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xx Abbreviations
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OII
ORA
OSI
OVX
OZ
PA
PAG
PB
PC
PCL/Cur/GLE-Ag NPs
PCNA
PDCO
PE
PEG
PEITC
PEN
PEO
PGI
2
PKs
PLA
PLGA
PMA
PN
PONT
PS
PSEN1
PTL
PUE
PUFAs
PVEF
PVP
QA
QBD
QCT
QNAR
QN-NLC
QN-NLC-Gel
QSAR
ocular irritation index
office of regulatory affairs
oxidative stress index
ovariectomized
oryzalin
phosphatidic acid
p-aminophenyl-1-thio-β-D-galactopyranoside
penta block
phosphatidyl choline
poly (-caprolactone)/curcumin/grape leaf
extract-Ag hybrid nanoparticles
proliferating cell nuclear antigen
pediatric committee
pomegranate extracts
polyethyleneglycol
phenethyl isothiocyanate
pentalinonsterol
poly (ethylene oxide)
prostacyclin
pharmacokinetics
polylactic acid
poly lactic-co-glycolic acid
premarket approval
papillary or nodular
partial optic nerve transaction
phosphatidylserine
processing, γ-secretases of presenilin 1
parthenolide
puerarin
polyunsaturated fatty acids
Prunella vulgaris ethylacetate fraction
polyvinylpyrrolidone
quercitin
quality by design
quercetin
quantitative nanostructure-activity relationships
NLC loaded with quercetin
QN-NLC based hydrogel
quantitative structure-activity relationship

xxi Abbreviations
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RA
RAGE
RES
RF
ROS
RP
RSM
RSV
RV
SCU
SEM
SGOT
SGPT
SLN
SMA
SMCS
SNEDDS
SOD
STZ
TAC
TET-CNP
TET-SOL
THC
TIMPs
TMC
TNF
TNF-α
TOS
TP-1
TPA
TQ
TQNE
TQ-NLC
TQRF
TQRFNE
TQ-SLN
TWH
UA
UANL
rheumatoid arthritis
receptor for advanced glycation end products
reticulo-endothelial system
rheumatoid factors
reactive oxygen species
reducing power
response surface methodology
resveratrol
right ventricular
scutellarin
scanning electron microscopy
serum glutamate oxaloacetate transaminase
serum glutamate pyruvate transaminase
solid lipid nanoparticle
styrene-maleic acid
sulfur S-methyl cysteine
self-nano emulsifying drug delivery system
superoxide dismutase
streptozotocin
total antioxidant capacity
tetrandrine-loaded cationic solid lipid nanoparticles
tetrandrineoccular solutions
tetrahydrocurcumin
tissue inhibitor metalloproteinase proteins
N-trimethyl chitosan
tumor necrosis factor
tumor necrosis factor-α
total oxidative status
topoisomerase I
trypanocidal activity
thymoquinone
thymoquinone nanoemulsion
TQ loaded nanostructured lipid carrier
thymoquinone rich fraction
thymoquinone rich fraction nanoemulsion
TQ-loaded solid lipid nanoparticles
Tripterygium wilfordii Hook F
ursolic acid
UA nanoliposomes

UDL
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UN
US-FDA
VAP
VAPL
VEGF
WHO
ZnPcAL
ultra-deformable liposomes
United Nations
United States-Food and Drug Administration
vitamin A palmitate
VAP-loaded liposomes
vascular endothelial growth factor
World Health Organization
zinc phthalocyanine

