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Medicinal Plants – Chemical, Biochemical, and Pharmacological Approaches
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Biomolecules Produced by
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Chapter 19
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Use of Medicinal Plants:
Interindividual Variability of
Their Effects from a Genetic and
Anthropological Perspective
Alda Pereirada Silva Oliveira, Mariado Céu Costa
and Manuel PiresBicho
Abstract
T
he use of plants for nutritional and therapeutic purposes has been constant over
the centuries. The variability of enzymatic activity between individuals and populations in an attempt to adapt has been a conditioning mechanism, reflected in the
incidence and prevalence of certain diseases, possible adverse effects of plant-derived
nutrients and their interaction with medications, in addition to interference in natural
selection and consequent geographical distribution of specific genetic polymorphisms in harmony with indigenous medicinal plants. The metabolizer type may
influence the anticancer protective effect of certain plant-derived constituents, with
interindividual variability to be considered. This chapter will deepen and develop the
role of using plants in different geographic areas and populations over the centuries
in producing the genetic variability of the metabolism of plant constituents in the
context of environmental adaptation and ecogenetics. Possible therapeutic/adverse
effects due to this variability will be discussed.
Keywords: medicinal plants, nutrigenetics, pharmacogenetics, ecogenetics, genetic
variability, anthropology
. Introduction
Since time immemorial, medicinal plants have been a fundamental aspect of
human health and continue to play a vitally important role in different cultures
worldwide. Primitive medicine before the Christian era was based from a therapeutic
point of view, on a powerful psychological component supported by magical beliefs
and rites combined with medicinal plants.
Today, however, it is known that medicinal plants’ effects can vary significantly
between individuals and interfere with medicinal substances. This variability involves
aspects ranging from inherent to the medicinal plant to complex genetic and anthropological factors.
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The interindividual variability of the effects of medicinal plants arises from the
complex interaction between the plant phenotype and genetic and anthropological
factors specific to each individual and community. It is essential to recognize and
respect this variability in the use of medicinal plants for health purposes.
Nutrigenetics and pharmacogenomics make it possible to identify genetic markers
associated with responses to specific food or medicinal plants. The patient’s genetic
background, cultural environment, and lifestyle must be considered when recommending medicinal plants or herbal medicines.
Furthermore, the importance of collaboration between therapists from alternative
or traditional approaches and modern healthcare providers stands out for a holistic
and personalized approach to recommending herbal medicines, within integrative
medicine programs.
It is currently recognized as imperative to understand the modes of interaction
between different medicines from conventional and traditional healthcare systems
when used in treatment combinations. Both synthetic and natural medicinal chemical
entities are metabolized by the same enzyme systems in the human body, resulting in
pharmacokinetic and pharmacodynamic interactions, the properties of which are still
largely unknown/unquantified.
This chapter will address these three aspects, plant, individual, and anthropological,
which lead to interindividual variability and its effects, highlighting the growing importance of medicine that respects variability and, increasingly, is centered on the person.
. Medicinal plant variability
The variability of the response to therapeutically beneficial plants begins with its
natural variability. The plant has variability depending on its phenotype, the seed
quality, the climatic conditions, and the terrain where it grows.
Chemical variation in a plant sample can influence the effectiveness of medicines
formulated against a specific disease. Therefore, selecting raw materials based on
their chemical composition is a prerequisite [1].
Preparations based on medicinal plants still require detailed scientific analytical studies for quantification of markers and active ingredients or just for chemical
standardization purposes, so that they can guarantee the reproducibility of their
effects in in vitro biological tests and in pre-clinical animal models. For the clinical
evaluation stage, quality control is a completely indispensable practice in accordance
with international standards.
The already validated quality control methods for some medicinal plants
are present in monographs found in all European Pharmacopoeia: United
States Pharmacopoeia, Chinese Pharmacopoeia, WHO Monographs, Japanese
Pharmacopoeia, Brazilian Pharmacopoeia—they are universal reference works,
updated in all countries on different continents.
