Search results for: drug administration

Authors: Gagan Dhawan

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Mycobacterium tuberculosis was described as ‘captain of death’ with an inherent property of multiple drug resistance majorly caused by the competent mechanism of efflux pumps. In this study, various open source tools combining chemo-informatics with bioinformatics were used for efficient in-silico drug designing. The efflux pump, Rv1218c, belonging to the ABC transporter superfamily, which is predicted to be a tetronasin-transporter in M. tuberculosis was targeted. Recent studies have shown that Rv1218c forms a complex with two more efflux pumps (Rv1219c and Rv1217c) to provide multidrug resistance to the bacterium. The 3D structure of the protein was modeled (as the structure was unavailable in the previously collected databases on this gene). The TMHMM analysis of this protein in TubercuList has shown that this protein is present in the outer membrane of the bacterium. Virtual screening of compounds from various publically available chemical libraries was performed on the M. tuberculosis protein using various open source tools. These ligands were further assessed where various physicochemical properties were evaluated and analyzed. On comparison of different physicochemical properties, toxicity and docking, the ligand 2-(hydroxymethyl)-6-[4, 5, 6-trihydroxy-2-(hydroxymethyl) tetrahydropyran-3-yl] oxy-tetrahydropyran-3, 4, 5-triol was found to be best suited for further studies.

Keywords: drug resistance, efflux pump, molecular docking, virtual screening

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Authors: Donna M. Morrison, Lambert Chester, Coretta A. N. Samuels, David R. Ledoux

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A survey was conducted in the five rice-growing regions in Guyana to determine the presence of aflatoxins in multiple fractions of rice in June/October 2015 growing season. The fractions were paddy, steamed paddy, cargo rice, white rice and parboiled rice. Samples were analyzed by High Performance Liquid Chromatography. A subset of the samples was further analyzed by enzyme-linked immunosorbent assay (ELISA) for concurrence. All analyses were conducted at the University of Missouri, USA. Of the 186 samples tested, 16 had aflatoxin concentrations greater than 20 ppb the recommended limit for aflatoxins in food according to the United States Food and Drug Administration. An additional three samples had aflatoxin B₁ concentrations greater than the European Union Commission maximum levels for aflatoxin B₁ in rice at 5 µg/kg and total aflatoxins (B₁, B₂, G₁ and G₂) at 10 µg/kg. The survey indicates that there is no widespread aflatoxin problem in rice in Guyana. The incidence of aflatoxins appears to be localized.

Keywords: aflatoxin, enzyme-linked immunosorbent assay (ELISA), high-performance liquid chromatography (HPLC), rice fractions

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Authors: Syed Asif Hassan, Tabrej Khan

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Multiple sclerosis (MS) is a chronic demyelinating autoimmune disorder, of the central nervous system (CNS). In the present scenario, the current therapies either do not halt the progression of the disease or have side effects which limit the usage of current Disease Modifying Therapies (DMTs) for a longer period of time. Therefore, keeping the current treatment failure schema, we are focusing on screening novel analogues of the available DMTs that specifically bind and inhibit the Sphingosine1-phosphate receptor1 (S1PR1) thereby hindering the lymphocyte propagation toward CNS. The novel drug-like analogs molecule will decrease the frequency of relapses (recurrence of the symptoms associated with MS) with higher efficacy and lower toxicity to human system. In this study, an integrated approach involving ligand-based virtual screening protocol (Ultrafast Shape Recognition with CREDO Atom Types (USRCAT)) to identify the non-toxic drug like analogs of the approved DMTs were employed. The potency of the drug-like analog molecules to cross the Blood Brain Barrier (BBB) was estimated. Besides, molecular docking and simulation using Auto Dock Vina 1.1.2 and GOLD 3.01 were performed using the X-ray crystal structure of Mtb LprG protein to calculate the affinity and specificity of the analogs with the given LprG protein. The docking results were further confirmed by DSX (DrugScore eXtented), a robust program to evaluate the binding energy of ligands bound to the ligand binding domain of the Mtb LprG lipoprotein. The ligand, which has a higher hypothetical affinity, also has greater negative value. Further, the non-specific ligands were screened out using the structural filter proposed by Baell and Holloway. Based on the USRCAT, Lipinski’s values, toxicity and BBB analysis, the drug-like analogs of fingolimod and BG-12 showed that RTL and CHEMBL1771640, respectively are non-toxic and permeable to BBB. The successful docking and DSX analysis showed that RTL and CHEMBL1771640 could bind to the binding pocket of S1PR1 receptor protein of human with greater affinity than as compared to their parent compound (Fingolimod). In this study, we also found that all the drug-like analogs of the standard MS drugs passed the Bell and Holloway filter.

Keywords: antagonist, binding affinity, chemotherapeutics, drug-like, multiple sclerosis, S1PR1 receptor protein

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Authors: Reynaldo Esquivel, Pedro Hernandez, Aaron Martinez-Higareda, Sergio Tena-Cano, Enrique Alvarez-Ramos, Armando Lucero-Acuna

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Stimuli-responsive nanomaterials play an essential role in loading, transporting and well-distribution of anti-cancer compounds in the cellular surroundings. The outstanding properties as the Lower Critical Solution Temperature (LCST), hydrolytic cleavage and protonation/deprotonation cycle, govern the release and delivery mechanisms of payloads. In this contribution, we experimentally determine the load efficiency and release of antineoplastic Vincristine Sulfate into PNIPAM-Interpenetrated-Chitosan (PIntC) nanoparticles. Structural analysis was performed by Fourier Transform Infrared Spectroscopy (FT-IR) and Proton Nuclear Magnetic Resonance (1HNMR). ζ-Potential (ζ) and Hydrodynamic diameter (DH) measurements were monitored by Electrophoretic Mobility (EM) and Dynamic Light scattering (DLS) respectively. Mathematical analysis of the release pharmacokinetics reveals a three-phase model above LCST, while a monophasic of Vincristine release model was observed at 32 °C. Cytotoxic essays reveal a noticeable enhancement of Vincristine effectiveness at low drug concentration on HeLa cervix cancer and MDA-MB-231 breast cancer.

