Bioenhancers In Pharmaceuticals and Nutraceuticals: A Gateway to Improved Pharmacokinetics and Pharmacodynamics

INTERNATIONAL JOURNAL OF RESEARCH AND SCIENTIFIC INNOVATION (IJRSI)
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Bioenhancers In Pharmaceuticals and Nutraceuticals: A Gateway to
Improved Pharmacokinetics and Pharmacodynamics

Sirichandana Kurakual, Meghana Singampalli, Swathi Putta

Raghu College of Pharmacy, Dakamarri, Visakhapatnam, India

DOI: https://doi.org/10.51244/IJRSI.2025.120800270

Received: 24 Sep 2025; Accepted: 30 Sep 2025; Published: 04 October 2025

ABSTRACT

Bioenhancers are compounds that improve the bioavailability and therapeutic efficacy of co-administered
drugs and nutrients without producing significant pharmacological effects at their own administered dose.
They act by modulating drug absorption, metabolism, distribution, and excretion, thereby enhancing both
pharmacokinetic and pharmacodynamic outcomes. Naturally derived phytochemicals, such as alkaloids
(piperine, capsaicin), terpenoids (menthol, limonene), flavonoids (quercetin, naringin), glycosides
(glycyrrhizin, ginsenosides), phenolics (curcumin, eugenol), and essential oils, are widely studied for their
bioenhancing potential, while synthetic agents like surfactants and bile salts contribute to pharmaceutical
formulations. Piperine remains the most extensively reported bioenhancer, shown to increase the systemic
availability of several drugs and nutraceuticals, including rifampicin, phenytoin, curcumin, resveratrol, and
CoQ10. Other bioenhancers, such as quercetin and glycyrrhizin, potentiate therapeutic effects by overcoming
multidrug resistance, extending plasma half-life, and improving membrane permeability. By enabling dose
reduction, minimizing side effects, and reviving poorly bioavailable drug candidates, bioenhancers hold
significant promise in pharmaceuticals, nutraceuticals, and modern drug delivery systems.

INTRODUCTION

Bioenhancers are compounds that significantly increase the bioavailability and bioefficacy of active substances
with which they are co-administered, without exerting any pharmacological activity of their own at the
administered dose (Wagner et al., 2011). The concept of bioenhancement has gained considerable importance
in both modern pharmacology and traditional medicine, particularly in the context of optimizing therapeutic
regimens and reducing the dosage requirements of drugs (Khajuria et al., 2002). These agents may influence
the absorption, metabolism, distribution, or excretion of drugs and nutrients, thereby improving their
pharmacokinetic and pharmacodynamic profiles (Johri & Zutshi, 1992).

The scope of bioenhancers extends beyond conventional allopathic drugs to include vitamins, nutrients, and
even toxins, depending on their mechanism of action (Wagner et al., 2011). A well-studied example is piperine,
an alkaloid derived from Piper nigrum (black pepper) and Piper longum (long pepper), which enhances the
bioavailability of several nutrients such as beta-carotene, vitamin A, vitamin B6, and coenzyme Q10 (Badmaev
et al., 2000; Lambert et al., 2004). In pharmacological contexts, piperine has been reported to increase the
plasma concentration and therapeutic effectiveness of drugs such as phenytoin, theophylline, and propranolol
(Bano et al., 1991; Atal et al., 1985). Interestingly, piperine has also been shown to affect the absorption of
toxins such as aflatoxin B1, raising implications for both therapeutic and toxicological outcomes (Zhou et al.,
1999).

It is important to distinguish between bioavailability and bioefficacy. Increased bioavailability refers to the
higher concentration of a drug or nutrient reaching systemic circulation, making it more available for
pharmacological action (Shargel & Yu, 2015). In contrast, increased bioefficacy relates to the enhancement of
the therapeutic effect of a drug, which may occur as a result of improved bioavailability or through other
pharmacokinetic and pharmacodynamic modifications (Wagner et al., 2011). Thus, bioenhancers hold potential
for reducing drug dosage, minimizing side effects, and improving overall treatment outcomes.

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Classification of Bioenhancers

Bioenhancers can be classified based on their origin, chemical nature, and mechanism of action. The most
widely studied bioenhancers are of natural origin, particularly phytochemicals derived from medicinal plants,
though some synthetic agents also exhibit bioenhancing properties (Atal et al., 1985; Johri & Zutshi, 1992).

