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Phytomedicine
Phytomedicine
Research and Development
Edited by
Parimelazhagan Thangaraj
Professor
Department of Botany
Bharathiar University
Coimbatore 641046
Tamil Nadu, India
First edition published 2020
by CRC Press
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Typeset in Times
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Contents
Foreword....................................................................................................................................................................................... ix
Preface.......................................................................................................................................................................................... xi
Editor..........................................................................................................................................................................................xiii
Contributors................................................................................................................................................................................. xv
Chapter 1 Ethnic Uses and Commercial Applications of Capsicum assamicum (Bhut jolokia)............................................ 1
Ajitabh Bora, Khonamai S. Nakhuru, Baikuntha J. Gogoi, Pronobesh Chattopadhyay,
and Sanjai K. Dwivedi
Chapter 3 Ethnomedicinally Important Pteridophytes of Kolli Hills from Eastern Ghats, India........................................ 13
Muniappan Ayyanar and Jeyalatchagan Sureshkumar
Chapter 4 Bioprospecting of Antimicrobial Carica papaya Leaf Extract for Finishing of Fabrics
in Health Care Industries...................................................................................................................................... 23
B. Sathya Priya, T. Stalin, and Olivier Nzamwita
Chapter 5 Analysis of Discrete and Combined Effect of Solvent, Extraction Time, and Extraction Temperature
on Polyphenol Compounds Extraction from Roxburgh Fig (Ficus auriculata Lour.) Fruit Using
Response Surface Methodology........................................................................................................................... 27
Gayathri Jagadeesan, Kasipandi Muniyandi, M. Ashwini Lydia, Gayathri Nataraj, Suman Thamburaj,
Saikumar Sathyanarayanan, and Parimelazhagan Thangaraj
Chapter 6 GC-MS Analysis of Methanolic Extract of Rubus ellipticus: A Wild Edible Fruit............................................. 37
Elizabeth George, Blassan P. George, Sajeesh Thankarajan, Parimelazhagan Thangaraj,
Kasipandi Muniyandi, and Saikumar Sathyanarayanan
Chapter 8 Anti-microbial and Anti-oxidant Properties of Solvent Extract of Lichen Species Collected from
Kodaikanal Hills, Western Ghats of Tamil Nadu................................................................................................ 53
R. Kalidoss, M. Mariraj, M. Shenbagam, J. Merlin Seles, K. Arun Prasath, N. Rajaprabu,
and P. Ponmurugan
Chapter 9 Preliminary Phytochemical Screening and Identification of Bioactive Compounds from Banana
Inflorescence and to Find the Interactions on Molecular Docking for PCOS...................................................... 63
M. C. Kamaraj, Suman Thamburaj, R. Akshaya, and V. Bhanu Deepthi
Chapter 10 Effect of Anti-oxidant-Rich Nutraceutical on Serum Glucose, Lipid Profile, and Oxidative Stress
Markers of Salt-Induced Metabolic Syndrome in Rats........................................................................................ 73
N. Lawal, L. S. Bilbis, R. A. Umar, and A. A. Sabir
v
vi Contents
Chapter 11 Pharmacognostic Studies on Ormocarpum sennoides (Willd.) DC.: A Bone Fracture Healing
Plant from Fabaceae............................................................................................................................................. 83
M. M. Sudheer Mohammed, A. Narayanasamy, and S. Mahadevan
Chapter 12 Flowering Plants of Govind Pashu Vihar Wildlife Sanctuary, Western Himalaya: With Emphasis
on High Altitude Threatened Medicinal Plants.................................................................................................... 93
Ramasamy Manikandan, Chithambaram Murugan, Nithya Sivagami Ponnurangam,
and Mehala Devi Ramasamy
Chapter 13 Anti-oxidant and Anti-microbial Activities of Flavonoids from the Fruit Extract of Dacryodes edulis............131
R. O. Omosimua, B. D. Macham, A. Onanuga, B. T. Thomas, C. O. Ugbomor,
G. Iyappan, S. Ramalingam, A. S. Afolabi, and Sunday Asuquo Thomas
Chapter 14 Anti-diabetic and Cytotoxicity Studies of Ethanol Extract of Mundulea sericea: A Threatened
Medicinal Plant................................................................................................................................................... 139
S. Gangadevi, K. Kalimuthu, and P. Viswanathan
Chapter 15 Evaluation of In Vitro and In Vivo Anti-oxidant and Anti-inflammatory Potential of Aloe vera Gel Extract........ 145
S. Govindarajan, Spoorthy N. Babu, and Ayesha Noor
Chapter 18 Evaluation of Anti-diabetic Activity of Cleome gynandra in Alloxan Induced Diabetic Wistar Albino Rats.......... 179
T. Shanmuganathan and A. V. P. Karthikeyan
Chapter 19 To Evaluate the Role of a Novel Herbal Formulation by Topical Application in Cancer Therapeutics
(Mouse Model)................................................................................................................................................... 183
Umrao Ankita, Rao Gururaj A., Rao S. G. A., and Rao Jyothsna A.
