Complementary Practices in Pharmacy and Their Relation to Glaucoma—Classification, Definitions, and Limitations

Abstract

Background: Traditional and evidence-based medicines, as seen depicted throughout human history, reportedly first begin with the application of medicinal plants, animal products, or inorganic minerals as a basic framework towards effectively engineering the prototypes generally aligned to pharmaceuticals and medical nutrition. The growing global trend of complementary treatments for glaucoma can be explained by the intraocular pressure (IOP)-independent mechanisms of the disease and its interpretation as a progressive neurodegenerative disorder. Unfortunately, the categorical positions of the major fields of applied popular complementary therapies and their relation to glaucoma are consistently neglected. Methods: In consideration of bibliographic resources, the most well-known online scientific databases were searched. Conclusion: The rising popularity and the trends of products coming onto the market cannot escape the attention of pharmacists and ophthalmologists, as their patients suffering from eye diseases are also increasingly looking for such medicinal products. Most of them still lack knowledge of the appropriate evidence and side effect profiles. Our proposed systematic charts demonstrate the position of each mainstream complementary therapy throughout the applied medical sciences and are distinctively unique; we could not find any similar relevant illustration or resource among the published international literature.

Full text

Citation: Rák, T.; Csutak, A.
Complementary Practices in
Pharmacy and Their Relation to
Glaucoma—Classication,
Denitions, and Limitations. Sci.
Pharm. 2024,92, 16. hps://doi.org/
10.3390/scipharm92010016
Academic Editor: William
A. Donaldson
Received: 31 January 2024
Revised: 10 March 2024
Accepted: 12 March 2024
Published: 14 March 2024
Copyright: © 2024 by the authors.
Licensee MDPI, Basel, Swierland.
This article is an open access article
distributed under the terms and
conditions of the Creative Commons
Aribution (CC BY) license (hps://
creativecommons.org/licenses/by/
4.0/).
Scientia
Pharmaceutica
Review
Complementary Practices in Pharmacy and Their Relation
to Glaucoma—Classication, Denitions, and Limitations
Tibor Rák1, 2, * and Adrienne Csutak 1
1Department of Ophthalmology, Medical School Clinical Centre, University of Pécs, Rákóczi út 2.,
H‑7624 Pécs, Hungary; csutak.adrienne@pte.hu
2Department of Pharmacognosy, Faculty of Pharmacy, University of Pécs, Rókus utca 2.,
H‑7624 Pécs, Hungary
*Correspondence: rak.tibor@pte.hu; Tel.: +36‑706032399
Abstract: Background: Traditional and evidence‑based medicines, as seen depicted throughout hu‑
man history, reportedly rst begin with the application of medicinal plants, animal products, or
inorganic minerals as a basic framework towards eectively engineering the prototypes generally
aligned to pharmaceuticals and medical nutrition. The growing global trend of complementary treat‑
ments for glaucoma can be explained by the intraocular pressure (IOP)‑independent mechanisms of
the disease and its interpretation as a progressive neurodegenerative disorder. Unfortunately, the
categorical positions of the major elds of applied popular complementary therapies and their rela‑
tion to glaucoma are consistently neglected. Methods: In consideration of bibliographic resources,
the most well‑known online scientic databases were searched. Conclusion: The rising popularity
and the trends of products coming onto the market cannot escape the aention of pharmacists and
ophthalmologists, as their patients suering from eye diseases are also increasingly looking for such
medicinal products. Most of them still lack knowledge of the appropriate evidence and side eect
proles. Our proposed systematic charts demonstrate the position of each mainstream complemen‑
tary therapy throughout the applied medical sciences and are distinctively unique; we could not nd
any similar relevant illustration or resource among the published international literature.
Keywords: apitherapy; aromatherapy; Bach ower remedies; gemmotherapy; mycotherapy;
phytotherapy
1. Introduction
It is estimated by the World Health Organization (WHO) that 60–80% of the popula‑
tion, especially in the developing world [1,2], are dependent upon complementary med‑
ical practices to relieve symptoms or to treat their health conditions, and 85% of these
individuals rely on the use of herbs or herb‑based products. These therapies represent a
holistic approach to the human organism and its function [2]. Human history, in reference
to traditional medicine, reportedly rst began with the application of medicinal plants,
animal products, or inorganic minerals as a basic framework to engineer prototypes re‑
garding pharmaceuticals and medical nutrition. Classic examples characteristic of natu‑
ral substances are salicylates (Salix spp.), digitalis glycosides (Digitalis lanata Ehrh. and
D. purpurea L.), pilocarpine (Pilocarpus jaborandi Holmes), quinine (Cinchona ocinalis L.),
etc. [3,4]. The evolution of medicine is based upon empirical experience and prescientic
observations leading to the construction of systematic therapy methods and practices. Re‑
cently, developing and ongoing evidence‑based medical research and studies have yielded
far more complex standardized therapies for the treatment of disease. Today, our world
has far greater access to contemporary pharmacotherapy; however, developing countries,
especially their rural areas, are indeed lacking in adequate healthcare and are confronted
with unsatisfactory sanitation. Therefore, the only option is traditional medicine, which is
sometimes either harmful or scientically not yet fully substantiated. However, a growing
Sci. Pharm. 2024,92, 16. https://doi.org/10.3390/scipharm92010016 https://www.mdpi.com/journal/scipharm

Sci. Pharm. 2024,92, 16 2 of 17
tendency witnessed among developed nations is a return to classic ethnomedicinal prac‑
tices, in particular, herb‑based preparations [5]. The regular use of complementary ther‑
apies among mainstream European countries hovers at 49% in France, 46% in Germany,
35% in the United Kingdom, 31% in Belgium, and 25% throughout Northern Europe. In
the majority of the countries, these naturopathic medical methods have not been ocially
recognized; however, an increasing demand emanating from both patients and healthcare
professionals is reported [6]. The role of the classical medical substances can be factu‑
ally demonstrated; statistically, 56% of prescribed pharmaceuticals are synthetic, of which
24% are herbal derivatives, 6% are directly extracted from plants, and 5% are of animal
origin [3].
2. Challenges in Glaucoma
The heterogenous disease group of glaucoma is a progressive optic neuropathy caus‑
ing vision loss; in 2022, it was the second leading cause of vision loss after cataracts [4].
The degeneration of retinal ganglion cells accelerates in the retinal nerve ber layer, and
its eect inuences the visual pathway up to the visual cortex, causing visual eld decits.
Early detection and proper treatment can decelerate the progression and preserve long‑
term visual function. Lowering the intraocular pressure (IOP), as the only modiable
risk factor, is the primary evidence‑based therapeutic strategy, including topical medica‑
tions, selective laser trabeculoplasty, and ltration surgeries. The growing global trend of
complementary treatments for glaucoma can be further explained by the IOP‑independent
mechanisms, focusing on herbal remedies and diet. These molecular mechanisms create a
cascade, rather than discrete events, and include the withdrawal of neurotrophic factors,
oxidative stress, mitochondrial dysfunction, glutamate excitotoxicity, autophagy, protein
misfolding, ischemia, and hypoxia [4,7].
Complementary medical practices consist in the application of several traditional and
well‑established herbal, mineral, or animal‑related substances, mostly taught throughout
pharmaceutical education. Moreover, these products can mostly be found in pharmacies
in the form of dietary supplements, herb‑based medications, foods (ltered teas), and cos‑
metics (essential oils, etc.) [8]. The number of herbal preparations used in ophthalmology,
especially in the treatment of glaucoma, is currently low, but their increase can be pre‑
dicted [9]. In a survey, 13.6% of glaucoma patients stated that they use complementary
medicine in addition to their antiglaucoma eye drops, while 62.5% did not inform their
treating ophthalmologist. Among their applied methods, 34.5% consisted of herbal ther‑
apy, 22.7% of diet, and 18.8% of dietary supplements [7,10]. An interesting result obtained
from this study is that the use of complementary therapies was related to younger age, the
severity of glaucoma disease, earlier diagnosis, greater use of topical therapy, previous
anti‑glaucoma surgery, higher education, and, nally, the eect of glaucoma on quality of
life. At the same time, almost the same proportion of participants (40.5%) were satised
with their complementary treatment as those who were not pleased (40.2%). Another in‑
teresting result is that only 16.7% of the patients were able to obtain information from their
treating ophthalmologist about the complementary remedies used in glaucoma, while the
role of the media (37.1%) was more representative [7,10]. Although North America was the
primary site of the mentioned study, the growing trend of complementary treatments for
glaucoma can be interpreted for the rest of the world. The rising popularity and the trend
of even more products coming onto the market cannot escape the aention of ophthalmol‑
ogists, as their patients suering from cataracts, glaucoma, age‑related macular degener‑
ation (AMD), and diabetic retinopathy are also increasingly looking for such medicinal
products [10–12]. As a recent example, in 2021, 22–67% of Middle Eastern patients applied
complementary medicine, especially for their ophthalmic disease [13]. Most patients still
lack knowledge of the appropriate evidence and side eect proles [12].
In this article, we propose a novel classication system including appropriate de‑
nitions to demonstrate the complementary pharmacy‑related medical sciences and their
relation to glaucoma therapy. The categorical position regarding these complementary

