Therapeutic approaches to drug targets in atherosclerosis

AbstractNon-communicable diseases such as cancer, atherosclerosis and diabetes are responsible for major social and health burden as millions of people are dying every year. Out of which, atherosclerosis is the leading cause of deaths worldwide. The lipid abnormality is one of the major modifiable risk factors for atherosclerosis. Both genetic and environmental components are associated with the development of atherosclerotic plaques. Immune and inflammatory mediators have a complex role in the initiation and progression of atherosclerosis. Understanding of all these processes will help to invent a range of new biomarkers and novel treatment modalities targeting various cellular events in acute and chronic inflammation that are accountable for atherosclerosis. Several biochemical pathways, receptors and enzymes are involved in the development of atherosclerosis that would be possible targets for improving strategies for disease diagnosis and management. Earlier anti-inflammatory or lipid-lowering treatments could be useful for alleviating morbidity and mortality of atherosclerotic cardiovascular diseases. However, novel drug targets like endoglin receptor, PPARα, squalene synthase, thyroid hormone analogues, scavenger receptor and thyroid hormone analogues are more powerful to control the process of atherosclerosis. Therefore, the review briefly focuses on different novel targets that act at the starting stage of the plaque form to the thrombus formation in the atherosclerosis

Annona reticulata Linn. (Bullock's heart): Plant profile, phytochemistry and pharmacological properties

From the beginning of human civilization plants and plant based chemicals are the most important sources of medicines. Phytochemical and different products obtained from plant are used as medicines, pharmaceuticals, cosmetics and food supplements. Annona reticulata Linn. (牛心果 niú xīn guǒ; Bullock's heart) is a versatile tree and its fruits are edible. Parts of A. reticulata are used as source of medicine and also for industrial products. It possesses several medicinal properties such as anthelmintic, analgesic, anti-inflammatory, antipyretic, wound healing and cytotoxic effects. It is widely distributed with phytochemicals like tannins, alkaloids, phenols, glycosides, flavonoids and steroids. Present article is an attempt to highlight over taxonomy, morphology, geographical distribution, phytoconstituents and pharmacological activities of A. reticulata reported so far

Evaluation of anthelmintic activity and in silico PASS assisted prediction of Cordia dichotoma (Forst.) root extract

Background: Worm infection and associated complications are severe problems that afflict a large population worldwide. Failure of synthetic drugs in worm infections because of drug resistance has made alternative drug therapy desirable. Cordia dichotoma (Forst.) is an ethnomedicinal plant which is rich in several secondary metabolites. Traditionally, the plant has been claimed to have high medicinal properties including antimicrobial activity and cytotoxicity. Materials and Methods: The study begun with an aim to explore plant-based natural anthelmintic agents against Pheretima posthuma, an Indian earthworm. Methanol extract of the drug was obtained by successive soxhlet extraction. The extract was tested for different phytochemicals. Worms were exposed to 10 mg/ml, 25 mg/ml, 50 mg/ml, and 75 mg/ml concentrations of extract and standard drug, albendazole. A software-based tool, prediction of activity spectra for substances was used to estimate anthelmintic efficacy of plant metabolites. Result: The phytochemical analysis revealed presence of alkaloids, tannins, glycosides, saponins, flavonoids, and phenols. The extract showed dose-dependent effects, affecting worm motility, viability, and mortality. It was also found that the biological activity spectrum of the plant phytoconstituents such as octacosanol, lupeol, caffeic acid, and hentricontanol were >0.5 (probable activity > 0.5). Conclusion: The findings of the present work suggest that the extract of C. dichotoma significantly interferes with motility pattern of P. posthuma. The paralysis and mortality of P. posthuma might be due to the combined effects different phytoconstituents. The extract of C. dichotoma promises natural sources to control worm infection

Evaluation of anthelmintic activity and in silico PASS assisted prediction of Cordia dichotoma (Forst.) root extract

