic receptor, which modulates several neurotransmitters including histamine and various essential physiological processes, such as feeding, arousal, cognition, and pain. The H3R is considered as a drug target for the treatment of several central nervous system disorders. We have synthesized and identified a novel series of 4-aryl-6-methyl-5,6,7,8-tetrahydroquinazolinamines that act as selective H3R antagonists. Among all the synthesized compounds, in vitro and docking studies suggested that the 4-methoxy-phenyl-substituted tetrahydroquinazolinamine compound 4c has potent and selective H3R antagonist activity (IC50 < 0.04 µM). Compound 4c did not exhibit any activity on the hERG ion channel and pan-assay interference compounds liability. Pharmacokinetic studies showed that 4c crosses the blood brain barrier, and in vivo studies demonstrated that 4c induces anorexia and weight loss in obese, but not in lean mice. These data reveal the therapeutic potential of 4c as an anti-obesity candidate drug via antagonizing the H3R.

CD44 targeting hyaluronic acid coated lapatinib nanocrystals foster the efficacy against triple-negative breast cancer.

Lapatinib (LPT) is an orally administered drug for the treatment of metastatic breast cancer. For expanding its therapeutic horizon, we have prepared its nanocrystals (LPT-NCs) that were subsequently coated with hyaluronic acid (HA) to produce LPT-HA-NCs. The detailed in-vitro and in-vivo investigation of LPT-HA-NCs showed the superior anticancer activity due to active targeting to CD44 receptors than the counterparts LPT-NCs and free LPT. In the triple negative 4T1 cells induced breast tumor bearing female Balb/C mice; LPT-HA-NCs treatment caused significant retardation of tumor growth and overall increase in animal survival probability because of their higher tumor localization, increased residence time. Our findings clearly suggest that HA coated LPT-NCs formulation enhances the activity of LPT against triple negative breast cancer. It exhibited magnificent therapeutic outcome at low dose thus presenting a strategy to reduce dose administrations and minimize dose related toxicity.

In Silico and In Vitro Anticancer Activity of Isolated Novel Marker Compound from Chemically Modified Bioactive Fraction from Curcuma longa (NCCL).

BACKGROUND: Turmeric (Curcuma longa) is reported to possess wide array of biological activities. Herbal Medicament (HM) is a standardized hexane-soluble fraction of C. longa and is well known for its neuroprotective effect. OBJECTIVE: In this study, we attempted to synthesize a novel chemically modified bioactive fraction from HM (NCCL) along with isolation and characterization of a novel marker compound (I). MATERIALS AND METHODS: NCCL was prepared from HM. The chemical structure of the marker compound isolated from NCCL was determined from 1D/2D nuclear magnetic resonance, mass spectroscopy, and Fourier transform infrared. The compound so isolated was subjected to in silico and in vitro screenings to test its inhibitory effect on estrogen receptors. RESULTS: Molecular docking studies revealed that the binding poses of the compound I was energetically favorable. Among NCCL and compound I taken for in vitro studies, NCCL had exhibited good anti-cancer activity over compound I against MCF-7, MDA-MB-231, DU-145, and PC-3 cells. CONCLUSION: This is the first study about the synthesis of a chemically modified bioactive fraction which used a standardized extract since the preparation of the HM. It may be concluded that NCCL fraction having residual components induce more cell death than compound I alone. Thus, NCCL may be used as a potent therapeutic drug. SUMMARY: In the present paper, a standardized hexane soluble fraction of Curcuma longa (HM) was chemically modified to give a novel bioactive fraction (NCCL). A novel marker compound was isolated from NCCL and was characerized using various spectral techniques. The compound so isolated was investigated for in-silico screenings. NCCL and isolated compound was subjected to in-vitro anti-cancer screenings against MCF 7, MDA MB 231 (breast adenocarcinoma) and DU 145 and PC 3 cell lines (androgen independent human prostate cancer cells). The virtual screenings reveals that isolated compound has shown favourable drug like properties. NCCL fraction having residual components induces more cell death in these four cancer cell lines than isolated compound alone. Abbreviations used: HM: Herbal Medicament; NCCL: Chemically modified HM; FT-IR: Fourier transform-infrared spectroscopy; NMR: Nuclear magnetic resonance spectroscopy; MS: Mass spectroscopy; HPLC: High-performance liquid chromatography; ER: Estrogen receptor; MTT: 3-(4,5 dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide; MIC: Minimum inhibitory concentration; TAM: Tamoxifen KBr: Potassium bromide; DMSO: Dimethyl sulfoxide; ACN: Acetonitrile; PDB: Protein Data Bank; PDA: Photodiode array detector.

