Progress in Drug Research. Fortschritte der Arzneimittelforschung. Progrès des Recherches Pharmaceutiques

The focus of molecular docking is to computationally simulate the molecular recognition process. A binding interaction between a small molecule ligand and protein may result in activation or inhibition of the protein. The docking method using BRCA1 or BRCA2 genes and COX proteins is carefully texted in this chapter to check docking of the best inhibitor molecule.

Plants are the storehouse of many chemical compounds that possess various biological activities. Identification of these compounds becomes critical in understanding the exact mechanism behind the therapeutic potential of these plants. Screening and isolation of compounds from plants important to human health involves various methods that need careful handling and attention. A detailed method of isolation using thin layer chromatography (TLC) and column is explained.

High performance thin layer chromatography (HPTLC) is a sophisticated instrumental technique based on the full capabilities of thin layerchromatography. The advantages of automation, scanning, full optimization, selective detection principle, minimum sample preparation,hyphenation, etc., enable it to be a powerful analytical tool for chromatographic information of complex mixtures of inorganic, organic andbiomolecules which are characterized in this chapter.

All the nutrients in food are not absorbed by our system. The relative amount of nutrition from an administered dosage through which it enters the system of circulation and the rate at which the level of nutrition appears in the systemic circulation is called 'bioavailability'. Although plant foods have high nutrient contents our digestion system cannot absorb it fully. Hence, it becomes necessary to determine the bioavailability of the administered sample to check the overall effect on the living system. Animal food preparation, protein bioavailability in animal model, food efficiency, apparent digestibility, protein digestibility tests, etc...

Experimental tumours have great importance for the purposes of modelling where Dalton's ascites lymphoma (DAL) and Ehrlich ascites carcinoma (EAC) are the commonest. It appeared firstly as a spontaneous breast cancer in a female mouse and then Ehrlich and Apolant (Berlin KlinWshr 28:871-874, 1905) used it as an experimental tumour by transplanting tumour tissues subcutaneously from mouse to mouse. In 1932, Loewenthal and Jahn obtained the liquid form in the peritoneum of the mouse and named it as 'Ehrlich ascites carcinoma' due to the ascites liquid, together with the carcinoma cells...

The apoptotic activity of plants is checked to confirm its anti-tumour and anti-cancer activity. Apoptosis is a specific process that leads to intrinsic programmed cell death which is essential in the homeostasis of normal tissues of the body and occurs in various physiological and pathological situations. Method to check apoptosis in EAC cells and DNA analysis are featured in this chapter as a preliminary test manner.

Cytotoxicity assays are used for drug screening and cytotoxicity tests of chemicals. Nowadays, various reagents are used for cell viability detection. They are based on various cell functions such as enzyme activity, cell membrane permeability, cell adherence, ATP production, co-enzyme production and nucleotide uptake activity. Many have established methods such as colony formation method, crystal violet method, tritium-labelled thymidine uptake method, MTT and WST methods, which are used for counting the number of live cells...

Wound healing has emerged as a major treatment issue which has provoked the development of drugs that can improve the healing process. Studies using plant drugs have revealed many interesting results about existing commercial drugs. Effective wound healing leads to the restoration of tissue integrity and occurs through a highly organized multistage. Use of plant-derived medicines against excision, incision, and dead space models accelerates the wound healing process, which is briefly discussed in a manner to be followed easily during experimental sessions...

The diabetes-inducing agent streptozotocin (STZ) is a glucosamine-nitrosourea compound produced by Streptomyces achromogenes, which specifically induces DNA strand breakage in β-cells causing diabetes mellitus. The destruction of pancreatic β-cells by STZ is associated with a huge release of insulin in their first phase, and then in the second phase, the destruction has lead to deficiency of insulin causes hyperglycaemia. A detailed method on selection of diabetic animals, investigation of blood glucose levels, body weight, biochemical and histopathological parameters is presented in this chapter...

The hyperglycaemia continues to be a major health problem in India and other developing countries. This imbalance of blood glucose causes serious health problems such as damages to the blood vessel, poor healing of wounds, retinal damage, renal damage--kidney failure. The in vitro enzyme models and evaluation of hypoglycaemic effect of sample on normal and glucose-loaded rats has been used as a prediction experiment in this chapter before going for anti-diabetic experiment using animal models.