Sci. Pharm. 2024,92, 16 3 of 17
therapies in the major eld of applied human medicines is, unfortunately, consistently ne‑
glected. We suggest a new type of classication specically intended for phytomedicine‑
related applied complementary medical methods and well‑founded evidence‑based de‑
nitions, to eectively aid future healthcare professionals and medical researchers.
3. Materials and Methods
In consideration of the bibliographic resources, a thorough search was implemented
in the most frequently applied online scientic databases, including PubMed.org, ScienceDi‑
rect.com, and Researchgate.net, using the following keywords: “Phytotherapy”, “Aro‑
matherapy”, “Aromachology”, “Aromatology”, “Hydrosols”, “Apitherapy”, “Mycother‑
apy”, “Gemmotherapy”, “Hirudotherapy”, “Schüssler salts”, “Bach Flower Therapy”, “def‑
inition”, “classication”, “limitation”, “chart”, and various combinations.
4. Phytotherapy
4.1. Denitions and Description
Phytotherapy (or herbalism) is a major branch of medicine treating medical condi‑
tions, promoting health, and preventing diseases using plant‑based substances. The
origin of the term is Ancient Greek—“φυτóν” (plant) and “θεραπεία” (service, medical
treatment)—and was rst used in 1913 by Henri Leclerc, who described medicinal plants
and their empirical therapeutic use in clinical trials [14]. Originally, it was representa‑
tive of applied medicine and pharmacy; however, as of recently, it is now classied into
complementary medicine. Practically, it does not dier from evidence‑based pharmaceu‑
tical drug usage, yet in complementary medical practice, several plants may have non‑
ocial, non‑evidence‑based, or o‑label applications. Phytotherapy generally uses the
chemical composition and pharmacological activity of the source plant (either the entire
herb, or a processed portion, e.g., buds, leaves, sprouts, owers, fruits, seeds, bark, and/or
roots) for therapeutic purposes [6,15]. According to Bürgi’s law, plant‑derived remedies
have combined synergistic eects, rather than just one useful molecule, so they cannot
be simplied to a single pharmacologic mechanism [4]. Herb‑based therapies are widely
applied in all existing medical traditions, including anthroposophic medicine, Traditional
Chinese Medicine (TCM), Ayurvedic medicine, Tibetan–Mongolian medicine, etc., includ‑
ing evidence‑based medicine (EBM). Physicians and non‑medical health practitioners may
use either single‑herb monotherapies or synergistic polytherapy believed to have adjuvant
eects. Such therapies are often supported by non‑herbal supplements, such as minerals,
vitamins, or animal products [6,15].
4.2. Limitations
Most of the herbal formulas are not well established in human clinical research since
the majority of them have been tried and justied only in animal experimental models or
in vitro pilot studies. However, a few of them have become evidence based or been clini‑
cally trialed, while the rest of them were translated to possible human applications. Due
to inevitable environmental factors, some herbal formulae may even contain some heavy
metal contamination, and the eective molecular content cannot always be clearly identi‑
ed. Further, according to Bürgi’s law of herbal synergism, one extracted useful molecule
cannot always to be reduced to the same pharmacological eect that it has in synergism
with other plant substances. Therefore, it is more dicult to produce evidence‑based stan‑
dardized herbal pharmacotherapy [4]. However, the rapid growth of the herbal product
industry and the lack of corresponding regulations and legislation have caused the WHO
and other regulatory bodies to be increasingly concerned with the safety and ecacy of
herbal medicines. Phytotherapy is the most studied complementary medical eld, as high‑
lighted by the clinical and pharmacological results, but comprehensive evidence‑based
guidelines are still missing. Laymen and non‑medical therapists often rely on rural eth‑
nomedicinal oral or documented practices lacking scientic evidence, resulting in unin‑
tentional adverse side eects. Furthermore, patients are often exposed to internet fraud

