Preparation of Losartan Potassium Controlled Release Matrices and In-Vitro Investigation Using Rate Controlling Agents.

Controlled release matrices have predictable drug release kinetics, provide drugs for an extended period of time, and reduce dosing frequency with improved patient compliance as compared with conventional tablet dosage forms. In the current research work, losartan potassium controlled release matrix tablets were fabricated and prepared with rate altering agents; that is, Ethocel grade 100 combined with Carbopol 934PNF. Various drug to polymer ratios were used. HPMC, CMC, and starch were incorporated in some of the matrices by replacing some amount of filler (5%). The direct compression method was adopted for the preparation of matrices. In phosphate buffer (pH 6.8), the dissolution study was conducted by adopting the USP method-I as the specified method. Drug release kinetics was determined and dissolution profiles were also compared with the reference standard. Prolonged release was observed for all matrices, but those with Ethocel 100FP Premium showed more extended release. The co-excipient (HPMC, CMC, and starch) exhibited enhancement in the drug release rates, while all controlled release matrices released the drug by anamolous non-Fickian diffusion mechanism. This combination of polymers (Ethocel grade 100 with Carbopol 934PNF) efficiently extended the drug release rates up to 24 h. It is suggested that these matrix tablets can be given in once a day dosage, which might improve patient compliance, and the polymeric blend of Ethocel grade 100 with Carbopol 934PNF might be used in the development of prolonged release matrices of other water-soluble drugs.

Ethyl-acetate extract of tara mira (Eruca sativa) alleviates the inflammation and rheumatoid arthritis in rats.

Eruca sativa, member of family Brassicaceae, was evaluated for its anti-arthritic potential. Both in vitro and in vivo models were used to bring out a safe, effective and economical remedy. In vitro tests included egg albumin denaturation suppression, bovine serum albumin assay and human red blood cells maintenance assay. While in vivo formaldehyde-induced arthritic model was initiated to check effect on paw volume. Similarly, carrageenan produced inflammation was applied to check anti-inflammatory ability of the plant. Acute toxicity studies showed safety margin at 2000mg/kg. The plant showed concentration dependent denaturation protection and membrane stability in vitro assays. Likewise, the carrageenan and formaldehyde investigations revealed visible paw volume reduction in dose attributed manner, with maximum outcome at dose of 500mg/kg. Hence, it may be established on the ground of presented results that ethyl-acetate extract of Eruca sativa has significant anti-inflammatory and anti-arthritic effects and may be considered for further research to reveal the core mechanism.

Preventive Beneficial Effect of an Aqueous Extract of Phyllanthus amarus Schum. and Thonn. (Euphorbiaceae) on DOCA-Salt-Induced Hypertension, Cardiac Hypertrophy and Dysfunction, and Endothelial Dysfunction in Rats.

This study investigated the preventive effect of an aqueous extract of the whole plant of Phyllanthus amarus (AEPA) on blood pressure, cardiac, and endothelial function in the deoxycorticosterone acetate (DOCA) salt-induced hypertensive rat model. Male Wistar rats were assigned into 5 groups receiving either vehicle (control and DOCA salt), DOCA salt combined with AEPA at 100 or 300 mg/kg, or AEPA (100 mg/kg) alone for 5 weeks. In addition, DOCA salt-treated rats were allowed free access to water containing 1% NaCl. Systolic blood pressure, left ventricle parameters, vascular reactivity of primary mesenteric artery rings, the vascular level of oxidative stress, and the level of target proteins were determined, using respectively tail-cuff sphygmomanometry, echocardiography, organ chambers, dihydroethidium staining, and immunofluorescence methods. After 5 weeks, AEPA treatments (100 or 300 mg/kg per day) significantly prevented the increase in systolic blood pressure in DOCA salt-treated rats, respectively, by about 24 and 21 mm Hg, improved cardiac diastolic function, and reduced significantly the increased posterior and septum diastolic wall thickness and the left ventricle mass in hypertensive rats. Moreover, the DOCA salt-induced endothelial dysfunction and the blunted nitric oxide- and endothelium-dependent hyperpolarization-mediated relaxations in primary mesenteric artery were improved after the AEPA treatments. AEPA also reduced the level of vascular oxidative stress and the expression level of target proteins (eNOS, COX-2, NADPH oxidase subunit p22) in DOCA salt rats. Altogether, AEPA prevented hypertension, improved cardiac structure and function, and improved endothelial function in DOCA salt rats. Such beneficial effects seem to be related, at least in part, to normalization of the vascular level of oxidative stress.

