Elemental composition and contaminants of saffron from different origins and geographical discrimination using chemometrics.

Elements such as As, Cd, Cr and Pb are classified as contaminants of major concern for public health, due to their high degree of toxicity. Saffron is an important medicinal herbal spice used in variety of food items, pharmaceutical medicines, and cosmetics. Presence of heavy metals in saffron will increase the health risk to consumers. Also, authentication of geographical origin of saffron is an issue of utmost importance for global trading. The present study is focused on investigation of elemental contaminants in saffron and elemental composition of saffron from India (Jammu and Kashmir); Iran and Afghanistan are also explored for geographical discrimination, using Chemometrics. In total, 29 elements including Ag, Al, As, B, Ba, Be, Ca, Cd, Co, Cr, Cu, Fe, K, Li, Mg, Mn, Mo, Na, Ni, P, Pb, Sb, Se, Si, Sr, Ti, Tl, V and Zn were analyzed using ICP-OES. Toxic elemental contaminants including As, Cd, Pb were found below the maximum permissible limit. Using PCA, elements B, Ni, Ba, Fe, V, Si, Al, Ti, K, Na, Sr, and Zn were found as significant discriminators of geographical origin. Elemental composition of saffron may be utilized, to prevent cases of falsified geographical origin in trade.

Cetuximab-conjugated PLGA nanoparticles as a prospective targeting therapeutics for non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) is one of the most prevalent cancers diagnosed worldwide, yet managing it is still challenging. The epidermal growth factor receptor (EGFR) exhibits aberrant signalling in a wide range of human cancers, and it is reported to overexpress in most NSCLC cases. The monoclonal antibody [Cetuximab (Cet)] was conjugated onto the surface of the poly (lactide-co-glycolide) (PLGA) nanoparticles which were loaded with docetaxel (DTX) for the development of targeted therapy against lung cancer. This site-specific delivery system exhibited an enhanced cellular uptake in lung cancer cells which overexpress EGFR (A549 and NCI-H23). The nanoparticles also showed better therapeutic effectiveness against NSCLC cells, as evidenced by reduced IC50 values, cell cycle arrest at the G2/M phase, and increased apoptosis. The improved efficacy and in vivo tolerance of Cet-DTX NPs were demonstrated in benzo(a)pyrene (BaP)-induced lung cancer mice model. Histopathological analysis showed that intravenous injection of Cet-DTX NP to mice carrying lung cancer greatly reduced tumour development and proliferation. Comparing Cet-DTX NP to free drug and unconjugated nanoparticles, it also had negligible side effects and improved survival rates. Therefore, Cet-DTX NPs present a promising active targeting carrier for lung tumour-NSCLC-selective treatment.

A review on challenges and issues with carboxymethylation of natural gums: The widely used excipients for conventional and novel dosage forms.

Diverse properties of natural gums have made them quite useful for various pharmaceutical applications. However, they suffer from various problems, including unregulated hydration rates, microbial degradation, and decline in viscosity during warehousing. Among various chemical procedures for modification of gums, carboxymethylation has been widely studied due to its simplicity and efficiency. Despite the availability of numerous research articles on natural gums and their uses, a comprehensive review on carboxymethylation of natural gums and their applications in the pharmaceutical and other biomedical fields is not published until now. This review outlines the classification of gums and their derivatization methods. Further, we have discussed various techniques of carboxymethylation, process of determination of degree of substitution, and functionalization pattern of substituted gums. Detailed information about the application of carboxymethyl gums as drug delivery carriers has been described. The article also gives a brief account on tissue engineering and cell delivery potential of carboxymethylated gums.

Moringa gum and its modified form as a potential green polymer used in biomedical field.

Over the past few decades, natural gums are extensively investigated by the researchers due to their beneficial physicochemical properties. Among them, the polysaccharide exudates obtained from the stem of the plant Moringa oleifera, known as moringa gum, is investigated widely in the food, pharmaceutical, and other areas. The moringa gum is used in the form of dried powder as a pharmaceutical excipient in various formulations. It is also derivatized either by grafting or by other chemical modifications for enhancing its properties. The research on moringa gum and modified moringa gum has diversified in numerous biomedical fields. However, summarization of these progress are not available in the literature. This article gives an overview of the collection, purification, structural elucidation, and modification of moringa gum. Moreover, the present review furnishes complete information on the various aspects of moringa gum and its applications in various industrial and biomedical fields.

Anti-Ophidian Properties of Herbal Medicinal Plants: Could it be a Remedy for Snake Bite Envenomation?

