ABSTRACT
Efflux pump mechanisms perform important physiological functions such as prevention of toxin absorption from the gastrointestinal tract; elimination of bile from the hepatocytes; effective functioning of the blood-brain barrier and placental barrier; and renal excretion of drugs. They exist in all living cells; but those in the bacterial and mammalian cells are more important to the clinician and pharmacologist; as they constitute an important cause of antimicrobial drug resistance; which contributes to treatment failure; high medical bills; and increased mortality / morbidity. This review was aimed at highlighting the role of efflux pump mechanisms in microbial resistance to chemotherapeutic agents. It was also aimed to elucidate their structure and mechanisms of action so as to integrate the efflux pump mechanisms in the design and development of novel antimicrobial agents.Findings from previous studies and research on this subject assessed through Google search; Pubmed; Hinari websites; as well as standard textbooks on chemotherapy; provided the needed information in the process of this review. Efflux pump inhibitors are promising strategies for preventing and reverting efflux-mediated resistance to chemotherapeutic agents. They are usually employed as adjuncts in antimicrobial and cancer chemotherapy. Toxicity; more common with the older-generation inhibitors such as verapamil and reserpine; constitutes the greatest impediment to their clinical applications. No efflux pump inhibitor has been approved for routine clinical use; as a result of doubtful clinical efficacy and unacceptably high incidence of adverse effects; particularly inhibition of the P-450 drug metabolizing enzyme. At present; their applications are mainly restricted to epidemiological studies. Nonetheless; the search for efficacious and tolerable efflux pump inhibitors continues because of the potential benefits. There is a need to consider efflux pump substrate selectivity in the design and development of novel chemotherapeutic agents
Subject(s)
Anti-Bacterial Agents , Drug Resistance , Drug Therapy , GenesABSTRACT
Background : The treatment of peptic ulcer disease poses therapeutic challenges to both patients and physicians alike because of the tendency of ulcers to relapse. Drugs used in the treatment of this disease are either costly or are associated with high incidence of adverse effects. Synclisia scabrida is a plant used in ethnomedicine for the treatment of various forms of stomach disorders and menstrual pains. The medicinal properties of the plants are claimed to reside in the roots; stems; and the leaves. Aim : This study; therefore; is to verify this claim and elucidate the probable mechanism of action by using crude stem extracts of this plant on drug- and stress-induced ulcer models in albino mice. Materials and Methods : Crude ethanol and hot water extracts; EE and HWE respectively; of the stem were prepared. These extracts were fractionated and separated by chromatographic methods and the fractions pooled together as fractions (PF-1; PF-2; PF-3 respectively) based on their chromatographic mobility and color reactions. Phytochemical analysis was done on the extracts. Ulcer models were induced in albino mice by means of indomethacin; histamine; and stress after prior cytoprotection with orally administered crude extracts and control (cimetidine). Results : Phytochemical analysis of the crude extracts and their fractions revealed the presence of cardiac glycosides (+++); tannins (+++); saponins (+); flavonoids (++); carbohydrates (++) and alkaloids (+++). Acute toxicity study on the crude extracts and their fractions revealed relative safety at the dose of 5000 mg/kg. The crude extracts (EE and HWE) and their fractions (PF-1; PF-2; PF-3) significantly (P = 0.001) protected against indomethacin-; histamine- and stress-induced ulcers. The decrease in GIT motility produced by these extracts was comparable to that produced by atropine sulfate. Conclusion : The findings suggest that these extracts of Synclisia scabrida possess antiulcer and antispasmodic properties; which justify the claims for its use in the treatment of various forms of stomach disorders
Subject(s)
Peptic Ulcer , RatsABSTRACT
The treatment of peptic ulcer disease poses therapeutic challenges to both patients and physicians alike because of the tendency of ulcers to relapse. Drugs used in the treatment of this disease are either costly or are associated with high incidence of adverse effects. Synclisia scabrida is a plant used in ethnomedicine for the treatment of various forms of stomach disorders and menstrual pains. The medicinal properties of the plants are claimed to reside in the roots; stems; and the leaves. Aim : This study; therefore; is to verify this claim and elucidate the probable mechanism of action by using crude stem extracts of this plant on drug- and stress-induced ulcer models in albino mice. Materials and Methods : Crude ethanol and hot water extracts; EE and HWE respectively; of the stem were prepared. These extracts were fractionated and separated by chromatographic methods and the fractions pooled together as fractions (PF-1; PF-2; PF-3 respectively) based on their chromatographic mobility and color reactions. Phytochemical analysis was done on the extracts. Ulcer models were induced in albino mice by means of indomethacin; histamine; and stress after prior cytoprotection with orally administered crude extracts and control (cimetidine). Results : Phytochemical analysis of the crude extracts and their fractions revealed the presence of cardiac glycosides (+++); tannins (+++); saponins (+); flavonoids (++); carbohydrates (++) and alkaloids (+++). Acute toxicity study on the crude extracts and their fractions revealed relative safety at the dose of 5000 mg/kg. The crude extracts (EE and HWE) and their fractions (PF-1; PF-2; PF-3) significantly (P = 0.001) protected against indomethacin-; histamine- and stress-induced ulcers. The decrease in GIT motility produced by these extracts was comparable to that produced by atropine sulfate. Conclusion : The findings suggest that these extracts of Synclisia scabrida possess antiulcer and antispasmodic properties; which justify the claims for its use in the treatment of various forms of stomach disorders