Keywords: nanoparticles, vincristine, drug delivery, PNIPAM

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Authors: Akinsola Oluwatosin, Udofia Samuel, Odofin Mayowa

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The study is aimed at assessing the Geographic Information System (GIS)-based spatial analysis of Survival Pattern and Treatment Outcomes of Multi-Drug Resistant Tuberculosis (MDR-TB) cases for Lagos, Nigeria, with an objective to inform priority areas for public health planning and resource allocation. Multi-drug resistant tuberculosis (MDR-TB) develops due to problems such as irregular drug supply, poor drug quality, inappropriate prescription, and poor adherence to treatment. The shapefile(s) for this study were already georeferenced to Minna datum. The patient’s information was acquired on MS Excel and later converted to . CSV file for easy processing to ArcMap from various hospitals. To superimpose the patient’s information the spatial data, the addresses was geocoded to generate the longitude and latitude of the patients. The database was used for the SQL query to the various pattern of the treatment. To show the pattern of disease spread, spatial autocorrelation analysis was used. The result was displayed in a graphical format showing the areas of dispersing, random and clustered of patients in the study area. Hot and cold spot analysis was analyzed to show high-density areas. The distance between these patients and the closest health facility was examined using the buffer analysis. The result shows that 22% of the points were successfully matched, while 15% were tied. However, the result table shows that a greater percentage of it was unmatched; this is evident in the fact that most of the streets within the State are unnamed, and then again, most of the patients are likely to supply the wrong addresses. MDR-TB patients of all age groups are concentrated within Lagos-Mainland, Shomolu, Mushin, Surulere, Oshodi-Isolo, and Ifelodun LGAs. MDR-TB patients between the age group of 30-47 years had the highest number and were identified to be about 184 in number. The outcome of patients on ART treatment revealed that a high number of patients (300) were not ART treatment while a paltry 45 patients were on ART treatment. The result shows the Z-score of the distribution is greater than 1 (>2.58), which means that the distribution is highly clustered at a significance level of 0.01.

Keywords: tuberculosis, patients, treatment, GIS, MDR-TB

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Authors: Amr A. Fouad, Waleed H. Albuali, Iyad Jresat

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The protective effect of thymoquinone (TQ) was investigated in rats exposed to testicular injury induced by sodium arsenite (10mg/kg/day, orally, for two days). TQ treatment (10mg/kg/day, intraperitoneal injection) was applied for five days, starting three day before arsenic administration. TQ significantly attenuated the arsenic-induced decreases of serum testosterone, and testicular reduced glutathione level, and significantly decreased the elevations of testicular malondialdehyde and nitric oxide levels resulted from arsenic administration. Also, TQ ameliorated the arsenic-induced testicular tissue injury observed by histopathological examination. In addition, TQ decreased the arsenic-induced expression of inducible nitric oxide synthase and caspase-3 in testicular tissue. It was concluded that TQ may represent a potential candidate to protect against arsenic-induced testicular injury.

Keywords: thymoquinone, arsenic, testes, rats

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Authors: Amr A. Fouad, Waleed H. Albuali, Iyad Jresat

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The protective effect of hesperidin was investigated in rats exposed to liver injury induced by a single intraperitoneal injection of cyclophosphamide (CYP) at a dose of 150 mg kg-1. Hesperidin treatment (100 mg kg-1/day, orally) was applied for seven days, starting five days before CYP administration. Hesperidin significantly decreased the CYP-induced elevations of serum alanine aminotransferase, and hepatic malondialdehyde and myeloperoxidase activity, significantly prevented the depletion of hepatic glutathione peroxidase activity resulted from CYP administration. Also, hesperidin ameliorated the CYP-induced liver tissue injury observed by histopathological examination. In addition, hesperidin decreased the CYP-induced expression of inducible nitric oxide synthase, tumor necrosis factor-α, cyclooxygenase-2, Fas ligand, and caspase-9 in liver tissue. It was concluded that hesperidin may represent a potential candidate to protect against CYP-induced hepatotoxicity.

Keywords: hesperidin, cyclophosphamide, liver, rats

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Authors: Esra Turker, Umit Hakan Yildiz, Ahu Arslan Yildiz

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The key of regenerative medicine is mimicking natural three dimensional (3D) microenvironment of tissues by utilizing appropriate biomaterials. In this study, a synthetic biodegradable polymer; poly (L-lactide-co-ε-caprolactone) (PLLCL) and a natural polymer; collagen was used to mimic the biochemical structure of the natural extracellular matrix (ECM), and by means of electrospinning technique the real physical structure of ECM has mimicked. PLLCL/Collagen biocomposite scaffolds enables cell attachment, proliferation and nutrient transport through fabrication of micro to nanometer scale nanofibers. Biocomposite materials are commonly preferred due to limitations of physical and biocompatible properties of natural and synthetic materials. Combination of both materials improves the strength, degradation and biocompatibility of scaffold. Literature studies have shown that collagen is mostly solved with heavy chemicals, which is not suitable for cell culturing. To overcome this problem, a new approach has been developed in this study where polyvinylpyrrolidone (PVP) is used as co-electrospinning agent. PVP is preferred due to its water solubility, so PLLCL/collagen biocomposite scaffold can be easily and rapidly produced. Hydrolytic and enzymatic biodegradation as well as mechanical strength of scaffolds were examined in vitro. Cell adhesion, proliferation and cell morphology characterization studies have been performed as well. Further, on-chip drug screening analysis has been performed over 3D tumor models. Overall, the developed biocomposite scaffold was used for 3D tumor model formation and obtained results confirmed that developed model could be used for drug screening studies to predict clinical efficacy of a drug.

Keywords: biomaterials, 3D cell culture, drug screening, electrospinning, lab-on-a-chip, tissue engineering

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Authors: Hugo Reis, Isabel Rabiais

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The main purpose of the present study is to understand the nurse’s responsibility in preventing the septic shock in an oncological patient with febrile neutropenia submitted to chemotherapy. In order to do it, an integrative review of literature has been conducted. In the research done in many databases, it was concluded that only 7 out of 5202 articles compiled the entire inclusion standard present in the strict protocol of research, being this made up by all different methodologies. On the research done in the 7 articles it has resulted 8 text macro-units associated to different nursing interventions: ‘Health Education’; ‘Prophylactic Therapy Administration’; ‘Scales Utilization’; ‘Patient Evaluation’; ‘Environment Control’; ‘Performance of Diagnostic Auxiliary Exams’; ‘Protocol Enforcement/Procedure Guidelines’; ‘Antibiotic Therapy Administration’. Concerning the prevalence/result’s division there can be identified many conclusions: the macro-units ‘Patient Evaluation’, ‘Performance of Diagnostic Auxiliary Exams’, and ‘Antibiotic Therapy Administration’ present themselves to be the most prevalent in the research – 6 in 7 occurrences (approximately 85.7%). Next, the macro-unit ‘Protocol Enforcement/Procedure Guidelines’ presents itself as an important expression unit – being part of 5 out of the 7 analyzed studies (approximately 71.4%). The macro-unit ‘Health Education’, seems to be in the same way, an important expression unit – 4 out of the 7 (or approximately 57%). The macro-unit ‘Scales Utilization’, represents a minor part in the research done – it’s in only 2 out of the 7 cases (approximately 28.6%). On the other hand, the macro-units ‘Prophylactic Therapy Administration’ and ‘Environment Control’ are the two categories with fewer results in the research - 1 out of the 7 cases, the same as approximately 14.3% of the research results. Every research done to the macro-unit ‘Antibiotic Therapy Administration’ agreed to refer that the intervention should be strictly done, in a period of time less than one hour after diagnosing the fever, with the purpose of controlling the quick spread of infection – minimizing its seriousness. Identifying these interventions contributes, concluding that, to adopt strategies in order to prevent the phenomenon that represents a daily scenario responsible for the cost´s increase in health institutions, being at the same time responsible for the high morbidity rates and mortality increase associated with this specific group of patients.