Chapter 20 Coconut Sprouts as Phytomedicine: An Approach towards the Development of Nutraceuticals...................... 187
S. Abiraami Valli and S. Uma Gowrie
Chapter 21 Assessment of Secondary Metabolites in the Yams of Dioscorea oppositifolia L. & Dioscorea
pentaphylla L. . .................................................................................................................................................. 197
S. Vivek, Y. Aron Santhosh Kumar, and M. Palanisamy
Chapter 22 Evaluation of Anti-ulcer Potential of Sphenodesme involucrata var. paniculata (C.B. Clarke) Munir
Leaves on Various Gastric Aggressive Factors.................................................................................................. 203
P. S. Sreeja, K. Arunachalam, and Parimelazhagan Thangaraj
Contents vii
Chapter 24 Bioactive Compounds in Marine Macro Algae and Their Role in Pharmacological Applications................... 227
Subramaniam Kalidass, Lakshmanan Ranjith, Palavesam Arunachalam, Amarnath Mathan Babu,
and Karuppasamy Kaviarasan
Chapter 25 Fisher Folks Usage of Medicinal Plants against Gynecological Disorders........................................................ 245
Vijayakumar Dhaarani and Arumugam Rajendran
Chapter 26 In Vitro Anticancer Activity of Syzygium calophyllifolium on A549 Lung Cancer Cells................................. 251
Rahul Chandran and Heidi Abrahamse
Index.......................................................................................................................................................................................... 257
Foreword
Plants are the greatest boon to in the notion against proper health maintenance. Thus, the
mankind. The food, shelter, importance of phytomedicine is being realized and research
clothing, and medicines that should hold the potential to achieve social value. Also, the safety
we possess are only through and effectiveness of herbal medicines must be highly considered
them. They serve in raising the with reliable preclinical and clinical trials and should typically
economic status of the country, employ experimental research. This book indeed represents a
and meanwhile, India has a decisive step forward in understanding the importance of phyto-
rich biodiversity that can help medicine. This book serves as a fascinating reference guide to
people survive the drastic envi- develop new ideas in research and development. The excellent
ronmental conditions. Indians contribution of Prof. Dr. Parimelazhagan Thangaraj in bringing
use a folklore system of medic- about this book is highly appreciable, opening an inspirable
inal plants from ancient times foundation for gathering scientific information on medicinal
for their curative properties. Up plants. I would like to congratulate his exceptional commitment
to recent times, there is a deficiency prevailing in the scrutiny of in making this book possible. I hope this book is one of the best
the scientific validation of such medicinal plants. Current esti- pieces of green literature and also a convincing tool that helps to
mates also prove that most of the drugs utilized by India are of motivate and stimulate young minds toward the improvement of
plant origin. Traditional herbal medicines are getting significant modern science and technologies.
attention in global health debates, playing a prominent role in
the global health care. At present, there is a situation where syn- Prof. Dr. P. Kaliraj
thetic medicines have led to various side effects, such as the Vice Chancellor
growth of lifestyle related disorders, the issue of serious malnu- Bharathiar University
trition, a lack of remedies for chronic disorders, and an increase Coimbatore
ix
Preface
Nutrition, medicine, and food for health care are mainly different fields encompassing phytochemistry, molecular
derived through plant sources, which are natural gifts. They are biology, ethnopharmaceutics, nutritional biology, pharmacog-
presently being administered in both traditional and modern nosy, pharmatherapeutics, and biomedicine.
medicinal systems. Research has proved their efficacy in treat- The editor conveys his sincere gratitude to Professor
ing various diseases. The knowledge toward pharmacology, P. Kaliraj, vice chancellor, and the authorities of Bharathiar
phytomedicine, and herbalism is increasing swiftly to bring University for the endless guidance and support for this fruitful
about the improvement in remedial action and therapeutics, outcome. The editor extends his heartfelt thanks to all the authors
as the plants possess numerous bioactive compounds. Though for publishing their research work through their exceptional
current emerging research and interpretations of phytomedi- contributions and consistent cooperation. The support rendered
cine have been published in several books, pharmacopoeia’s by Prof. Dr. A. Rajendran and Head, Department of Botany,
Phytomedicine: Research and Development has unique prin- Bharathiar University is also acknowledged. The editor also
ciples proposed in different disciplines of phytomedicine, thanks the bioprospecting research team, Dr. Suman Thamburaj,
including ethnopharmacology, nutrition and dietetics, nutra- Mr. Saikumar Sathyanarayanan, Mr. Kasipandi Muniyandi,
ceuticals, and phytochemistry with innovative ideas and clear Ms. Ashwini Lydia Manoharan, Ms. Gayathri Jagadeesan, and
understanding. The information in this book is easy to read Ms. Gayathri Nataraj for their involvement in the compilation of
and will help readers find cutting-edge knowledge concern- the manuscripts in an elegant manner. The editor also extends
ing the scientific validation of medicinal plants. This book is his warm gratitude to the publishers and their team members for
intended to explore important medicinal plants with immense all the technical support and continuous back-up for bringing out
potential for treating various diseases through 26 research and this book in time successfully.