Sci. Pharm. 2024,92, 16 4 of 17
or the illegal market of herb‑based products. The quality and quantity of over‑the‑counter
herbal supplements and medications are questionable due to the unsatisfactory manufac‑
turing regulations. Herbal monographs (such as those by the European Medicines Agency
(EMA) and European Scientic Cooperative on Phytotherapy (ESCOP), etc.) comprise
all scientically proven botanical, pharmacological, and medical information, providing
a clinical and evidence‑based application “guideline” in support of phytotherapists [6].
4.3. Application in Glaucoma
In their review, Kovács‑Valasek et al. enumerated at least 16 herbs and herbal com‑
positions with possible pharmacologic roles in complementary glaucoma therapy. These
herbal compounds act on dierent molecular pathways that aect IOP change, inam‑
mation, apoptosis, neurodegeneration, ocular ischemia, and neovascularization [4]. Early
pharmacological treatments of glaucoma relied on herbal remedies and diet. Pilocarpine,
a parasympathomimetic alkaloid still used for primary angle closure glaucoma (PACG)
management, is extracted from Pilocarpus jaborandi Holmes and causes ciliary muscle con‑
traction, facilitating aqueous humor outow through the trabecular meshwork [4]. Herbal
remedies are not always safe for glaucomatous patients, as Edington et al. reported that
Hypericum perforatum L. may aect IOP control. It interacts with several drugs, including
β‑blockers, as it induces the cytochrome P450 system and causes faster drug metabolism
in the ciliary body, iris, and retinal pigment epithelium (RPE) in human eyes. The resulting
suboptimal IOP control can be improved on discontinuation of the herb [4].
5. Aromatherapy
5.1. Denitions and Description
Aromatherapy is the art and clinical science utilizing naturally extracted lipophilic es‑
sential and vegetal oils, including hydrophilic herbal essences, in medical curative pro‑
cesses while promoting mental–physical wellness [16,17]. The term was created by Dr.
RenéMaurice Gaefossé, in 1937 [18,19], and originates from Ancient Greek—“ἄρωµα”
(scent, fragranced oil or plant, and spices) and “θεραπεία” (service and medical treatment).
The essential products characteristic of aromatherapy include essential oils; their scien‑
tic pharmaceutical Latin name appears as aetheroleum, which has Greek roots (“αἰθήρ”—
heaven, upper purer air, and/or ether). Essential oils are mostly pleasant‑scented complex
mixtures of mono‑ and sesquiterpenes and phenylpropane derivatives. According to some
surveys, aromatherapy is the second most popular complementary medical practice in the
U.K. [20] and has become a worldwide, fast‑growing holistic treatment practice.
Aromachology describes the eects of essential oil scents on human cognitive functions,
behavior, emotional status, and, comprehensively, psychological interrelationships. The
aromatic scent characteristic of essential oils stimulates the cerebral olfactory pathways,
particularly the anatomical parts of the limbic system. The results are based on the sub‑
jective emotional status and well‑being [21]. Aromatology assesses the physicochemical
features and biological–pharmacological activity of essential oils. Furthermore, internal
(per os) application is connected to aromatology, characterizing the continental (French)
medical aromatherapy practices (excluding the English aromatherapy school) [21]. The
clinical practice is divided by its geographical origin: the popular and esoteric English aro‑
matherapy is based mostly on Ayurvedic medicine and aromachology, practiced in Great
Britain; the medical‑associated French aromatherapy, on the contrary, is characterized by
the scientic chemistry based on aromatology [21]. A relatively new eld is hydrosol aro‑
matherapy, anecdotally referred to as “the homoeopathic aqueous extracts of plants and
essential oils” (Figure 1.). Hydro‑distillation is the most well‑known technology applied
to obtain the main products used in aromatherapy. The distilled aqueous phase, in the
form of hydrosol, is a by‑product, yet it possesses hydrophilic or partially hydrophobic aro‑
matic components with appropriate pharmacological bioactivities. Hydrosol aromather‑
apy applies hydrosols with the same indications as those of essential oils as aordable
and safer alternatives [22–24]. Aromatherapists practice their eld of profession in several

Sci. Pharm. 2024,92, 16 5 of 17
ways. Ali et al. (2015) classied aromatherapy in their review into ve elds of application:
massage, medical, psycho‑, cosmetical, and olfactory aromatherapy [25].
Sci. Pharm. 2024, 92, x FOR PEER REVIEW 5 of 18
and essential oils” (Figure 1.). Hydro-distillation is the most well-known technology ap-
plied to obtain the main products used in aromatherapy. The distilled aqueous phase, in
the form of hydrosol, is a by-product, yet it possesses hydrophilic or partially hydrophobic
aromatic components with appropriate pharmacological bioactivities. Hydrosol aroma-
therapy applies hydrosols with the same indications as those of essential oils as affordable
and safer alternatives [22–24]. Aromatherapists practice their field of profession in several
ways. Ali et al. (2015) classified aromatherapy in their review into five fields of application:
massage, medical, psycho-, cosmetical, and olfactory aromatherapy [25].
Figure 1. Summarized chart representing the “Aroma-sciences”. The recent scientific literature and
databases lack an official description regarding “Aroma-sciences”; therefore, for this purpose, we
summarize them in a self-made chart.
5.2. Limitations
Essential oils are complex products comprising lipophilic herbal agents in a very con-
centrated means; therefore, the oral application of these oils is considerably limited. Alt-
hough essential oil demand is emerging in the global market, its “omnipotent” marketing
often leads to illegal plant harvesting and essential oil counterfeiting. In addition to the
ecological hazard, counterfeited essential oils have no pharmacological effect and are of-
ten toxic. Essential oils also have adverse side effects when applied either internally (nau-
sea, vomiting, liver, kidney damage, etc.) or externally (epilepsy, allergy, glaucoma, mi-
graine, burns, dermatitis, etc.). The most common effects are skin irritation and contact
dermatitis [20]. To prevent these harmful events and quackery, herbal monographs (EMA,
ESCOP, etc.) and the scientific aromatherapy literature also contain various medical de-
scriptions and applications of essential oils.
5.3. Application in Glaucoma
Aromatherapy may be an effective intervention for alleviating blindness-associated
anxiety (13–30%), depression (11–25%), and sleep disturbances in glaucomatous patients
(Flammer syndrome) [26–28]; however, to date, the effects remain inconclusive. Sabel et
al. (2018) summarized the psychological impact in glaucomatous patients, finding that
80% experienced negative emotional reactions after their glaucoma diagnosis, and one-
third were afraid of going blind [27]. Higher levels of anxiety and depressive symptoms
were associated with faster progression of perimetric visual field loss in more patients
with PACG than in those with primary open-angle glaucoma (POAG) [27]. In normoten-
sion glaucoma (NTG), stress was previously clearly identified as a major risk factor caus-
ing vascular dysregulation of the optic nerve head and retina [27,28]. Logically,
Figure 1. Summarized chart representing the “Aroma‑sciences”. The recent scientic literature and
databases lack an ocial description regarding “Aroma‑sciences”; therefore, for this purpose, we
summarize them in a self‑made chart.
5.2. Limitations
Essential oils are complex products comprising lipophilic herbal agents in a very con‑
centrated means; therefore, the oral application of these oils is considerably limited. Al‑
though essential oil demand is emerging in the global market, its “omnipotent” marketing
often leads to illegal plant harvesting and essential oil counterfeiting. In addition to the
ecological hazard, counterfeited essential oils have no pharmacological eect and are often
toxic. Essential oils also have adverse side eects when applied either internally (nausea,
vomiting, liver, kidney damage, etc.) or externally (epilepsy, allergy, glaucoma, migraine,
burns, dermatitis, etc.). The most common eects are skin irritation and contact dermati‑
tis [20]. To prevent these harmful events and quackery, herbal monographs (EMA, ESCOP,
etc.) and the scientic aromatherapy literature also contain various medical descriptions
and applications of essential oils.
5.3. Application in Glaucoma
Aromatherapy may be an eective intervention for alleviating blindness‑associated
anxiety (13–30%), depression (11–25%), and sleep disturbances in glaucomatous patients
(Flammer syndrome) [26–28]; however, to date, the eects remain inconclusive. Sabel et al.
(2018) summarized the psychological impact in glaucomatous patients, nding that 80% ex‑
perienced negative emotional reactions after their glaucoma diagnosis, and one‑third were
afraid of going blind [27]. Higher levels of anxiety and depressive symptoms were asso‑
ciated with faster progression of perimetric visual eld loss in more patients with PACG
than in those with primary open‑angle glaucoma (POAG) [27]. In normotension glaucoma
(NTG), stress was previously clearly identied as a major risk factor causing vascular dys‑
regulation of the optic nerve head and retina [27,28]. Logically, aromatherapy may have a
potential role in normalizing blood pressure or ameliorating the sleep paern and coping
with stress [26], although we do not know of any current aromatherapy‑related clinical
study treating glaucoma, proving the eect of the aforementioned risk factors.
An interesting question is the “citral” problem in glaucomatous eyes. Leach and
Lloyd, in 1955, found that orange oil, prepared from orange peel, and a hydrochloride ex‑
tract were both strongly active in raising the IOP in rabbits and monkeys. They identied