Alkaloids: The best-known examples include piperine from Piper nigrum and Piper longum, which enhances
the bioavailability of nutrients (e.g., vitamin A, beta-carotene) and drugs (e.g., phenytoin, propranolol,
rifampicin) primarily by inhibiting drug-metabolizing enzymes such as CYP3A4 and P-glycoprotein (Bano et
al., 1991; Khajuria et al., 2002). Other alkaloids like capsaicin from chili peppers have also demonstrated
bioenhancer activity through similar mechanisms (Reyes-Escogido et al., 2011).

Terpenoids and Terpenes: Compounds such as menthol (from peppermint) and limonene (from citrus fruits) act
as penetration enhancers by altering membrane fluidity, improving drug permeability across biological barriers
(Cornwell & Barry, 1994).

Flavonoids and Polyphenols: Flavonoids like quercetin and naringin modulate drug transporters and metabolic
enzymes, thereby enhancing the pharmacokinetic profiles of several drugs (Shen et al., 2012). Quercetin, for
instance, inhibits CYP3A4 and efflux transporters, increasing the systemic exposure of co-administered drugs.

Glycosides and Saponins: Compounds such as glycyrrhizin from licorice and ginsenosides from ginseng exert
bioenhancing effects by modulating intestinal permeability and enzyme activity (Gupta et al., 2017).

Fatty Acids and Essential Oils: Medium-chain fatty acids and oils like eugenol from clove oil can enhance
drug solubility and absorption, making them useful in formulation strategies (Pawar et al., 2011).

Synthetic and Semi-synthetic Agents: In addition to phytochemicals, certain excipients like surfactants (e.g.,
polysorbates, bile salts) and co-solvents function as bioenhancers in drug formulations by improving solubility,
permeability, and stability (Lo, 2016).

Thus, bioenhancers represent a diverse group of molecules with varying mechanisms of action, including
enzyme inhibition, modulation of drug transporters, and alteration of membrane dynamics, offering
opportunities to improve therapeutic efficacy and safety.

Table 1: Classification of Bioenhancers

classes Examples
Mechanism of

Action
Therapeutic
Relevance

References

Alkaloids

Piperine (Piper
nigrum),

Glycyrrhizin
(Glycyrrhiza

glabra)

Inhibition of
CYP450 enzymes

(CYP3A4,
CYP2C9) and

UDP-glucuronyl
transferases →
reduces drug
metabolism

Enhances the
bioavailability of

curcumin,
rifampicin, and

phenytoin

Shoba G.,
1998

Cao H.,

2012

Terpenoids / Terpenes
Limonene,

Carvone, Borneol

Alter membrane
fluidity and

permeability;
modulate transport

proteins

Improve intestinal
uptake of

hydrophobic drugs

Regan J.,
2008

Orr HJ., 2006

Flavonoids / Polyphenols Quercetin,
Naringin,

Inhibit CYP3A4,
CYP2C9, and

Enhance absorption
of anticancer drugs,

Ni F., 2018

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Catechins efflux pumps (P-
glycoprotein,
BCRP, MRP)

antivirals, and
nutraceuticals

Soardi FC.,
2008

Fatty Acids / Lipids
Oleic acid,

Linoleic acid,
Phospholipids

Improve solubility,
micelle formation,

and lymphatic
transport

Enhance absorption
of lipophilic drugs
and nutraceuticals

Rodrigo E.,
2006

Tournier N.,

2010

Saponins
Dioscin,

Glycyrrhizin

Increase
membrane

permeability;
interact with
cholesterol in
membranes

Improve uptake of
peptides, antivirals,

and antibiotics

Erfani M.,
2012

Enzyme Inhibitors
Piperine,
Quercetin

Block Phase I
(CYP450) and
Phase II (UGT)

metabolism

Extend the half-life
and systemic

exposure of co-
administered drugs

Shoba G.,
1998

Nah T.,2013

Efflux Pump Inhibitors
Naringin,
Quercetin,
Resveratrol

Inhibit P-gp,
BCRP, and MRP

transporters

Overcome
multidrug resistance

in cancer and
infections

Bugatti
V.,2019

Sheweita SA.,
2011

Permeation Enhancers
Terpenes,

Borneol, DMSO

Disrupt tight
junctions and lipid

bilayers in the
intestines

Improve absorption
of hydrophilic and
macromolecular

drugs

Regan J.,
2008

Onakoya OA.,
2018

Solubility/Absorption
Enhancers

Phospholipids,
Fatty acids

Improve drug
dissolution,

micellization, and
transport

Enhance
bioavailability of

poorly soluble
nutraceuticals (e.g.,
curcumin, CoQ10)