Oleanolic-bioenhancer coloaded chitosan modified nanocarriers attenuate breast cancer cells by multimode mechanism and preserve female fertility.

Addressing multidrug resistant stage of breast cancer is an impediment for chemotherapy. Moreover, breast cancer chemotherapy has potential enduring confrontations i.e. related toxicity including effect on fertility of young female patients. The co-delivery of polyphenolic bio-enhancers with oleanolic acid in chitosan coated PLGA nanoparticles was designed for oral delivery with enhanced antitumor effect consecutively preserving the female fertility. The optimized oleanolic- bio-enhancer nano formulation CH-OA-B-PLGA with particle size was 342.2±3.7nm and zeta potential of 34.2±3.1mV was capable of lowering viability in MDAMB 231 cell line 16 times than OA. Further, mechanistic studies in MDAMB-231 cells revealed that CH-OA-PLGA induces apoptosis by mitochondrial membrane disruption; follows ROS mediated and caspase dependent apoptosis. The antitumor effect studied in 4-T1 induced Balb/c mice mammary tumor model displayed augmented antitumor potency by CH-OA-B-PLGA in comparison to OA. In the in vivo toxicity on Sprague-Dawley rat model, CH-OA-B-PLGA significantly displayed the safe profile and also preserves fertility in female rats. The experiment result suggests co-delivery of oleanolic acid with bio-enhancers as a breakthrough for developing safe chemotherapy for hormone independent breast cancer therapy countering the toxicity issues.

S-Enantiomer of the Antitubercular Compound S006-830 Complements Activity of Frontline TB Drugs and Targets Biogenesis of Mycobacterium tuberculosis Cell Envelope.

A synthetic molecule S006-830, belonging to the class of thiophene-containing trisubstituted methanes, had shown good in vitro and in vivo bactericidal activity against drug-sensitive and drug-resistant Mycobacterium tuberculosis (Mtb). The molecule had also shown good druglike pharmacokinetic properties. However, S006-830 is a racemic mixture of two enantiomers, one of which could possess a better pharmacological profile than the other. We purified both the enantiomers on a chiral column and observed that S-enantiomer has a significantly higher inhibitory and cidal activity against Mtb than the R-enantiomer. Action of S-S006-830 was "synergistic" for rifampicin and "additive" for isoniazid and ethambutol. The combination of S-S006-830 and rifampicin produced 100% kill of Mtb within 8 days. In a chemical proteomics approach using matrix-bound compound to pull down its target protein(s) from Mtb membrane, FabG4 (ß-ketoacyl CoA reductase, EC 1.1.1.100) emerged as the most likely target for S-S006-830. In target validation assays, the compound exhibited 2-fold higher inhibitory concentration for an Mtb construct overexpressing FabG4. In addition, it inhibited mycolic acid biosynthesis and formation of biofilms by Mtb. Molecular docking of S-S006-830 with FabG4 was consistent with the experimental data. These results support the development of S-S006-830 as a novel lead against tuberculosis.

Correction to "S-Enantiomer of the Antitubercular Compound S006-830 Complements Activity of Frontline TB Drugs and Targets Biogenesis of Mycobacterium tuberculosis Cell Envelope".

[This corrects the article DOI: 10.1021/acsomega.7b01281.].

A combination of complexation and self-nanoemulsifying drug delivery system for enhancing oral bioavailability and anticancer efficacy of curcumin.