Preface
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Conventional medications have limited efficacy and high toxicity. Herbal drug
discovery based on biomarkers emerging as complementary and alternative
medicine have tremendous potential with wide structural diversity, which is
not usually seen with conventional/synthetic drug molecules. Recognition
of various herbal constituents such as terpenoids, fatty acids, flavonoids,
and steroids has been well explored in the management/treatment of various
disorders. These agents target various biomarkers such as nitric oxide (NO),
cytokines, chemokines, adhesion molecules, NF-kβ, lipoxygenase (LOX),
and arachidonic acid (AA).
The second part of this book is on nanomedicine; the word nano is a buzz
word today in the era of the twenty-first century. With the advent of nanotechnology, the world has witnessed a significant momentum in exploring
the precepts and perspectives of this evolutionary technology for diverse
applications in various fields.
Importantly, nanotechnology applications in the healthcare sector have
benefited a lot for their application in providing benefits to the patient
community by serving unmet medical needs. In this regard, the physicochemical properties of herbal drugs and vehicles are considered to be highly
significant for drug absorption. These factors restrict the site-specific action
and limited penetration through site. To avoid these shortcomings, nano/
submicromedicines have been developed to improve the absorption of such
bioactives via optimizing the physicochemical properties of herbal drugs,
vehicles, and barriers.
The present book, Biomarkers as Targeted Herbal Drug Discovery:
A Pharmacological Approach to Nanomedicines, focuses on their use in
targeting various biomarkers and what is involves in various dreadful disorders, including arthritis, cardiovascular, ocular disorders, cancers, etc.
Nanomedicines in particular focus on their use in the treatment of diseases.
Notwithstanding the benefits of nanotherapeutic devices, the healthcare
sector has tremendously benefited in terms of reducing the mortality rate
beyond the expectations.
A total of thirteen chapters encompassed in this book have been contributed by eminent scientists, researchers, and nanotechnologists across the
globe with the primary goal of highlighting the key advancements, challenges,

xxiv Preface
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and opportunities in the area of application of herbal drug discovery based
on biomarkers and their delivery by nanomedicines for disease treatment
and regulatory guidelines. The book, therefore, carries a lot of potential as
a repertoire of knowledge and package of information for herbal scientists,
pharmaceutical scientists, nanoscientists, and nanobiotechnologists.
A succinct account of the key highlights of each of the chapters included
in the book has been discussed in the below-mentioned text.
Chapter 1, which is entitled Inflammatory Biomarkers: An Important
tool for Herbal Drug Discovery, provides a comprehensive remark on the
finding of biomarkers, which played a key role in inflammatory disorders
and the emergence of herbals in targeting on biomarkers for the management
of Inflammatory disease.
Chapter 2, which is entitled Herbal Anti-Arthritic Drug Discovery Tool
Based on Inflammatory Biomarkers, discusses the inflammatory biomarkers
for specific arthritis and their targets by herbals for effective management of
the said disease.
Chapter 3, which is entitled Curcumin Nanomedicines and Their Appli-
cation in the Management of Disease, highlights the uses of curcumin from
the kitchen to clinics. The chapter will also serve as a guide for clinicians
and researchers in working on the development of curcumin-loaded nanomedicines as novel nanotherapeutic strategies for management of dreadful
disorders.
Chapter 4, which is entitled Ursolic Acid: A Pentacyclic Triterpene from
Plants in Nanomedicine, discusses the perspectives of ursolic acid and its
delivery by nanomedicine for treatment and management of several threatening disorders.
The Chapter 5 of this book is entitled as Phytoconstituent-Centered
Byproducts and Nanomedicines as Leishmanicidal Scavengers. Almost
1.6 million of new individual cases of cutaneous leishmaniasis (CL) and
more than half a million of new individual cases of visceral leishmaniasis
(VL) ensue every year all over the world. The natural products, chiefly
plant-originated phytoconstituents and their by-products of varied structural
groups and classes, display the anti-leishmanial activity (ALA). This chapter
emphasizes some biopharmaceutical nanotechnologies for designing varied
drug delivery approaches, including nanoparticles (NPs), nanocapsules
(NCs), liposomes, micelles, cochleates, and nanotubes that are effective in
its delivery.
Chapter 6 of this book is entitled as Delivery of Herbal Cardiovascular
Drugs in the Scenario of Nanotechnology: An Insight. According to WHO,