Tournier N.,
2010

Zhu W., 2014

Pharmacodynamic
Synergists

Glycyrrhizin,
Curcumin,
Piperine

Act synergistically
with drugs to

potentiate
therapeutic effects

Enhance the
efficacy of

antivirals, anticancer
drugs, and anti-
inflammatories

Cao H., 2012

Laohapand C.,
2015

Role of Bioenhancers According to Therapeutic Potency

The role of bioenhancers in improving therapeutic potency lies in their ability to increase the efficacy of drugs,

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nutrients, and natural compounds without altering their intrinsic pharmacological activity. By enhancing
bioavailability, absorption, and systemic circulation, bioenhancers enable the administration of lower drug
doses to achieve the same or greater therapeutic effects, thus reducing toxicity and adverse reactions (Atal et
al., 1985; Johri & Zutshi, 1992). For example, piperine co-administration with rifampicin in tuberculosis
therapy increases plasma drug concentration, thereby enhancing antibacterial potency and potentially lowering
the required dose (Khajuria et al., 2002). In oncology, flavonoids such as quercetin potentiate the anticancer
activity of chemotherapeutic agents by inhibiting multidrug resistance (MDR) transporters, improving drug
accumulation within tumor cells (Shen et al., 2012). Similarly, glycyrrhizin from licorice improves the
therapeutic efficacy of corticosteroids by prolonging their plasma half-life and enhancing anti-inflammatory
effects (Gupta et al., 2017).

In addition to small-molecule drugs, bioenhancers have shown promise in nutraceuticals by increasing the
potency of poorly bioavailable compounds such as curcumin, resveratrol, and coenzyme Q10 (Badmaev et al.,
2000; Lambert et al., 2004). By improving intestinal absorption and reducing first-pass metabolism,
bioenhancers amplify the therapeutic action of these natural compounds, making them more clinically relevant.
Importantly, bioenhancers also help in the revival of abandoned drugs with poor pharmacokinetics by making
them therapeutically viable (Wagner et al., 2011). Thus, bioenhancers contribute significantly to improving
therapeutic potency across diverse therapeutic areas, including anti-infectives, anticancer agents, anti-
inflammatory drugs, cardiovascular agents, and nutraceuticals.

Table 2: Role of Bioenhancers According to Therapeutic Potency

Therapeutic
Area

Bioenhancer(s)
Mechanism of

Potency Enhancement
Reported Application /

Outcome
Reference
(PubMed)

Anticancer
agents

Piperlongumine
(Piper longum),

Quercetin

Inhibit P-glycoprotein
and BCRP efflux

transporters; sensitize
tumor cells.

Enhance the cytotoxicity
of doxorubicin and

paclitaxel in cancer cells
that are resistant to these

treatments.

