Phytochemical and antimycobacterial studies on selected medicinal plants

Tuberculosis (TB) is an infectious disease caused by the pathogen Mycobacterium tuberculosis. Tuberculosis was first declared as a global health emergency in 1993 but is still a health crisis worldwide because of the emergence of extensively drug-resistant strains of M. tuberculosis coupled with the increased risk of infection in immune-compromised people and also by the fact that at least one third of the human population are latently infected with the TB causing bacilli. New, safer and more effective antimycobacterial compounds with novel mechanisms of action are urgently needed for treating resistant forms of tuberculosis. This has led to a renewed research interest in natural products, which offer an outstanding source of diverse bioactive chemical scaffolds with the hope of discovering novel anti-mycobacterial leads. This thesis describes phytochemical studies on the genera Allium and Andrographis. The antibacterial activity of the crude extracts, various fractions and isolated compounds were evaluated. Antibacterial studies were carried out using a panel of Gram-positive, Gram-negative and acid fast group of bacterial species including M. aurum, M. bovis BCG, M. tuberculosis H37Rv and multidrug-resistant clinical isolates of M. tuberculosis. Furthermore, analogues of naturally isolated disulfides from the genus Allium were synthesized and evaluated for antibacterial activity. Eukaryotic cytotoxicity was estimated in order to determine the therapeutic selectivity index of the selected compounds. In addition, inhibition of both drug efflux and biofilm formation was observed at the whole-cell phenotypic level. These analogues have demonstrated anti-TB activity with the lowest MIC being 4 mg/L. They also exhibited whole cell multidrug efflux and biofilm inhibitory effect. These findings would serve as useful contribution to the development of novel anti-TB drugs

Combating Biofilm and Quorum Sensing: A New Strategy to Fight Infections

Biofilms are structured aggregates of bacterial cells that are embedded in self-produced extracellular polymeric substances. Various pathogens initiate a disease process by creating organized biofilms that enhance their ability to adhere, replicate to accumulate, and express their virulence potential. Quorum sensing, which refers to the bacterial cell-to-cell communication resulting from production and response to N-acyl homoserine lactone signal molecules, also plays an important role in virulence and biofilm formation. Attenuation of microorganisms’ virulence such that they fail to adapt to the hosts’ environment could be a new strategic fight against pathogens. Thus, agents or products that possess anti-biofilm formation and/or anti-quorum sensing activities could go a long way to manage microbial infections. The incidence of microbial resistance can be reduced by the use of anti-biofilm formation and anti-quorum sensing agents

Antimicrobial Agents: Antibacterial Agents, Anti-biofilm Agents, Antibacterial Natural Compounds, and Antibacterial Chemicals

The surge in antimicrobial resistance coupled with the decline in the antimicrobial drug pipeline calls for the discovery and development of new agents to tackle antibiotic resistance and prevent a return to a post-antibiotic era. Several factors account for resistance of microbes; some are natural and others are acquired. Natural selection, presence of efflux pumps, impermeable cell wall, biofilm formation and quorum sensing are some of the factors. Though it is difficult to outwit the pathogens, the discovery and development of compounds with pleiotropic modes or mechanisms of action different from the conventional drugs currently being used can help us tackle antimicrobial resistance. Natural products have been known to be a rich source of bioactive compounds with diverse structures and functional group chirality. Various reports indicate medicinal plants with antibacterial, anti-biofilm, efflux pump inhibition, wound healing effects or properties and others used for upper respiratory and urinary tract infections. There is an urgent need to research into natural products particularly plants for antimicrobial agents including antibacterial agents, anti-biofilm agents, antibacterial natural compounds and antibacterial chemicals. This chapter throws more light on such antimicrobials

Investigating Ghanaian Allium species for anti-infective and resistance-reversal natural product leads to mitigate multidrug-resistance in tuberculosis

The bulbs of Allium species are a known source of antibacterial phytochemicals. Anti-infective, efflux pump and biofilm inhibitory activities of bulb extracts of selected Ghanaian shallots Allium cepa var aggregatum were evaluated using the HT-SPOTi assay and other whole-cell phenotypic screening techniques to determine their possible mechanisms of action. Ethanol and aqueous extracts of white A. cepa inhibited the growth of Mycobacterium smegmatis mc2 155 and Escherichia coli, respectively. The majority of the Allium extracts significantly (p < 0.05) exhibited efflux pump inhibitory activity against all the acid-fast, Gram-positive and Gram-negative strains used. Hexane and chloroform extract of the pink A. cepa and the aqueous extract of the white A. cepa significantly inhibited M. smegmatis biofilm formation. For Pseudomonas aeruginosa, the inhibition was observed at 250 µg/mL for the aqueous extract (~77.34%) and 125 µg/mL for the hexane extract (~76.51%). The results suggest that Ghanaian shallots could potentially be useful when further developed to tackle antimicrobial resistance, particularly in tuberculosis (TB)