Design, Preparation and evaluation of various parameters of controlled release matrices of losartan potassium using polymers combination.

Controlled release formulations are administered once a day and reduce frequency of dose and ensuring patient's compliance. In the current research controlled release matrices of losartan potassium formulated with polymeric combinations of ethocel grade 7 with carbopol 934P NF using different concentrations of polymers. In some polymeric tablets, Co-excipients like CMC, Starch, HPMC was added by replacing of 10% of filler in formulations at 10:5. Tablets were prepared by direct compression method and evaluated for physicochemical characteristics. USP Method-1 (rotating basket method) was used to carry out dissolution study in phosphate buffer pH 6.8. Drug release kinetics determined and comparison of dissolution patterns was done with reference tablets. The polymeric combinations well retarded drug release and drug was released by anamolous non-fickian diffusion mechanism. Dissolution profiles of tested tablets and reference tablets were found not similar. Drug release rate was increased by co-excipients. It was concluded from this research work that this polymeric combination can be used efficiently in designing of controlled release martices.

Thiol-disulfide exchange reactions occurring at modified bovine serum albumin detected using ellman's reagent (5, 5'-dithiobis (2-itrobenzoic acid).

Bovine serum albumin (BSA) is usually employed as a model protein because of being homologous with human serum albumin. Cysteine-34 of BSA has been oxidised with Ellman's reagent to produce BSA labelled with an Ellman's moiety (BSA-SE). The BSA-SE was then reacted with glutathione, N-acetylcysteine and D-penicillamine (D-pen). The two were able to release the Ellman's moiety bound at cysteine-34 while D-pen did not. Albumin labeled using Ellman's reagent was used to demonstrate the cleavage of a protein mixed disulphide. The kinetics of thiol disulfide interchange reactions involving formation of a chromophoric thiolate were determined by UV-visible spectroscopy. The reaction of thiolates with excess Ellman's reagent is used for quantitative estimation of thiol by measuring the absorption at λ, 412 nm. The disulfide exchange reactions occurring at Cys-34 of BSA was determined and the reduction of oxidized Cys-34 was studied in order to understand the reverse reaction. Spectroscopic evidence suggested that glutathione and N-acetylcysteine remove the label and produce BSA in a disulfide form. In contrast, D-pen reaction returned BSA to its thiolate form via mediation. It was observed that thio-disulfide exchange occurred at cysteine-34 labelled with Ellman's moiety. The implications to the redox status of plasma are discussed.

Inhibitory effects of Clematis orientalis aqueous ethanol extract and fractions on inflammatory markers in complete Freund's adjuvant-induced arthritis in Sprague-Dawley rats.

Clematis orientalis Linn has long been used as ethnopharmacy for the treatment of arthritis. This study is intended to evaluate the curative efficacy of Clematis orientalis in treating polyarthritis in rats. Aqueous ethanolic extract and fractions (hexane, butanol and aqueous) were administered orally at 200 mg/kg for 28 days after CFA immunization. Paw swelling, paw diameter, arthritic score, body weight, hematological parameters, radiographic and histological analysis of ankle joints were evaluated. Moreover, levels of various inflammatory markers through RT-PCR and ELISA were measured. DPPH and reducing power assays were used to appraise antioxidant capacity. Qualitative phytochemical analysis, determination of total phenolic and flavonoid contents were also carried out. Aqueous ethanolic extract and fractions significantly (p < 0.001) reduced paw volume, paw thickness and arthritic score and considerably prevented decrease in body weight along with anomalous alterations in hematological parameters in comparison with arthritic control. X-ray and histological examination revealed no significant structural changes in ankle joints of treated rats. Expression levels of IL-1ß, TNF-α, IL-6, COX-2 and NF-Kß were significantly (p < 0.05-0.001) suppressed as well as noteworthy increase in the levels of IL-4 and IL-10 among treated animals has been detected. Overproduction of TNF-α and PGE2 was substantially prevented in animals given different treatments. Aqueous ethanol extract and its fractions demonstrated significant and concentration-dependent antioxidant potential. In general, among fractions aqueous fraction exhibited a greater anti-arthritic effect. Phytochemical analysis of aqueous fraction confirmed the presence of flavonoids and glycosides, 215.29 mgGAE/ml phenolic content and 633.03 µgQE/ml flavonoid content. Thus, we suggest Clematis orientalis as a potent strategy for the treatment of rheumatoid arthritis.