Keywords: febrile neutropenia, oncology nursing, patient, septic shock

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Authors: Mahsa Fathollahzadeh

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The various nanoparticles employed in drug delivery applications include micelles, liposomes, solid lipid nanoparticles, polymeric nanoparticles, functionalized nanoparticles, nanocrystals, cyclodextrins, dendrimers, and nanotubes. Micelles, composed of amphiphilic block copolymers, can encapsulate hydrophobic molecules, allowing for targeted delivery. Liposomes, vesicular structures made up of phospholipids, can encapsulate both hydrophobic and hydrophilic molecules, providing a flexible platform for delivering therapeutic agents. Solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) are designed to improve the stability and bioavailability of lipophilic drugs. Polymeric nanoparticles, such as poly(lactic-co-glycolic acid) (PLGA), are biodegradable and can be engineered to release drugs in a controlled manner. Functionalized nanoparticles, coated with targeting ligands or antibodies, can specifically target diseased cells or tissues. Nanocrystals, engineered to have specific surface properties, can enhance the solubility and bioavailability of poorly soluble drugs. Cyclodextrins, doughnut-shaped molecules with hydrophobic cavities, can be complex with hydrophobic molecules, allowing for improved solubility and bioavailability. Dendrimers, branched polymers with a central core, can be designed to deliver multiple therapeutic agents simultaneously. Nanotubes and metallic nanoparticles, such as gold nanoparticles, offer real-time tracking capabilities and can be used to detect biomolecular interactions. The use of these nanoparticles has revolutionized the field of drug delivery, enabling targeted and controlled release of therapeutic agents, reduced toxicity, and improved patient outcomes.

Keywords: nanotechnology, nanopharmaceuticals, drug-delivery, proteins, ligands, nanoparticles, chemistry

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Authors: Meiling Yu, Nadia Rouatbi, Khuloud T. Al-Jamal

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Background: Treatment of neurological disorders with modern medical and surgical approaches remains difficult. Gene therapy, allowing the delivery of genetic materials that encodes potential therapeutic molecules, represents an attractive option. The treatment of brain diseases with gene therapy requires the gene-editing tool to be delivered efficiently to the central nervous system. In this study, we explored the efficiency of different delivery routes, namely intravenous (i.v.), intra-cranial (i.c.), and intra-nasal (i.n.), to deliver stable nucleic acid-lipid particles (SNALPs) containing gene-editing tools namely Cas9 mRNA and sgRNA encoding for GFP as a reporter protein. We hypothesise that SNALPs can reach the brain and perform gene-editing to different extents depending on the administration route. Intranasal administration (i.n.) offers an attractive and non-invasive way to access the brain circumventing the blood–brain barrier. Successful delivery of gene-editing tools to the brain offers a great opportunity for therapeutic target validation and nucleic acids therapeutics delivery to improve treatment options for a range of neurodegenerative diseases. In this study, we utilised Rosa26-Cas9 knock-in mice, expressing GFP, to study brain distribution and gene-editing efficiency of SNALPs after i.v.; i.c. and i.n. routes of administration. Methods: Single guide RNA (sgRNA) against GFP has been designed and validated by in vitro nuclease assay. SNALPs were formulated and characterised using dynamic light scattering. The encapsulation efficiency of nucleic acids (NA) was measured by RiboGreen™ assay. SNALPs were incubated in serum to assess their ability to protect NA from degradation. Rosa26-Cas9 knock-in mice were i.v., i.n., or i.c. administered with SNALPs to test in vivo gene-editing (GFP knockout) efficiency. SNALPs were given as three doses of 0.64 mg/kg sgGFP following i.v. and i.n. or a single dose of 0.25 mg/kg sgGFP following i.c.. knockout efficiency was assessed after seven days using Sanger Sequencing and Inference of CRISPR Edits (ICE) analysis. In vivo, the biodistribution of DiR labelled SNALPs (SNALPs-DiR) was assessed at 24h post-administration using IVIS Lumina Series III. Results: Serum-stable SNALPs produced were 130-140 nm in diameter with ~90% nucleic acid loading efficiency. SNALPs could reach and stay in the brain for up to 24h following i.v.; i.n. and i.c. administration. Decreasing GFP expression (around 50% after i.v. and i.c. and 20% following i.n.) was confirmed by optical imaging. Despite the small number of mice used, ICE analysis confirmed GFP knockout in mice brains. Additional studies are currently taking place to increase mice numbers. Conclusion: Results confirmed efficient gene knockout achieved by SNALPs in Rosa26-Cas9 knock-in mice expressing GFP following different routes of administrations in the following order i.v.= i.c.> i.n. Each of the administration routes has its pros and cons. The next stages of the project involve assessing gene-editing efficiency in wild-type mice and replacing GFP as a model target with therapeutic target genes implicated in Motor Neuron Disease pathology.

