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Use of Medicinal Plants: Interindividual Variability of Their Effects from a Genetic…
ITexLi.113841
for activating vitamin K, a cofactor of clotting factors. It was found that individuals
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with CT and TT genotypes of VKORC1 present a reduction in warfarin activity when
administered with cranberry extract by 22% and 11%, respectively [77]. This case is
an example of genetic polymorphisms in the pharmacodynamic pathway that may
also be involved in plant-drug interactions.
Numerous interactions between plants and medicines have been described and
explained by the pharmacodynamic and metabolization process [78–83] where CYP
play a role (Tables
Pharmacodynamics (PD) and pharmacokinetics (PK) are hard to predict in all
–).
patients, and best practice involves the use of standard dosing based on weight and
therapeutic drug monitoring (TDM).
Pharmacodynamics (PD) and pharmacokinetics (PK) are hard to predict in all
patients, and best practice involves the use of standard dosing based on weight and
therapeutic drug monitoring (TDM). Pharmacogenetics (PG) is the use of genetic
screening to predict metabolic responses to different drugs and enables more accurate
predictions of PD and PK to be made. The biggest challenge in reducing metabolic
Pharmacodynamic and/or
pharmacokinetic changes
Increased concentration of
*
ARV
Concentration reduction Alteration of GPP Celiprolol Therapeutic failure
Concentration reduction Inhibition of CYP1A2 Antipsychotics and
Increased concentration Unknown Sulfasalazine Increased ADR risk
Synergistic effect Unknown Warfarin Increased
Increased concentration Unknown Palbociclib Increased ADR risk
Concentration reduction Talinolol Therapeutic failure
Increased concentration Inhibition of CYPA4/5 Tacrolimus Increased ADR risk
Concentration reduction Inhibition of GPP Azatioprin,
Increased concentration Inhibition of CYP3A4 Everolimus Increased ADR risk
Reduced bioavailability (dose
dependant)
References: [, –].
*
ARV: antirretrovirals.
**
ADR: adverse drug reaction.
Pharmacokinetic
Inhibition of CYP3A4
(intestinal)
Inhibition of CYP2D6 Ritonavir
Inhibition of GPP
Inhibition of GPP Digoxin Therapeutic failure
Examples of
influenced drugs
Indinavir Increased ADR risk
Cobicistat
antidepressants
Capecitabine
Enzalutamide
ciclosporin
Probable outcome
Therapeutic failure
hemorrhagic risk
Hepatotoxicity
**
Table 1.
Curcuma: approved use for dyspeptic problems [12]. Some studies show a potential role as an immune modulator
and anti-inflammatory [73, 82].
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Pharmacodynamic and/or
pharmacokinetic changes
Increased bioavailability Unknown Antirretrovirals Increased ADR
Increased AUC Inhibition of GPP Simvastatin Increased ADR
Inhibition of folic acid
absortion
Antagonism Unknown Warfarin Therapeutic
Increased AUC Inhibition of OATP1A1 and
Reduced bioavailability Nadolol Therapeutic
Decreased absorption Inhibition of OATP1B1,
Decreased absorption Inhibition of MATE1,
Antagonism Unknown Lisinopril Therapeutic
Increased bioavailability Inhibition of GPP Tacrolimus,
Decreased bioavailability Inhibition of OATP1B1,
References: [, –, –].
*
OCT, OCT: organic cation influx transporters. They are responsible for the hepatic and renal transport of
Met for min.
**
ADR: adverse reaction to the drug.
Pharmacokinetic
OATP1A2
OATP1B3
MATE 2
Inhibition of OCT1, OCT2
(when in interaction with
Metformin)
OATP2B1, OATP1A2 (gut)
Activation of OATP1B3
Examples of
influenced drugs
Tacrolimus,
ciclosporin
Beta-blockers Increased ADR
Fluoroquinolones Increased ADR
Statins Increased ADR
Atorvastatin Increased ADR
Atorvastatin Increased ADR
*
ciclosporin
Rosuvastatin Therapeutic
Probable
outcome
**
risk
Toxicity/
therapeutic
failure
risk
failure
risk
risk
risk
failure
risk
risk
failure
Increased ADR
risk
failure
Table 2.
Green tea: approved use [52] to combat asthenia and also described as having anti-inflammatory, antibacterial,
and antiviral potential [87].
instability arises when we face different crops, plant selection, preparation methods
and dosage that can vary and contribute to variations in the effectiveness of herbal
medicines.
