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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_6035_Библиотеки_им_академика_М_И_Перельмана.pdf
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and characterize these metabolites to better understand the overall biological effects of
phytoestrogens. Moreover, phytoestrogens may interact with multiple receptors and
signaling pathways in the body . While ERs have been the primary tar get for phytoestrogen
research, there is a need to identify new molecular targets for these compounds. This could
include other nuclear receptors, such as androgen and progesterone receptors, as well
as nonnuclear receptors and signaling pathways, such as GPCRs and ion channels. By
identifying and studying new molecular targets, researchers can expand their understanding
of the full range of effects that phytoestrogens have on the body. This could pave the way
for the creation of highly efficient and precision-targeted drugs.
15.10.3 SYNTHESIS OF NOVEL COMPOUNDS
Chemical synthesis provides a promising strategy for drug discovery because it enables the
modification of the structure of natural compounds to create novel molecules with improved
properties. In the case of phytoestrogens, chemical synthesis can be used to optimize the
structure of natural compounds to improve their potency , efficacy, and selectivity . For instance,
modification of the functional groups and substitution patterns of natural compounds can lead
to an increase in their biological activity. Chemical synthesis also enables the development
of more stable compounds that have better solubility and are easier to manufacture than
their natural counterparts. Additionally, chemical synthesis allows for the creation of analogs
with modified pharmacokinetic properties that can increase the half-life of the compound
or improve its bioavailability. However, the synthesis of novel phytoestrogens requires
extensive chemical expertise, as well as a thorough understanding of the structure–activity
relationships of the target compounds. Therefore, additional investigation is required to fully
uncover the capabilities of chemical synthesis in the development of novel phytoestrogens
and to optimize the process for greater efficiency and effectiveness.
15.10.4 DEVELOPMENT OF SPERMS
SPERMs, or selective phytoestrogen receptor modulators, are a subclass of SERMs that
are derived from plant-based sources. They can bind to ERs and function as either agonists
or antagonists depending on the type of tissue. In clinical practice, SERMs are utilized to
prevent and manage estrogen-associated conditions such as breast cancer and osteoporosis.
Nonetheless, their clinical application is frequently restricted due to undesirable side effects,
such as a heightened likelihood of blood clot formation and hot flashes. When targeting
specific ERs, SPERMs can provide the beneficial effects of estrogen while avoiding the
unwanted side effects associated with nonselective ER agonists, such as HRT. Developing
SPERMs from phytoestrogens could therefore provide a safer and more effective alternative
to HRT, which has been associated with increased risks of breast cancer, stroke, and heart
disease. There is growing interest in the development of SPERMs from phytoestrogens
due to their potential therapeutic benefits. For example, researchers have identified many
phytoestrogens that show promise as SPERMs, including coumestrol, liquiritigenin,
404
and isoliquiritigenin. These compounds have been shown to selectively bind to ERs and
modulate their activity in a tissue-specific manner. Further research is needed to identify
and characterize additional phytoestrogens that have the potential to act as SPERMs.
This will involve the use of advanced molecular and cellular techniques to elucidate the
mechanisms by which these compounds interact with ERs and modulate their activity.
Once identified, these compounds can be developed into novel drugs with the potential to
provide safe and effective alternatives to traditional HRT.
15.10.5 SAFETY ASSESSMENT
While phytoestrogens are generally considered safe, their use as drugs requires careful
evaluation of their safety profile. Safety assessment is a critical aspect of drug development, and it involves the identification and mitigation of potential adverse effects that may
arise from the use of a drug. Long-term studies are necessary to evaluate the safety and
potential risks associated with phytoestrogen use. These studies should focus on assessing
the safety of various phytoestrogen doses, the duration of use, and the impact of these
compounds on different patient populations. In addition, research should aim to identify
potential interactions between phytoestrogens and other medications that patients may be
taking. Moreover, the safety evaluation of phytoestrogens should extend beyond the scope
of human health and include potential environmental impacts. The production and use
of phytoestrogens as drugs can have unintended consequences on the environment, such
as the disruption of natural ecosystems and the contamination of water sources. Therefore, research should also focus on assessing the environmental safety of phytoestrogens,
including their biodegradability, toxicity, and potential effects on nontarget organisms.
Overall, the future of phytoestrogens in drug discovery is promising. Further research and
development in this area have the potential to provide safe and effective alternatives to
conventional HRT and other estrogen-related therapies.
15.11 CONCLUSION
In this chapter, the author explores the mechanisms of action and safety assessment of
phytoestrogens in drug discovery . Phytoestrogens, naturally occurring compounds in plants,
bear a structural resemblance to estrogen and can function as either estrogen agonists or
antagonists in the human body. These substances may provide therapeutic advantages in
preventing or treating a range of diseases, including osteoporosis, cardiovascular disease,
and cancer. However, the safety of phytoestrogens has been a subject of controversy, as
some studies suggest that high doses could harm the body, disrupt the endocrine system,
and raise certain cancer risks. Therefore, it is critical to understand the mechanisms of
action and safety of phytoestrogens before using them as potential drugs. To assess the
safety of phytoestrogens, numerous studies both in the laboratory and in living organisms
have been carried out to examine their toxicity, pharmacokinetics, and metabolism.