Geographical origin and climatic conditions are the notable factors that affect the
metabolome of a plant. Plants are adapted to different geographic, climatic, and soil
conditions through genotypic and phenotypic changes. Genotypic change also influences plants’ production and accumulation of secondary metabolites [2, 3].
Although the specialized metabolic profile is unique to individuals within a species
or a closely related taxonomic group, it can be altered if its biosynthetic pathways are
influenced by environmental conditions such as climate, soil, pathogen infection,
and pest infestation. Therefore, regional variation may be due to different mixtures
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or proportions of active compounds, which links the geography and climate of the
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medicinal plant habitat.
Genetic diversity can help evaluate the evolution and conservation of varieties
[4]. Genetic diversity is generally estimated through DNA sequences (polymorphisms
between varieties) and cytological and morphological markers. However, morphological characteristics are often influenced by the environment. Therefore, molecular
markers are relatively more stable and popular than morphological markers [5].
Inbreeding and evolution events can alter allele frequency and reduce genetic diversity [6]. Therefore, it is vital to accurately estimate the correlation between different
germplasm resources to ensure high-efficiency utilization and management and to
maintain adequate genetic variability for breeding diverse plant varieties [7].
Genetic diversity and population structure analysis have examined various
plant species. An analysis of 1151 ramie germplasms using SSR and phenotypic
markers reveals that the genetic diversity of wild germplasms is greater than that of
domesticated germplasms. This finding of diversity and subpopulations [8] has been
observed in several plants such as cannabis [9], sunflower from Iran [10], beans from
Brazil [11], allowing technological advances. This wealth of variability is substantial
and needs to be preserved by this observation of genetic diversity and the population
structure of plants, whether they are sources of medicines, nutrition, or fiber.
. The case for turmeric (Curcuma longa L.)
Curcuma longa
L., rhizoma (turmeric root; Figure
) with long-standing use, was
approved in Europe as a traditional herbal medicinal product for the relief of digestive disturbances, such as feelings of fullness, slow digestion, and flatulence [12].
However, there are also studies showing a potential role as an immune modulator and
anti-inflammatory [13–15].
The characteristic compounds are curcuminoids, of which curcumin makes up
approximately 90% of the curcuminoid content in turmeric [16]. Chemically, curcumin is a diferuloylmethane, i.e., a beta-diketone derived from methane in which
two of the hydrogens are substituted by feruloyl groups (Figure
). These phenolic
groups in the structure of curcumin explain the ability of curcumin to eliminate
oxygen-derived free radicals [17]. However, as generally observed in medicinal plants’
bioactive markers, the curcumin content of the Curcuma longa rhizome is very low, as
it varies from 0.6 to 5% of the dry mass [18].
Recently, Chen et al. [19] studied the genetic and chemical variability among five
Curcuma species, and the results showed that the similarity of the chemical composition of medicinal plants was the primary evidence for the selection of the original
plants of Curcuma medicinal materials [19]. In this study, the ITS2 and trnK intron
gene sequences were used to analyze the genetic distance between different Curcuma
species—chemical composition by HPLC. The authors found that the correlation
between genetic distance based on finite genetic sequence and chemical variability
showed a relatively low level. The pharmacodynamic potential of new species can
be predicted by analyzing the genetic distance between them of the same genus and
known medicinal plants.
According to this research, genetic distance data could provide some reference
clues for finding new medicinal plant resources.
The huge variety of secondary metabolites produced by plants used to treat vari-
ous diseases and illnesses are often difficult to obtain in large quantities, limiting their
industrial use.
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Figure 1.
Curcuma plant (hand-drawn illustration: In Franz Eugen Köhler, Köhler’s Medizinal-Pflanzen (1887)).
Figure 2.
Chemical structure of curcumin, (1E,6E)-1,7-bis(4-hydroxy-3-methoxyphenyl)hepta-1,6-diene-3,5-dione.
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