Evaluation of antibiotic resistant bacteria in underground drinking water and transfer of their resistant character to normal flora of the body.

The untreated surface water for drinking and domestic use is an alarming situation to public health especially in prevalence of antibiotics resistant bacteria. This investigation aimed to isolate and identify the antibiotic resistance bacteria in underground water samples in district Dera Ismail Khan, Pakistan. The underground water samples were collected from four different places using hand pumps (Khyber town, riverside, Gomal University and united town). Cultured on nutrient agar media, identified by Gam staining and biochemical tests. There after antibiotic resistance assay were performed by measuring zone of inhibition of different antibiotics by disc diffusion method. Six different bacterial colonies were isolated and identified as Enterobacteriaceae, Serriata specie, Proteues, Pseudomonas, all these bacterial colonies were 33% resistant to chloramphenicol with and 100% resistant to amoxicillin. Some colonies were also considered as resistant, according to the criteria of National Committee for Clinical Records (NCCL) that less than 10mm zone of inhibition are considered as resistant. Subsequently, the chloramphenicol resistance bacteria were analyzed for their ability to transfer resistant gene to sensitive bacteria. In in-vitro method, an isolate M1b (resistant) was found capable to transfer resistance gene to M1a isolate (sensitive) in nutrient rich environment. It was concluded that antibiotics resistance bacteria found in underground water, moreover capable of transferring the antibiotic resistant character to suitable recipient i.e. normal flora of the body or to other pathogens by conjugation.

Short Communication - Urease inhibitory activity of Hippophae rhamnoids and Cassia fistula.

The rational use of plants as medicine is traced back over five epochs to ancient documents of early civilizations and is certainly as old as mankind. These medicines originally developed from crude drugs like tinctures and tinctures. Minimum 119 chemical substances are derived from 90 plant species and used all over the world as medicines, several of them containing compounds derived from or modelled after naturally occurring lead molecules and 74% of these derived from orthodox medicinal plants. 252 drugs (11%) are believed to be basic and essential by the WHO and are exclusively of plant origin. We have examined anti-urease activity of ethyl alcohol (Et-OH) and methyl alcohol (Me-OH) extracts of H. rhamnoides and Cassia fistula. Berthelot assay was used for the determination of anti-urease activity. The enzyme activity and inhibition was measured through catalytic effects of urease on urea by measuring change in absorbance in the absence and in the presence of inhibitor at 625nm using UV spectrophotometer. In the study, both Et-OH and Me-OH extracts of H. rhamnoides (91.69%±1.21) and C. fisstula (79.44%±0.55) showed stronger action against urease activity. An overview on the medicinal uses of H. rhamnoides and C. fisstula showing anti-urease activity may predict their possible alternative use for stomach problems. This study may help to explain the beneficial effects of these plants against stomach infection associated with pathogenic strains of H. pylori as Urease is the most prominent protein component of H. pylori.

Downregulation of hepatic fat accumulation, inflammation and fibrosis by nerolidol in purpose built western-diet-induced multiple-hit pathogenesis of NASH animal model.