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about 80% of the population still believes that drugs from natural sources
have the potential for advancement on the clinical platform. Nanotechnology
bears much hope for the development of many of these poor bioavailable
herbal drugs. Therefore, the present chapter converting herbal drugs to the
nanoscale delivery system using various fabrication approaches can result
in the improvement of many pharmacokinetic profiles as well as in vivo
stability and controlled absorption of the drug at the desired site.
Chapter 7, which is entitled Nigella sativa Encapsulated Nano-Scaffolds
and Their Bioactivity Significance, has its active constituent thymoquinone,
which has a wide potential to shows anti-tumor, anti-microbial, immunomodulatory, anti-inflammatory, and anti-oxidant effects. The present book
chapter highlights the encapsulation of herbal drug into the nano-scaffold
that makes them more effective than the traditional dosage form. The drug
nano-scaffold is able to enhance the therapeutic potential by enhancing
bioavailability and targeting in the management of various disorders.
Chapter 8, which is entitled Phytoconstituent-Loaded Nanomedicines for
Arthritis Management, addresses the available anti-arthritic synthetic treatment for the management of arthritis that are found to have multiple disadvantages, such as serious side effects, high costs of treatment, the requirement
of parenteral administrations and incomplete relief to the patient in respect to
pain intensity and joint movements. Therefore, the present chapter highlights
the research conducted, in recent years, using nanomedicines in combination with herbal drugs as an effective therapy in arthritis and concludes with
several important investigations with promising results for the treatment of
chronic disease in an efficient way.
Chapter 9, which is entitled Phytoconstituent-Based Nanotherapeutics
as Ocular Delivery Systems, discusses the popularity of herbals all over the
globe because of their natural origin and lesser side effects. The application
of nanoformulation opened the door in a disease like glaucoma, eye cancer,
and other anterior ocular diseases by significantly modifying the properties
of drugs and their carriers. This chapter summarizes the latest research
reports regarding the possible administration of phytoconstituent-loaded
nanoformulations for different ocular diseases.
Chapter 10, which is entitled Rosmarinic Acid: A Boon in the Manage-
ment of Cardiovascular Disease, discusses the therapeutic application of
rosmarinic acid in cardiovascular disease. Several research reports have
demonstrated the therapeutic effects in said disease management.
Chapter 11, which is entitled Long-Term Toxicity and Regulations for
Bioactive-Loaded Nanomedicines, summarizes the incorporation of natural

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bioactives into nanomedicines; their applications and evaluation have aggressively been put forward during the last couple of decades. The enormous
ability of nanocarriers in enhancing the bioavailability, targeting, and efficacy of natural molecules have been well documented. This chapter outlines
the suitability of various bioactive-loaded nanocarriers in therapeutics, their
toxicity, and regulatory considerations.
Chapter 12, which is entitled Resveratrol-Loaded Phytomedicines for
Management of Cancer, discusses the therapeutic application of resveratrol
in cancer, and the role of nanomedicines in optimizing pharmacokinetics
(PKs) and pharmacodynamics in cancer disease.
Finally, the last chapter of this book, i.e., Chapter 13, which is entitled
Thymoquinone-Loaded Nanocarriers for Healthcare Applications, summarizes the occurrence of thymoquinone in nature, their traditional uses, and
modern uses on the basis of various research that have done in various
healthcare.

CHAPTER 1
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Inflammat
Tool for Her
MAHF
OOZUR RAHMAN,
S
ARWAR BEG
1
Department of Pharmaceutic
Allied Sciences, Sam Higginbottom University of Agriculture, Technology,
and Sciences, Allahabad, Uttar Pradesh, India
2
School of Pharmaceutical Education and Research,
Nanomedicine Research Lab, Jamia Hamdard, New Delhi, India
ABSTRACT
The conventional pharmacotherapeutics are more often restricted to non-targeted
action, reducing safety, and effectiveness in the treatment of immune-related
disorders, cancer, and other disorders. While the herbal benefits provided by
conventional dosage forms are only suboptimal, complexities and obstructions
are present. The increased interest in herbal medicines clearly shows that they
are more safe and effective. Herbals are natural and have enormous potential
and a wide range of structures, which are not common with synthetic/semisynthetic medicament molecules. Herbal medicinal drugs have lately received a
wide range of treatments for various conditions including autoimmune immune
disorders and other terrible conditions, including Alzheimer’s, diabetes, cancer,
etc. To date, there are various available phytoconstituents for treating the abovementioned disease by targeting various inflammatory biomarkers including
terpenoids, flavonoids, fatty acids, and steroids. All these products are very
effective in the management by taking intervention on specific biomarkers
including nitric oxide (NO), cytokines, chemokines, adhesive molecules,
NF-Kβ, interleukins (ILs), lipoxygenase, and arachidonic acid (AA).
ory Biomar
bal Drug Disco
1
ANKIT S
2
AHOOe,
al Scienc
kers: An Important
very
1
MOHAMMAD A
s, Shalom Institut
1
TIF,
and
e of Healt
h and