Sci. Pharm. 2024,92, 16 6 of 17
the active substance as citral, and its additive oral ingestion might be an important factor
causing secondary glaucoma. Citral is a monoterpene aldehyde covering two geometric
isomers, geranial (trans(E)‑citral or citral A) and neral (cis(Z)‑citral or citral B). Aromather‑
apist guidelines discourage patients with glaucoma from applying high‑citral‑containing
essential oils, e.g., Backhousia citriodora F.Muell. (90–98%), Litsea cubeba (Lour.) Pers. (90%),
Cymbopogon schoenanthus Spreng. and Cymbopogon citratus (DC.) Stapf (65–85%), Leptosper‑
mum petersonii F.M.Bailey (70–80%), Ocimum gratissimum L. (66.5%), Corymbia citriodora
(Hook.) K.D. Hill & L.A.S.Johnson (65%), Citrus ×aurantium L. (36%), Aloysia citriodora
Paláu (30–35%), Eucalyptus staigeriana F.Muell. ex F.M.Bailey (26%), Melissa ocinalis L.
(11%), Citrus ×aurantiifolia (Christm.) Swingle (6–9%), and Citrus ×limon (L.) Osbeck
(2–5%). Later, Rodger and Saiduzzafar et al. repeated the experiments, but they could not
reproduce the same eect conclusively [29–32]. With the lack of a proven IOP‑increasing
eect, aromatherapists must not discourage the usage of citral‑containing essential oils in
glaucomatous patients, but regular ophthalmic examinations are recommended.
6. Gemmotherapy
6.1. Denitions and Description
Gemmotherapy is a recently developed therapeutic technique based on the applica‑
tion of extracts obtained by the ethanolic or glycerolic maceration of fresh meristematic
plant tissues, primarily buds (gemma in Latin) and sprouts, on the basis of the plant’s med‑
ical properties [6]. These principles originate from the experiments of the Ukrainian re‑
searcher Professor Filatov (Odessa University); however, the evolution of gemmotherapy
as a therapeutic method is credited to the Belgian physician Dr. Paul Henry, from Brus‑
sels, who announced his results in 1954. These bud preparations reportedly contain a vital
source of energy (high levels of vitamins and terpenic and phenolic compounds) and con‑
sist of herbs with much more potential agents than in the classic phytotherapeutic use of
adult plants. The active substances are characterized by the presence of growth factors,
such as gibberellins and auxins. In comparison with adult herb preparations, buds con‑
tain pharmacologically more active compounds, which are considerably more suitable in
eectively treating denitive human diseases and/or promoting health. As a raw material,
they are applied in both the herbal and cosmetic industries [6,33].
6.2. Limitations
Bud derivatives are a novelty in complementary medicine, yet they are still poorly
studied. Regarding gemmotherapeutic preparations, therapists encounter several dicul‑
ties: Fresh buds must be harvested, generally from spontaneously grown plants, in a very
limited period (late winter and/or early spring) corresponding to the annual germination
of the chosen medical plant. During this time, the plant may not present its distinctive
characteristics; hence, the aribution of the species may prove dicult for the collector.
From another perspective, the manufacturing process and the extraction protocols are not
strictly dened, regulations are rarely enforced, and results are decient [6].
6.3. Application in Glaucoma
Vaccinium myrtillus L. is used to cure retinal vascular fragility, glaucoma, and AMD,
but its bud preparation has not been properly researched. Among the four major antho‑
cyanins discovered in the buds of Ribes nigrum L., delphinidin‑3‑O‑rutinoside was the most
prevalent, followed by cyanidin‑3‑O‑rutinoside. In healthy humans, the administration
of blackcurrant anthocyanins for 2 weeks signicantly decreased the IOP. The eect on
visual function was also studied on glaucoma patients: 24 months of administration de‑
creased the IOP, delayed visual eld loss, and elevated ocular blood ow. The exact mech‑
anisms have not been thoroughly studied, but one proposed hypothesis mentioned plasma
endothelin‑1 (ET‑1), serving as a potent vasoconstrictor, which has been suggested to play
a role in the local autoregulation of blood ow in glaucomatous patients, especially in
NTG [4,27,34].

Sci. Pharm. 2024,92, 16 7 of 17
7. Bach Flower Therapy
7.1. Denitions and Description
Bach Flower Remedies (BFRs) or Bach Flower Therapies are alcoholic fresh ower tinc‑
tures, highly diluted and similar to homoeopathy in principle. These remedies are manu‑
factured using two steps: rst, obtain the “mother tincture” by placing a fresh ower into
rock water with plenty of sunshine; second, add the rst solution to brandy (alcoholic com‑
ponent). The products are based on a denite thirty‑eight remedies (thirty‑seven plants
and rock water), which do not contain pharmacologically relevant active agents; however,
they are scientically unproven and believed to possess subtle forms of self‑healing en‑
ergy [35,36]. The remedies and the theory regarding this therapy were invented by the
British physician Dr. Edward Bach in the 1930s, and they were recognized by the WHO in
1974 [2,36]. According to Bach’s principles, BFRs can be used on any kind of medical con‑
dition; however, they are widely used in civilization‑associated psychological problems,
such as for treating stress and anxiety [36,37]. Dr. Bach distinguished seven emotional
or personality groups, across which the thirty‑eight ower essences are categorized, as
depicted in Table 1[36,38].
Table 1. Basic materials of Bach Flower Remedies classied by Dr. Edward Bach according to the
seven emotions. (Self‑edited table based on the studies of Dr. Bach and other reviews [36,38].) The
table demonstrates the numeric ordinal, traditional English and scientic names, and indications of
Bach owers.
1. Fear
2 Aspen Populus tremula L. Vague fears of unknown objects and events
6 Cherry Plum Prunus cerasifera Ehrh. Fear of losing mental control
20 Mimulus Erythranthe guata (Fisch. DC.) G.L.Nesom Phobia of known things with withdrawn and nervous personality
25 Red Chestnut Aesculus ×carnea Zeyh. Excessive worry and over‑anxiety for the welfare of relatives
26 Rock rose Helianthemum nummularium (L.) Mill. Extreme phobia, terror, panic (generalized anxiety disorder), and nightmares (nocturnal
panic aack)
2. Uncertainty
5 Cerato Ceratostigma willmoianum Stapf Lack of condence in own decisions; repeatedly seeking advice of others
(approval‑seeking behavior)
12 Gentian Gentiana amarella (L.) Börner Doubt and discouragement after an unfortunate event; pessimism
13 Gorse Ulex europaeus L. Great hopelessness and despair
17 Hornbeam Carpinus betulus L. Procrastination; lack of the strength to full daily tasks
28 Scleranthus Scleranthus annuus L. Indecisiveness between alternatives
36 Wild Oat Bromus ramosus Huds. Dissatisfaction and uncertainty over one’s direction in life (existential depression)
3. Lack of Interest
7 Chestnut Bud Aesculus hippocastanum L. Failure to learn from mistakes and negative experiences
9 Clematis Clematis vitalba L. Daydreaming of the future with insucient interest in the present; absent‑mindedness
16 Honeysuckle Lonicera caprifolium L. Living in the past with overwhelming nostalgia
21 Mustard Sinapis arvensis (L.) Andrz. ex Besser Major depression for no reason
23 Olive Olea europaea L. Fatigue induced by physical and mental exertion
35 White Chestnut Aesculus hippocastanum L. Unwanted worrying and intrusive thoughts; concentration inability
37 Wild Rose Rosa canina L. Resignation, learned helplessness, and apathy
4. Loneliness
14 Heather Calluna vulgaris (L.) Hull Fear against loneliness contributes to talkative, self‑centered, and
self‑concerned individuals
18 Impatiens Impatiens glandulifera Royle Impatience, frustration, and irritability
34 Water Violet Hoonia palustris L. Self‑reliant individuals; pride and arrogance
5. Over‑Sensitivity
1 Agrimony Agrimonia eupatoria L. Hidden worries and mental torture masked by a cheerful face (“smiling depression”)
4 Centaury Centaurium erythrea Rafn. Inability to refuse
15 Holly Ilex aquifolium L. Resentment, envy, jealousy, suspicion, and revenge; victim mentality
33 Walnut Juglans regia L. Protection from changing and unwanted inuences (at birth, puberty, divorce etc.);
strongly inuenced by opinions of others