OBJECTIVE: Curcumin, the golden spice from Indian saffron, has shown chemoprotective action against many types of cancer including breast cancer. However, poor oral bioavailability is the major hurdle in its clinical application. In the recent years, self-nanoemulsifying drug delivery system (SNEDDS) has emerged as a promising tool to improve the oral absorption and enhancing the bioavailability of poorly water-soluble drugs. In this context, complexation with lipid carriers like phospholipid has also shown the tremendous potential to improve the solubility and therapeutic efficacy of certain drugs with poor oral bioavailability. METHODS: In the present investigation, a systematic combination of both the approaches is utilized to prepare the phospholipid complex of curcumin and facilitate its incorporation into SNEDDS. The combined use of both the approaches has been explored for the first time to enhance the oral bioavailability and in turn increase the anticancer activity of curcumin. RESULTS: As evident from the pharmacokinetic studies and in situ single pass intestinal perfusion studies in Sprague-Dawley rats, the optimized SNEDDS of curcumin-phospholipid complex has shown enhanced oral absorption and bioavailability of curcumin. The cytotoxicity study in metastatic breast carcinoma cell line has shown the enhancement of cytotoxic action by 38.7%. The primary tumor growth reduction by 58.9% as compared with the control group in 4T1 tumor-bearing BALB/c mice further supported the theory of enhancement of anticancer activity of curcumin in SNEDDS. CONCLUSION: The developed formulation can be a potential and safe carrier for the oral delivery of curcumin.

Phospholipid complexation of NMITLI118RT+: way to a prudent therapeutic approach for beneficial outcomes in ischemic stroke in rats.

Withania somnifera Dunal (Solanaceae) known as Ashwagandha, a popular plant of Indian origin is known to possess tremedous medicinal potential, often used as anti-inflammatory, anti-platelet, antihypertensive, hypoglycemic, hypolipidemic and adaptogenic candidate. Some of its chemotypes developed by CSIR, India includes NMITLI-101, NMITLI-118, NMITLI-128. In this study the investigators have attempted development of a phytosomal complex of NMITLI118RT + (standardized ethanolic extract of a new chemotype of W. somnifera Dunal.), its pharmaceutical characterization and evaluation of its neuro-protective potential against experimenal stroke in rats in continuation with their previous work in this area. The phytosomal complex (NIMPLC) was prepared by following a cohesive optimization design and was characterized on the basis of solubility, dissolution profile, FT-IR, DSC-TGA analysis, zeta potential, physical stability, forced degradation and photolytic degradation. Results were suggestive of a pharmaceutically acceptable formulation. NIMPLC was taken up further for biological evaluation using the middle cerebral artery occlusion (MCAO) model in rats. It could be demonstrated that the beneficial effects of NMITLI118RT + could be augmented by NIMPLC in 1 h pre and 6 h post treatment as was evident from reduction in MDA levels, increment in GSH levels, reduction in neurological deficit (ND) scores and reduction in infarct size. The study could successfully demonstrate the beneficial effects of NIMPLC in brain function restoration following stroke.

PEGylated chitosan nanoparticles potentiate repurposing of ormeloxifene in breast cancer therapy.

AIM: Development and optimization of ormeloxifene-loaded PEGylated chitosan nanoparticles (CNPs) for enhancing its literature profound therapeutic activity against breast cancer. METHODS: CNPs were prepared by ionotropic gelation method and characterized. RESULTS: Optimized formulation (CNPs10) had average 304 nm particle size with 0.247 polydispersity index and spherical shape with +31 mV surface charge. CNPs10 had 88.37% entrapment efficiency and 20.93% loading efficiency. CNPs10 demonstrated dose-dependent enhancement in cytotoxicity, cellular uptake, apoptosis, disruption of mitochondrial membrane potential and activation of caspase-3 in breast cancer MDA-MB-231 and MCF-7 cells over free ormeloxifene. In vivo studies divulged improved pharmacokinetic parameters, reduced toxicity, suppressed tumor burden and increased survival in CNPs10-treated female Sprague-Dawley rats. CONCLUSION: PEGylated CNPs enhanced anticancer activity of ormeloxifene.

Effect of polydimethylsiloxane and ethylcellulose on in vitro permeation of centchroman from its transdermal patches.