Snake bite envenoming causes high rates of morbidity and mortality and is one of the serious health-related concerns all over the globe. Around 3200 species of snakes have been discovered till date. Amid these species, about 1300 species of snakes are venomous. On account of its severity, World Health Organization (WHO) recently included snakebite envenoming in the list of neglected tropical diseases. Immunotherapy has partially solved the issues related to snakebite envenomation. However, it is associated with numerous adverse effects, due to which alternative treatment strategies are required for the treatment of snakebite. Traditionally, a large repository of herbal medicinal plants is known to possess activity against snake venom. An exploration of the therapeutic benefits of these medicinal plants used for the treatment of snakebites reveals the presence of various potential phytochemicals. The aim of the present review is to provide an outline regarding poisonous snakes all over the world, various compositions of snake venom, adverse effects related to anti-snake venom and numerous medicinal plants used for the anti-ophidian activity.

Structural Analysis of CD59 of Chinese Tree Shrew: A New Reference Molecule for Human Immune System Specific CD59 Drug Discovery.

BACKGROUND: Chinese tree shrews (Tupaia belangeri chinensis) bear several characteristics that are considered to be very crucial for utilizing in animal experimental models in biomedical research. Subsequent to the identification of key aspects and signaling pathways in nervous and immune systems, it is revealed that tree shrews acquire common as well as unique characteristics, and hence offer a genetic basis for employing them as a prospective model for biomedical research. CD59 glycoprotein, commonly referred to as MAC-inhibitory protein (MAC-IP), membrane inhibitor of reactive lysis (MIRL), or protectin, is encoded by the CD59 gene in human beings. It is the member of the LY6/uPAR/alpha-neurotoxin protein family. OBJECTIVES: With this initial point, the objective of this study was to determine a comparative composite based structure of CD59 of Chinese tree shrew. The additional objective of this study was to examine the distribution of negatively and positively charged amino acid over molecular modeled structure, distribution of secondary structural elements, hydrophobicity molecular surface analysis and electrostatic potential analysis with the assistance of several bioinformatical analytical tools. METHODS: CD59 Amino acid sequence of Chinese tree shrew was collected from the online database system of National Centre for Biotechnology Information. SignalP 4.0 online server was employed for detection of signal peptide instance within the protein sequence of CD59. Molecular model structure of CD59 protein was generated by the Iterative Threading ASSEmbly Refinement (I-TASSER) suite. The confirmation for three-dimensional structural model was evaluated by structure validation tools. Location of negatively and positively charged amino acid over molecular modeled structure, distribution of secondary structural elements, and hydrophobicity molecular surface analysis was performed with the help of Chimera tool. Electrostatic potential analysis was carried out with the adaptive Poisson-Boltzmann solver package. Subsequently validated model was used for the functionally critical amino acids and active site prediction. The functionally critical amino acids and ligand- binding site (LBS) of the proteins (modeled) were determined using the COACH program. RESULT: Analysis of Ramachandran plot for Chinese tree shrew depicted that overall, 100% of the residues in homology model were observed in allowed and favored regions, sequentially leading to the validation of the standard of generated protein structural model. In case of CD59 of Chinese tree shrew, the total score of G-factor was found to be -0.66 that was generally larger than the acceptable value. This approach suggests the significance and acceptability of the modeled structure of CD59 of Chinese tree shrew. The molecular model data in cooperation to other relevant post model analysis data put forward molecular insight into protecting activity of CD59 protein molecule of Chinese tree shrew. CONCLUSION: In the present study, we have proposed the first molecular model structure of uncharted CD59 of Chinese tree shrew by significantly utilizing the comparative composite modeling approach. Therefore, the development of a structural model of the CD59 protein was carried out and analyzed further for deducing molecular enrichment technique. The collaborative effort of molecular model and other relevant data of post model analysis carry forward molecular understanding to protecting activity of CD59 functions towards better insight of features of this natural lead compound.

Inhibitory effect of a new orally active cedrol-loaded nanostructured lipid carrier on compound 48/80-induced mast cell degranulation and anaphylactic shock in mice.

