The use of remedies based on medicinal plants continues to expand rapidly around the
world, with many people now resorting to this type of product for the treatment and
prevention of several pathologies. The past decade has seen a huge wave of acceptance
and public interest in this area, with “natural” therapies gaining widespread use
and becoming well consolidated in numerous countries. For such reasons, medicinal
plants are currently the subject of great interest in research. Firstly, considering
that of the approximately 400,000 species of existing botanicals, it is believed that
less than 10% about have been studied for their biological activity, it is evident
that the vegetable kingdom represents a source of molecules that are still largely
unexplored, and therefore of great potential interest in drug discovery. There is
so a demanding need to improve our knowledge regarding the pharmacological and biological
activity of plant products. In this topic collection, we have collected 40 articles,
summarized as below.
Zimmermann et al. in their study offer a procedure for making thapsigargin (Tg) and
its derivatives more accessible in a sustainable way, facilitating the preparation
of Tg prodrugs for the treatment of slowly developing cancer diseases like hepatocellular
carcinoma and prostate cancer [1]. Azuama et al. have reported for the first time
the anti-virulence activity of the medicinal plant Azorella atacamensis against the
human opportunistic pathogen Pseudomonas aeruginosa. Interestingly, the mulinane-like
diterpenoids putatively identified from A. atacamensis appear to be responsible for
the observed virulence attenuation [2]. Fursenco et al. reviewed the evidence relating
to Solidago virgaurea, a medicinal plant widely used in Europe and other parts of
the world for its potential activities including its anti-inflammatory, analgesic,
antifungal, antiparasite, cytotoxic, antitumor, antidiabetic, cardioprotective and
antisenescence effects [3]. Hussain et al. have provided two potentially potent lead
compounds—chalcone and anthraquinone, isolated from Ranunculus muricatus—which can
be further developed for the design of novel and efficient drugs for the treatment
of Alzheimer’s disease and type 2 diabetes, respectively [4]. Okon et al. evaluated
the potential activity of magnoflorine (MGN), a quaternary aporphine alkaloid isolated
from the roots of Berberis cretica L., as an anti-neoplastic therapy for lung, breast,
glioma and rhabdomyosarcoma cancers, demonstrating that at high doses MGN inhibits
proliferation, induces apoptosis and inhibits the cell cycle in S/G2 phases in a dose-dependent
manner [5]. Mohamed et al. investigated the protective effect of linalool on renal
function and tissues in a cisplatin-induced kidney injury rat model, with many mechanisms
suggested for its activity. Linalool potentiated the cisplatin-cytotoxic effect, significantly
reducing IC50, suggesting a reduction in cisplatin dose and consequently reducing
side effects [6]. Utami et al. discussed the available evidence related to hydroxytyrosol
(HT) activity in wound healing enhancement. HT is an essential molecule isolated from
Olea europea, known for its antioxidative capacity. This review highlights the positive
influence towards wound healing by the actions mediated by HT, becoming a bioactive
compound highly recommended for wound care applications [7]. Kim et al. demonstrated
that soybean embryo extract (SEE), which is a bioactive phytoestrogen, exerts anti-obesity
effects through the activation of adipose tissue metabolism and exhibits a synergistic
effect upon co-treatment with enzymatically modified isoquercitrin (EMIQ) [8].The
study of Piatczak et al. examined the phenolic compounds in hydromethanolic extracts
of Salix alba (L.) leaves and bark, as well as their antioxidant activity and cytotoxic
potential. Leaf extract may be used as a potential new source of bioactive polyphenols
with applications in cosmetics, and bark extracts can also be used but at lower concentrations
[9]. Zahara et al. summarized information on the pharmacology, traditional uses, active
constituents, safety and toxicity of Holarrhena pubescens, a medicinal plant extensively
used in Ayurveda for treating various ailments such as rheumatism, leprosy, skin diseases,
diarrhea, dysentery, etc. Some of its major bioactive components need further investigation
to evaluate their potential as drug candidates [10]. Lammel et al. probed the potential
to suppress the expression of the inflammatory markers shown by some natural remedies
traditionally used against different inflammatory diseases, finding that among them
the extract derived from the roots and rhizomes of Peucedanum ostruthium showed a
pronounced and a dose-dependent inhibitory effect [11]. Leite et al. studied the chemical
composition of the pulp of the Brazilian Savanna fruit Dipteryx alata and evaluated