This research aims at the development of controlled release contraceptive transdermal patches of centchroman using ethylcellulose (EC) as film-forming polymer, polydimethylsiloxane (PDMS) as pressure sensitive adhesive with propylene glycol and Di-n-butyl-phthalate for their penetration enhancer and plasticizing properties, respectively. The physicochemical compatibility of the drug and the polymers was performed by differential scanning calorimetry and Fourier transform infrared (FTIR) spectroscopic technique. Effects of EC and PDMS ratios on moisture uptake, moisture content, tensile strength (TS), Young's modulus, adhesive strength, water vapor transmission rate (WVTR) and in vitro permeation of centchroman through Sprague-Dawley rats abdominal skin using Franz's diffusion cell were evaluated. A 3(2) full factorial design was employed to observe the effect of independent variables; concentration of ethyl cellulose and PDMS on drug permeated after 32 h, which was selected as dependent variable. Compatibility studies suggested that there were no significant interaction between the drug and polymers used. It was found that incorporation of only EC resulted in too hard patches and addition of PDMS produced patches with lower TS, increased percentage elongation, WVTR and Young's modulus. Statistical analyses suggested that independent variables have a significant effect on the dependent variable. All formulation follows zero-order release kinetics with r(2) > 0.990. In conclusion, drug in adhesive transdermal patches can be successfully fabricated for non-steroidal contraceptive centchroman to obtain a zero-order release systems.

Development, characterization and toxicological evaluations of phospholipids complexes of curcumin for effective drug delivery in cancer chemotherapy.

The purpose of this study was to prepare and characterize the complexes between curcumin (CU) phosphatidylcholine (PC) and hydrogenated soya phosphatidylcholine (HSPC) and to evaluate their anticancer activity. These CU-PC and CU-HSPC complexes (CU-PC-C and CU-HSPC-C) were evaluated for various physical parameters like Fourier transform infrared spectroscopy, melting point, solubility, scanning electron microscopy and the in vitro drug release study. These data confirmed the formation of phospholipids complexes. The in vitro hemolysis study showed that the complex was non-hemolytic. The anti-cancer potential of the complexes was demonstrated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay in MCF-7 cell line. This increase may be due to the amphiphilic nature of the complexes, which significantly enhances the water and lipid solubility of the CU. Unlike the free CU (which showed a total of only 90% drug release at the end of 8 h), complex showed around 40-60% release at the end of 8 h in dissolution studies. It showed that (when given in equimolar doses) complexes have significantly decreased the amount of CU available for absorption as compared with CU-free drug. Both CU-PC-C and CU-HSPC-C were found to be non-toxic at the dose equivalent to 2000 mg/kg of body weight of CU in the toxicity study. Acute and subacute toxicity studies confirmed the oral safety of the formulation. A series of genotoxicity studies was conducted, which revealed the non-genotoxicity potential of the developed complexes. Thus, it can be concluded that the phospholipid complexes of CU may be a promising candidate in cancer therapy.

Neuro-protective potential of a vesicular system of a standardized extract of a new chemotype of Withania somnifera Dunal (NMITLI118RT+) against cerebral stroke in rats.

Withania somnifera Dunal is an Indian medicinal plant with significant pharmacological properties, such as adaptogenic, anti-inflammatory, anti-oxidant, anti-platelet, anti-hypertensive, hypoglycemic and hypolipidemic effects. Several chemotypes of W. somnifera include NMITLI-101, NMITLI-118 and NMITLI-128. The present work elaborates the optimization and development of a liposomal delivery system for efficient delivery of NMITLI118RT+ [a standardized ethanolic extract of a new chemotype of W. somnifera Dunal (NMITLI-118) roots] against cerebral stroke in rats. Liposomal systems were prepared using thin-film hydration method and characterized on the basis of size, zeta potential, physical stability, FT-IR, DSC-TGA analysis and surface morphological studies by TEM. NMITLI118RT+ and its formulations (NMITLI118RT+LF) were evaluated for biological activity utilizing middle cerebral artery occlusion model in rats. The Z average of the developed liposomal formulation was about 142.6 ± 0.09 nm with a zeta potential of -31.20 ± 1.0 mV. Results of TEM revealed spherical particles in the range of 200 nm. The entrapment efficiency was found to be 94.603 ± 2%. The formulation was found to be physically stable over a 3-week period. Results were suggestive of the fact that both NMITLI118RT+ and its delivery system possess significant neuroprotective activity in cerebral ischemia. The liposomal system largely exhibits better performance over NMITLI118RT+ precisely in the post-treatment group. The present studies could elucidate the successful development of a delivery system for NMITLI118RT+ and demonstrate their beneficial neuro-protective potential in overcoming and reversing the consequences of I/R injury following stroke.