Sci. Pharm. 2024,92, 16 8 of 17
Table 1. Cont.
6. Despondency and Despair
10 Crab Apple Malus pumila Mill. Fear of contamination (mysophobia), sensation of uncleanliness, also for self‑hatred and
body image distortion
11 Elm Ulmus minor Mill. Overwhelmed by responsibilities (responsibility fatigue) and pressures of workload
(workload paralysis)
19 Larch Larix decidua Mill. Low self‑esteem; lack of condence, fear of failure (maladaptive perfectionism)
22 Oak Quercus robur L. Perseverance to overcome adversity without losing hope
24 Pine Pinus sylvestris L. Self‑blame, self‑criticism, guilt
29 Star of
Bethlehem Ornithogalum umbellatum L. Sensation of shock and loss, traumatic events, grief of tragedy, post‑traumatic stress
disorder (PTSD)
30 Sweet Chestnut Castanea sativa Mill. Extreme mental anguish and emotional agony; hopelessness despite all aempts
38 Willow Salix alba var. vitellina (L.) Stokes Resentfulness, self‑pity, and bierness
7. Overcare for others
3 Beech Fagus sylvatica L. Intolerance and hyperreactivity; critical, inexible, and perfectionist mindset
8 Chicory Cichorium intybus L. Selsh and egoistic mindset; demand appreciation from others; possessive, controlling,
and critical behaviors (narcissistic personality)
27 Rock water Aqua petraea Self‑discipline, self‑denial, and self‑repression; asceticism
31 Vervain Verbena ocinalis L. Enthusiastic strain and pressure; perfectionism and overexertion
32 Vine Vitis vinifera L. Dominance‑seeking behavior and cognitive inexibility
BFRs are also available in the following application forms in clinical practice: tinc‑
tures, skin creams, pastilles, chewing gums, dissolvable capsules, lozenges, eervescent
tablets, and liquid sprays. Dr. Bach created a special combination remedy, the Rescue
Remedy, for emergency cases (combating fear, panic, shock, and fear of losing control),
which consists of Prunus cerasifera Ehrh., Clematis vitalba L., Impatiens glandulifera Royle,
Helianthemum nummularium (L.) Mill., and Ornithogalum umbellatum L. [36,39].
7.2. Limitations
More studies suggest that Bach Flower Therapy has a lower rate of evidence, and
while its therapeutic use is limited and uncertain, it is likely safe [36]. Although BFRs have
demonstrated potential roles in pain management and minor psychiatric disorders, there
is no specic evidence beyond the placebo eect. BFRs’ mode of action is dependent not
on molecular or pharmacological mechanisms but on the subtle forms of “energy”. The
application of ower remedies may likely become hazardous when treating severe forms
of disease. Professional BFR organizations set up the following indications: anxiety/stress,
depression, general mental stress, lack of condence, etc., associated with emotional and
physical traumas; however, various studies report successful results treating other diseases
(e.g., temporal–mandibular joint dysfunction, teething diculties, low back pain, eczema,
hypertension, migraines, aention‑decit hyperactivity disorder, drug and alcohol addic‑
tions, motion sickness, allergies, asthma, insomnia, nocturnal enuresis, etc.). Conclusions
from the available clinical trials have failed to demonstrate convincing evidence dieren‑
tiating from the use of a placebo [35,39].
7.3. Application in Glaucoma
There is no mention of BFRs in evidence‑based literature, even in nonscientic texts as‑
sociated with glaucoma. BFRs are produced to relieve psychosocial and mental symptoms;
therefore, glaucomatous patients can take them regardless of their ocular disease. How‑
ever, psychosocial distresses, depression, fear of blindness, and other mental disorders are
quite frequent in glaucomatous patients, and there is no evident relationship between BRFs
and glaucoma progression [4,27,36].
8. Mycotherapy
8.1. Denitions and Description
Culinary and medicinal mushrooms and their extracts (such as Pleurotus giganteus
(Berk.) Karun. & K.D.Hyde, Ganoderma lucidum Karst, Hericium erinaceus (Bull.) Per‑

Sci. Pharm. 2024,92, 16 9 of 17
soon, Lentinula edodes (Berk.) Pegler, etc.) are commonly produced and applied world‑
wide as dietary supplements, nutraceutical foods, and pharmaceutical drugs. The impor‑
tant health benets demonstrated comprise a broad spectrum of pharmacological bioactiv‑
ities, including anti‑inammatory, antioxidative, immunomodulating, and neuroprotec‑
tive eects [40–43]. The most popular indication of these natural mushroom compounds
has been linked primarily to the modulation of the immune system and specic molec‑
ular targets of cell functions, including cell proliferation, cell survival, and angiogenesis,
by branched polysaccharides (glucans), sesquiterpenes, glycoproteins, or peptide/protein‑
bound polysaccharides. They also have a large number of bioactive compounds, such as
alkaloids, antibiotics, and metal‑chelating agents, making them useful pharmaceutic ingre‑
dients. Medicinal mushrooms are a rich source of carbohydrates, proteins, bers, minerals,
and vitamins (e.g., thiamin, riboavin, ascorbic acid, and vitamin D) and are low in calo‑
ries and fat, contributing to overall health benets. Recently, they have become popular
throughout Europe, although they have been applied in Asian traditional medicine and
cuisine for thousands of years [40–43].
8.2. Limitations
The growing interest in mycotherapy requires a strong commitment towards expand‑
ing scientic clinical trials. Most of the data originate from in vitro and in vivo experimen‑
tal models. The small number of studies unfortunately limits the evidence‑based applica‑
tion of mycotherapy in everyday practice [42].
8.3. Application in Glaucoma
Bioactive metabolites from fungal endophytes are important sources for mycotherapy.
The Ganoderma genus produces many biologically active triterpenoids, and 35 compounds
from Ganoderma lucidum were screened by Amen et al. for their Rho‑kinase inhibitory ac‑
tivity. Their results suggest that the traditional uses of G. lucidum, with its lanostane triter‑
penes, might be in part due to its ROCK‑I and ROCK‑II inhibitory potential. Synthetic
Rho‑kinase inhibitors have emerged as potential therapeutic agents to treat disorders such
as glaucoma, so these ndings would be helpful for the design of natural Rho‑kinase in‑
hibitors [44,45]. The Xylariaceae family comprises mostly small ascomycetous fungi, and
their metabolites have shown antioxidant and anti‑inammatory activities. Lin et al. exam‑
ined the retinoprotective compound Theissenolactone C (LC53), which is a fungal derivate
extracted from Theissenia cinerea Y.M. Ju, J.D. Rogers & H.M. Hsieh (Xylariaceae). According
to their results, the application exerted a retinal protective eect through NF‑κB inhibition
and was highly potent against MMP‑9 activities after high‑IOP‑induced retinal injury. This
suggests a promising drug possibility for glaucoma or ocular‑related medical conditions
aributed to retinal ischemia [45]. The results of both above‑mentioned studies need to
be examined in human glaucomatous patients in clinical trials to obtain evidence‑based
information about the possible potential in glaucoma complementary therapy.
9. Apitherapy
9.1. Denitions and Descriptions
Apitherapy is the application of honeybee (Apis mellifera L.) and beehive‑related prod‑
ucts such as honey, pollen, propolis, royal jelly, bee bread, bee venom (apitoxin), beeswax,
apilarnil, and beehive air in disease prevention, health promotion, and curative
treatment [8,46–48] (Figure 2). Globally, this is a well‑known aspect of traditional medicine
that was popularly used in the past much as it is today. According to the oldest human
historical ndings, honey collecting dates back some 9000 years. In wrien sources, its
use stretches back to ancient Egypt, and it is also used in Traditional Chinese and Tibetan
Medicine. Hippocrates, the great ancient Greek physician, described the biological prop‑
erties of honey and pollen applied to sores and wounds [8,46,49].