Anti-infective, anti-inflammatory and antipyretic activities of the bulb extracts of Crinum jagus (J. Thomps.) Dandy (Amaryllidaceae)

The bulbs of Crinum jagus (J. Thomps.) Dandy commonly known as St. Christopher lily or Harmattan lily and locally in Akan as “sukooko” is used in Ghana as a decoction to manage infections, fever, asthma and wounds. The current study seeks to evaluate the anti-infective, antipyretic and anti-inflammatory effects of the aqueous, methanol, ethanol and hexane extracts of Crinum jagus. The High-throughput spot culture growth inhibition (HT-SPOTi) assay, baker's yeast induced pyrexia in rat model and the carrageenan induced foot edema in rats were used to screen for the anti-infective, antipyretic and anti-inflammatory activities of the various extracts of Crinum jagus respectively. The extracts were administered at doses of 30, 150 and 300 mg/kg orally to the rats. Broad-spectrum antimicrobial activity was shown by the methanol extract of Crinum jagus when tested against a panel of microorganisms with MIC values ranging between 1 and 500 mg/L. The activity against Mycobacterium smegmatis, Salmonella typhi and Pseudomonas aeruginosa, which are difficult to eradicate was remarkable. The aqueous extract of Crinum jagus also showed significant anti-inflammatory activity at the lowest dose of 30 mg/kg used in the experiment (p < 0.0001). The ethanol extract showed significant antipyretic activity at all doses tested with the highest dose of 300 mg/kg showing activity comparable to the 30 mg/kg dose of paracetamol (p < 0.01). The anti-infective, antipyretic and anti-inflammatory properties of Crinum jagus are very promising as this study affirms its traditional uses. Bio-guided isolation and characterization of compounds from Crinum jagus could help in the identification of bioactive compounds that can serve as potential leads in the discovery and development of drugs to manage inflammation and fever as well as to tackle infections and antimicrobial resistance

Early diagnosis and effective treatment regimens are the keys to tackle antimicrobial resistance in tuberculosis (TB): a report from Euroscicon's international TB Summit 2016

To say that tuberculosis (TB) has regained a strong foothold in the global human health and wellbeing scenario would be an understatement. Ranking alongside HIV/AIDS as the top reason for mortality due to a single infectious disease, the impact of TB extends far into socio-economic context worldwide. As global efforts led by experts and political bodies converge to mitigate the predicted outcome of growing antimicrobial resistance, the academic community of students, practitioners and researchers have mobilised to develop integrated, inter-disciplinary programmes to bring the plans of the former to fruition. Enabling this crucial requirement for unimpeded dissemination of scientific discovery was the TB Summit 2016, held in London, United Kingdom. This report critically discusses the recent breakthroughs made in diagnostics and treatment while bringing to light the major hurdles in the control of the disease as discussed in the course of the 3-day international event. Conferences and symposia such as these are the breeding grounds for successful local and global collaborations and therefore must be supported to expand the understanding and outreach of basic science research

Antimicrobial Compounds from Microorganisms

Antimicrobial resistance is an exigent public health concern owing to the emergence of novel strains of human resistant pathogens and the concurrent rise in multi-drug resistance. An influx of new antimicrobials is urgently required to improve the treatment outcomes of infectious diseases and save lives. Plant metabolites and bioactive compounds from chemical synthesis have found their efficacy to be dwindling, despite some of them being developed as drugs and used to treat human infections for several decades. Microorganisms are considered untapped reservoirs for promising biomolecules with varying structural and functional antimicrobial activity. The advent of cost-effective and convenient model organisms, state-of-the-art molecular biology, omics technology, and machine learning has enhanced the bioprospecting of novel antimicrobial drugs and the identification of new drug targets. This review summarizes antimicrobial compounds isolated from microorganisms and reports on the modern tools and strategies for exploiting promising antimicrobial drug candidates. The investigation identified a plethora of novel compounds from microbial sources with excellent antimicrobial activity against disease-causing human pathogens. Researchers could maximize the use of novel model systems and advanced biomolecular and computational tools in exploiting lead antimicrobials, consequently ameliorating antimicrobial resistance

Evaluation of the Knowledge, Attitude and Perception of Healthcare Students on Antibiotics and Antibiotic Resistance: A Study in Central University, Ghana