Keywords: CRISPR, nanoparticles, brain diseases, administration routes

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Authors: Lin Po-Hsi, Sheu Ming-Thau

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Urea cycle disorders (UCD) are rare genetic metabolic disorders that compromise the body's urea cycle. Sodium phenylbutyrate (SPB) is a medication commonly administered in tablet or powder form to lower ammonia levels. Nonetheless, its high sodium content poses risks to sodium-sensitive UCD patients. This necessitates the creation of an alternative drug formulation to mitigate sodium load and optimize drug delivery for UCD patients. This study focused on crafting a novel oral drug formulation for UCD, leveraging choline bicarbonate and phenylbutyric acid. The active pharmaceutical ingredient-ionic liquids (API-ILs) and therapeutic deep eutectic systems (THEDES) were formed by combining these with choline chloride. These systems display characteristics like maintaining a liquid state at room temperature and exhibiting enhanced solubility. This in turn amplifies drug dissolution rate, permeability, and ultimately oral bioavailability. Incorporating choline-based phenylbutyric acid as a substitute for traditional SPB can effectively curtail the sodium load in UCD patients. Our in vitro dissolution experiments revealed that the ILs and DESs, synthesized using choline bicarbonate and choline chloride with phenylbutyric acid, surpassed commercial tablets in dissolution speed. Pharmacokinetic evaluations in SD rats indicated a notable uptick in the oral bioavailability of phenylbutyric acid, underscoring the efficacy of choline salt ILs in augmenting its bioavailability. Additional in vitro intestinal permeability tests on SD rats authenticated that the ILs, formulated with choline bicarbonate and phenylbutyric acid, demonstrate superior permeability compared to their sodium and acid counterparts. To conclude, choline salt ILs developed from choline bicarbonate and phenylbutyric acid present a promising avenue for UCD treatment, with the added benefit of reduced sodium load. They also hold merit in formulation engineering. The sustained-release capabilities of DESs position them favorably for drug delivery, while the low toxicity and cost-effectiveness of choline chloride signal potential in formulation engineering. Overall, this drug formulation heralds a prospective therapeutic avenue for UCD patients.

Keywords: phenylbutyric acid, sodium phenylbutyrate, choline salt, ionic liquids, deep eutectic systems, oral bioavailability

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Authors: Gajanan M. Sonwane

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Nowadays, the entire pharmaceutical industry is facing the challenge of increasing efficiency and innovation. The major hurdles are the growing cost of research and development and a concurrent stagnating number of new chemical entities (NCEs). Hence, the challenge is to select the most druggable targets and to search the equivalent drug-like compounds, which also possess specific pharmacokinetic and toxicological properties that allow them to be developed as drugs. The present research work includes the studies of developing new anticancer heterocycles by using molecular modeling techniques. The heterocycles synthesized through such methodology are much effective as various physicochemical parameters have been already studied and the structure has been optimized for its best fit in the receptor. Hence, on the basis of the literature survey and considering the need to develop newer anticancer agents, new phenazinamine derivatives were designed by subjecting the nucleus to molecular modeling, viz., GQSAR analysis and docking studies. Simultaneously, these designed derivatives were subjected to in silico prediction of biological activity through PASS studies and then in silico toxicity risk assessment studies. In PASS studies, it was found that all the derivatives exhibited a good spectrum of biological activities confirming its anticancer potential. The toxicity risk assessment studies revealed that all the derivatives obey Lipinski’s rule. Amongst these series, compounds 4c, 5b and 6c were found to possess logP and drug-likeness values comparable with the standard Imatinib (used for anticancer activity studies) and also with the standard drug methotrexate (used for antimitotic activity studies). One of the most notable mutations is the threonine to isoleucine mutation at codon 315 (T315I), which is known to be resistant to all currently available TKI. Enzyme assay planned for confirmation of target selective activity.

Keywords: drug design, tyrosine kinases, anticancer, Phenazinamine

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Authors: Neha Singh

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Background: Nowadays, the nanoparticle is gaining unexceptional attention in targeted drug delivery. But before proceeding to this episode of accomplishment, the journey and closure of these nanoparticles inside the cells should be disentangle. Being foreign for the cells, nanoparticles will easily getcleared off without any effective outcome. As the cancer cells withhold these nanoparticles for a longer period of time, more will be the drug’s effect. Chlorpromazine is a cationic amphiphilic drug which is believed to inhibit clathrin-coated pit formation by a reversible translocation of clathrin and its adapter proteins from the plasma membrane to intracellular vesicles. Chlorpromazine has a role in increasing the retention of nanoparticles in cancer cells. The mechanism of action how this small molecule increases the retention of nanoparticles is still uncovered. Method: Polymeric nanoparticle (PLGA) with Cyanine3.5 dye were synthesized by solvent evaporation method and characterized for size and zeta potential. FTIR was also done. Pulse and chase studies with and without inhibitor were done to check the retention of nanoparticle using fluorescence microscopy. Mean fluorescence intensity was measured by ImageJ software. Results: Increased retention of nanoparticle with inhibitor was observed in both pulse and chase studies. Conclusion: Our results demonstrate that by repurposing these small molecule inhibitor, we can increase the retention of nanoparticle at the targeted site.

Keywords: nanoparticle, endocytosis, clathrin inhibitor, cancer cell

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Authors: Eitedal Daoud, Reda M.Daoud, Khaled Abdel-Wahhab, Maha M.Saber, Lobna Saber

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Background: Cis-platin is a widely used chemotherapeutic drug to treat many malignant disorders including head and neck malignancies. Oto-nephrotxicity is an important and dose - limiting side effect of cis - platin therapy. Nowadays, more attention had been paid to oto-toxicity caused with cis-platin. Aim of the Work: This study was designed to investigate the potential protective effect of Whey protein (WP) against cis-platin induced ototoxicity compared to the effect of N-acetylcysteine (NAC) in rats. Methodology: Male albino rats were randomly divided into 6 groups: untreated rats (control), rats orally treated with whey protein (1g/kg b.w/day) for seven executive days, rats treated orally with N-acetylcysteine (500 mg/kgb.w /day) for seven executive days, rates intoxicated intraperitoneal (ip) with cis- platin (10 mg/kgb.w. once), rats treated with whey protein (1g/kgb.w./day) for seven executive days) followed by one injection (ip) of cis-platin(10 mg/kg b.w.) one hour after the last oral administration of whey protein, rats treated with N- acetylcysteine (for seven executive days followed by one injection (ip) of cis-platin (10 mg/kgb.w) one hour after the last oral administration of N-acetylcysteine. The organ of Corti, the stria vascularis and spiral ganglia were visualized by light microscopy at different magnifications. Results: Cis-platin intoxicated animals showed a significant decrease in serum level of total antioxidant capacity (TAC),with inhibition in the activity of serum glutathione-s transferase(GST) and paraoxonnase-1 (PON-1) in comparison with control. Group treated with either NAC or WP with cis-platin showed significant elevation in the activity of both GST & PON-1 with increased serum level of TAC when compared with cis-platin intoxicated rats. Animals treated with NAC or WP with cis-platin compared to those treated with cis-platin alone showed marked degree of improvement towards control rats as there was significant drop in the serum level of cortecosterone, nitric oxide (NO), and melandialdehyde (MDA).Histopathologic, in NAC pretreated group there was no changes in stria vascularis or spiral ganglia. In group pretreated with WP, there was no histopathologic alteration detected in the organ of Corti and Reissers membrane but oedema and haemorrhage were founded in the stria vascularis in small focal manner. Conclusion: Our finding showed that Whey protein is a natural dietary supplement product proved its ability of protection of anti-oxidant system and the cochlea against cis-platin induced ototoxicity.