Sci. Pharm. 2024,92, 16 10 of 17
Sci. Pharm. 2024, 92, x FOR PEER REVIEW 10 of 18
8.3. Application in Glaucoma
Bioactive metabolites from fungal endophytes are important sources for mycother-
apy. The Ganoderma genus produces many biologically active triterpenoids, and 35 com-
pounds from Ganoderma lucidum were screened by Amen et al. for their Rho-kinase inhib-
itory activity. Their results suggest that the traditional uses of G. lucidum, with its lanos-
tane triterpenes, might be in part due to its ROCK-I and ROCK-II inhibitory potential.
Synthetic Rho-kinase inhibitors have emerged as potential therapeutic agents to treat dis-
orders such as glaucoma, so these findings would be helpful for the design of natural Rho-
kinase inhibitors [44,45]. The Xylariaceae family comprises mostly small ascomycetous
fungi, and their metabolites have shown antioxidant and anti-inflammatory activities. Lin
et al. examined the retinoprotective compound Theissenolactone C (LC53), which is a fun-
gal derivate extracted from Theissenia cinerea Y.M. Ju, J.D. Rogers & H.M. Hsieh (Xylaria-
ceae). According to their results, the application exerted a retinal protective effect through
NF-κB inhibition and was highly potent against MMP-9 activities after high-IOP-induced
retinal injury. This suggests a promising drug possibility for glaucoma or ocular-related
medical conditions aributed to retinal ischemia [45]. The results of both above-men-
tioned studies need to be examined in human glaucomatous patients in clinical trials to
obtain evidence-based information about the possible potential in glaucoma complemen-
tary therapy.
9. Apitherapy
9.1. Definitions and Descriptions
Apitherapy is the application of honeybee (Apis mellifera L.) and beehive-related
products such as honey, pollen, propolis, royal jelly, bee bread, bee venom (apitoxin),
beeswax, apilarnil, and beehive air in disease prevention, health promotion, and curative
treatment [8,46–48] (Figure 2). Globally, this is a well-known aspect of traditional medi-
cine that was popularly used in the past much as it is today. According to the oldest hu-
man historical findings, honey collecting dates back some 9000 years. In wrien sources,
its use stretches back to ancient Egypt, and it is also used in Traditional Chinese and Ti-
betan Medicine. Hippocrates, the great ancient Greek physician, described the biological
properties of honey and pollen applied to sores and wounds [8,46,49].
Figure 2. Classification and illustration of products used in apitherapy. (Self-edited and photo-
graphed image. The central image is of Apis mellifera L., courtesy of the photographer, Dr. Gina
Vágó, Bőszénfa, Hungary, 2020.).
Figure 2. Classication and illustration of products used in apitherapy. (Self‑edited and pho‑
tographed image. The central image is of Apis mellifera L., courtesy of the photographer,
Dr. Gina Vágó, Bőszénfa, Hungary, 2020.).
Honey (mel in Latin) is a supersaturated aqueous, slightly acidic (pH 3.2 to 4.5) so‑
lution with high nutritional value collected and processed by various Apis spp. through
repeated digestion and regurgitation of the nectar of plants. The chemical structure of this
pure and functional food is dependent upon geographical and botanical diversity, con‑
taining 70–80% carbohydrates (glucose and fructose), a‑tocopherol, ascorbic acid, pheno‑
lics, amino acids, minerals, vitamins, trace elements, and enzymes such as glucose oxidase,
catalase, and peroxidase [50,51]. Honey can be classied into four clusters based on its ori‑
gin: Pure, monooral honey is derived from a single herb and has a higher market value
when compared with multioral honey, which contains more bioactive compounds from
a variety of herbs. Aromatic honey is a natural and not‑human‑made product using es‑
sential oils or herbal parts to add bioactive components into the base honey. Adulterated
honey (or “pseudo‑honey”) is a totally or partially human‑made product using fructose or
other plant‑based carbohydrates [52–54] (Figure 2).
Propolis is a resinous material collected and produced by Apis spp. from the buds and
exudates of plants, mixed with bee enzymes, pollen, and beeswax. The term originates
from Ancient Greek—“πρó” (before) and “πóλις” (city). This antiseptic–antimicrobial ma‑
terial defends the structure and the colony of the beehive [55].
Pollen is a natural product in the anthers of spermatophytes and has an essential role
in the reproduction of entomophilous (insect‑pollinated) plant species. It is collected by
Apis spp. and utilized as a valuable nutrient, rich in proteins, vitamins, and minerals. Bee
bread (perga) is a special mixture of pollen in the form of granules which is fermented and
agglutinated by nectar and enzymes (e.g., amylase and catalase) secreted by honeybee
salivary glands [48,56].
Royal jelly (some resources reference it as bee milk) is a white and viscous jelly‑like
“super‑food” and is dened as a form of hypopharyngeal and mandibular gland secretion
from the worker bees, consumed by the queen bee and larvae. Royalactin is the main