Western diet style (fast food), which includes fatty frozen junk food, lard, processed meats, whole-fat dairy foods, cream, mayonnaise, butter, snacks, and fructose, is a primary etiological determinant for developing nonalcoholic steatohepatitis (NASH) worldwide. Here the primary focus is to see the impact of naturally identified essential oil on disease mechanisms developed in an animal model using the same ingredients. Currently, symptomatic therapies are recommended for the management of NASH due to non-availability of specific treatments. Therefore, the present study was designed to evaluate the potential anti-NASH effect of nerolidol in a rat model fed with a purpose-built diet. The diet substantially induced insulin resistance, hepatic steatosis, dyslipidemia, and elevation of liver enzymes in the experimental animals. The levels of liver oxidative stress markers, nitrites (NO2-), serum pro-inflammatory cytokine (TNF-α) and hepatic collagen were increased in disease control rats. Nerolidol oral treatment in ascending dose order of 250 and 500 mg/kg substantially reduced the steatosis (macrovesicular and microvesicular), degeneration of hepatocytes, and inflammatory cells infiltration. The amounts of circulatory TNF-α and tissue collagen were also reduced at 500 mg/kg dose of nerolidol, expressing its anti-fibrotic effect. The current study described the multiple-hit pathophysiology of NASH as enhanced steatosis, pro-inflammatory markers, and oxidative stress in rats, which resulted in the development of vicious insulin resistance. Nerolidol treatment significantly reduced hepatic lipid accumulation and halted disease progression induced by a hypercaloric diet.

Polymeric Microparticles: Synthesis, Characterization and In Vitro Evaluation for Pulmonary Delivery of Rifampicin.

Rifampicin, a potent broad-spectrum antibiotic, remains the backbone of anti-tubercular therapy. However, it can cause severe hepatotoxicity when given orally. To overcome the limitations of the current oral therapy, this study designed inhalable spray-dried, rifampicin-loaded microparticles using aloe vera powder as an immune modulator, with varying concentrations of alginate and L-leucine. The microparticles were assessed for their physicochemical properties, in vitro drug release and aerodynamic behavior. The spray-dried powders were 2 to 4 µm in size with a percentage yield of 45 to 65%. The particles were nearly spherical with the tendency of agglomeration as depicted from Carr's index (37 to 65) and Hausner's ratios (>1.50). The drug content ranged from 0.24 to 0.39 mg/mg, with an association efficiency of 39.28 to 96.15%. The dissolution data depicts that the in vitro release of rifampicin from microparticles was significantly retarded with a higher L-leucine concentration in comparison to those formulations containing a higher sodium alginate concentration due to its hydrophobic nature. The aerodynamic data depicts that 60 to 70% of the aerosol mass was emitted from an inhaler with MMAD values of 1.44 to 1.60 µm and FPF of 43.22 to 55.70%. The higher FPF values with retarded in vitro release could allow sufficient time for the phagocytosis of synthesized microparticles by alveolar macrophages, thereby leading to the eradication of M. tuberculosis from these cells.

Phytochemicals targeting NAFLD through modulating the dual function of forkhead box O1 (FOXO1) transcription factor signaling pathways.

Literature evidence reveals that natural compounds are potential candidates for ameliorating obesity-associated non-alcoholic fatty liver disease (NAFLD) by targeting forkhead box O1 (FOXO1) transcription factor. FOXO1 has a dual and complex role in regulating both increase and decrease in lipid accumulation in hepatocytes and adipose tissues (AT) at different stages of NAFLD. In insulin resistance (IR), it is constitutively expressed, resulting in increased hepatic glucose output and lipid metabolism irregularity. The studies on different phytochemicals indicate that dysregulation of FOXO1 causes disturbance in cellular nutrients homeostasis, and the natural entities have an enduring impact on the mitigation of these abnormalities. The current review communicates and evaluates certain phytochemicals through different search engines, targeting FOXO1 and its downstream cellular pathways to find lead compounds as potential therapeutic agents for treating NAFLD and related metabolic disorders. The findings of this review confirm that polyphenols, flavonoids, alkaloids, terpenoids, and anthocyanins are capable of modulating FOXO1 and associated signaling pathways, and they are potential therapeutic agents for NAFLD and related complications. HIGHLIGHTS: • FOXO1 has the potential to be targeted by novel drugs from natural sources for the treatment of NAFLD and obesity. • FOXO1 regulates cellular autophagy, inflammation, oxidative stress, and lipogenesis through alternative mechanisms. • Phytochemicals treat NAFLD by acting on FOXO1 or SREBP1c and PPARγ transcription factor signaling pathways.