Students undergoing programmes in healthcare will play an important role in the management of antibiotic resistance which is still a global problem. Their knowledge and attitude should be adequately documented. This study is carried out to evaluate the knowledge, attitudes and perceptions of antibiotic use and antibiotic resistance among healthcare students in Central University, Ghana. In this study, 1027 students offering courses in pharmacy, nursing and physician assistantship participated in a survey to evaluate their knowledge, attitudes and perception on antibiotic use and antibiotic resistance. Data obtained was analyzed using STATA statistics DATA analysis software version 12.0. Descriptive statistics and chi-squared test was employed. Students displayed very good knowledge of antibiotic use and antibiotic resistance with students studying physician assistantship and nursing showing greater knowledge. The attitude of the respondents on the use of antibiotics was slightly above average. There was a significant difference (p = 0.029) between students’ programme of study and how they obtained their last course of antibiotics. Students displayed average knowledge on antibiotic use and antibiotic resistance but there is a need for more education to improve their perception and attitudes in order to contribute towards curbing the global problem of antibiotic resistance

Marburg virus in Ghana: A public health threat to Ghanaians and to Africans

Abstract The Marburg virus disease (MVD) outbreak in Ghana and the re‐emergence of other infectious diseases in Africa require a unified effort to fight these highly infectious health threats.  Although no new cases have been reported after the three MVD confirmed cases, Ghana Health Service (GHS), and Health Authorities of neighbouring countries are on the alert to identify any new cases and deal with them at the earliest. Public health measures, however, inadequate, are in place in Ghana.   Varied challenges remain in the fight against these outbreaks. All known public health measures must be brought to bear in the fight. African governments must resource the African Centre for Diseases Control and Prevention, in its efforts to augment the various country‐level health services in the fight against the threats. African governments, citizens, development partners, and foreign governments must commit to fighting these diseases before they turn into pandemics

Betulin and Crinum asiaticum L. bulbs extract attenuate pulmonary fibrosis by down regulating pro-fibrotic and pro-inflammatory cytokines in bleomycin-induced fibrosis mice model

Background: Pulmonary fibrosis (PF) is a lung disease characterized by scaring of lung tissue that impairs lung functions. The estimated survival time of patients with pulmonary fibrosis is 3–5 years. Bleomycin (BLM) is used clinically in the treatment of Hodgkin lymphoma and testicular germ-cell tumors. Bleomycin’s mechanism of action is the inhibition of DNA and protein synthesis. This happens when leukocytes induce the release of cytokines and chemokines which increase the pro-fibrotic and pro-inflammatory cytokines such as IL-6, TNF-alpha, IL-13, IL-1β and transforming growth factor-beta 1 (TGF-β). Crinum asiaticum L. bulbs (CAE) are widely found in parts of Africa, Asia and Indian Ocean Island. It is also prevalent in southern part of Ghana and traditionally used by the indigenes to treat upper respiratory tract infections, and for wound healing. Betulin (BET) is found in the bulbs of Crinum asiaticum L. but widely isolated from the external bark of birches and sycamore trees. Betulin as a lupine type triterpenes has been researched for their pharmacological and biological activities including anticancer, anti-inflammatory, antimicrobial activities and anti-liver fibrosis effects.Aim of the study: The aim was to study the anti-pulmonary fibrosis effect of Crinum asiaticum L. bulbs extract and betulin in bleomycin-induced pulmonary fibrosis in mice. Materials and method: There was a single oropharyngeal administration of bleomycin (80 mg/kg) in mice followed by the treatment of CAE and BET after 48 h of exposure to BLM. Results: There was increased survival rate in CAE and BET treatment groups compared to the BLM induced group. There was a marked decreased in the levels of hydroxyproline, collagen I and III in the CAE and BET treatment groups compared to BLM-treated group. The treatment groups of CAE and BET significantly down regulated the levels of pro-fibrotic and pro-inflammatory cytokines concentrations such as TGF-β1, MMP9, IL-6, IL-1β and TNF-alpha compared to an increased in the BLM treated groups. The histological findings of the lungs suggested the curative effects of CAE and BET following BLM induced pulmonary fibrosis in mice, the study showed improved lung functions with wide focal area of viable alveolar spaces and few collagen fibers deposition on lungs of treatment groups. Conclusion: CAE and BET attenuated pulmonary fibrosis by down regulating pro-fibrotic and pro-inflammatory cytokines as well as improving lung function. This could be a lead in drug discovery where compounds with anti-fibrotic effects could be developed for the treatment of lung injury