Sci. Pharm. 2024,92, 16 11 of 17
compound in royal jelly, which allows the morphological change of a larva into the queen
bee. It is widely used as a dietary supplement with various pharmacological uses [57].
Apilarnil is a bee‑related product rich in androgenic substances, obtained from drone
bee larvae, containing dry maer (25–35%), proteins (9–12%), carbohydrates (6–10%), lipids
(5–8%), ash (2%), and 3% other materials. Its bioactivity is mostly aphrodisiac and neuro‑
protective [58,59].
Beeswax (Cera ava, “yellow wax”) is naturally produced by the wax glands of Apis
mellifera L. using honey sugars (fructose, glucose, and sucrose) as raw materials. Puried
or bleached beeswax is referred to as Cera alba (“white wax”) [60].
Notably, bee venom (or apitoxin) is essentially a very complex mixture of natural sec‑
ondary metabolites extracted from Apis mellifera L. containing more than sixty identiable
bioactive components such as peptides, enzymes, biologically active amines, and non‑
peptides. There are several documented health conditions in which bee venom has been
used therapeutically, such as treating arthritis or neurodegenerative disorders. Introduc‑
ing bee venom into the human body by manual injection or by direct living bee stings is
referred to as apipuncture. Bee venom also can be used in topical skin ointments [49,61,62].
9.2. Limitations
The potential benet of bee‑related products is supported by the positive experiences
of a large group of beekeepers and apitherapists, who use these products to treat a wide
range of medical conditions without substantiated scientic evidence. An important factor
associated with apitherapeutic medicines is human safety. Additionally, reasons of con‑
traindications and lack of compliance regarding an allergic history or intolerance against
even smaller amounts of honey, or disliking the taste of pollen and royal jelly, obscure the
issue regarding the actual benets [8,46,47,56,63]. Furthermore, apipuncture treatments
lead to pain and subsequent local or general edema, and in some cases, allergic reactions
have been reported from areas such as South Korea, in which bee venom apitherapy is
traditionally used. Apitherapy practitioners should be trained in managing anaphylactic
reactions in patients until they can be admied to an intensive care unit [56,62,63]. Finally,
the potential risks regarding the consumption of organic bee pollen, honey, etc., include
contamination by fungal mycotoxins, pesticides, or toxic metals. Due to the presence of Bo‑
tulinum toxin, the consumption of honey by toddlers under 1–2 years old must be avoided.
Lastly, the limited amounts of genuine honey samples result in the potential degradation of
herbal proteins and bioactive compounds during the conversion of nectar into honey. On
the other hand, honey contains several other compounds that were not originally present
in the nectar. Therefore, the pharmacological properties of the original herbs and honey
are not consistently equivocal [8,46,47,56,63,64].
9.3. Application in Glaucoma
Even Aristotle (350 BC) mentioned that honey is a good medicine for eye diseases. The
application of honey in glaucoma therapy, according to the medical literature, is mainly
based on the principles of Ayurvedic medicine. Therefore, to reduce the IOP and improve
the ow of aqueous humor, it is recommended to use a solution of honey with Camphora
ocinarum Nees, Zingiber ocinale Roscoe, and Citrus ×limon (L.) Osbeck in the form of
drops for patients with glaucoma. The formula needs further scientic proof due to a
lack of clinical evidence. Okuda et al. experimentally placed honeycombs with honey in
rabbits as an adhesive barrier during glaucoma ltration procedures. The honeycombs
were placed inside the subconjunctival pocket. Lower IOP values and a lower percentage
of inammatory postoperative complications were observed compared to the other group
of rabbits treated with mitomycin C in trabeculectomy [54]. In TCM, dense honey‑based
solutions are given to glaucomatous patients to drink in case of elevated IOP. The honey is
not equivalent to glycerol or mannitol, but osmotically active substances have been applied
since ancient times to reduce the IOP [65].

Sci. Pharm. 2024,92, 16 12 of 17
10. Hirudotherapy
10.1. Denitions and Description
Hirudotherapy (or Medicinal Leech Therapy) is the application of farm‑cultured
medicinal leeches (Hirudo spp.) to a human host’s skin, which is used to treat several
disorders and has been in existence for thousands of years, throughout the history of hu‑
man ethnomedicine and in every culture spanning the globe. Hirudotherapy reached its
therapeutic peak of popularity on the European continent in the 17th century, and it has
since been revived in the last decade among complementary human and veterinary forms
of medicine. Today, more than 300 prescriptions containing Hirudo spp. exist in the clinical
practice of Traditional Chinese Medicine, a practice lasting some 2000 years, referred to as
Shu�zhìor M�huáng. Hirudo medicinalis L. saliva has more than twenty reported bioac‑
tive compounds (the most relevant include the following ingredients: hirudin, bdellin,
apyrase, eglin, destabilase, hyaluronidase, lipase, esterase, anti‑elastase, and calin) as va‑
sodilative, anti‑inammatory, analgesic, antimicrobial, and anticoagulant agents [66–72].
The application of the bioactive components of Hirudo medicinalis L. in dermal ointments
is used to alleviate the symptoms of crural varices or skin hematomas and is also a form
of hirudotherapy.
10.2. Limitations
The complications of hirudotherapy, according to various studies, are classied into
ve clusters—infection (51%), allergy (21%), prolonged bleeding (15%), migration to dif‑
ferent body parts (8%), and other (5%). Bacterial infection is inevitable without the use of
prophylactic antibiotics (ciprooxacin, sulfamethoxazole/trimethoprim, and second‑ and
third‑generation cephalosporins). The most common allergic reactions are skin erythema,
edema, and the formation of a central black eschar on the skin, for instance. Prolonged
bleeding is dened as bleeding continuously for more than two hours despite compres‑
sion, which can cause severe anemia and hemorrhagic shock. A hirudotherapist should
be aware of contraindications—hemophilia, leukemia, arterial insuciency, hypotension,
septic disorders, cachexia, hepatobiliary diseases, HIV infection, and the use of antico‑
agulants and immunosuppressants—while avoiding the treatment of pregnant or lactat‑
ing individuals and children under sixteen years of age. The skin surfaces of the epi‑
gastric, liver, spleen, and gluteal regions must be avoided. Daily clinical assessment is
necessary [66,72,73].
10.3. Application in Glaucoma
Currently, in some countries of Eastern Europe, Russia, and South Asia (Indian penin‑
sula, Sri Lanka), hirudotherapy is ocially recognized as a classic alternative therapy for
diseases and symptoms such as glaucoma. In South Asia, hirudotherapy (Irsal‑e‑Alaq), as
a part of Unani medicine (which has its roots in Ancient Greco‑Roman medicine), can oer
a complementary approach for all forms of glaucoma (maa‑e‑aksa). The hirudotherapists
place 2–4 leeches on the lower temporal and supraorbital regions. An important reduction
in the IOP is usually observed in about 3 h. A signicant reduction in the IOP and improve‑
ments in visual acuity and ocular hydro‑ and hemodynamics were observed by Belezkaya
et al. after a course of hirudotherapy (2–6 leeches daily for 2 weeks). They recommend it
in the terminal stages of glaucoma, when almost all therapeutic and surgical methods of
treatment are unsuccessful. However, while hirudotherapy was able to prevent complete
blindness in some studies, it lacks scientic evidence for validation. Therefore, hirudother‑
apy is generally not recommended as a complementary cure for glaucoma [72,73].
11. Systematic Overview and Future Prospects
Medicine is a continuously developing universal system comprising all the holistic ap‑
proaches regarding human pathology–pathophysiology and various therapeutic methods.
The most recently ocially recognized medicine is referred to as EBM. Those countries
in which parallel medical systems exist are characterized as “Western Medicine” or “Allo‑