Numakura
K., 2016

Antitubercular
drugs

Gallic acid,
Glycyrrhizin

Inhibit drug-
metabolizing enzymes,

improve intestinal
retention

Increase the bioavailability
of rifampicin and isoniazid

Werner RA.,
2019

Antiviral drugs
Thymol,

Resveratrol

Modulate viral entry
pathways, improve
systemic exposure

Potentiate the efficacy of
acyclovir and protease

inhibitors

Hernandez T.,
2021

Anti-
inflammatory

drugs

Naringenin,
Apigenin

Inhibit CYP enzymes
and oxidative
degradation

Enhance the activity of
NSAIDs and

corticosteroids

Drobniewski
M., 2021

Antidiabetic
agents

Berberine,
Curcumin

Inhibit intestinal efflux
pumps, improve AMPK

activation

Increase the potency of
metformin and insulin

sensitizers

Janssen B.,
2018

Nutraceuticals Piperine, Rutin
Inhibit glucuronidation,
improve solubility and

absorption

Enhance oral
bioavailability of

curcumin, resveratrol, and
CoQ10

Shoba G.,
1998

CNS drugs Harmine, Menthol Inhibit MAO enzymes,
enhance nasal-to-brain

Improve CNS penetration
of antidepressants and

Park JH.,

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transport peptides 2016

Phytochemicals and Suitable Bioenhancers

Phytochemicals, the biologically active compounds derived from plants, often exhibit poor oral bioavailability
due to limited solubility, rapid metabolism, and efflux by intestinal transporters. This pharmacokinetic
limitation frequently hinders their therapeutic application despite their potent pharmacological activities
(Gupta et al., 2017). Bioenhancers play a crucial role in overcoming these challenges by improving absorption,
inhibiting metabolic enzymes, or modulating drug transporters, thereby enhancing the pharmacological
efficacy of phytochemicals (Atal et al., 1985; Johri & Zutshi, 1992).

For instance, curcumin, a polyphenol from Curcuma longa, has poor systemic availability due to rapid
metabolism, but its bioavailability is significantly improved by piperine, which inhibits hepatic and intestinal
glucuronidation (Shoba et al., 1998). Similarly, resveratrol, a stilbene from grapes, demonstrates improved
plasma concentrations when co-administered with piperine or quercetin, both of which inhibit CYP3A4-
mediated metabolism (Johnson et al., 2011). Epigallocatechin gallate (EGCG), the major catechin in green tea,
suffers from instability and poor absorption; however, piperine and quercetin enhance its oral bioavailability
and anticancer potential (Lambert et al., 2004). Quercetin itself, despite being an effective antioxidant and anti-
inflammatory flavonoid, shows limited oral absorption; co-administration with naringin or piperine has been
shown to improve its plasma half-life (Shen et al., 2012). In addition, silymarin from milk thistle demonstrates
poor solubility and undergoes extensive metabolism, but its bioavailability is enhanced when administered
with piperine (DiCostanzo et al., 2016).

Thus, the use of suitable bioenhancers with phytochemicals not only amplifies therapeutic potency but also
helps in developing clinically viable formulations of natural compounds. These synergistic strategies represent
a promising area in nutraceuticals, phytomedicine, and drug development.

Table 3: Phytochemicals and Suitable Bioenhancers

Phytochemical
Source /

Plant
Challenges

(Absorption/Metabolism)
Suitable

Bioenhancer
Mechanism of

Bioenhancement
Reference
(PubMed)

Curcumin
Curcuma

longa
Poor solubility, rapid

metabolism

Piperine
(Piper

nigrum)

Inhibits
glucuronidation
and CYP3A4 →
increases plasma

concentration

Shoba G.,
1998

Resveratrol
Grapes,

Polygonum
cuspidatum

Rapid metabolism, low
bioavailability

Piperine,
Naringin

Inhibit
glucuronidation,

CYP3A4, P-gp →
improves

absorption

Zhu W.,
2014

Quercetin
Onions,
Apples

Efflux by P-gp, rapid
metabolism

Naringin,
Kaempferol

Inhibit P-gp, CYP
enzymes →

increases
systemic exposure

Ni F.,
2018

Berberine
Berberis
vulgaris

Poor intestinal absorption
Piperine,
Chitosan

Inhibit CYP450
metabolism,

increase
paracellular
permeability

Janssen
B., 2018

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Curcuminoids
(other than
curcumin)

Curcuma
longa

Poor solubility, fast
metabolism

Phospholipids
(e.g., lecithin)

Form drug-
phospholipid
complexes →

improve solubility
and absorption

Tournier
N., 2010

Catechins
Green tea
(Camellia
sinensis)

Low stability, rapid
metabolism

Piperine,
Lecithin

Inhibit
metabolism,

improve intestinal
absorption

Zhu W.,
2014

Silymarin
Milk thistle

(Silybum
marianum)

Poor water solubility
Glycyrrhizin,
Phospholipids

Improve
solubility, inhibit
metabolism →

enhance
bioavailability

Chen X.,
2012

Coenzyme Q10
(CoQ10)

Endogenous,
supplements

Poor water solubility
Piperine,

Fatty acids
(oleic acid)