BACKGROUND: Type I hypersensitivity is an allergic reaction characterized by the overactivity of the immune system provoked by normally harmless substances. Glucocorticoids, anti-histamines, or mast cell stabilizers are the choices of treatment for type I hypersensitivity. Even though these drugs have the anti-allergic effect, they can have several side effects in prolong use. Cedrol is the main bioactive compound of Cedrus atlantica with anti-tumor, anti-oxidative, and platelet-activating factor inhibiting properties. METHODS: In this study, the preparation and anti-anaphylactic effect of cedrol-loaded nanostructured lipid carriers (NLCs) were evaluated. NLCs were prepared using Compritol® 888 ATO and triolein as lipid phase and vitamin E d-α-tocopherylpolyethyleneglycol 1000 succinate, soya lecithin, and sodium deoxycholate as nanoparticle stabilizers. RESULTS: The average diameter of cedrol-NLCs (CR-NLCs) was 71.2 nm (NLC-C1) and 91.93 nm (NLC-C2). The particle had negative zeta potential values of -31.9 mV (NLC-C1) and -44.5 mV (NLC-C2). Type I anaphylactoid reaction in the animal model is significantly reduced by cedrol and cedrol-NLC. This in vivo activity of cedrol resulted that cedrol suppressed compound 48/80-induced peritoneal mast cell degranulation and histamine release from mast cells. Furthermore, compound 48/80-evoked Ca2+ uptake into mast cells was reduced in a dose-dependent manner by cedrol and cedrol-NLC. Studies confirmed that the inhibition of type I anaphylactoid response in vivo in mice and compound 48/80-induced mast cell activation in vitro are greatly enhanced by the loading of cedrol into the NLCs. The safety of cedrol and CR-NLC was evaluated as selectivity index (SI) with prednisolone and cromolyn sodium as positive control. SI of CR-NLC-C2 was found to be 11.5-fold greater than both prednisolone and cromolyn sodium. CONCLUSION: Administration of CR-NLC 24 hours before the onset of anaphylaxis can prevent an anaphylactoid reaction. NLCs could be a promising vehicle for the oral delivery of cedrol to protect anaphylactic reactions.

Discovery of an Unexplored Protein Structural Scaffold of Serine Protease from Big Blue Octopus (Octopus cyanea): A New Prospective Lead Molecule.

BACKGROUND: Serine proteases are a group of enzymes that hydrolyses the peptide bonds in proteins. In mammals, these enzymes help in the regulation of several major physiological functions such as digestion, blood clotting, responses of immune system, reproductive functions and the complement system. OBJECTIVE: Serine proteases obtained from the venom of Octopodidae family is a relatively unexplored area of research. In the present work, we tried to effectively utilize comparative composite molecular modeling technique. Our key aim was to propose the first molecular model structure of unexplored serine protease 5 derived from big blue octopus. The other objective of this study was to analyze the distribution of negatively and positively charged amino acid over molecular modeled structure, distribution of secondary structural elements, hydrophobicity molecular surface analysis and electrostatic potential analysis with the aid of different bioinformatic tools. METHODS: In the present study, molecular model has been generated with the help of I-TASSER suite. Afterwards the refined structural model was validated with standard methods. For functional annotation of protein molecule we used Protein Information Resource (PIR) database. Serine protease 5 of big blue octopus was analyzed with different bioinformatical algorithms for the distribution of negatively and positively charged amino acid over molecular modeled structure, distribution of secondary structural elements, hydrophobicity molecular surface analysis and electrostatic potential analysis. The functionally critical amino acids and ligand- binding site (LBS) of the proteins (modeled) were determined using the COACH program. RESULT: The molecular model data in cooperation to other pertinent post model analysis data put forward molecular insight to proteolytic activity of serine protease 5, which helps in the clear understanding of procoagulant and anticoagulant characteristics of this natural lead molecule. CONCLUSION: Our approach was to investigate the octopus venom protein as a whole or a part of their structure that may result in the development of new lead molecule.

Molecular Modeling and Structural Analysis of Arylesterase of Ancylostoma Duodenale.

Parasitic worm infection of humans is one of the most commonly prevalent helminth infection that has imposed great impact on society and public health in the developing world. The two species of hookworm, namely Ancylostoma duodenale and Necator americanus may be primarily responsible for causing parasitic infections in human beings. The highly prevalent areas for Ancylostoma duodenale infections are mainly India, Middle East, Australia, northern Africa and other parts of the world. The serum arylesterases/paraoxonases are family of enzymes that is involved in the hydrolysis of a number of organophosphorus insecticides to the nontoxic products. The participation of the enzymes in the breakdown of a variety of organophosphate substrates that is generally made up of paraoxon and numerous aromatic carboxylic acid esters (e.g., phenyl acetate), and hence combats the toxic effect of organophosphates. The aim of the present investigation is to evaluate the arylesterases of Ancylostoma duodenale giving special importance to structure generation, validation of the generated models, distribution of secondary structural elements and positive charge distribution over the structure. By the implementation of comparative modeling approach we propose the first molecular model structure of arylesterases of Ancylostoma duodenale.