Chiral Separation of Ormeloxifene Hydrochloride, a Non-steroidal Contraceptive Agent.

Ormeloxifene hydrochloride (Centchroman) is once-a-week non-steroidal oral contraceptive agent marketed in India and other countries. In this study, we report a validated isocratic high-performance liquid chromatographic (HPLC) method for chiral separation of D- and L-ormeloxifene hydrochloride. This method is capable of baseline separation of its D- and L-isomers. HPLC separation was achieved on a Lux 5µ cellulose-1 with a mobile phase comprising hexane, isopropanol, methanol and triethylamine (90:10:1:0.5). Validation parameters such as limit of detection, limit of quantitation, linearity, precision, accuracy, specificity and preformulation studies were conducted according to new guidelines of International Conference on Harmonization.

Curcuma oil ameliorates insulin resistance & associated thrombotic complications in hamster & rat.

BACKGROUND & OBJECTIVES: Curcuma oil (C. oil) isolated from turmeric (Curcuma longa L.) has been shown to have neuro-protective, anti-cancer, antioxidant and anti-hyperlipidaemic effects in experimental animal models. However, its effect in insulin resistant animals remains unclear. The present study was carried out to investigate the disease modifying potential and underlying mechanisms of the C. oil in animal models of diet induced insulin resistance and associated thrombotic complications. METHODS: Male Golden Syrian hamsters on high fructose diet (HFr) for 12 wk were treated orally with vehicle, fenofibrate (30 mg/kg) or C. oil (300 mg/kg) in the last four weeks. Wistar rats fed HFr for 12 wk were treated orally with C. oil (300 mg/kg) in the last two weeks. To examine the protective effect of C. oil, blood glucose, serum insulin, platelet aggregation, thrombosis and inflammatory markers were assessed in these animals. RESULTS: Animals fed with HFr diet for 12 wk demonstrated hyperlipidaemia, hyperglycaemia, hyperinsulinaemia, alteration in insulin sensitivity indices, increased lipid peroxidation, inflammation, endothelial dysfunction, platelet free radical generation, tyrosine phosphorylation, aggregation, adhesion and intravascular thrombosis. Curcuma oil treatment for the last four weeks in hamsters ameliorated HFr-induced hyperlipidaemia, hyperglycaemia, insulin resistance, oxidative stress, inflammation, endothelial dysfunction, platelet activation, and thrombosis. In HFr fed hamsters, the effect of C. oil at 300 mg/kg [ ] was comparable with the standard drug fenofibrate. Curcuma oil treatment in the last two weeks in rats ameliorated HFr-induced hyperglycaemia and hyperinsulinaemia by modulating hepatic expression of sterol regulatory element binding protein 1c (SREBP-1c), peroxisome proliferator-activated receptor-gamma co-activator 1 (PGC-1)α and PGC-1ß genes known to be involved in lipid and glucose metabolism. INTERPRETATION & CONCLUSIONS: High fructose feeding to rats and hamsters led to the development of insulin resistance, hyperglycaemia, endothelial dysfunction and oxidative stress. C. oil prevented development of thrombotic complications associated with insulin resistance perhaps by modulating genes involved in lipid and glucose metabolism. Further studies are required to confirm these findings.

Assay method for quality control and stability studies of a new anti-diabetic and anti-dyslipidemic flavone (S002-853).