Enhance
solubility and

intestinal uptake

Zhu W.,
2014

Curcumin
analogs

Curcuma
longa

Low bioavailability
Naringin,
Quercetin

Efflux pump
inhibition, CYP

enzyme
modulation

Ni F.,
2018

Type of Bioenhancers vs. Their Activity

Bioenhancers are diverse compounds, and their classification according to type—based on chemical class or
origin—helps in understanding their biological activity and mechanism of action. The most widely studied
alkaloid bioenhancers, such as piperine from Piper nigrum, enhance drug activity by inhibiting cytochrome
P450 enzymes (CYP3A4, CYP2E1) and efflux transporters like P-glycoprotein, leading to increased systemic
exposure of drugs such as rifampicin, propranolol, and curcumin (Atal et al., 1985; Shoba et al., 1998).
Another alkaloid, capsaicin from chili peppers, enhances membrane permeability and improves the intestinal
absorption of co-administered molecules (Reyes-Escogido et al., 2011).

Terpenoids and terpenes, such as menthol (peppermint) and limonene (citrus oils), are effective permeation
enhancers that increase transdermal and oral delivery of poorly absorbed drugs by altering membrane fluidity
(Cornwell & Barry, 1994). Flavonoids and polyphenols, including quercetin and naringin, exert bioenhancing
activity by inhibiting metabolic enzymes (CYP3A4, CYP2C9) and efflux transporters, thereby increasing the
oral bioavailability and therapeutic efficacy of anticancer and antiviral agents (Shen et al., 2012; Johnson et al.,
2011).

Glycosides and saponins, such as glycyrrhizin from licorice and ginsenosides from ginseng, increase
bioactivity by modulating intestinal permeability and prolonging the plasma half-life of drugs, thereby
potentiating the efficacy of corticosteroids, antivirals, and antibiotics (Gupta et al., 2017). Fatty acids and
essential oils, such as eugenol (from clove) and oleic acid, improve solubility, alter membrane dynamics, and
facilitate drug absorption, enhancing the potency of antifungals and NSAIDs (Pawar et al., 2011). Finally,
synthetic bioenhancers such as surfactants (e.g., polysorbates, bile salts) act as solubilizers and permeability
enhancers, widely used in formulations to improve drug stability and systemic delivery (Lo, 2016).

Thus, depending on their type, bioenhancers exhibit activities ranging from enzyme inhibition and efflux
modulation to membrane alteration and solubilization, collectively improving therapeutic efficacy across drug
classes.

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Table 4: Type of Bioenhancer vs. Activity

Type of Bioenhancer Examples
Primary Activity /

Mechanism
Reported

Applications
Reference

(PubMed/PMC)

Probiotics &
Postbiotics

Lactobacillus
rhamnosus, Butyrate

Modulate gut
microbiota, enhance
mucosal absorption,

reduce first-pass
metabolism.

Improve oral
delivery of
antibiotics,

peptides, and
nutraceuticals

Garcia del Muro
X., 2002

Phospholipids
(Lipid-based

carriers)

Phosphatidylcholine,
Phosphatidylserine

Form
liposomes/niosomes,
increase membrane

fusion and drug
retention

Enhance the
bioavailability
of curcumin,

anticancer, and
CNS drugs

Andraos E., 2021

Cyclodextrins
(Inclusion
complexes)

Hydroxypropyl-β-
cyclodextrin, γ-

cyclodextrin

Increase the solubility
of poorly soluble

drugs, protect from
degradation

Widely used in
antifungal,

antiviral, and
hormone

formulations

Cleuren AC., 2012

Phytosterols
β-Sitosterol,
Campesterol

Compete with
cholesterol, modulate
membrane properties,

and enhance
absorption of

lipophilic compounds.

Used in
cardiovascular

drugs and
nutraceuticals

Weigl BH., 2014

Marine-derived
Bioenhancers

Fucoxanthin,
Astaxanthin

Improve lipid
metabolism, enhance

intestinal uptake

Increase the
efficacy of

anticancer and
anti-

inflammatory
agents

Faja S., 2012

Spices &
Condiments (other

than
piperine/capsaicin)

Mustard oil (allyl
isothiocyanate),

Gingerol

Modulate gastric
motility, enhance
permeability, and

solubility

Improve
absorption of
herbal drugs

and antibiotics

Bahdila D., 2022

Nano-bioenhancers
Solid lipid

nanoparticles (SLN),
Nanocrystals

Improve dissolution
rate, protect drugs

from degradation, and
enhance lymphatic

absorption.