its toxic effects, its influence on the life expectancy of the nematode Caenorhabditis
elegans, and its antioxidant activities in vitro and in vivo, demonstrating its potential
use as a functional and nutraceutical food [12]. Lee et al. investigated whether coumarin
ameliorated impaired bone turnover and remodeling under diabetic condition, finding
that this positive effect from coumarin is mediated by suppressing the interaction
between advanced glycation end product (AGE) and its receptor (RAGE) [13]. Lee et
al. aimed to determine whether the gintonin-enriched fraction, a glycolipoprotein
component of ginseng, has a preventive effect against obesity and found that it reduced
lipid accumulation by reducing the expression of pro-adipogenic and lipogenic factors
and increased lipolysis and thermogenesis, representing a potential treatment for
obesity [14]. Panda et al. investigated the active principles of Holigarna caustica
Oken that are responsible for its anthelmintic activity. The rationale of the study
was based on its use by tribes of Northeast India for the treatment of intestinal
problems, and the results of the study support the use of this plant for this this
kind of problem [15]. Weber et al. evaluated the effects of a traditional herbal medicinal
product containing myrrh (Commiphora molmol Engl.), coffee charcoal (Coffea arabica
L.) and chamomile flower dry extract (Matricaria chamomilla L.) on the inflammatory
crosstalk between immune and intestinal epithelial cells. The results provide a mechanistic
basis for the use of the herbal combination of myrrh, coffee charcoal and chamomile
flower extract in inflammatory bowel disease treatment and underline the potential
benefits of the phytotherapeutic multi-component/multi-target approach in this complex
pathogenesis [16]. Baldim et al. argued about the safety aspects of using some natural
products and their several pharmacological properties that are attributed to ergot
alkaloids as a result of their antibacterial, antiproliferative, and antioxidant effects,
in particular for the treatment of glaucoma and the use of nanoparticles to improve
the residence time of the particles in the eye, although further research is needed
[17]. Alvarez-Collazo et al. studied whether the citrus flavanone hesperetin (HSP)
has potentially beneficial effects on LQT3 syndromes (type 3 long QT syndromes), associated
with arrhythmogenic gain of function mutations in the cardiac voltage-gated Na+ channel.
Their conclusions were that HSP, despite its potential value for LQT3 treatment, is
inadequate to treat some genetic variants [18]. Fecker et al. evaluated the phytochemical
composition and biological activity of Oenothera biennis L. (OB) hydroalcoholic extract
and aimed to provide directions for its antimicrobial effect, as well as its antiproliferative
and pro-apoptotic potential against the A375 melanoma cell line, and its anti-angiogenic
and anti-inflammatory capacity [19]. In their review, de Almeida Magalhães et al.
performed a search for literature and technological patents aiming to treat and prevent
diseases, as well as to prepare pharmaceutical formulations, suggesting a growing
interest in Euterpe oleracea Mart. (EO) leaves, fruits and oil, with a set of actions
pointing to the development of promising new drugs for clinical use, although more
studies should be done to consolidate initial results [20]. Gall et al. revealed the
effect of long-term cannabidiol (CBD) treatment on the chronic unpredictable mild
stress (CUMS) model of depression. CBD exerted a prohedonic effect in rats subjected
to CUMS, demonstrated by the increased sucrose preference after three weeks of treatment
[21]. In their work, Vieira et al. studied the role of terpineol, a monoterpenoid
alcohol, in depression. Molecular docking suggested that CB1 and CB2 receptors are
the most promising targets of terpineol action, corroborated by the terpineol antidepressant-like
modulation of CB1, CB2 and also D2-dopaminergic receptors [22]. Ali et al. investigated
the reproductive actions of hookah smoke (HS) exposure on a murine model and the possible
positive effects mediated by the prebiotic agent gum acacia (GA). Their work showed
that concomitant administration of GA significantly mitigated all of the measured
indices of oxidative and nitrosative stress and inflammation in the testicular homogenates
from mice exposed to HS, which caused some adverse effects on the reproductive hormone
levels in the plasma and on the indices of oxidative and nitrosative stress and inflammation
in the testes. These results suggest that the intake of GA supplement may be recommended
as a useful agent that can mitigate the adverse effect of tobacco use [23]. de Andrade
de Carvalho et al. proposed a new solvent that accelerated the extraction method of
Brazilian red propolis, a proposed new source of compounds with cytotoxic activity.