2
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Biomarkers as Targeted Herbal Drug Discovery
Inflammation is a biological response which is very complex and derived
from the Latin word ‘inflammationem.’ It is a response triggered by the
damaged body tissue such as irritants pathogens or injured cells (Abbas,
2009), and is a defensive response involving molecular mediators, immune
cells, and blood vessels. The primary function of inflammation is the
location and removal of the original cell injuries and the removal of the
tissue element harmed to enable the body to start repairing the tissue. The
main inflammation symptoms are redness, heat pain, swelling, and loss of
function (Abbas, 2009). Inflammation is regarded as an innate immunity
system compared to adaptive immunity, since inflammation is a generic
response and is unique to each pathogen (Abbas, 2009). Minor inflammation could lead to rapid tissue loss by stimuli (e.g., bacteria), and could
affect organism growth and in chronic inflammation leads to hay fever,
rheumatoid arthritis (RA), periodontitis, atherosclerosis, and sometimes
cancer (e.g., gall bladder carcinoma). The word biomarker, a portmanteau
of biological marker, relates to a wide subcategory of medical signs that
can be corrected and measured reproducibly-that is, an objective indication
of medical condition observed from outside the patient. Regarding medical
signs and symptoms, signs of health are restricted or disorder perceived by
patients themselves. In the literature, there are many accurate definitions
of biomarkers and they’re certainly significantly varied. In 1998, the NIH
described a biomarker as “a characteristic that is objectively measured and
measured as an indicator of normal biological and pathogenic processes
or pharmacological responses to therapeutic intervention” (Abbas, 2009).
A joint project on chemical safety, the International Chemical Safety
program, headed by the World Health Organization (WHO) and in collaboration with the United Nation and the International Labor Organization
(ILO), defined a biomarker as “any process, structure, or substance, that
can be measured and influencing or predicting the effect or outcomes or
disease in the body or its products” (Abbas, 2009). A much wider concept
requires into consideration not only the incidence and result of disease,
but also the impacts of procedures, medicines, and even unintended access
to the environment, such as chemicals or nutrients. In its research on
biomarkers’ efficacy in financial risk assessments, the WHO has stated
that almost every measurement of a true notion of biomarkers involves an
exchange between the prospective danger and a biological system that may
be either physical, chemical, or biologicals. The assessed reaction can be

3
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operational and biochemical, physiological at the molecular interaction,
or the cellular level (Ferrero-Miliani, 2007). Biomarker examples include
everything from pulse and blood pressure (BP) through fundamental
chemistries to more complicated blood and other tissue laboratory tests.
Medical indication has a wide history of use in clinical practice, the most
significant quantifying medical signs modern laboratory science enables us
to reproductively assess, as well as medical instruction itself and biological
manufacturers.
From the ancient time, medicinal plants are globally used to prevent and
to treat disease. The early manuscripts of herbal drugs data back to 5,000
years in India and China, gives the importance of plants in the management of
health. According to the WHO more, than half of the world population uses the
medicinal plant-based system for the primary healthcare and medicinal plant
to contribute near about 80% of the raw material in the traditional medicinal
system. The demand of herbal drug is increasing day by day as the side effect
and toxicity of the allopathic drug cause increase in the use of an herbal drug
which leads to the drastic development of herbal drug industry. The demand of
herbal medicines has been constantly rising every year (Vishal, 2014; Mishra,
2016). In developing countries, peoples use herbal drugs for the treatment of
disorders and diseases as it is a part of their culture in those communities.
Now researchers gave more attention to plants to discover new leads, thereby
fullling the health care needs and reducing the number of deaths due to
untreatable infections. In the development of various human diseases, inammation plays an essential role including Asthma, inammatory bowel disease,
RA, Crohn’s disease, and tendonitis. Chronic inammatory response, however,
is a driving force for the advancement of cancer, atherosclerosis, Alzheimer’s
disease, diabetes, and obesity. When inammatory is under control, it is helpful
to protect the organ against complete collapse, while uncontrolled treatment
leads to unwanted physical decay.
Herbal medicine used for the treatment or preventing diseases like inflammatory diseases and indeed a priceless source of valuable chemical compounds
that developed into indispensable drug medical practice and their valuable
effects in inflammatory diseases have not been thoroughly studied. Herbal
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