Applied in
anticancer,

antiviral, and
CNS drug
delivery

Li M., 2015

Bioenhancers: Pharmacokinetic vs Pharmacodynamic Actions

Bioenhancers exert their effects through two major mechanisms: pharmacokinetic (PK) actions and
pharmacodynamic (PD) actions. Pharmacokinetic actions involve changes in the absorption, distribution,
metabolism, or excretion (ADME) of drugs, thereby increasing their bioavailability and systemic exposure. For
example, piperine enhances the plasma concentration of drugs such as rifampicin, phenytoin, and curcumin by
inhibiting intestinal and hepatic metabolism (glucuronidation, CYP3A4) and efflux transporters such as P-

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glycoprotein (Atal et al., 1985; Shoba et al., 1998). Similarly, flavonoids such as quercetin improve the
bioavailability of chemotherapeutics and antivirals by inhibiting CYP enzymes and drug transporters (Shen et
al., 2012). These pharmacokinetic actions reduce drug clearance and increase systemic half-life, making lower
doses therapeutically effective.

Pharmacodynamic actions, on the other hand, are independent of drug concentration in plasma and involve
direct enhancement of drug efficacy at the target site. For instance, glycyrrhizin potentiates the anti-
inflammatory action of corticosteroids by prolonging their receptor-binding effects and synergistically
enhancing immunomodulatory pathways (Gupta et al., 2017). Capsaicin, besides improving absorption, also
enhances anti-inflammatory and analgesic activity by desensitizing TRPV1 receptors (Reyes-Escogido et al.,
2011). Similarly, gingerols from Zingiber officinale exert synergistic antiemetic effects when combined with 5-
HT3 antagonists, improving clinical efficacy (Lete & Allué, 2016).

Table 5: Pharmacokinetic vs Pharmacodynamic Actions of Bioenhancers

Type of Action
Examples of

Bioenhancers
Mechanism of

Action
Therapeutic Outcome

/ Effect
Reference
(PubMed)

Pharmacokinetic
(PK) Actions

Harmine (Peganum
harmala), Palmatine
(Coptis chinensis)

Inhibit CYP2D6 and
glucuronidation;
reduce first-pass

metabolism

Prolongs the half-life
and systemic exposure
of antidepressants and
neuroprotective drugs

Menthol, Perillyl
alcohol

Alter intestinal
membrane fluidity,
improve nasal-to-

brain transport

Enhances CNS drug
absorption and

bioavailability of
peptides

Liu Z.,
2011

Platycodin D
(Platycodon

grandiflorus), Escin
(Aesculus

hippocastanum)

Open tight junctions,
increase paracellular

transport

Improves oral
absorption of peptides,
vaccines, and steroidal

drugs

Yan X.,
2018

Pharmacodynamic
(PD) Actions

Ellagic acid, Ferulic
acid

Antioxidant and anti-
inflammatory

signaling modulation

Enhances the efficacy
of nutraceuticals and

anti-inflammatory
drugs

Rubinelli
S., 2019

Thymol, Carvacrol

Modulate microbial
cell membrane and

inflammatory
signaling

Increases the
effectiveness of

antimicrobials and anti-
inflammatory agents

Morin V.,
2012

Icariin, Resveratrol
Modulate AMPK or
estrogenic pathways.

Enhances the potency
of antidiabetic,

anticancer, and bone-
protective drugs

Brunetti O.,
2019

Bioenhancers by Phytochemical Type

Phytochemicals constitute one of the richest sources of bioenhancers, and their classification according to

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chemical type helps in understanding their bioenhancing properties. Alkaloids, such as piperine from Piper
nigrum and capsaicin from Capsicum annuum, are among the most studied. They act primarily by inhibiting
drug-metabolizing enzymes (CYP3A4, CYP2E1, UDP-glucuronyl transferase) and efflux transporters (P-
glycoprotein), thereby enhancing the bioavailability of drugs such as rifampicin, curcumin, and phenytoin
(Atal et al., 1985; Shoba et al., 1998). Terpenoids and terpenes, including menthol and limonene, improve drug
absorption by altering membrane fluidity and permeability, which is particularly useful in enhancing
transdermal and oral delivery (Cornwell & Barry, 1994).