Keywords: anti-oxidant, cis-platin, N-acetylcysteine, ototoxicity, whey protein

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Authors: Beata Skibska, Andrzej Stanczak, Agnieszka Skibska

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Nanodiamond (ND) is a carbon nanomaterial that has high biocompatibility, and it has a very positive effect on a number of biochemical processes. NDs have great potential in treating multiple inflammation-associated diseases. The purpose of this study was to investigate the anti-inflammatory effect of nanodiamonds and lipoic acid (LA) (as antioxidants) on rats' cardiovascular systems after lipopolysaccharide (LPS) administration. Animal experiments enabled the determination of how nanodiamonds act when applied independently or in combination with lipoic acid. The effect of NDs and LA on C-reactive protein (CRP) levels and heart edema was evaluated. NDs and LA administered after LPS administration attenuated heart edema and significantly decreased the CRP level. The results suggest that NDs and LA play an important role in LPS-induced inflammation in the heart. NDs find new applications in modern biomedical science and biotechnologies.

Keywords: nanodiamonds, lipoic acid, inflammation, cardiovascular system

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Authors: Kun Hua O., Dong Woon Kim, Won Hyung Lee

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Introduction: Neuropathic pain induced by spinal or peripheral nerve injury is highly resistant to common painkillers, nerve blocks, and other pain management approaches. Recently, several new therapeutic drug candidates have been developed to control neuropathic pain. In this study, we used the spinal nerve L5 ligation (SNL) model to investigate the ability of intrathecal or intravenous Evans blue to decrease pain behavior and to study the relationship between Evans blue and the neural structure of pain transmission. Method: Neuropathic pain (allodynia) of the left hind paw was induced by unilateral SNL in Sprague-Dawley rats(n=10) in each group. Evans blue (5, 15, 50μg/10μl) or phosphate buffer saline(PBS,10μl) was injected intrathecally at 3days post-ligation or intravenously(1mg/200 μl) 3days and 5days post-ligation . Mechanical sensitivity was assessed using Von Frey filaments at 3 days post-ligation and at 2 hours, days 1, 2, 3, 5,7 after intrathecal Evans blue injection, and on days 2, 4, 7, and 11 at 14 days after intravenous injection. In the intrathecal group, microglia and glutaminergic neurons in the dorsal horn and VNUT(vesicular nucleotide transporter) in the dorsal root ganglia were tested to evaluate co-staining with Evans blue. The experimental procedures were performed in accordance with the animal care guideline of the Korean Academy of Medical Science(Animal ethic committee of Chungnam National University Hospital: CNUH-014-A0005-1). Results: Tight ligation of the L5 spinal nerve induced allodynia in the left hind paw 3 days post-ligation. Intrathecal Evans blue most significantly(P＜0.001) alleviated allodynia at 2 days after intrathecal, but not an intravenous injection. Glutaminergic neurons in the dorsal horn and VNUT in the dorsal root ganglia were co-stained with Evans blue. On the other hand, microglia in the dorsal horn were partially co-stained with Evans blue. Conclusion: We confirmed that Evans blue might have an analgesic effect through the central nervous system, not another system in neuropathic pain of the SNL animal model. These results suggest Evans blue may be a potential new drug for the treatment of chronic pain. This research was supported by the National Research Foundation of Korea (NRF-2020R1A2C100757512), funded by the Ministry of Education.

Keywords: neuropathic pain, Evas blue, intrathecal, intravenous

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Authors: Saeed Abbasi, Davood Farsi, Soudabeh Shafiee Ardestani, Neda Valizadeh

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Objectives: Peripheral vertigo is a common complaint of patients who are visited in emergency departments. In our study, we wanted to evaluate the effect of betahistine as an oral drug vs. intravenous diazepam for the treatment of acute peripheral vertigo. We also wanted to see the possibility of substitution of parenteral drug with an oral one with fewer side effects. Materials and Methods: In this randomized, double-blind study, 101 patients were enrolled in the study. The patients were divided in two groups in a double-blind randomized manner. Group A took oral placebo and 10 mg of intravenous diazepam. Group B received 8mg of oral betahistine and intravenous placebo. Patients’ symptoms and signs (Vertigo severity, Nausea, Vomiting, Nistagmus and Gate) were evaluated after 0, 2, 4, 6 hours by emergency physicians and data were collected by a questionnaire. Results: In both groups, there was significant improvement in vertigo (betahistine group P=0.02 and Diazepam group P=0.03). Analysis showed more improvement in vertigo severity after 4 hours of treatment in betahistine group comparing to diazepam group (P=0.02). Nausea and vomiting were significantly lower in patients receiving diazepam after 2 and 6 hours (P=0.02 & P=0.03).No statistically significant differences were found between the groups in nistagmus, equilibrium & vertigo duration. Conclusion: The results of this randomized trial showed that both drugs had acceptable therapeutic effects in peripheral vertigo, although betahistine was significantly more efficacious after 4 hours of drug intake. As for higher nausea and vomiting in betahistine group, physician should consider these side effects before drug prescription.

Keywords: acute peripheral vertigo, betahistine, diazepam, emergency department

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Authors: Sanjay Singh, Parameswara Rao Vuddanda

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The aim of the present study is study the factual benefit of nano size and surface coating of p-gp efflux inhibitor on enhancement of bioavailability of Berberine chloride (BBR); a p-gp substrate. In addition, 28 days sub acute oral toxicity study was also conducted to assess the toxicity of the formulation on chronic administration. BBR loaded polymeric nanoparticles (BBR-NP) were prepared by nanoprecipitation method. BBR NP were surface coated (BBR-SCNP) with the 1 % w/v of vitamin E TPGS. For bioavailability study, total five groups (n=6) of rat were treated as follows first; pure BBR, second; physical mixture of BBR, carrier and vitamin E TPGS, third; BBR-NP, fourth; BBR-SCNP and fifth; BBR and verapamil (widely used p-gp inhibitor). Blood was withdrawn at pre-set timing points in 24 hrs study and drug was quantified by HPLC method. In oral chronic toxicity study, total four groups (n=6) were treated as follows first (control); water, second; pure BBR, third; BBR surface coated nanoparticles and fourth; placebo BBR surface coated nanoparticles. Biochemical levels of liver (AST, ALP and ALT) and kidney (serum urea and creatinine) along with their histopathological studies were also examined (0-28 days). The AUC of BBR-SCNP was significantly 3.5 folds higher compared to all other groups. The AUC of BBR-NP was 3.23 and 1.52 folds higher compared to BBR solution and BBR with verapamil group, respectively. The physical mixture treated group showed slightly higher AUC than BBR solution treated group but significantly low compared to other groups. It indicates that encapsulation of BBR in nanosize form can circumvent P-gp efflux effect. BBR-NP showed pharmacokinetic parameters (Cmax and AUC) which are near to BBR-SCNP. However, the difference in values of T1/2 and clearance indicate that surface coating with vitamin E TPGS not only avoids the P-gp efflux at its absorption site (intestine) but also at organs which are responsible for metabolism and excretion (kidney and liver). It may be the reason for observed decrease in clearance of BBR-SCNP. No toxicity signs were observed either in biochemical or histopathological examination of liver and kidney during toxicity studies. The results indicate that administration of BBR in surface coated nanoformulation would be beneficial for enhancement of its bioavailability and longer retention in systemic circulation. Further, sub acute oral dose toxicity studies for 28 days such as evaluation of intestine, liver and kidney histopathology and biochemical estimations indicated that BBR-SCNP developed were safe for long use.

