Abstract and Introduction
Abstract
The increasing incidence of drug-resistant pathogens has drawn the attention of the pharmaceutical and scientific communities towards studies on the potential antimicrobial activity of plant-derived substances, an untapped source of antimicrobial chemotypes, which are used in traditional medicine in different countries. The aim of this review is to provide recent insights regarding the possibilities of the most important natural antimicrobial compounds derived from plant sources containing a wide variety of secondary metabolites, which are useful as alternative strategies to control infectious diseases. This review will focus on natural plant products as a useful source of antimicrobial molecules, active in particular, on bacteria and fungi. When considering that many of these compounds, which have been used for centuries, are a source of new drugs and that there are ever-increasing technical breakthroughs, it can be envisaged that in the next years some different molecules discovered by ingenious screening programs and obtained from different plant oils and extracts will become useful therapeutic tools.
Introduction
The antibiotic era during the 20th century has substantially reduced the threat of infectious diseases. Nevertheless, over the years, there has been a decrease in microbial susceptibility to existing antimicrobial agents responsible for critical point drug resistance in hospitals and in communities. In fact, the theme of the World Health Day 2011 was 'Antimicrobial resistance: no action today, no cure tomorrow.' Recently different authors have reported the urgent need for new antimicrobial agents to replenish the arsenal of anti-infective agents.[1–4] However, owing to different, mostly financial, problems, a failure of antibiotic discovery was observed. In addition, for fungi and protozoa, current chemotherapeutic options are very limited and far from ideal, especially for undesirable side effects or toxicity.[5] Among the known plant species on earth (estimated at 250,000–500,000) only a small fraction have been investigated for the presence of antimicrobial compounds and only 1–10% of plants are used by humans.[6–7] However, a recent review reports the marked influence of natural products in the anti-infective area, accounting for the most part, in the antibacterial area.[8]
In fact, during the last few years, medicinal plants have attracted the attention of pharmaceutical and scientific communities, and evidence has demonstrated the promising potential of antimicrobial plant-derived substances.[9–14] The antimicrobial effect of plant oils and extracts has formed the basis of many applications, including raw and processed food preservation, pharmaceuticals, alternative medicine and natural therapies.
Plant materials are of wide use in traditional systems of medicine, and in several communities of the developing world, are the only resources available for the treatment of different infections. In some Asian and African countries, 80% of the population depends on traditional medicine for primary healthcare and more than 100 countries have regulations for herbal medicines.[11] Ginsburg and Deharo recently reported the rationale for further development of ethnic/traditional medicine, with specific consideration to antimalarial drugs.[12] Thus, innovative scientific methods for the discovery and validation of multicomponent botanical therapeutics are important for the development of medicine and both the standardization of extracts and the identification of the efficient chemical and/or biological compounds; therefore, emphasis must be placed on the preservation of plant populations to guarantee pharmacologically active sources of material for herbal medicine.
Ethnopharmacology, an area inside ethnobotany focused on the medicinal use of plants, is important in selecting raw materials for future drugs and studying bioactive chemical entities from natural sources. Plants are rich in several secondary metabolites and are a major source of chemical diversity; therefore, they are a potential source of new drugs for man whose use to control diseases is a centuries-old practice. Currently, numerous reviews have described the importance of natural compounds to treat human diseases.[13–15] Among 109 new antibacterial drugs, approved in the period 1981–2006, 69% originated from natural products, and 21% of antifungal drugs were natural derivatives or compounds mimicking natural products.[16]
The potential of different plant species to yield newer antibacterial agents was illustrated by Shahid et al., even if no toxicity tests were reported.[17] They divided the compounds in a first generation of plant drugs – simply botanicals – employed on empirical evidence by traditional societies from different parts of the world in more or less their crude form; a second generation, based on scientific processing of the plant extract to isolate their active constituents; and a third developed generation of phytotherapeutic agents assessed for detailed pharmacological/biochemical studies.