The liver performs a vital role in metabolism, secretion, storage, and detoxification of endogenous and exogenous substances. Oxidative stress and free radicals enhance the severity of hepatic damage, which can be overcome by the antioxidant mechanism. Plant extracts can be the best source of such antioxidants and mediate hepatoprotective activity. In this chapter, high-dose paracetamol-induced hepatotoxicity in rat model is discussed with explanations of biochemical and histopathological studies.

This chapter explains the procedure of ethanol-induced ulcer to check the protective effect of drugs over induced ulcer in rats. Ulcer is defined as the erosion in the lining of the stomach or duodenum and is caused by the disruptions of the gastric mucosal defence and repair systems. Ulceration of stomach is called gastric ulcer and that of duodenum is called duodenal ulcer and together peptic ulcer. In clinical practice, peptic ulcer is one of the most prevalent gastrointestinal disorders, which commonly occurs in developed countries...

Diarrhoea is characterized by an increase in the frequency of bowel movements, wet stool and abdominal pains. It is the world's third highest killer disease, contributing substantially to paediatric morbidity and mortality, especially in the malnourished. Antibiotics used as anti-diarrhoeal drugs sometimes provoke adverse effects and microorganisms tend to develop resistance towards them. Therefore, the search for safe and more effective agents from plant origin using standard protocols of charcoal meal-induced diarrhoea has been defined in this chapter...

Formaldehyde-induced arthritis and complete Freund's adjuvant (CFA)-induced arthritis in rats are well-known models to determine the anti-arthritic activity. Arthritis is a symptom of chronic inflammation. It is a chronic progressive disorder, developing over months or years and involving essentially the synovial joints of the body. Hence, these two models become the basis of this chapter to analyse the anti-arthritic activity.

Inflammation response plays an important role in host survival, and it also leads to acute and chronic inflammatory diseases such as rheumatoid arthritis, bowel diseases, allergic rhinitis, asthma, atopic dermatitis and various neurodegenerative diseases. During the course of inflammation, the ROS level increases. In addition to ROS, several inflammatory mediators produced at the site lead to numerous cell-mediated damages. Inflammatory bowel disease (IBD), including ulcerative colitis and Crohn's disease, is a chronic intestinal disorder resulting from a dysfunctional epithelial, innate and adaptive immune response to intestinal microorganisms...

The concept regarding the pathogenesis of pyrexia is almost exclusively concentrated on humoral mediatory mechanism. As per these views, exogenous pyrogens first persuade the formation of pyrogenic cytokines and these endogenous pyrogens order to increase the synthesis of prostaglandin E in different structures of the central nervous system (CNS). The subsequent alterations of CNS functions are reflected in the modifications of peripheral thermoregulatory effector functions, which hoist body temperature during the development of fever and maintain it during the whole fever course...

Inflammation is the body's first response to infection or injury and is critical for both innate and adaptive immunity. It can be considered as part of the complex biological response of vascular tissues to harmful stimuli such as pathogens, damaged cells, or irritants. The search for natural compounds and phytoconstituents that are able to interfere with these mechanisms by preventing a prolonged inflammation could be useful for human health. Here, the anti-inflammatory properties of plant-based drugs are put together with both in vitro and acute (carrageenan, egg albumin and croton oil) and chronic (cotton pellet) in vivo models...

Analgesics are agents which selectively relieve pain by acting in the CNS and peripheral pain mediators without changing consciousness. Analgesics may be narcotic or non-narcotic. The study of pain in animals raises ethical, philosophical, and technical problems. Both peripheral and central pain models are included to make the test more evident for the analgesic property of the plant. This chapter highlights methods such as hot plate and formalin and acetic acid-induced pain models to check the analgesic activity of medicinal plants...

Oxidative stress and antioxidant deficiency have been implicated in the pathophysiology of a wide range of diseases and conditions. Consequently, over recent years many different supplementation trials have been implemented, aimed at improving clinical outcomes by boosting antioxidant levels. These trials included supplementation with individual antioxidants, antioxidant combinations, and antioxidant-rich foods such as fruit and vegetable juices and other plant extracts. To ensure that data from these trials are interpreted correctly, it is essential that suitable biomarkers are used to assess changes in in vivo antioxidant activity resulting from supplementation...

Toxicity studies in the animal models are done to determine the dose level recommended for the treatment of disease as drug. This guideline enables the characterization of adverse effects following repeated daily inhalation exposure to a test. This chapter includes oral and dermal toxicity studies which are discussed as per OECD guidelines. Both acute and subacute toxicity studies are given special emphasis.