Tacrolimus-Loaded Solid Lipid Nanoparticle Gel: Formulation Development and In Vitro Assessment for Topical Applications.

The currently available topical formulations of tacrolimus have minimal and variable absorption, elevated mean disposition half-life, and skin irritation effects resulting in patient noncompliance. In our study, we fabricated tacrolimus-loaded solid lipid nanoparticles (SLNs) that were converted into a gel for improved topical applications. The SLNs were prepared using a solvent evaporation method and characterized for their physicochemical properties. The particle size of the SLNs was in the range of 439 nm to 669 nm with a PDI of ≤0.4, indicating a monodispersed system. The Zeta potential of uncoated SLNs (F1-F5) ranged from -25.80 to -15.40 mV. Those values reverted to positive values for chitosan-decorated formulation (F6). The drug content and entrapment efficiency ranged between 0.86 ± 0.03 and 0.91 ± 0.03 mg/mL and 68.95 ± 0.03 and 83.68 ± 0.04%, respectively. The pH values of 5.45 to 5.53 depict their compatibility for skin application. The surface tension of the SLNs decreased with increasing surfactant concentration that could increase the adherence of the SLNs to the skin. The release of drug from gel formulations was significantly retarded in comparison to their corresponding SLN counterparts (p ≤ 0.05). Both SLNs and their corresponding gel achieved the same level of drug permeation, but the retention of the drug was significantly improved with the conversion of SLNs into their corresponding gel formulation (p ≤ 0.05) due to its higher bioadhesive properties.

Physicochemical Characterization of Chitosan-Decorated Finasteride Solid Lipid Nanoparticles for Skin Drug Delivery.

Finasteride is considered the drug of choice for androgenic alopecia and benign prostate hyperplasia. The aim of the study was to formulate nanodrug carriers of finasteride with enhanced retentive properties in the skin. The finasteride was formulated as solid lipid nanoparticles that were decorated with different concentrations of chitosan for improved retentive properties. Solid lipid nanoparticles (SLNs) were synthesized by "high-speed homogenization technique" using stearic acid as a solid lipid while PEG-6000 and Tween-80 were used as surfactants. The SLNs were evaluated for particle size, polydispersity index (PDI), zeta potential, drug entrapment efficiency, and drug release behavior. The mean particle size of SLNs was in the range of 10.10 nm to 144.2 nm. The PDI ranged from 0.244 to 0.412 while zeta potential was in the range of 8.9 mV to 62.6 mV. The drug entrapment efficiency in chitosan undecorated formulations was 48.3% while an increase in drug entrapment was observed in chitosan-decorated formulations (51.1% to 62%). The in vitro drug release studies of SLNs showed an extended drug release for 24 hours after 4 hours of initial burst release. The extended drug release was observed in chitosan-coated SLNs in comparison with uncoated nanoparticles. The permeation and retention study revealed higher retention of drug in the skin and low permeation with chitosan-decorated SLNs that ranged from 39.4 µg/cm2 to 13.2 µg/cm2. TEM images depicted spherical shape of SLNs. The stability study confirmed stable formulations in temperature range of 5°C and 40°C for three months. It is concluded from this study that the SLNs of finasteride were successfully formulated and chitosan decoration enhanced the drug retention in the skin layers. Therefore, these formulations could be used in androgenic alopecia and benign prostate hyperplasia to avoid the side effects, drug degradation, and prolonged use of drug with conventional oral therapy.

Phytochemical analysis of crude extract of Delphinium brunonianum and its effect on hypertension and metabolic perturbations in fructose fed rats.