The large spectrum of activity of natural resins derived mostly from plants and their secondary metabolites suggests their potential application as antimicrobial agents, in particular the main natural resins that belong to the family of Pinaceae, Cupressaceae, Apiaceae, Burseraceae, Anacardiaceae, Palmaceae, Euphorbiaceae, Dracenaceae and Fabaceae. Natural gums and extracts of the whole resins, as well as specific extracts, fractions, essential oils and isolated compounds from the above resins revealed antifungal, antibacterial and antiprotozoal activity.[18,19]
Different species of the plant genus Hypericum, used in traditional medicine, contained several compounds including hyperenone A, hypercalin B and hyperphorin, responsible for antibacterial activity on resistant Staphylococcus aureus and also on Mycobacterium tuberculosis.[6,20] In particular, hyperenone A inhibited the ATP-dependent MurE ligase of M. tuberculosis, a crucial enzyme in the cytoplasmic steps of peptidoglycan biosynthesis.
Numerous extracts and compounds derived from Cameroonian plants have recently been tested for antimicrobial activity;[21] it was shown that phenolics and alkaloids were the most bioactive compounds revealing significant activity (MIC <10 µg/ml).
Termentzi et al. also discussed the effectiveness of propolis; this is an apicultural term characterizing all the resins that honey bees collect from various plants and mix with wax, and exudates from their salivary glands.[18] The chemical texture of propolis varies according to the geographical region and the type of vegetal resins that bees use. Whilst assessing two propolis specimens, our group demonstrated that the extract richer in the flavonoids pinocembrin and galangin, as shown by using high-performance liquid chromatography, was more active against Streptococcus pyogenes strains.[22] The antimicrobial effect of Korean propolis was studied against Streptococcus mutans suggesting the use of this product for the prevention of dental caries.[23]
Using a multidisciplinary approach Wangchuk et al. effected a scientific validation of selected Bhutanese medicinal plants establishing the major classes of phytochemicals responsible for the broad range of biological activities.[24] They selected plants of different families containing tannins, alkaloids and flavonoids, plants ethnopharmacologically indicated apt to treat bacterial, fungal, malarial and Trypanosoma brucei rhodesiense diseases. Their study demonstrated the significant scientific evidence of the ethnodirected biorational approach. Also, caper (Capparis sp.) – a shrub and aromatic plant with a large natural distribution, in particular in the Mediterranean Sea Basin – have been used in traditional medicines to cure some diseases.[25] Phytochemical studies indicated the presence of different compounds, such as spermidine, rutin, quercetin, kaempferol, stigmasterol, campesterol, tocopherol and carotenoids, responsible for antimicrobial, anti-oxidative, anti-inflammatory, immunomodulatory and antiviral properties. Seed extracts of Capparis decidua in particular showed antibacterial, antifungal and antileishmanial activity probably due to quaternary ammonium and glucosinolate.
Essential oils, derived from aromatic medicinal plants (e.g., fennel, peppermint, thyme and lavender) and containing mixtures of volatile substances, such as monoterpenes, sesquiterpenes and/or phenylpropanoids, have been reported to be active on Gram-positive and Gram-negative bacteria and on yeasts, fungi and viruses.[3,5,17,26–31] Helicobacter pylori was susceptible to different essential oils, in particular carrot (Daucus carota) seed oil and Mycoplasma pneumoniae to tea tree (Melaleuca alternifolia) oil, which seems to affect the intracellular cytoskeleton structure.[24] Essential oil mixtures, primarily composed of terpenoids and aromatic and aliphatic constituents have been studied for antimicrobial activity also against caries-related bacteria. Some components acts as inhibitors of bacterial growth, some as inhibitors of exopolysaccharide synthesis and others inhibit bacterial adherence.[32,33]
The aim of this review is to report, based on the consultation of the up-to-date literature, the antimicrobial activity of natural products derived from plants, focusing on the mechanisms of action of the compounds contained that may constitute a reservoir of substances that can be used against bacteria and fungi.
Future Microbiol. 2012;7(8):979-990. © 2012 Future Medicine Ltd.