Anthropological studies can help preserve, understand, and respect the cultural
context of practices in the use of medicinal plants and understand aspects linked to
the variability of responses associated with the environment, adaptability, and the
evolution of the human species.
Use of Medicinal Plants: Interindividual Variability of Their Effects from a Genetic…
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Pharmacodynamic and/or
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pharmacokinetic changes
Risk of increased viral load Inhibition of CYP3A4 ARV
Concentration reduction CYP3A4 induction Midazolam Therapeutic
Concentration reduction Unknown Imunossupressors Therapeutic
References: [, –, , , , ].
*
ARV: antirretrovirals.
**
ARD: adverse reaction to the drug.
Table 3.
Echinacea-approved use for common cold and acne [93].
Pharmacokinetic
Inhibition of CYP1A2,
CYP2C9
Examples of
influenced drugs
*
Caffeinne, tolbutamid ADR risk
Warfarin Therapeutic
Probable
outcome
Therapeutic
failure
**
failure
failure
failure
. The anthropological case of cannabis
Cannabis has been used for various purposes across cultures and throughout
history. It has been used not only for medicinal but also for recreational, spiritual, and
industrial purposes.
Different cultures have developed unique traditions and practices related to cannabis consumption. Over time, and in different rules, cannabis has been used as an
analgesic, for pain relief, as an anti-inflammatory, and to treat various medical conditions. Traditional knowledge about the properties and aspects linked to the uses of
the plant has been observed to vary between different cultures, often linked to beliefs
and practices that are not only cultural but also religious and spiritual. For example,
Rastafarians use it as a sacrament and certain Native American tribes use it in sacred
rituals. Industrial uses such as hemp fiber production are historically known for
manufacturing textiles, ropes, paper, and other products [95]. However, recreational
use for its psychoactive properties in many parts of the world, both historically and
in contemporary times, is recognized as the “anthropological marker of cannabis,”
although different varieties and methods of consumption have emerged based on
cultural preferences. The legal status and social acceptance of cannabis vary widely
from one region to another. Some countries and states have legalized its recreational
and medicinal use, while others maintain strict prohibitions [96].
Gathering data to develop medicinal cannabis use may lead to two types of products: herbal medicines based on padronized and/or quantified extracts on one side and
medicines based on specific cannabinoids or combinations of the cannabinoids on the
other. In any case, an integrated systematic approach shall consider the interindividual
variability of their effects from a genetic and anthropological perspective (Figure ).
Finally, high-quality evidence on the short- and long-term safety of medicinal
cannabis is still lacking. Although there is no known level of cannabinoid ingestion
that will result in a toxic or lethal dose in humans, it is reported that the median lethal
dose of THC in animal models ranges from 800 to >9000mg/kg (depending on the
species). Thus, the estimates of a lethal dose of THC for a 70kg human range up to
>15g, and for CBD, doses of ca. 1000mg/kg have been tolerated in humans [97, 98].
Medicinal Plants – Chemical, Biochemical, and Pharmacological Approaches
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Figure 7.
Research on the therapeutical potential of specific cannabis strains.
. Conclusions
In conclusion, understanding the interindividual variability of the effects of
medicinal plants from a genetic and anthropological perspective is crucial to maximizing their benefits while minimizing potential risks. This approach can contribute
to developing personalized and culturally sensitive herbal medicine practices based
on nutrigenetics and ecogenetics aspects.
In the food supplements market, numerous plants are freely available for sale that
people use, either by prescription or self-medication, intending to treat a health problem and often in combination with chemically synthesized medicines. Due to their
multifactorial variability, this aspect denotes the concern and attention necessary to
guarantee herbal supplements’ standardization and quality control.
Furthermore, this guarantee is fundamental for the safety of consumers and
healthcare providers, who already have the factor of interindividual variability to
consider in responding to the use of medicinal plants and possible interactions with
medications.
The domain of pharmacogenetics and pharmacogenomics, through the understanding of mechanisms of genetic variations and associations of differences in physiological actions of medicinal plants, allows us to understand how the interindividual
variability, in part due to genetic composition, added to the genotypic biodiversity
inherent to plants, can influence their physiological effects on the human body. This
information can help personalize herbal remedies in a person-centered, holistic
healthcare professional approach.
Use of Medicinal Plants: Interindividual Variability of Their Effects from a Genetic…
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