To evaluate the cytotoxicity profile of the obtained bioactives, a cell viability
assay was performed in different tumor cell lines. Most of the extracts exhibited
moderate cytotoxic activity [24]. Lopes et al. studied the anti-inflammatory and antinociceptive
effects of hydroalcoholic extracts from the Machaerium hirtum twig (HEMh), a medicinal
plant commonly used in folk medicine to treat ulcers, cough and diarrhea, using in
vivo experimental models. The study revealed the effect of HEMh action on TRPA1 receptors,
associated with its effect on the opioid system, which is responsible for a diminished
release of glutamate and NO, which partially explains this extract’s antinociceptive
properties. Another important outcome of this study is the anti-inflammatory effect
the extract exhibited, which is related to the inhibition of cyclooxygenase action
[25]. Steroids are a pivotal class of hormones with a key role in growth modulation
and signal transduction in multicellular organisms. Brassinosteroids (BRs) are a natural
collection of phytosterols, which have structural similarity with animal steroids.
Recent studies have indicated anticancerous, antiangiogenic, antiviral, antigenotoxic,
antifungal and antibacterial bioactivities of BRs in animal test systems. In their
review, Kohli et al. update this information with recent studies [26]. de Almeida
et al. examined the anti-inflammatory and neuroprotective potential of the flavonoid
agathisflavone (FAB), which is derived from the Brazilian plant Poincianella pyramidalis,
in in vitro models of neuroinflammation. The major immunomodulatory effects on microglia
and astrocytes are likely to be central to the neuroprotective action of FAB. Moreover,
it may be a potential anti-inflammatory and neuroprotective agent to prevent and treat
neuroinflammatory-related diseases [27]. Adnan et al. investigated innovative therapeutic
effects of Holigarna caustica (Dennst.), a popular plant used in folk medicine in
Bangladesh, which is often used by the local folk practitioner to treat a variety
of chronic diseases. The methanol extract of H. caustica leaves (MEHC) has been proven
to have promising anxiolytic and antidepressant efficacy. Additionally, further evidence
of suppressing the release of inflammatory mediators indicates an anti-inflammatory
potential, a preventive role in oxidative-stress-prompted anxiety and depression and
a promising binding affinity towards various receptors in molecular docking analysis
of this plant. Therefore, H. caustica can be considered a potential candidate for
possible therapeutic intervention in neuropsychiatric disorders [28]. Sinan et al.
attempted to elucidate the in vitro inhibitory action of Piptadeniastrum africanum
stem bark (PA-SB) extracts on enzymes involved in the pathogenesis of complications
such as type II diabetes, Alzheimer’s disease and skin hyperpigmentation disorders.
Overall, data from the study contribute to the biological assessment of P. africanum,
which appears to be a promising source of natural compounds with protective and neuromodulatory
effects [29]. Liu et al. reviewed compounds of botanical origin and published since
2002. Most of them need further studies of their toxicity, mechanisms and structure–activity
relationships to assess more fully their potential as drugs to control infections
by intestinal parasitic nematodes. Medicinal plants hold great promise as a source
of effective treatments, including anthelmintic therapy [30]. Athamneh et al. aimed
to reveal the anti-colon cancer potential of Origanum majorana essential oil (OMEO)
and its underlying mechanisms of action. This study demonstrated that OMEO exerts
anti-colon cancer activity through activation of p38 MAPK signaling, induction of
protective autophagy associated with downregulation of the mTOR/p70S6K pathway and
activation of the extrinsic and intrinsic apoptotic pathway [31]. Nam et al. investigated
the protective effects of gintonin, a novel ginseng-derived lysophosphatidic acid
receptor ligand, that improves brain functions and protects neurons from oxidative
stress, on the developing cerebellum after prenatal and postnatal Pb exposure. The
study revealed the ameliorating effects of gintonin against Pb, suggesting the potential
use of gintonin as a preventive agent in Pb poisoning during pregnancy and lactation
[32]. Batiha et al. discussed the traditional uses, bioactive chemical constituents
and pharmacological and toxicological activities of Glycyrrhiza glabra L. (licorice),
a small perennial herb that has been traditionally used to treat many diseases, such
as respiratory disorders, hyperdipsia, epilepsy, fever, sexual debility, paralysis,
stomach ulcers, rheumatism, skin diseases, hemorrhagic diseases and jaundice [33].