BACKGROUND: Flavonoid-rich extract of the plant is long known for its anti-diabetic activities in traditional medicine. S002-853, a new flavone derivative synthesized by Central Drug Research Institute (CDRI) has been used for the present study. OBJECTIVES: The present study aimed at development of an assay method for quality control (QC) and stability studies of a new anti-diabetic and anti-dyslipidemic agent CDRI compound S002-853. MATERIALS AND METHODS: A validated high-performance liquid chromatography analysis method for S002-853 was developed for in process QC and stability studies. The separation was achieved on a RP-C18 (25 cm × 0.4 cm, 5 µm, Phenomenex) at 240 nm with flow rate of 1.0 ml/min. This method was applied successfully in establishing forced degradation and drug-excipient testing protocols as per International Conference on Harmonization guidelines. RESULTS: The result of estimation and stress testing studies indicated a high degree of selectivity of this method. S002-853 was most stable at pH 7 and under photolytic conditions. The temperature degradation pattern of S002-853 was found to follow the zero order degradation. CONCLUSION: The method described is easy and simple hence can be easily reproduced. This method can be very useful for bulk manufacture QC, and drug development process.

Validation of RP-HPLC Method for Simultaneous Quantification of Bicalutamide and Hesperetin in Polycaprolactone-Bicalutamide-Hesperetin-Chitosan Nanoparticles.

Bicalutamide is a non-steroidal anti-androgen drug used for the treatment of androgen-dependent prostate cancer. Hesperetin is a natural bioflavonoid that can be used in combination with bicalutamide to improve efficacy and decrease tolerance. The aim of the present work was to develop and validate a simple, sensitive, rapid reverse phase-high performance liquid chromatographic method for simultaneous estimation of bicalutamide and hesperetin. The validation parameters such as specificity, linearity, precision and accuracy, limit of detection (LOD) and limit of quantification (LOQ) were determined according to International Conference on Harmonization ICH Q2 (R1) guidelines. Chromatographic separation was achieved on Lichrocart(®) CN column (250 × 4 mm, 5 µm, MERCK) with isocratic elution. The retention times and detection wavelength, for hesperetin and bicalutamide were 4.28 min, 288 nm and 5.90 min, 270 nm respectively. The intra-day and inter-day assay precision and accuracy were found to be <2% over linearity of 50-2000 ng/mL with R(2) 0.999. LOD and LOQ, of bicalutamide and hesperetin was 14.70, 44.57 ng/mL and 16.11, 48.84 ng/mL, respectively. The method was successfully applied for encapsulation efficiency and drug release studies from bicalutamide and hesperetin loaded nanoparticles.

Antipsychotic activity of standardized Bacopa extract against ketamine-induced experimental psychosis in mice: Evidence for the involvement of dopaminergic, serotonergic, and cholinergic systems.

CONTEXT: Schizophrenia is a chronic disabling psychiatric disorder affecting 1% of the population worldwide. Due to the adverse effects of available antipsychotic medications, recent investigations have focused on the search for well-tolerated, safe molecules from natural resources to control the severity and progression of schizophrenia. OBJECTIVE: To screen the standardized extract of Bacopa monniera Linn. (Scrophulariaceae) (BM) for its antipsychotic potential in the ketamine-induced psychosis model with mice. MATERIALS AND METHODS: Graded dose of BM (40, 80, and 120 mg/kg, p.o.) were given to the mice 1 h prior to ketamine administration and tested for positive symptoms and cognitive deficits. A chronic ketamine treatment regimen was used to study the effect of BM on negative symptoms such as immobility enhancement. Each mouse was used once for the behavioral studies. RESULTS: BM reduced ketamine-induced hyperactivity with an EC50 value of 76.60 mg/kg. The 80 mg/kg dose was used for all other behavior analysis. Pretreatment with BM at 80 mg/kg showed two-fold increases in transfer latency time (TLT) in passive avoidance task. Chronic BM pretreatment (80 mg/kg p.o. daily × 10 d) ameliorated the ketamine-induced enhanced immobility effect by 21% in the forced swim test. BM treatment reversed ketamine-induced increase in monoamine oxidase activity in both cortex and striatum and normalized the acetylcholinesterase activity and the glutamate levels in the hippocampus. DISCUSSION AND CONCLUSION: Overall our findings suggest that BM possesses antipsychotic properties which might be due to its modulatory action on dopamine, serotonin, and glutamate neurotransmission.

Arteether nanoemulsion for enhanced efficacy against Plasmodium yoelii nigeriensis malaria: an approach by enhanced bioavailability.