Background: Worm infection and associated complications are severe problems that afflict a large population worldwide. Failure of synthetic drugs in worm infections because of drug resistance has made alternative drug therapy desirable. Cordia dichotoma (Forst.) is an ethnomedicinal plant which is rich in several secondary metabolites. Traditionally, the plant has been claimed to have high medicinal properties including antimicrobial activity and cytotoxicity. Materials and Methods: The study begun with an aim to explore plant-based natural anthelmintic agents against Pheretima posthuma, an Indian earthworm. Methanol extract of the drug was obtained by successive soxhlet extraction. The extract was tested for different phytochemicals. Worms were exposed to 10 mg/ml, 25 mg/ml, 50 mg/ml, and 75 mg/ml concentrations of extract and standard drug, albendazole. A software-based tool, prediction of activity spectra for substances was used to estimate anthelmintic efficacy of plant metabolites. Result: The phytochemical analysis revealed presence of alkaloids, tannins, glycosides, saponins, flavonoids, and phenols. The extract showed dose-dependent effects, affecting worm motility, viability, and mortality. It was also found that the biological activity spectrum of the plant phytoconstituents such as octacosanol, lupeol, caffeic acid, and hentricontanol were >0.5 (probable activity > 0.5). Conclusion: The findings of the present work suggest that the extract of C. dichotoma significantly interferes with motility pattern of P. posthuma. The paralysis and mortality of P. posthuma might be due to the combined effects different phytoconstituents. The extract of C. dichotoma promises natural sources to control worm infection

Helicobacter pylori and cardiovascular complications: a mechanism based review on role of Helicobacter pylori in cardiovascular diseases

Heart disease comprises a wide class of cardiovascular abnormalities, including ischemic heart disease, myocardial infarction, atherosclerosis, and coronary artery disease. It is the leading cause of death all over the world. Several traditional and novel risk factors, such as infectious and noninfectious agents, have been associated with heart disease. Out of these, Helicobacter pylori has been recently introduced as an important etiological factor for heart disease. Numerous seroepidemiological findings observed H. pylori antibodies in the blood of a patient with cardiovascular complications. The bacteria survive in the epithelial cells of gastric organs and cause digestive complications. Excess inflammatory pathogenesis and prognosis stimulate an immune response that further causes significant disturbances in various factors like cytokines, fibrinogen, triglycerides, high density lipoprotein, C-reactive protein, heat shock protein, and white blood cell count, and provoke a number of problems such as atherosclerosis and prothrombic state, and cross-reactivity which eventually leads to heart diseases. H. pylori releases toxigenic nutrients, chiefly vacuolating cytotoxin gen A (Vac A) and cytotoxin associated gene A (Cag A), of which Cag A is more virulent and involved in the formation of cholesterol patches in arteries, induction of autoimmune disorder, and release of immune mediated response. Although numerous mechanisms have been correlated with H. pylori and heart disease, the exact role of bacteria is still ambiguous

In silico PASS analysis and determination of antimycobacterial, antifungal, and antioxidant efficacies of maslinic acid in an extract rich in pentacyclic triterpenoids

Objective/background: Microbial infections such as tuberculosis is a major cause of mortality worldwide. Plant-derived phytochemicals have a long history of providing much-needed novel therapeutics. Triterpenoids are among the prominent phytochemicals that possess numerous biological activities. Among them is maslinic acid (MA), a biologically active olean-type pentacyclic triterpenoid. In search of a novel antimicrobial agent, we aimed to evaluate the antimicrobial potential of MA. Methods: Antibacterial and antifungal activity was evaluated through the agar well diffusion method. Antitubercular activity was analysed through the agar well diffusion and disc diffusion methods, respectively. Antioxidant capacity was determined through assays for total antioxidant capacity, 2,2-diphenyl-1-picrylhydrazyl radical scavenging, hydrogen peroxide radical scavenging, and Fe3+ reducing power. The program Prediction of Activity Spectra for Substances was used to calculate the possible biological activity of MA. Results: MA showed dose-dependent antioxidant activity similar to that of ascorbic acid. It had no inhibitory effect on bacterial strains, but it had moderate activity against the fungi Aspergillus flavus and Ustilago maydis, with Aspergillus niger being the most sensitive to MA. MA also exhibited strong antimycobacterial activity. Probable antioxidant, antibacterial, and antifungal activity of MA based on software calculations are 0.479, 0.363 and 0.589 respectively. Conclusion: This work provides scientific evidence of the antioxidant, antifungal, and antimycobacterial activities of MA, showing its potential application in the development of natural antioxidants and antimicrobial agents for the agro-food and pharmaceutical industries