The literature reports the importance of monoterpenes based on the extensive pharmacological
action of this class, including wound healing and anti-ulcerogenic agents. Thus, Perico
et al. reviewed the pharmacological actions and mechanism of action of monoterpenes
used for peptic ulcer disease, providing the scientific basis for future translation
in which the knowledge from preclinical research may be applied to the clinical practice
of new therapies for this disease [34]. Desrosiers et al. studied the dried leaves
of Artemisia annua (DLA) and pure artemisinin, which have been used for millennia
to treat malaria. They showed that the distribution of artemisinin to several tissues
and serum significantly increased when delivered as DLA in male and female rats. Furthermore,
the data suggest that artemisinin is differentially eliminated in males compared to
females and differentially metabolized from DLA vs. pure artemisinin. Overall, these
results enhance our understanding of how artemisinin delivered from A. annua is more
bioavailable than when delivered as a pure drug [35]. Batiha et al. reviewed traditional
uses, bioactive chemical constituents and pharmacological and toxicological activities
of Syzygium aromaticum L., a traditional spice that has been used for food preservation
and possesses various pharmacological activities, rich in many phytochemicals as follows:
sesquiterpenes, monoterpenes, hydrocarbon and phenolic compounds. Pharmacologically,
cloves and their main constituents possess antimicrobial, antioxidant, anti-inflammatory,
analgesic, anticancer and anesthetic effects. Moreover, they showed insecticidal,
mosquito repellant, aphrodisiac, and antipyretic activities [36]. Nguyen et al. evaluated
ethanol and aqueous extracts of Adenosma bracteosum, used in traditional and modern
medicine in Vietnam for curing hepatitis, for their alpha-glucosidase inhibitory activities
and anti-hyperglycemic effects on glucose-loaded hyperglycemic and streptozotocin-induced
diabetic mice. The results obtained indicate that A. bracteosum has a great antidiabetic
potential [37]. Withania somnifera Dunal (Ashwagandha) is a widely used medicinal
herb in traditional medicinal systems, with extensive research having been carried
out on various plant parts. Surprisingly, the seeds of W. somnifera have never been
investigated for their therapeutic potential, so Balkrishna et al. aimed to investigate
it. Here, they show that the fatty acids from W. somnifera seeds have strong anti-inflammatory
properties, along with remarkable therapeutic potential on psoriasis-like skin etiologies
[38]. In a review, Nugraha et al. investigated ethnopharmacological uses, chemical
composition and biological activities of vascular epiphytic medicinal plants. These
epiphytic medicinal plants are able to produce a range of secondary metabolites, including
alkaloids, and a total of 842 phytochemicals have been identified to date. As many
as 71 epiphytic medicinal plants were studied for their biological activities, showing
promising pharmacological activities, including as anti-inflammatory, antimicrobial
and anticancer agents [39]. Salehi et al. aimed to summarize the studies on biological
effects of the avocado–soybean unsaponifiable (ASU) mixture, its chemical composition
and pharmacotherapy, as well as applications in autoimmune, osteoarticular and menopausal
disorders. In fact, characterized by its potent anti-inflammatory effects, the ASU
mixture is recommended to act as an adjuvant treatment for osteoarthritic pain and
as a slow-acting symptomatic treatment of hip and knee osteoarthritis, autoimmune
diseases, diffuse scleroderma and scleroderma-like states [40].