Plants produce many secondary metabolites, which reveal biological activity. Among
them, alkaloids demonstrate a broad spectrum of activities. In nature, they not only
are produced against herbivores but also reduce bacterial or fungal infestation. Therefore,
they are substances that possess high potential in medicine, plant protection, veterinary,
or toxicology. Hence, the research on these substances and their properties develops
intensively in many areas. The studies describing the physiological, pharmacological,
and toxicological activity of alkaloids for different organisms belonging to every
kingdom are of very wide interest. Both pure alkaloids and extracts are studied, and
their activities are compared. In the Special Issue “Biological Activities of Alkaloids:
From Toxicology to Pharmacology", 15 manuscripts describing ecological, biological,
pharmacological, and toxicological effects as well as structural and analytical aspects
of plant alkaloids, their mode of action, and possible application in veterinary,
medicine, and plan protection were collected. The subjects focused on two main areas
of interest, the structure/activity nexus and the application of alkaloids against
pathogens.
Although the number of research articles on alkaloids increases, our knowledge of
them is still far from completeness. This is due to the very high number of alkaloids
produced by many different organisms, mostly plants, diffused all over the world.
Therefore, the identification, characterization, and quantification of alkaloids present
in plant species and their parts is very important and brings interesting data [1,2].
The spectrum of alkaloids’ activity is also very wide. Among them, there are substances
showing antiviral, antibacterial, anti-inflammatory, and anticancer properties. Thus,
many studies deal with curative aspects of alkaloids and their mode of action. Mahonia
aquifolia, Meconopsis cambrica, Corydalis lutea, Dicentra spectabilis, Fumaria officinalis,
and Macleaya cordata plant extracts showed cytotoxic activity against the tested human
squamous carcinoma and adenocarcinoma cells [1]. The extracts obtained from the stem
bark of Rutidea parviflora (R. parviflora) revealed significant cytotoxic activity
against ovarian cancer. In this study, palmatine from the stem bark of R. parviflora
was more toxic for human ovarian cancer cells than for human ovarian noncancerous
cells [3]. Such basic studies are necessary and determine a very important point for
the development of new anticancer drugs and therapies. In addition, sanguinarine and
berberine, the isoquinoline alkaloids, revealed cytotoxic activity against hematopoietic
cancer cell lines and induced apoptosis in the tested cell lines [4]. Curine—a bisbenzylisoquinoline
alkaloid—was proven to modulate inflammatory effects in mice, due to the inhibition
of macrophage activation and neutrophil recruitment, the inhibition of the production
of cytokines and the decreased level of nitric oxide. The effects may be probably
linked to the decreased level of nitric oxide and induced possibly by negatively modulating
a Ca2+ influx [5]. The regulatory mode of the action of alkaloids refers also to other
mechanisms within cellular membranes. Lindoldhamine (a bisbenzylisoquinoline alkaloid)
was shown as a novel antagonist of acid-sensing ion channels (ASICs). Lindoldhamine
significantly inhibited the ASIC1a channel’s response to physiologically relevant
stimuli [6]. This observation is especially important, since only some molecules were
described as modulators of ASIC1. That opens a new research area about bisbenzylisoquinoline
alkaloids as important molecules in neurobiology. On the other hand, dehydrocrenatidine,
a β-carboline alkaloid, suppresses voltage-gated sodium channels and leads to decreased
allodynia. The alkaloid is the main component of Picrasma quassioides—a plant used
in medicine, since it reveals antiviral activity, which is also known as an anti-inflammatory
and analgesic agent. The research of Zhao and co-workers [7] brought important data
on the mode of the action of this alkaloid.
Unfortunately, not all gold glitters: the consumption of some alkaloids may lead to
toxic effects. Among them, there is arecoline, an alkaloid found for example in betel
nuts. Overconsumption may lead to cancerogenesis and tumor formation. The mechanism
of this effect is not fully known. Chang and co-workers described important aspects
of the cancerogenic activity of arecoline [8]. The authors postulated that the mechanism
uses a muscarinic acetylcholine receptor and the pathway that is triggered by the
activation of this receptor. The authors described the effects of arecoline on cell
migration and actin organization. The studies of that type may appear to be very important
from the cytotoxicological, pharmacological, and clinical points of view.