Sci. Pharm. 2024,92, 16 13 of 17
pathic Medicine” to EBM. It is universally described that every medical system possesses
its own pharmaceutical practice based on plants, fungi, animal products, and minerals.
Phytomedicinals are the most ancient materials used in disease prevention, health promo‑
tion, and curative treatment; therefore, phytotherapy (or herbalism) is a major element
in pharmacy. In countries in which phytotherapy is an ocially recognized therapeutic
process with a state‑accredited examination, including certication, phytotherapic prac‑
tice consists of subspecializations including aromatherapy, mycotherapy, and apitherapy.
In the authors’ professional opinion, gemmotherapy, as a new entity, is also a branch of
phytotherapy according to its products. BFRs, sold mostly in pharmacies, are plant‑based
alcoholic tinctures; however, the pharmacologic agents and the philosophy of the therapy
have a homoeopathic basis. Therefore, we suggest Bach Flower Therapy as a frontier eld
including both homoeopathy and phytotherapy. Fungi also possess pharmacologically
active components applied in human and veterinarian medicine; therefore, mycotherapy
is also growing in importance. Schüssler Cell/Tissue Salts contain homeopathically poten‑
tized doses of essential minerals [74] and are not plant‑based inorganic products; how‑
ever, their manufacturing process is homoeopathic‑based. Additional characteristics are
not available, due to the lack of clinical trials and scientic evidence associated with the
Schüssler Salts, which can be considered as a limitation. Distinctly, Figure 3demonstrates
the systematic position of each complementary medical science.
Sci. Pharm. 2024, 92, x FOR PEER REVIEW 14 of 18
Figure 3. Positions of plant-based therapy systems and their frontier areas in contemporary medi-
cine—self-edited chart. Applied human and veterinary medicine systems holistically consist of the
subdivisions “Western” or “Allopathic” EBM and complementary medicinal systems (TCM, Ayur-
vedic medicine, Tibetan–Mongolian medicine, anthroposophic medicine, etc.).
The rate of regular use of complementary therapies among the main European coun-
tries hovers between 25% and 49% [6]. In the majority of these countries, naturopathic
medical methods have not been officially recognized, yet an increasing demand by both
patients and healthcare professionals is distinctly observed [6]. Complementary medical
practices consist in the application of several traditional and well-established herbal, min-
eral, or animal-related substances, mostly taught throughout pharmaceutical education.
Moreover, these products are found mostly in pharmacies in the form of dietary supple-
ments, herb-based medications, foods (filtered teas), and cosmetics (essential oils, etc.).
[8]. In the future, more and more bioactive compounds of plant and animal origin may
become official medicines. However, identifying the right formulation, the purity of the
active ingredients, and the possibility of illegal additives and synthetic counterfeiting that
prioritize profit could be a serious problem. Supervision of natural medicines is important
to ensure that they remain safe for patients. Reliable pharmacobotanic analytical tech-
niques (such as high-performance liquid chromatography (HPLC), high-performance
thin-layer chromatography (HPTLC), liquid chromatography–tandem mass spectrometry
(LC-MS/MS), nuclear magnetic resonance (NMR) analysis, capillary electrophoresis (CE),
thin-layered chromatography combined with surface-enhanced Raman spectroscopy
(TLC-SERS), and densitometry) [75] are already at our service and will play an increas-
ingly prominent role in the future.
12. Conclusions
The rising popularity and the trends of medicinal products coming onto the market
cannot escape the aention of ophthalmologists, as their patients suffering from eye dis-
eases are increasingly looking for such products. According to surveys, a significant num-
ber of glaucoma patients are applying complementary medication without disclosing it to
their treating ophthalmologist or pharmacist. Most of them still lack knowledge of the
appropriate evidence and side effect profiles. In this article, we proposed a novel classifi-
cation system highlighting appropriate definitions to demonstrate the complementary
Figure 3. Positions of plant‑based therapy systems and their frontier areas in contemporary
medicine—self‑edited chart. Applied human and veterinary medicine systems holistically consist
of the subdivisions “Western” or “Allopathic” EBM and complementary medicinal systems (TCM,
Ayurvedic medicine, Tibetan–Mongolian medicine, anthroposophic medicine, etc.).
The rate of regular use of complementary therapies among the main European coun‑
tries hovers between 25% and 49% [6]. In the majority of these countries, naturopathic
medical methods have not been ocially recognized, yet an increasing demand by both
patients and healthcare professionals is distinctly observed [6]. Complementary medical
practices consist in the application of several traditional and well‑established herbal, min‑
eral, or animal‑related substances, mostly taught throughout pharmaceutical education.
Moreover, these products are found mostly in pharmacies in the form of dietary supple‑
ments, herb‑based medications, foods (ltered teas), and cosmetics (essential oils, etc.) [8].
In the future, more and more bioactive compounds of plant and animal origin may become
ocial medicines. However, identifying the right formulation, the purity of the active in‑
gredients, and the possibility of illegal additives and synthetic counterfeiting that prioritize
prot could be a serious problem. Supervision of natural medicines is important to ensure

Sci. Pharm. 2024,92, 16 14 of 17
that they remain safe for patients. Reliable pharmacobotanic analytical techniques (such
as high‑performance liquid chromatography (HPLC), high‑performance thin‑layer chro‑
matography (HPTLC), liquid chromatography–tandem mass spectrometry (LC‑MS/MS),
nuclear magnetic resonance (NMR) analysis, capillary electrophoresis (CE), thin‑layered
chromatography combined with surface‑enhanced Raman spectroscopy (TLC‑SERS), and
densitometry) [75] are already at our service and will play an increasingly prominent role
in the future.
12. Conclusions
The rising popularity and the trends of medicinal products coming onto the market
cannot escape the aention of ophthalmologists, as their patients suering from eye dis‑
eases are increasingly looking for such products. According to surveys, a signicant num‑
ber of glaucoma patients are applying complementary medication without disclosing it
to their treating ophthalmologist or pharmacist. Most of them still lack knowledge of the
appropriate evidence and side eect proles. In this article, we proposed a novel classi‑
cation system highlighting appropriate denitions to demonstrate the complementary
pharmacy‑related medical sciences. The proposed systematic charts demonstrating the
position of each mainstream complementary therapy in the applied medical sciences are
distinctly unique, since there is no trace of any similar relevant illustration or resource
throughout the published international literature. Healthcare professionals should be pre‑
pared for the popular pharmacy‑related complementary sciences to serve the needs of their
patients, while alerting them to the limitations, hazards, and contraindications of these
products and interventions.
Author Contributions: T.R.: Conceptualization, Methodology, Investigation, Resources, Writing,
Visualization. A.C.: Professional review and editing. All authors have read and agreed to the pub‑
lished version of the manuscript.
Funding: This research received no external funding.
Institutional Review Board Statement: Not applicable.
Informed Consent Statement: Not applicable.
Data Availability Statement: No new data were created or analyzed in this study. Data sharing is
not applicable to this article.
Acknowledgments: The authors express their gratitude to Gina Vágófor the photographed image
used for Figure 2.
Conicts of Interest: The authors declare no conicts of interest.
Abbreviations
AMD Age‑Related Macular Degeneration
BFRs Bach Flower Remedies
EBM Evidence‑Based Medicine
EMA European Medicines Agency
ESCOP European Scientic Cooperative on Phytotherapy
ET‑1 Endothelin‑1
IOP Intraocular Pressure
MMP‑9 Matrix Metalloproteinase‑9
NF‑κB Nuclear Factor Kappa B
NTG Normotension Glaucoma
PACG Primary Angle Closure Glaucoma
POAG Primary Open‑Angle Glaucoma
RPE Retinal Pigment Epithelium
TCM Traditional Chinese Medicine
WHO World Health Organization

Sci. Pharm. 2024,92, 16 15 of 17
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