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.

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 Some Snake Venom Specific Toxin Proteins and Cognate Non-Toxin Proteins of Other Chordates.

BACKGROUND: Protein three-dimensional structures are very much important in terms of functional and evolutionary context. In the present work we evaluated the snake venom constituent cytotoxin, short neurotoxin and related non-toxin proteins of other chordates with reference to structure prediction, validation of the models, distribution of secondary structural elements, hydrophobicity molecular surface analysis, functional annotation and functionally critical binding site identification with the assistance of different bioinformatical tools. METHODS: Homology models have been generated with the help of Swiss-model and ITASSER suite during the present study. Afterwards the refined structural models were validated with standard methods. For functional annotation of protein molecules we used Protein Information Resource (PIR) database. The functionally critical amino acids and ligand- binding site (LBS) of the proteins (modeled) was determined using the COACH program. RESULTS: Structural analysis of snake venom toxin proteins and related non-toxin proteins of other chordates elucidated their structural level conservation of molecular structural surfaces and biophysical characteristics to different extents. Different structural level improvement strategies were observed which are necessary for better system dependent adaptation to diverse biological environment and functional necessities of these protein molecules. CONCLUSION: Molecular models and their structural characterization of these proteins as documented in this study may provide a valuable aid for drug designing in future.

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.

Sequence analysis and phylogenetic study of some toxin proteins of snakes and related non-toxin proteins of chordates.

Snakes are equipped with their venomic armory to tackle different prey and predators in adverse natural world. The venomic composition of snakes is a mix of biologically active proteins and polypeptides. Among different components snake venom cytotoxins and short neurotoxin are non-enzymatic polypeptide candidates with in the venom. These two components structurally resembled to three-finger protein superfamily specific scaffold. Different non-toxin family members of three-finger protein superfamily are involved in different biological roles. In the present study we analyzed the snake venom cytotoxins, short neurotoxins and related non-toxin proteins of different chordates in terms of amino acid sequence level diversification profile, polarity profile of amino acid sequences, conserved pattern of amino acids and phylogenetic relationship of these toxin and nontoxin protein sequences. Sequence alignment analysis demonstrates the polarity specific molecular enrichment strategy for better system adaptivity. Occurrence of amino acid substitution is high in number in toxin sequences. In non-toxin body proteins there are less amino acid substitutions. With the help of conserved residues these proteins maintain the three-finger protein scaffold. Due to system specific adaptation toxin and non-toxin proteins exhibit a varied type of amino acid residue distribution in sequence stretch. Understanding of Natural invention scheme (recruitment of venom proteins from normal body proteins) may help us to develop futuristic engineered bio-molecules with remedial properties.

Physicochemical characterization and functional analysis of some snake venom toxin proteins and related non-toxin proteins of other chordates.

Snake venom contains a diverse array of proteins and polypeptides. Cytotoxins and short neurotoxins are non-enzymatic polypeptide components of snake venom. The three-dimensional structure of cytotoxin and short neurotoxin resembles a three finger appearance of three-finger protein super family. Different family members of three-finger protein super family are employed in diverse biological functions. In this work we analyzed the cytotoxin, short neurotoxin and related non-toxin proteins of other chordates in terms of functional analysis, amino acid compositional (%) profile, number of amino acids, molecular weight, theoretical isoelectric point (pI), number of positively charged and negatively charged amino acid residues, instability index and grand average of hydropathy with the help of different bioinformatical tools. Among all interesting results, profile of amino acid composition (%) depicts that all sequences contain a conserved cysteine amount but differential amount of different amino acid residues which have a family specific pattern. Involvement in different biological functions is one of the driving forces which contribute the vivid amino acid composition profile of these proteins. Different biological system dependent adaptation gives the birth of enriched bio-molecules. Understanding of physicochemical properties of these proteins will help to generate medicinally important therapeutic molecules for betterment of human lives.

Nanoencapsulation of quercetin enhances its dietary efficacy in combating arsenic-induced oxidative damage in liver and brain of rats.

AIMS: This study was performed to evaluate the therapeutic efficacy of nanocapsulated flavonoidal quercetin (QC) in combating arsenic-induced reactive oxygen species (ROS)-mediated oxidative damage in hepatocytes and brain cells in a rat model. MAIN METHODS: Hepatic and neuronal cell damage in rats was made by a single injection (sc) of sodium arsenite (NaAsO(2), 13 mg/kg b. wt. in 0.5 ml of physiological saline). A single dose of 500 microl of quercetin suspension (QC) (QC 8.98 micromol/kg) or 500 microl of nanocapsulated QC (NPQC) (QC 8.98 micromol/kg) was given orally to rats at 90 min prior to the arsenite injection. KEY FINDINGS: Inorganic arsenic depositions (182+/-15.6 and 110+/-12.8 ng/g protein) were found in hepatic and neuronal mitochondrial membranes. Antioxidant levels in hepatic and neuronal cells were reduced significantly by arsenic. NPQC prevented the arsenite-induced reduction in antioxidant levels in the liver and brain. Arsenic induced a substantial decrease in liver and brain cell membrane microviscosities, and NPQC treatment resulted in a unique protection against the loss. A significant correlation between mitochondrial arsenic and its conjugated diene level was observed both in liver and brain cells for all experimental rats. SIGNIFICANCE: Arsenic-specific antidotes are used against arsenic-induced toxicity. However, the target site is poorly recognized and therefore achieving an active concentration of drug molecules can be a challenge. Thus, our objective was to formulate NPQC and to investigate its therapeutic potential in an oral route against arsenite-induced hepatic and neuronal cell damage in a rat model.

Nanoparticulated quercetin in combating age related cerebral oxidative injury.

Reactive oxygen species e.g. O(2)(*-), H(2)O(2) and *OH generated by the induction of oxidative stress exert a potential threat on the activity of endogenous antioxidant enzymes and substantially influence the aging process and age-dependant neuropathology. Chemical antioxidant is almost ineffective in protecting neuronal cells from oxidative damage as Blood Brain Barrier exists in between blood and brain interstitial fluid that restricts undegradable influx from the circulation into cerebral region. Quercetin (QC), a flavonoidal antioxidant is known as a potent antioxidant for its polyphenolic configuration. Formulation of QC in polylactide nanocapsule has been done and the efficacy of this vesicular flavonoid has been tested against cerebral ischemia induced oxidative damage in young and old rat brains. Antioxidant potential of QC loaded in nanocapsule (QC 7.2 mmol/kg b.wt., size 50 nm) was investigated by an in vivo model of cerebral ischemia and reperfusion on Sprague Dawley young (2 months, b.wt. 160-180 g) and aged (20 months, b.wt. 415-440 g) rats. Diene level, the index of lipid peroxidation and GSSG/GSH ratio were found to be higher in normal aged, compared to normal young rat brain. Endogenous antioxidants activities were lower in aged rat brain compared to young. Further reduction of these antioxidants were observed in aged rat brain by the induction of cerebral ischemia - reperfusion. Nanocapsule encapsulated QC treatment resulted a significant protection to endogenous antioxidant enzymes against ischemia induced oxidative damage in neuronal cells of young and old rats.