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May be due to its large surface area, the respiratory tract is one of the major target for free radical attack. Air pollution can be considered as a major source of ROS. Current studies propose that free radicals may be concerned in the progress of pulmonary disorders such as asthma. Cellular damage caused by free radicals is thought to be partly responsible for the bronchial inflammation characteristic of this disease. It has been recommended that increased antioxidant intake may reduce oxidant stress and prevent or diminish the advancement of asthmatic symptoms (Kinnula and Crapo, 2003).
Other main pathologies that may involve free radicals include neurological disorders, cataracts, hemolysis, diabetics Atherosclerosis, Cataracts, Arthritis, and inflammatory diseases Diabetes, Shock, trauma, ischemia, Renal disease and Haemodialysis (Mark, 1998).
All the living organisms are victim to infection. Humans are susceptible to diseases caused by viruses, bacteria, protozoa, fungi and helminths. The successful development of such agents, particularly the antibiotic revolution, constitutes one of the most important therapeutic advances in the entire history of medicine (Rang et al., 2005).
1.12.1. Definition and characteristics
Antibiotics are substances obtained from different classes of microorganisms (bacteria, viruses and fungi) that restrain the growth of other microorganisms. Understanding the mechanisms of bacterial replication greatly supports the development of antimicrobials (Tripathi, 2007).
1.12.2. Mechanism of action and classification
Antimicrobial agents are grouped based on proposed mechanism of action and chemical structures are like follows:
Anti microbial agents that stop the synthesis of bacterial cell walls - Including the ÃŸ-lactam class of antibiotics, different agents such as cycloserine, vancomycin, and bacitracin.
Agents that act on the cell membrane of the microorganism - polymyxin, polyene antifungal agents and daptomycin.
Agents that disrupt role of 30S or 50S ribosomal subunits to reversibly inhibit protein synthesis - chloramphenicol, tetracyclines, erythromycin, clindamycin, streptogramins, and linezolid
Agents that connect to the 30S ribosomal subunit and revise protein synthesis - aminoglycosides.
Agents that affect bacterial nucleic acid metabolism,
Rifamycins e.g., rifampin and rifabutin - inhibit RNA polymerase.
Quinolones - inhibit topoisomerases.
Trimethoprim and the sulfonamides - block essential enzymes of folate metabolism.
Acyclovir or ganciclovir - selectively inhibit viral DNA polymerase.
Zidovudine or lamivudine - inhibit HIV reverse transcriptase.
Non-nucleoside HIV reverse transcriptase inhibitors - nevirapine, efavirenz.
Inhibitors of other essential viral enzymes
Inhibitors of HIV protease or influenza neuraminidase
Fusion inhibitors like enfuvirtide.
Supplementary groups with more complex mechanisms are elucidated. The accurate mechanism of action of some antimicrobial agents still mysterious (Chambers, 2006).
1.13. Bacterial resistance to antimicrobial agents
Bacterial resistance is a major medical problem, because it seriously limits the usefulness of many antibiotics. Usually some species of microorganisms may be susceptible to some chemotherapeutic agent and resistant to others. But development of strains against the drug, which are effective against the species, is serious (Levy and Marshall, 2004).Bacterial resistance is either natural or acquired.
220.127.116.11. Natural resistance
This type of resistance is genetically determined and depends upon the absence of metabolic process or pathway in the microorganism. Most of the time natural resistance is confined to a particular species (Baquero, 1997).
18.104.22.168. Acquired resistance
Acquired resistance refers to resistance developing in a previously sensitive bacterial species. The development of acquired resistance involves a stable genetic change, heritable from generation to generation. Resistance may acquire to the organism through various mechanisms like mutation, adaptation, transformation, transduction or conjugation (Barar, 2000).
1.14. Test for microbial sensitivity to antimicrobial agents
1.14.1. Bacteria and fungi
Preliminary screening of plants may be performed with pure substances or crude extracts. The screening methods used for both bacteria and fungi are similar. The most commonly used screens to establish antimicrobial susceptibility are the broth dilution assay, the disc diffusion assay and agar well diffusion assay. In some cases, plates or tubes inoculated with microorganisms are exposed to UV light to screen for the existence of light-sensitizing phytochemicals. Antifungal phytochemicals can also be screened by a method known spore germination assay. After initial screening of phytochemicals, more specific media can be used to conduct the specific microorganisms and Minimum inhibitory concentration can be efficiently compared to those of presently used antibiotics (Cowan, 1999).
A number of methods are offered to detect either virucidal or antiviral plant activity. Investigators can assess cytopathic effects, plaque formation, transformation and proliferative effects on cell lines. Viral replication is a measure of antiviral activity. This may be quantified by detection of viral products such as RNA, DNA and polypeptides. Antiviral assays often screen for active substances, those have the capacity to inhibit adsorption of the microorganism to host cells (Ahmad, 2010).
1.14.3. Protozoa and helminths
Compared to the screening of plant extract for their activity against bacteria, fungi, or viruses screening against helminths and protozoa can be more difficult. Culturing the organism is very difficult and very less number of organisms is obtained. Assays are particular for the microorganism. (Vital, 2009).