Flavonoids and polyphenols, such as quercetin, naringin, and catechins, are strong modulators of metabolic
enzymes and drug transporters, enhancing the bioavailability of antivirals, anticancer agents, and anti-
inflammatory compounds (Shen et al., 2012; Johnson et al., 2011). Saponins and glycosides, such as
glycyrrhizin (licorice) and ginsenosides (ginseng), enhance drug absorption by modulating intestinal
permeability and prolonging plasma half-life of co-administered drugs, thereby potentiating corticosteroids,
antivirals, and antibiotics (Gupta et al., 2017). Phenolic compounds, including eugenol (from clove) and
curcumin, increase solubility, stability, and absorption of poorly soluble drugs, while also providing synergistic
pharmacodynamic effects (Pawar et al., 2011).

In addition, essential oils containing phytochemicals like thymol and carvacrol act as permeation enhancers by
disrupting lipid bilayers, whereas fatty acids such as oleic acid improve solubility and intestinal absorption of
hydrophobic drugs (Lo, 2016). Together, these phytochemical classes demonstrate a wide array of
pharmacokinetic and pharmacodynamic bioenhancing activities, making them valuable tools in drug
development and nutraceutical formulations.

Table 6: Bioenhancers by Phytochemical Type

Phytochemical
Type

Examples
Natural
Source

Mechanism
of Action

Reported
Applications

References
(PubMed/PMC)

Carotenoids
β-Carotene,
Lycopene

Carrots,
Tomatoes,
Red fruits

Enhances
intestinal
uptake of

fat-soluble
compounds

and
antioxidant
modulation

Improves absorption
of vitamin A and
anticancer agents

Bonnard T.,
2014

Tannins
Tannic acid,

Proanthocyanidins
Tea, Grapes,

Berries

Inhibits
efflux

transporters
and

enzymes;
stabilizes

drug
compounds

Potentiates
antimicrobial and
anticancer drugs

Brady TJ., 1998

Coumarins
Umbelliferone,

Esculetin
Parsley,

Citrus peels

Inhibits
CYP450
enzymes,
modulates
oxidative

metabolism

Enhances
anticoagulant and

anticancer therapies
Lee YY., 2013

Stilbenes
Pterostilbene,

Blueberries,
Grapes,

Modulates
P-

Potentiates
anticancer and

Ryu M., 2020

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Page 3020 www.rsisinternational.org

Resveratrol Peanuts glycoprotein
and drug-

metabolizing
enzymes

cardioprotective
drugs

Lignans
Sesamin,

Schisandrin

Sesame
seeds,

Schisandra
chinensis

Inhibits
CYP3A4,
enhances
intestinal

drug
retention

Improves
bioavailability of

immunosuppressants
and antivirals

Gramiccia T.,
2008

Organosulfur
Compounds

Allicin,
Sulforaphane

Garlic,
Broccoli

Modulates
phase II
detox

enzymes,
improves
cellular
uptake

Enhances anticancer
and antimicrobial

effects

Mégarbané A.,
2009

Polysaccharides
β-Glucans,
Fucoidan

Mushrooms,
Brown

seaweed

Modulates
gut

microbiota,
enhances
immune-
mediated

absorption

Improves the
bioactivity of
vaccines and

anticancer agents

Washington, DC,
1999.

CONCLUSIONS:

Bioenhancers represent a promising and versatile approach to improving the therapeutic potential of drugs and
nutraceuticals by enhancing their bioavailability and efficacy without contributing intrinsic pharmacological
effects. Their diverse mechanisms of action—ranging from enzyme inhibition and efflux modulation to
permeability enhancement and half-life prolongation—highlight their importance in both pharmacokinetic and
pharmacodynamic optimization. Natural phytochemicals such as piperine, quercetin, glycyrrhizin, and
ginsenosides, along with synthetic agents like surfactants, have demonstrated wide applicability across
therapeutic areas, including infectious diseases, oncology, cardiovascular disorders, and inflammatory
conditions. The ability of bioenhancers to reduce drug dosage, minimize side effects, and revive abandoned
compounds with poor pharmacokinetic profiles underscores their clinical and pharmaceutical significance.
Moreover, their integration into novel formulations such as nanoparticles, liposomes, and transdermal systems
expands their utility in modern drug delivery. As research continues to explore new bioenhancers and refine
their mechanisms, these agents hold substantial potential in shaping future strategies for drug discovery,
development, and personalized medicine.

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