The present work is focused on the preparation of nanoemulsions (NEs) loaded with arteether (ART) for its enhanced efficacy against malaria parasites. ART-NEs have been prepared using high pressure homogenization (HPH) technique with the aim of improving its solubility and thus its bioavailability. ART-NEs were optimized in terms of pressure and number of cycles. Globule size and size distributions were chosen as quality parameters. The maximum drug loading was achieved up to 93 ± 7.4% with globule size 156 ± 10.2 nm and zeta potential of -23.3 ± 3.4 mV. The developed ART-NEs were found to be stable in terms of globule size and size distribution at different pH. The in vitro release profile of the ART-NEs showed 62% drug release within 12h. The percentage cell viability of blank NEs were within acceptable limits. A sensitive assay method for the determination of ART in rat plasma by liquid chromatography-mass spectrometry (LC-MS) was employed after oral administration of ART-NEs. The pharmacokinetic study showed significantly enhanced bioavailability of ART in ART-NE-V. The area under curve (AUC) of ART-NE-V was AUC0-t 1988.411 ± 119.66 h ng/ml which was significantly higher (p<0.05) than ART in ground nut oil (GNO) AUC0-t 671.852 ± 187.05 h ng/ml. The Cmax of ART-NE-V (1506 ± 161.22 ng/ml) was also significantly higher (p<0.05) than ART in GNO (175.2 ± 16.54 ng/ml) and ART given intramuscularly (IM) (278.05 ± 38.59 ng/ml). The ART-NE-V was having significantly high antimalarial efficacy and survival rate of mice giving 80% cure rate at 12.5 mg/kg for 5 days in comparison to 30% cure rate of ART in GNO at the same daily dose and it was also comparable to the 100% cure rate at 12.5 mg/kg for 5 days for ART given intramuscularly. In conclusion ART-NE can be a promising oral delivery system for ART.

Curcuma oil attenuates accelerated atherosclerosis and macrophage foam-cell formation by modulating genes involved in plaque stability, lipid homeostasis and inflammation.

In the present study, the anti-atherosclerotic effect and the underlying mechanism of curcuma oil (C. oil), a lipophilic fraction from turmeric (Curcuma longa L.), was evaluated in a hamster model of accelerated atherosclerosis and in THP-1 macrophages. Male golden Syrian hamsters were subjected to partial carotid ligation (PCL) or FeCl3-induced arterial oxidative injury (Ox-injury) after 1 week of treatment with a high-cholesterol (HC) diet or HC diet plus C. oil (100 and 300 mg/kg, orally). Hamsters fed with the HC diet were analysed at 1, 3 and 5 weeks following carotid injury. The HC diet plus C. oil-fed group was analysed at 5 weeks. In hyperlipidaemic hamsters with PCL or Ox-injury, C. oil (300 mg/kg) reduced elevated plasma and aortic lipid levels, arterial macrophage accumulation, and stenosis when compared with those subjected to arterial injury alone. Similarly, elevated mRNA transcripts of matrix metalloproteinase-2 (MMP-2), MMP-9, cluster of differentiation 45 (CD45), TNF-α, interferon-γ (IFN-γ), IL-1ß and IL-6 were reduced in atherosclerotic arteries, while those of transforming growth factor-ß (TGF-ß) and IL-10 were increased after the C. oil treatment (300 mg/kg). The treatment with C. oil prevented HC diet- and oxidised LDL (OxLDL)-induced lipid accumulation, decreased the mRNA expression of CD68 and CD36, and increased the mRNA expression of PPARα, LXRα, ABCA1 and ABCG1 in both hyperlipidaemic hamster-derived peritoneal and THP-1 macrophages. The administration of C. oil suppressed the mRNA expression of TNF-α, IL-1ß, IL-6 and IFN-γ and increased the expression of TGF-ß in peritoneal macrophages. In THP-1 macrophages, C. oil supplementation prevented OxLDL-induced production of TNF-α and IL-1ß and increased the levels of TGF-ß. The present study shows that C. oil attenuates arterial injury-induced accelerated atherosclerosis, inflammation and macrophage foam-cell formation.