Keywords: bioavailability, berberine nanoparticles, p-gp efflux inhibitor, nanoprecipitation method

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Authors: Mabroka Omar Sherehe

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Despite the great efficacy of isoniazid (INH) and rifampicine (RIF) combination in the treatment of tuberculosis, hepatotoxicity is the most common serious complication. The potential protective effect of simvastatin (sim) against combination-induced hepatotoxicity was investigated in the present study. The administration of INH-RIF combination (50mg/kg each for 14 days) resulted in a significant increased activities of serum alanine and aspartate aminotransferases, such effects were further supported by histopathological studies. INH-RIF combination produced a significant increase in liver lipid, decreased SOD and CAT, and a significant depletion of GSH level. Additionally, treatment with INH-RIF combination resulted in a significant increase in liver MPO activity. The lipid-lowering drug, Sim demonstrated in the current study an evident antioxidant action, such effect was mediated via decreasing the elevated MDA, MPO, and restoring liver CAT activity. Additionally, Sim restored liver NO level to near basal value Furthermore, one cannot rule out the lipid-lowering effect of Sim that would probably add to its beneficial hepatoprotective antioxidant activity, where Sim decreased the elevated cholesterol, TGs and LDL cholesterol level and increased the serum HDL cholesterol level.

Keywords: isoniazid, rifampicine, oxidative stress, nitric oxide

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Authors: Ahmad Shah Farhat, Anahita Alizadeh Qamsari, Ashraf Mohammadzadeh, Hamid Reza Goldouzian, Ezat Khodashenas

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Introduction: Newborns may be treated with phenobarbital for many reasons. Because in each region, depending on different races and genetic factors, different pharmacokinetic conditions govern the drug. It is essential to control blood levels of certain drugs, especially phenobarbital, and maintain these levels during treatment. Methods: In this study, venous blood was collected from 50 neonates who received intravenous phenobarbital at a loading dose of 20 mg/kg weight and at least three days had passed since the maintenance dose of 5 mg/kg body weight. in 24 hours. and sent to the laboratory. Phenobarbital blood levels were measured, then the results were analyzed descriptively. Results: In this study, the average weight of newborns was 9.93 ± 2.58. The mean blood concentration of phenobarbital, three days after starting the maintenance dose in the group of infants weighing more than 2.5 kg, was 3.33 ± 9.1 micrograms/liter in the group of infants weighing less than 2 kg. and half a kilogram or LBW was 5.9 ± 9.5 micrograms/liter and in the group weighing less than 1.5 kg VLBW was 14.4 ± 15.46 micrograms/liter. There was no significant difference between groups (p>0.05). Three days after starting the maintenance dose in all three groups, the mean blood phenobarbital concentration was 9.86 ± 0.86 micrograms/liter. Conclusion: Blood phenobarbital levels in our newborns are below therapeutic levels, so phenobarbital levels should be evaluated.

Keywords: poisining, neonats, phenobarbital, drug

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Authors: Andri Andri, Susanthy Djajalaksana, Iin Noor Chozin

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Background: Despite advances in asthma therapies, a proportion of patients with asthma continue to have difficulty in gaining adequate asthma control. Complex immunological mechanisms and oxidative stress affect this condition, including the role of malondialdehyde (MDA) as a marker of inflammation. This research aimed to determine the effect of polyphytopharmaca administration on the value of asthma control test (ACT), blood eosinophils level and markers of MDA serum inflammation in patients with asthma. Method: Quasi experimental approach was conducted toward 15 stable asthma patients who were not fully controlled in outpatient pulmonary clinic, Public Hospital of Dr. Saiful Anwar Malang. Assessments of ACT values, eosinophil levels, and serum MDA levels were carried out before and after administration of polyphytopharmaca which contained a combination of 100 mg Nigella sativa extract, Kleinhovia hospita 100 mg, Curcuma xanthorrhiza 75 mg, and Ophiocephalus striatus 100 mg, three times daily with two capsules for 12 weeks. The ACT value was determined by the researcher by asking the patient directly, blood eosinophil levels were calculated by analyzing blood type counts, and serum MDA levels were detected by the qPCR method. Result: There was a significant enhancement of ACT value (18.07 ± 2.57 to 22.06 ± 1.83, p = 0.001) (from 60% uncontrolled ACT to 93.3% controlled ACT), a significant decrease in blood eosinophils levels (653.15 ± 276.15 pg/mL to 460.66 ± 202.04 pg/mL, p = 0.038), and decreased serum MDA levels (109.64 ± 53.77 ng / ml to 78.68 ± 64.92 ng/ml, p = 0.156). Conclusion: Administration of polyphytopharmaca can increase ACT value, decrease blood eosinophils levels and reduce MDA serum in stable asthma patients who are not fully controlled.

Keywords: asthma control test, eosinophils levels, malondialdehyde, polyphytopharmaca

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Authors: J. P. Lavande, A. V.Chandewar

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Mouth dissolving tablet is the speedily growing and highly accepted drug delivery system. This study was aimed at development of Ketorolac Tromethamine mouth dissolving tablet (MDTs), which can disintegrate or dissolve rapidly once placed in the mouth. Conventional Ketorolac tromethamine tablet requires water to swallow it and has limitation like low disintegration rate, low solubility etc. Ketorolac Tromethamine mouth dissolving tablets (formulation) consist of super-disintegrate like Heat Modified Karaya Gum, Co-treated Heat Modified Agar & Filler microcrystalline cellulose (MCC). The tablets were evaluated for weight variation, friability, hardness, in vitro disintegration time, wetting time, in vitro drug release profile, content uniformity. The obtained results showed that low weight variation, good hardness, acceptable friability, fast wetting time. Tablets in all batches disintegrated within 15-50 sec. The formulation containing superdisintegrants namely heat modified karaya gum and heat modified agar showed better performance in disintegration and drug release profile.