The present study aims at phytochemical profiling and valuating the effect of crude extract of Delphinium brunonianum on fructose mediated rise in blood pressure and metabolic abnormalities in rats. Therefore, rats were fed on fructose (10%w/v) for 6 weeks. Rats in treatment groups received amlodipine 250, 500 and 1000 mg/kg of DB-Cr separately in concurrent to fructose. Various parameters of metabolic perturbations were assessed at the end of study. Further, DB-Cr was analyzed using LC-MS technique. DB-Cr exerted remarkable antihypertensive effect whereas, sympathetic hyperactivity and hyperinsulinemia in these rats was significantly blunted, further, endothelium functionality was successfully restored. LC-MS analysis of DB-Cr revealed the presence of a variety of chemical constituents (41) including quinic acid, scopolin, gingerol, Robinetin 3-rutinoside, KAPA and maleic acid. In conclusion, D. brunonianum possess the potential to combat the fructose mediated hypertension and metabolic perturbations, which may partially be due to its chemical constituents.

In vitro and in vivo evaluation of gellan gum hydrogel films: Assessing the co impact of therapeutic oils and ofloxacin on wound healing.

Herein, we report co-encapsulation of ofloxacin with tea tree or lavender oil in gellan gum based hydrogel films by solvent casting ionotropic gelation method as wound dressing. Prepared films were transparent, flexible, and displayed antioxidant activity with superior antibacterial response against common inhabitants of wound i.e. gram positive and negative bacteria. Solid-state characterization of optimized formulation (OL3 and OT3) revealed successful incorporation of drug and oils in hydrogel structure without any noticeable interaction. In vitro release studies showed an initial burst release but remaining portion released in controlled manner over 48 h from the films and furthermore, presence of oils did not affected the ofloxacin release. Optimized formulation containing ofloxacin and 25% w/w lavender/tea tree oil showed 98% wound contraction in rats after ten days of treatment. Histological images displayed completely healed epidermis. Taken together, our prepared hydrogel films demonstrated favorable features with appreciable antibacterial, wound healing activity and could be useful for the treatment of full thickness wounds.

Phytochemicals targeting matrix metalloproteinases regulating tissue degradation in inflammation and rheumatoid arthritis.

PURPOSE: Matrix metalloproteinases, zinc dependent proteolytic enzymes, have significant implications in extracellular matrix degradation associated with tissue damage in inflammation and Rheumatoid arthritis. Numerous orchestrated pathways affects instigation and blockade of metalloproteinases as well as various factors that increase the expression of MMPs including inflammatory cytokines, hormones and growth factors. Direct inhibition of these proteolytic enzymes or modulation of these pathways can provide protection against tissue destruction in inflammation and rheumatoid arthritis. Inclination towards use of plant derived phytochemicals to prevent tissue damage has been increasing day by day. Diversity of phytochemicals have been known to directly inhibit metalloproteinases. Hence, thorough knowledge of phytochemicals is very important in novel drug discovery. METHODS: Present communication evaluates various classes of phytochemicals, in effort to unveil the lead molecules as potential therapeutic agents, for prevention of MMPs mediated tissue damage in inflammation and rheumatoid arthritis. Data have been analyzed through different search engines. RESULTS: Numerous phytochemicals have been studied for their role as MMPs inhibitors which can be processed further to develop into useful drugs for the treatment of inflammation and rheumatoid arthritis. CONCLUSION: In search of new drugs, phytochemicals like flavonoids, glycosides, alkaloids, lignans & terpenes offer a wide canvas to develop into valuable forthcoming medicaments.

Potential Application of Venom Proteins in Designing of Medicines for Treating Human Neurodegenerative Disorders.

BACKGROUND: Neurodegenerative disorder are persistently increasing and relentlessly affecting the individuals, families and society as whole. Regrettably these disorders are resistant to the available drugs, the outcomes are only palliative while the side effects of the therapy harm the patient compliance as well as treatment. Drugs from venomous source have been considered as an effective alternative for such types of disorders, particularly neurodegenerative diseases. Due to emerging advancement in the field of proteomics, genomics and molecular biology, characterization and screening of these novel compounds become more assessable. CONCLUSION: In this reverence, the present study reviews the current consideration of the mode of action and the future prediction concerning the use of novel compounds isolated from arthropods and other venomous animals in the treatment of major neurodegenerative diseases such as Parkinson disease, Alzheimer disease, Multiple Sclerosis, Epilepsy and Amyotrophic Lateral Sclerosis.