Not only are cancer cells susceptible to alkaloids. The antiviral and antibacterial
activity of alkaloids has already been described. This area of research appears to
be important especially in the light of increasing the resistance of pathogenic bacteria
to antibiotics. Casciaro and his co-workers presented an interesting study showing
that nigritanine, an alkaloid obtained from Strychnos nigritana—a flowering plant
that belongs to the family of Loganiaceae - possess high antibacterial activity against
Staphylococcus aureus (S. aureus), which is recognised to be one of the most important
pathogenic bacteria diffused worldwide [9]. What appeared extremely important is the
tested alkaloid did not reveal significant toxicity for mammalian red blood cells
and human keratinocytes. The authors compared also the monomer/dimer structure–antibacterial
activity relationship, which brought important information on the mechanism of activity
against S. aureus. The research presented by Zielińska and her colleagues [10] included
them in the same area of research. The authors showed a range of research on the presence
of alkaloids in organs of Chelidonium majus and combined these observations with the
activity of extracts and single metabolites against certain microorganisms: S. aureus,
Pseudomonas aeruginosa, Klebsiella pneumonia, Escherichia coli, and Candida albicans.
The results are in tune with the abovementioned research of Casciaro et al. [9] due
to the described overall lower toxicity against eukaryotic cells (fibroblasts) than
against microorganisms.
However, there are alkaloids that reveal toxic activity against animals. This seems
obvious, since one of their main roles is to deter herbivory. Therefore, the wide
range of alkaloids is described not only as substances with antimicrobial or anticancer
agents but also as substances revealing insecticidal activity [11]. However, the nature
of the toxic action of alkaloids on insects is still insufficiently described. In
this issue, the effects of the activity of crude extracts obtained from Solanum tuberosum,
Solanum lycopersicum, Solanum nigrum (Solanaceae), and Armoracia rusticana (Brassicaceae),
as well as purified alkaloids, on the heart contractility of Tenebrio molitor—a pest
of stored products—have been described [12]. In this research, chaconine was stated
to be the most cardioactive substance among those tested. Apart from the information
on the activity of alkaloids in insect science, the investigation methods issued in
this kind of research can be of interest in medical research. Due to economical and
ethical reasons, invertebrates, including insects, became important models in the
first stage of drug designing.
The pharmacological ranges of concentrations and toxic levels are often close. Therefore,
emphasis must be put on concentrations and doses, which may cause lethal and sublethal
effects in mammals. This is important in the case of substances that are used in plant
protection, food preservation, and hygiene of storage chambers and containers. From
the human point of view, the toxic activity of substances, which are used as medicines,
is equally, if not more important. Aconitum alkaloids are used in ethnomedicine and
modern medicine, and their toxicity may be lethal for mammals. The data on the distribution
of toxic alkaloids within the organs of the exposed individual is crucial for clinical
toxicology [13]. In addition, some endophytes, like Epichloe, produce secondary metabolites
that are toxic to insects. Therefore, they are potential sources of insecticides.
Chanoclavine, an ergot alkaloid, was tested by Finch and co-workers against mice,
to estimate their toxicity for a mammal model organism [14]. Although the mice revealed
some neurotoxic symptoms, they were not permanent, and the median lethal dose was
higher than 2000 mg per kg body weight. That suggested that the substance is relatively
safe for mammals. However, further research is necessary, due to the reported toxicity
of ergot alkaloids to mammals, including human. Additionally, the livestock that consumes
ergot alkaloids shows various toxic symptoms, including endocrine disruption, reproductive
and developmental malfunctions, and blood circulation [15]. The two review manuscripts
present in this Special Issue proved the need for further extensive studies on the
activity of alkaloids [11,15].
All the abovementioned studies proved the enormous potential of alkaloids in veterinary,
pharmacology, medicine, and plant protection. Additionally, they showed multifold
aspects of alkaloids and alkaloid-containing extracts toxicity from cytotoxicity through
the malfunctions of organs and systems to lethal effects. Due to the increasing resistance
of bacteria to antibiotics, they may become crucial for fighting microbial diseases.
The description of postulated metabolic pathways influenced by the tested substances
appeared to be very important for the planning of possible drugs in veterinary and
medicine, as well as for basic science, like neurobiology or cell physiology. Similarly
to bacteria developing resistance to antibiotics, insects develop resistance to insecticides.
Hence, there is a need for new formulas, which may fight herbivore insects, with high
selectivity against pests. Alkaloids are among the substances that are postulated
as such novel insecticides. To sum up, the scientific and applicatory potential of
alkaloids is immense. The research on their structure and activity develops intensively
in various fields of science, which was proven by the variety of research topics present
in this Special Issue. For sure, the number of research papers showing interesting
and applicable pharmacological and toxicological aspects of alkaloids’ activity will
be increasing.