Keywords: mouth dissolving tablet, Ketorolac tromethamine, disintegration time, heat modified karaya gum, co-treated heat modified agar

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Authors: Mandisi Matyana

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Although the South African local government is doing all the best in ensuring improved service delivery for the citizens, service delivery disparity still remains the real challenge for other municipalities. The unequal distribution of services within municipal wards is causing unequal happiness among the citizens; hence others do enjoy different provided municipal services, while others do not. It is acknowledged that less access to municipal services infringes one’s rights, such as the right to human dignity and the right to life. Some of the municipal services are basic services and they are the mainstay of human survival, such as water, housing, etc. It is quite evident that the service delivery disparity could be caused by the various factors within the local municipality affairs, including both administrative and political factors. Therefore, this study is undertaken to check and evaluate the main foundations of service delivery disparity in ensuring equal development of the state, particularly for local communities. The study used the qualitative method to collect the data from the citizens of Winnie Madikizela Mandela Local Municipality. An extensive literature was also conducted in understanding the causes of service delivery disparity. Study findings prove that the service delivery disparity could be caused by factors such as political interference in administration, corruption and fraud, elevated unemployment levels, inadequate institutional capacity, etc. Therefore, the study recommends strong community participation and constant external supervision in the local government so as to encourage openness in local government to ensure fair administration towards services to be provided.

Keywords: administration, development, municipal services, service delivery disparity, Winnie Madikizela Mandela local municipality

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Authors: Ponshano Kaselekela, Simooya O. Oscar, Lunshano Boyd

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The Copperbelt University Health Services (CBUHS) was designated by the Zambia Medicines Regulatory Authority (ZAMRA), formally the Pharmaceutical Regulatory Authority (PRA) as a regional pharmacovigilance centre to carryout activities of drug safety monitoring in four provinces in Zambia. CBUHS’s mandate included stimulating the reporting of adverse drug reactions (ADRs), as well as collecting and collating ADR reports from health institutions in the four provinces. This report covers the researchers’ experiences from May 2008 to September, 2016. The main objectives are 1) to monitor ADRs in the Zambian population, 2) to disseminate information to all health professionals in the region advising that the CBU health was a centre for reporting ADRs in the region, 3) to monitor polypharmacy as well as the benefit-risk profile of medicines, 4) to generate independent, evidence based recommendations on the safety of medicines, 5) to support ZAMRA in formulating safety related regulatory decisions for medicines, and 6) to communicate findings with all key stakeholders. The methodology involved monthly visits, beginning in early May 2008 to September, 2016, by the CBUHS to health institutions in the programme areas. Activities included holding discussions with health workers, distribution of ADR forms and collection of ADRs reports. These reports, once collected, were documented and assessed at the CBUHS. A report was then prepared for ZAMRA on quarterly basis. At ZAMRA, serious ADRs were noted and recommendations made to the Ministry of Health of the Republic of Zambia. The results show that 2,600 ADRs reports were received at the pharmacovigilance regional centre. Most of the ADRs reports that received were due to antiretroviral drugs, as well as a few from anti-malarial drugs like Artemether/Lumefantrine – Coartem®. Three hundred and twelve ADRs were entered in the Uppsala Monitoring Centre WHO Vigiflow for further analysis. It was concluded that in general, 2008-16 were exciting years for the pharmacovigilance group at CBUHS. From a very tentative beginning, a lot of strides were made and contacts established with healthcare facilities in the region. The researchers were encouraged by the support received from the Copperbelt University management, the motivation provided by ZAMRA and most importantly the enthusiasm of health workers in all the health care facilities visited. As a centre for drug safety in Zambia, the results show it achieves its objectives for monitoring ADRs, Pharmacovigilance (drug safety monitoring), and activities of monitoring ADRs as well as preventing them. However, the centre faces critical challenges caused by erratic funding that prevents the smooth running of the programme.

Keywords: adverse drug reactions, drug safety, monitoring, pharmacovigilance

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Authors: Sahar Iqrar, Malik Adeel Anwar, Zain Akram, Maria Noor

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Introduction: Oral lichen planus is a chronic inflammatory condition of unknown etiology. Oral lichen planus may be related with several other diseases. Grinspan's Syndrome is characterized by a triad of oral lichen planus, hypertension, and diabetes mellitus. Other associations reported in the literature are with chronic liver disease and, with dyslipidemia. The nature of these associations is still not fully understood. Material and methods: Study was conducted in Department of Oral Medicine, Fatima Memorial Hospital College of Medicine and Dentistry, Lahore, Pakistan. A total of n=89 clinically diagnosed patients of oral lichen planus of both gender and all age groups were recruited and detailed history were recorded in the designed performs. Results: A total of n=89 patients were taken with male to female ratio of 3:8 in which 24 were male and 65 females. Mean age was 48.8 ± 13.8 years. Age range of 10-74 years was seen. Among these patients suffering from oral lichen planus, 41.6% (n=37) had a positive history for hypertension with 59.5% (n=22) of these patients were taking different medication for their condition. Whereas Diabetes Mellitus was found in 24.7% (n=22) patients with 72.7% (n=16) of these patients using the hypoglycemic drug (oral or injectable) to control their blood glucose levels. Out of these n=89 lichen planus patients 21.3% had both hypertension and diabetes mellitus (fulfilling the criteria for Grinspan's Syndrome). Out of this Grinspan's Syndrome pool 94.7% (n=19) were taking drug atleast for one of the two conditions. Conclusion: As noticed form the medical history of the patients, most of them were using hypoglycemic drugs for diabetes mellitus and beta blockers, diuretics and calcium channel blockers for hypertension. These drugs are known for lichenoid reaction. Therefore, it should be ruled out at histopathological/ immunological and molecular level whether these patients are suffering from lichen planus or lichenoid drug reaction to truly declare them as patients with Grinspan’s Syndrome.