Additionally , computational methods, such as molecular docking and dynamic simulations
405
at the molecular level, have been employed to predict the binding affinity of phytoestrogens
to ERs and any potential adverse effects. In conclusion, the study of phytoestrogens in drug
discovery is a promising area of research that requires a comprehensive understanding of
their mechanisms of action and safety assessment. This knowledge can help researchers
design safer and more effective phytoestrogen-based drugs with minimal side effects. With
the increasing interest in natural products and the demand for safe and effective drugs, the
investigation of phytoestrogens in drug discovery is of utmost importance.
KEYWORDS
• bioavailability
• drug discovery
• hormone replacement therapy
• mechanisms of action
• phytoestrogens
• safety assessment
• structure–activity relationship
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CHAPTER 16
Honey Bee Products with Antimicrobial Properties
JELENA ĆIRIĆ* and TATJANA BALTIĆ
*Corresponding author
ABSTRACT
Modern medicine is undergoing a major crisis because of the adverse effects of synthetic
drugs on human health and increased antimicrobial resistance. Increased rates of different
cancers, autoimmune diseases, chronic noninfective diseases, and so on have led to a search
for new, reliable, nonsynthetic, traditional, and natural therapeutic products. Science is
now returning to natural products with new approaches in an endeavor to understand older
medicinal applications. In that case, apitherapy or bee therapy is defined as very ancient
medical practice and is one of the areas in which bee products are used.
16.1 INTRODUCTION
According to the European Commission (2016), around 600,000 European beekeepers
produce around 250,000 tons of honey per year, generating more than 400 million € per
year in the European Union (EU) (Sperandio et al., 2019). Figure 16.1 shows one of the
apiaries in the central part of Serbia.
FIGURE 16.1 Apiary in Central Serbia (Šumadija).
Source: Photographed by J. Ćirić.
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Numerous studies from different countries have presented out the high biological
value and medical benets of bee products (honey, bee bread, bee pollen, beeswax, bee
toxin, propolis, royal jelly, and bee brood. All of them have a positive impact on human
health (antioxidant, antimicrobial, antifungal, anti-inammatory, etc.) which correlated
to the elevated content of bioactive compounds. Similarly, different studies have found
the phenolic composition of different honey and presented they were rich in p-coumaric
acid, kaempferol, chrysin, and apigenin. A strong correlation was found between the
content of phenolic compounds and antioxidant activity . Flavanol glycosides of quercetin,
isorhamnetin, patulin, and kaempferol were detected as major components of the honey
bee pollen.
16.2 HONEY
Codex Alimentarius (2001) define honey as a natural sweet substance produced by honey
bees from the nectar of plants or from secretions of living parts of plants or excretions of
plant-sucking insects on the living parts of plants, which the bees collect, and transform by
combining with specific substances of their own, deposit, dehydrate, store, and leave in the
honeycomb to ripen and mature.
Different studies show that honey have high nutritional and biological effects (Oryan
et al., 2016; Ávila et al., 2019; Graikou et al., 2022; Tsavea et al., 2022). The honey is an
excellent source of energy; 100 g honey supplies about 306 kcal. Similarly, 20 g of honey
is the usual quantity per serving or tablespoon provides about 61.2 kcal, which represents
more or less 3% of the energy necessary per day (Bogdanov et al., 2008). The main
constituents of honey are the simple carbohydrates (60–85%) that are used for human body
energy requirements after being rapidly absorbed into the blood without previous digestion
(Ajibola et al., 2012). Chemically honey is composed of different sugars, predominantly
fructose and glucose as well as other substances such as organic acids, enzymes, vitamins,
proteins, volatile compounds, several bioactive substances (phenols and avonoids), and
micro and macroelements (Machado De-Melo et al., 2018) (Figures 16.2–16.4).
The water content of honey is related to different factors such as the botanical origin
and geographical area of nectar, season of harvesting, intensity of nectar ux, degree of
maturation, manipulation by beekeepers during the period of harvest, as well as extraction,
processing, and storage conditions (Estupinan et al., 1998; Sainz-Laın and Gomez-Ferreras,
2000; Gonzalez, 2002; Ojeda de Rodrıguez et al., 2004; Sabatini, 2007; Pontara et al.,
2012; Ciric et al., 2018; Ćirić et al., 2020). The physicochemical characteristics and quality
are dened in different national and EU regulations.
The antioxidant activity of different honey samples has been determined using several in
vitro methods, as 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2′-azinobis (ABTS), and photo-
chemiluminescence (PCL) assays, and reducing activity by cupric reducing antioxidant
capacity and ferric reducing antioxidant power (ferric reducing antioxidant power [FRAP])
methods (Martinello and Mutinelli, 2021). Several compounds were identied in honey
samples, 11 of which were avonoids and so on, quercetin 3-O-glucuronide, orientin, vitexin,
quercetin, epicatechin, kaempferol, pinobanksin, and apigenin), phenolic acids (gallic,