In vitro anthelmintic efficacy of ethno-medicinal plant Annona reticulata L. roots against Indian earthworms (Pheretima posthuma)

The present study was envisaged to evaluate the ethno-medical claims of Annona reticulata L. roots for anthelmintic efficacy in vitro in comparison with the standard chemotherapeutic agent, albendazole on adult Indian earthworms (Pheretima posthuma). The efficacy was evaluated by monitoring gross visual motility, paralysis and mortality time and new software based tool, PASS (Prediction of Activity Spectra for Substances). Literature confirmed that roots of the plant are rich in aporphine alkaloids and acetogenins. Therefore, study includes investigation and correlation of the biological activity spectrum of the aporphine alkaloids and acetogenins using PASS with in vitro anthelmintic activity. In vitro anthelmintic trials of extract was conducted at 20, 40, 60 mg/mL. The extract was found to be effective at all concentrations but a more significant result was at concentration 60 mg/mL. This could be due to synergistic effect of both the phytoconstituents. However, exact mechanism of action need to be studied

Software based approaches for drug designing and development: A systematic review on commonly used software and its applications

Drug discovery include drug designing and development, is a multifarious and expensive endeavor, where least number of drugs that pass the clinical trials makes it to market. Software based drug discovery and development methods have major role in the development of bioactive compounds for over last three decades. Novel software based methods such as molecular modeling, structure-based drug design, structure-based virtual screening, ligand interaction and molecular dynamics are considered to be powerful tool for investigation of pharmacokinetic and pharmacodynamic properties of drug, and structural activity relationship between ligand and its target. Computational approaches such as docking confer interaction of small molecules with structural macromolecules and thereby hit identification and lead optimization. These methods are faster, and accurately provide valuable insights of experimental findings and mechanisms of action. In addition, appropriate implementation of these techniques could lead to a reduction in cost of drug designing and development. Currently in biomedicine sciences these software are exhibiting imperative role in the different phases of drug discovery. The review discusses working principle and successful applications of most commonly used software for drug designing and development. Keywords: Drug discovery, Docking, Structural activity relationship, Molecular modeling, Computational method

<i style="mso-bidi-font-style:normal">In vitro</i> anthelmintic efficacy of ethno-medicinal plant <i style="mso-bidi-font-style:normal">Annona reticulata </i>L.<i style="mso-bidi-font-style:normal"> </i>roots<i style="mso-bidi-font-style:normal"> </i>against Indian earthworms (<i style="mso-bidi-font-style:normal">Pheretima posthuma</i>)

152-157The present study was envisaged to evaluate the ethno-medical claims of Annona reticulata L.<i style="mso-bidi-font-style: normal"> roots for anthelmintic efficacy in vitro in comparison with the standard chemotherapeutic agent, albendazole on adult Indian earthworms (Pheretima posthuma). The efficacy was evaluated by monitoring gross visual motility, paralysis and mortality time and new software based tool, PASS (Prediction of Activity Spectra for Substances). Literature confirmed that roots of the plant are rich in aporphine alkaloids and acetogenins. Therefore, study includes investigation and correlation of the biological activity spectrum of the aporphine alkaloids and acetogenins using PASS with in vitro anthelmintic activity. In vitro anthelmintic trials of extract was conducted at 20, 40, 60 mg/mL. The extract was found to be effective at all concentrations but a more significant result was at concentration 60 mg/mL. This could be due to synergistic effect of both the phytoconstituents. However, exact mechanism of action need to be studied