Storage quality of shelled green peas under modified atmosphere packaging at different storage conditions.

Storage quality of shelled green peas (Pisum sativum var. sativum L) was investigated under modified atmosphere packaging (MAP: perforated and non perforated) compared to unsealed samples, respectively, at T1 (4 ± 1 °C and 94 ± 2 % RH) and T2 (10 ± 1 °C and 90 ± 2 % RH) for each sample and during period of storage (8, 16 and 24 days). Modified atmosphere (MA) was created using low density polyethylene (LDPE) film packages having 107 µm of film thickness and package size of 0.022 m(2). Quality parameters viz., weight loss (WL), total phenolic content (TPC), instrumental colour, ascorbic acid (AA) and sensory characteristics were evaluated during storage period. Weight loss was in the range of 0.18 to 3.54 (zero perforation at T1), 0.21 to 6.48(unsealed samples at T2) and 0.31 to 9.64 % (zero perforation at T1) after 8, 16 and 24 days of storage, respectively. Total phenolic content significantly increased to 102.47-161.54 mg/100 g from an initial value of 91.53 mg/100 g for all the samples and treatments studied. The MAP non perforated sample stored at T2 recorded maximum Hunter 'L' and '-a' colour values than all other samples. A significant decrease in AA content was observed in all the samples with maximum loss (53.77 %) in unsealed sample stored at T2, whereas MAP (3 perforations) sample stored at T1 retained maximum AA (90.50 %). Sensory quality analysis revealed that MAP (3 perforations) sample stored at T1 was in acceptable quality, with good appearance and overall acceptance. The study shows that shelled green peas can be stored in MAP with 3 perforations (0.4 mm dia) in the temperature range of 4 to 10 °C and 90-94 % RH to extend shelf life with marketable quality for 24 days.

Synthesis of Ca+2-Al+3-xanthan biopolymer particles and evaluation of in vitro protein release behaviors.

In this work, a hydrogelation method was used for the development of protein-loaded xanthan biopolymer particles. The gelation of the aqueous polymer droplets was accomplished in a mixture of calcium chloride and aluminium chloride solution. The particles were less than 900 µm in diameter and appeared spherical under scanning electron microscope. The particles retained a maximum of 90% of its initial load and released the protein molecules over an extended period in phosphate buffer saline solution (pH 7.4). The protein release was <13% in acidic medium (pH 1.2). The protein release was interrelated with pH-dependent swelling of the particles. The polymer relaxation phenomenon predominated over simple diffusion mechanism in anomalous protein release process as the ratio of di- and trivalent metal ions was decreased. No protein-biopolymer interaction was evident by FTIR spectroscopy. The divalent and trivalent metal ion cross-linked xanthan particles showed immense potential in controlled oral delivery of macromolecules.

Role of herbal bioactives as a potential bioavailability enhancer for Active Pharmaceutical Ingredients.

The current review emphasizes on the herbal bioenhancers which themselves do not possess inherent pharmacological activity of their own but when co-administered with Active Pharmaceutical Ingredients (API), enhances their bioavailability and efficacy. Herbal bioenhancers play a crucial role in enhancing the bioavailability and bioefficacy of different classes of drugs, such as antihypertensives, anticancer, antiviral, antitubercular and antifungal drugs at low doses. This paper highlights various natural compounds that can be utilized as an efficient bioenhancer. Several herbal compounds including piperine, quercetin, genistein, naringin, sinomenine, curcumin, and glycyrrhizin have demonstrated capability to improve the pharmacokinetic parameters of several potent API. This article also focuses on various United States patents on herbal bioenhancers, which has proved to be beneficial in improving oral absorption of nutraceuticals like vitamins, minerals, amino acids and certain herbal compounds. The present paper also describes proposed mechanism of action, which mainly includes absorption process, drug metabolism, and action on drug target. The herbal bioenhancers are easily available, safe, free from side effects, minimizes drug toxicity, shortens the duration of treatment, lowers the drug resistance problems and minimizes the cost of treatment. Inspite of the fact that herbal bioenhancers provide an innovative concept for enhancing the bioavailability of several potent drugs, there are numerous bioenhancers of herbal origin that are yet to be explored in several vital areas. These bioenhancers must also be implied to enhance the bioavailability and bioefficacy through routes other than the oral route of drug delivery. There is a vast array of unexploited plants which can be investigated for their drug bioenhancing potency. The toxicity profiles of these herbal bioenhancers must not be overlooked. Researches must be carried out to solve these issues and to deliver a safe and effective dose of drugs to attain desired pharmacological response.