Hyaluronidases: A Therapeutic Enzyme.

BACKGROUND: Hyaluronidase is the most important enzyme found in the interstitial matrix, effectively degrading the hyaluronic acid. Hyaluronidases are extensively found in the venom of various animals such as snake, scorpion, spider and others. Up till now five venom hyaluronidases are identified with a defined three-dimensional structure. These enzymes are involved in different biochemical, physiological and pathological conditions like degradation of hyaluronic acid, embryogenesis, transmembrane diffusion of drugs and toxins, inflammatory and allergic response to antigens, healing of wounds, bacterial meningitis, bacteremia and pneumonia. These enzymes are used as an adjuvant therapy in cancer and to expedite the dispersion and absorption of drugs as well as to reduce the tissue edema. and to reduce the progression of metastatic breast cancer as well as used in ophthalmological procedures in combination with local anesthetics, reduction of dermatological aging, regulation of hyaluronan, as a spreading factor and with numerous clinical applications. CONCLUSION: In this review an attempt was made to summarize the physiological, adjuvaent and therapeutic significance of hyaluronidase enzymes from different animal sources.

Simulation Studies and Dynamic Interaction of Venom Peptides with Ion Channels.

BACKGROUND: Arthropods such as scorpion, snake, insects, and spider as well as the marine animals like sea anemone and cone snails are venomous animals producing venoms with a complex mixture of peptide, poly peptides and small proteins. The disulfide rich peptides isolated from these animals are potent substances which specifically and selectively modulate different ion channels. The significant characteristics of these distinctive pharmacologically potent compounds highlights the molecular details of their peptide-ion channels interactions as well as provides the opportunities for the development of novel and natural therapeutic agents to treat various diseases including neurological disorders also. A good deal is going into the understanding of their therapeutic applications by unrevealing their mode of action. CONCLUSION: In this review, an attempt is made to summarizes the molecular behavior of these venom peptides, their pattern of interactions that how molecular simulation studies are used to investigate the dynamic interaction between these peptides and ion channels, structural prediction of peptide channel complex and calculation of binding free energy.

Potential Applications of Venom Peptides as Anti-Thrombotic Agents for Management of Arterial and Deep-Vein Thrombosis.

BACKGROUND: Thrombus is composed of two main substances i.e. red blood cells and aggregated platelets which make a web of inter-connected fibrin proteins. During injury it prevents bleeding, so it is very useful but it can be very dangerous if it is produced in healthy blood vessels and block the blood flow through it. Mural thrombi attaches with the blood vessels but in most cases do not block it completely. Venoms are an incredible source of peptides having amazing bioactivities with varying number of amino acid residues. Anticoagulant venom peptides however inhibit the enzyme taking part in coagulation like factor Xa and thrombin. The anticoagulant potential of venom peptides have also been reported by the degradation of the fibrin or fibrinogen related to serine or metalloproteases. Designing and development of numerous therapeutic agents or lead molecules mostly for cardiovascular diseases have been motivated from toxins/proteins from snake venoms. For example, disintegrins, a large family of platelet aggregation inhibitors found in viperid and crotalid snake venoms were the basis for designing of platelet aggregation inhibitors such as eptifibatide and tirofiban. CONCLUSION: Ancrod isolated from Malayan pit viper venom can cause reduction in level of blood fibrinogen and has been effectively tried in various ischemic conditions, including stroke. In order to search for novel lead molecules, the emphasis should be on isolation and characterization of pharmacologically active snake venoms proteins affecting blood coagulation and platelet aggregation. In this review an attempt has been made to recapitulates and discuss venoms of different animals and arthropod having anticoagulant peptides for their potential use in therapeutics and diagnostics.