1.15. Choice of antimicrobial agent
Selection from among several drugs depends on host factors that include the following: (1) concomitant disease states (eg, AIDS, severe chronic liver disease); (2) prior adverse drug effects; (3) impaired elimination or detoxification of the drug (may be genetically predetermined but more frequently is associated with impaired renal or hepatic function due to underlying disease); (4) age of the patient; and (5) pregnancy status. Pharmacologic factors include (1) the kinetics of absorption, distribution, and elimination; (2) the ability of the drug to be delivered to the site of infection; (3) the potential toxicity of an agent; and (4) pharmacokinetic or pharmacodynamic interactions with other drugs. Finally, increasing consideration is being given to the cost of antimicrobial therapy, especially when multiple agents with comparable efficacy and toxicity are available for a specific infection (Harry and Daniel, 2007).
Use of a combination of antimicrobial agents may be justified (1) for empirical therapy of an infection in which the cause is unknown, (2) for treatment of polymicrobial infections, (3) to enhance antimicrobial activity (i.e., synergism) for a specific infection, or (4) to prevent emergence of resistance. Combination therapy has been advocated for the treatment of infections caused by other gram-negative rods. However, the benefits of using a drug combination over a single, effective agent remain largely unproven (Waterer, 2005).
1.16. Clinical failure of antimicrobial agents
Disadvantages of antimicrobials include super infection, treatment of non responsive infection, and therapy of diseases of unknown origin, improper dosage, inappropriate reliance on chemotherapy alone and lack of adequate bacteriological information (Flammer, 1997).
Superinfection, defined as the appearance of bacteriological and clinical evidence of a new infection during the chemotherapy of a primary one. This phenomenon is relatively common and potentially very dangerous because the microorganisms responsible for the new infection can be misuses of Antibiotics. There are methods to optimize the use of antimicrobial agents to prevent drug resistance and the transmission of infections (Serra et al., 1985).
1.16.2. Treatment of nonresponsive infections
A frequent exploitation of these agents is in infections that have been proved by experimental and clinical examination to be nonresponsive to treatment with antimicrobial agents. Most of the diseases caused by viruses are self-limited and do not respond to any of the currently available anti-infective compounds.
1.16.3. Therapy of diseases of unknown origin
Fever of undetermined cause may persist for only a few days to a week or for a longer period. Some of these infections may require treatment with antimicrobial agents that are not used commonly for bacterial infections. Others, such as occult abscesses, may require surgical drainage or prolonged courses of pathogen-specific therapy, as in the case of bacterial endocarditis. In appropriately administered antimicrobial therapy may mask an underlying infection, delay the diagnosis, and by rendering cultures negative, prevent identification of the infectious pathogen (Miller, 2008).
1.16.4. Improper dosage
Dosing errors, which can be the wrong frequency of administration or the use of either an excessive or a sub therapeutic dose, are common. Although antimicrobial drugs are among the safest and least toxic of drugs used in medical practice, excessive amounts can result in significant toxicities, including seizures (e.g., penicillin), vestibular damage (e.g., aminoglycosides), and renal failure (e.g., aminoglycosides), especially in patients with impaired drug excretion or metabolism. The use of too low a dose may result in treatment failure (Garcia, 2009).
1.16.5. Inappropriate reliance on chemotherapy alone
Infections complicated by abscess formation, the presence of necrotic tissue, or the presence of a foreign body often cannot be cured by antimicrobial therapy alone. As a general rule, when an appreciable quantity of pus, necrotic tissue, or a foreign body is present, the most effective treatment is an antimicrobial agent given in adequate dose plus a properly performed surgical procedure.
1.16.6. Lack of adequate bacteriological information
Antimicrobial therapy administered to patients too often is given in the absence of supporting microbiological data. Frequent use of drug combinations or drugs with the broadest spectra is a cover for diagnostic imprecision (Chambers, 2006).
1.17. Advantages of herbal products over synthetic products
These days the word natural products are rather frequently understood to refer to herbs, herbal decoctions, dietary supplements, traditional medicine, or alternative medicine. The World Health Organization estimates that more or less 80 percent of the worldâ€™s population primarily using traditional systems of medicines for their normal health care (Spainhour, 2005).
Herbal drugs have been used since the olden times as a therapy for the treatment of a wide variety of diseases like malaria, jaundice etc. Medicinal plants have significant role in maintaining world health by means of traditional systems of medicines. Regardless of the great advances observed in modern medicine, plants build an important contribution to health care. Medicinal plants are seen worldwide, but they are most plentiful in tropical countries. Interest in drugs derived from higher plants, particularly the phytotherapeutic ones, has increased expressively. It is estimated that about 25% of all modern medicines are directly or indirectly derived from higher plants. (Bozzuto,1998).
Natural products may be the most creative source of lead compound for the further development of new drugs. More than hundred new products are o the way of clinical investigations, predominantly as anti infectives and anti-cancer agents. Various screening approaches are being utilized to improve and reveal the effectiveness of natural products. It therefore seems advisable to do research on such plants, which have been utilized over the centuries for treatment and curative purposes (Harvey, 2008).