Keywords: diabetes mellitus, grinspan's syndrome, lichenoid drug reaction, oral lichen planus

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Authors: Pritika Ramharack, Mahmoud E. S. Soliman

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The re-emerging Zika virus is an arthropod-borne virus that has been described to have explosive potential as a worldwide pandemic. The initial transmission of the virus was through a mosquito vector, however, evolving modes of transmission has allowed the spread of the disease over continents. The virus already been linked to irreversible chronic central nervous system (CNS) conditions. The concerns of the scientific and clinical community are the consequences of Zika viral mutations, thus suggesting the urgent need for viral inhibitors. There have been large strides in vaccine development against the virus but there are still no FDA-approved drugs available. Rapid rational drug design and discovery research is fundamental in the production of potent inhibitors against the virus that will not just mask the virus, but destroy it completely. In silico drug design allows for this prompt screening of potential leads, thus decreasing the consumption of precious time and resources. This study demonstrates an optimized and proven screening technique in the discovery of two potential small molecule inhibitors of Zika virus Methyltransferase and RNA-dependent RNA polymerase. This in silico “per-residue energy decomposition pharmacophore” virtual screening approach will be critical in aiding scientists in the discovery of not only effective inhibitors of Zika viral targets, but also a wide range of anti-viral agents.

Keywords: NS5 protein inhibitors, per-residue decomposition, pharmacophore model, virtual screening, Zika virus

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Authors: E. Kilicay, Z. Karahaliloglu, B. Hazer, E. B. Denkbas

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In this study, we have prepared concanavaline A (ConA) functionalized curcumin (CUR) loaded PHBHHx (poly(3-hydroxybutyrate-co-3-hydroxyhexanoate)) nanoparticles as a novel and efficient drug delivery system. CUR is a promising anticancer agent for various cancer types. The aim of this study was to evaluate therapeutic potential of curcumin loaded PHBHHx nanoparticles (CUR-NPs) and concanavaline A conjugated curcumin loaded NPs (ConA-CUR NPs) for ovarian cancer treatment. ConA was covalently connected to the carboxylic group of nanoparticles by EDC/NHS activation method. In the ligand attachment experiment, the binding capacity of ConA on the surface of NPs was found about 90%. Scanning electron microscopy (SEM) and atomic force microscopy (AFM) analysis showed that the prepared nanoparticles were smooth and spherical in shape. The size and zeta potential of prepared NPs were about 228±5 nm and −21.3 mV respectively. ConA-CUR NPs were characterized by FT-IR spectroscopy which confirmed the existence of CUR and ConA in the nanoparticles. The entrapment and loading efficiencies of different polymer/drug weight ratios, 1/0.125 PHBHHx/CUR= 1.25CUR-NPs; 1/0.25 PHBHHx/CUR= 2.5CUR-NPs; 1/0.5 PHBHHx/CUR= 5CUR-NPs, ConA-1.25CUR NPs, ConA-2.5CUR NPs and ConA-5CUR NPs were found to be ≈ 68%-16.8%; 55%-17.7 %; 45%-33.6%; 70%-15.7%; 60%-17%; 51%-30.2% respectively. In vitro drug release showed that the sustained release of curcumin was observed from CUR-NPs and ConA-CUR NPs over a period of 19 days. After binding of ConA, the release rate was slightly increased due to the migration of curcumin to the surface of the nanoparticles and the matrix integrities was decreased because of the conjugation reaction. This functionalized nanoparticles demonstrated high drug loading capacity, sustained drug release profile, and high and long term anticancer efficacy in human cancer cell lines. Anticancer activity of ConA-CUR NPs was proved by MTT assay and reconfirmed by apoptosis and necrosis assay. The anticancer activity of ConA-CUR NPs was measured in ovarian cancer cells (SKOV-3) and the results revealed that the ConA-CUR NPs had better tumor cells decline activity than free curcumin. The nacked nanoparticles have no cytotoxicity against human ovarian carcinoma cells. Thus the developed functionalized nanoformulation could be a promising candidate in cancer therapy.

Keywords: curcumin, curcumin-PHBHHx nanoparticles, concanavalin A, concanavalin A-curcumin PHBHHx nanoparticles, PHBHHx nanoparticles, ovarian cancer cell

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Authors: Latifeh Navidpour, Shabnam Shabani, Alireza Heidari, Manouchehr Bashiri, Azadeh Ebrahim-Habibi, Soraya Shahhosseini, Hamed Shafaroodi, Sayyed Abbas Tabatabai, Mahsa Toolabi

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A new series of 5-(2-aryloxy-4-nitrophenyl)-4H-1,2,4-triazoles and 5-(2-aryloxy-3-pyridyl)-4H-1,2,4-triazoles, possessing C-3 thio or alkylthio substituents, was synthesized and evaluated for their benzodiazepine receptor affinity and anti-seizure activity. These analogues revealed similar to significantly superior affinity to GABAA/ benzodiazepine receptor complex (IC50 values of 0.04–4.1 nM), relative to diazepam as the reference drug (IC50 value of 2.4 nM). To determine the onset of anti-seizure activity, the time-dependent effectiveness of i.p. administration of compounds on pentylenetetrazole induced seizure threshold was studied and a very good relationship was observed between the lipophilicity (cLogP) and onset of action of studied analogues (r2 = 0.964). The minimum effective dose of the compounds, determined at the time the analogues showed their highest activity, was demonstrated to be 0.025–0.1 mg/kg, relative to diazepam (0.025 mg/kg).

Keywords: 1, 2, 4-triazole, flexible benzodiazepines, GABAA/bezodiazepine receptor complex, onset of action, PTZ induced seizure threshold

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Authors: Jin-Feng Hu

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Over the past decades, the global biodiversity has continued to decline. The threats to the terrestrial plant species have increased under anthropogenic activities and other massive ecological change impacts. The situation is much more serious in China, the third richest countries regarding plant biodiversity in the world. It was not until 1992 that the first volume of the China Plant Red Data Book was published. Nowadays, a significant number of Chinese endemic plants have been threatened (The IUCN Red List). Nevertheless, plant-originated natural products (NPs) have continued to play a crucial role in the drug discovery and development process. The opportunity for identifying new chemical entities for emerging and malignant diseases depends on a diversity of drug-producing species. Several statistical surveys unveiled that the rare and endangered plants (REPs) have proven to be better sources for drug discovery than other botanic sources. The identification of bioactive NPs from REPs reveals the importance of conservation efforts in preventing species diversity loss and addressing human diseases at the same time. Thus, there is an urgent need to investigate these fragile REPs. Since 2013, our group has initially launched a special program to systematically identify bioactive/novel NPs from REPs native to China. The selected plant species were generally collected from the remote Mountain areas, and have never been chemically or pharmacologically investigated. Due to the difficult collection of the mass-limited samples of REPs, studies on the secondary metabolites of REPs-associated endophytes would provide a promising alternative potential solution. This presentation details the achievements that related to a series of “Phytochemical and biological studies on rare and endangered plants endemic to China”.

Keywords: bioactive naturally-occrring compounds, rare and endengered plants (REPs), plant endophytes, drug discovery

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