review chapters written by eminent academicians and research
scientists. This book is completely composed of the scientific Prof. Dr. Parimelazhagan Thangaraj
information behind the valuable medicinal plants studied in Coimbatore, India
xi
Editor
Prof. Dr. Parimelazhagan Government of India, Tura, Meghalaya. He has 20 years of
Thangaraj completed his research and 12 years of teaching experience. He has been
education from St. Joseph’s awarded the Raman Fellowship for Post-Doctoral Research
College (autonomous), for Indian Scholars in the United States by the University
Trichy, and PhD from Grants Commission, Government of India, and he undertook
Bharathiar University, research for one year. In addition to these credits, he has
Coimbatore, India. His areas authored several books and book chapters in his field of spe-
of specialization include cialization. He has filed for four patents and has two patents
bioprospecting of medicinal granted. He has more than 80 research publications in interna-
plants. Dr. Parimelazhagan tional and national peer-reviewed journals. He has received
has worked as a scientist in the National Science Day Medal 2005 and Laboratory
the Defence Research & Scientist of the Year award 2005 from DRDO, New Delhi.
Development Organization, Currently, he is engaged in the investigation of phytomedicine
Ministry of Defence, to discover novel herbal drugs and nutraceuticals products to
Government of India. He has also worked as a scientist in the treat some of the most common human diseases like diabetes
Rubber Research Institute of India, Ministry of Commerce, and cancer.
xiii
Contributors
S. Abiraami Valli Palavesam Arunachalam
Department of Plant Biology and Plant Biotechnology Department of Animal Science
Ethiraj College for Women (Autonomous) Manonmanium Sundaranar University
Chennai, India Tirunelveli, India
Ajitabh Bora
Adriano A. S. Araújo
Defence Research Laboratory (DRDO)
Laboratory of Pharmaceutical Assays and Toxicity (LeFT)
Tezpur, Assam-India
Department of Pharmacy
Federal University of Sergipe Rahul Chandran
São Cristóvão, Brazil Laser Research Centre
Faculty of Health Sciences
Y. Aron Santhosh Kumar University of Johannesburg
Botanical Survey of India Doornfontein, South Africa
Southern Regional Centre
Coimbatore, India Pronobesh Chattopadhyay
Defence Research Laboratory (DRDO)
K. Arun Prasath Tezpur, Assam-India
Biomedical Research Laboratories
Department of Botany Vijayakumar Dhaarani
Bharathiar University Department of Botany
Coimbatore, India Bharathiar University
Coimbatore, India
K. Arunachalam
Department of Basic Sciences in Health, Area Pharmacology Sanjai K. Dwivedi
Faculty of Medicine Defence Research Laboratory (DRDO)
Federal University of Mato Grosso (UFMT) Tezpur, Assam-India
Cuiabá, Brazil
xv
xvi Contributors
S. Gangadevi R. Kalidoss
PG and Research Department of Botany Biomedical Research Laboratories
Government Arts College (Autonomous) Department of Botany
Coimbatore, India Bharathiar University
Coimbatore, India
Blassan P. George
Laser Research Centre K. Kalimuthu
Faculty of Health Sciences PG and Research Department of Botany
University of Johannesburg Government Arts College (Autonomous)
Doornfontein, South Africa Coimbatore, India
D. Inbakandan R. Krishnamurthy
Centre for Ocean Research C. G. Bhakta Institute of Biotechnology
Sathyabama Institute of Science and Technology Uka Tarsadia University
Chennai, India Surat, India
G. Iyappan N. Lawal
Genes, Repair, and Regeneration of Ophthalmic Department of Biochemistry & Molecular Biology
Workstation Federal University Dutsinma
Narayana Nethralaya Foundation Dutsin-Ma, Nigeria
Bommasandra, India
B. D. Macham
Gayathri Jagadeesan Chemistry Advanced Research Centre
Bioprospecting Laboratory Sheda Science and Technology Complex
Department of Botany FCT-Abuja, Nigeria
Bharathiar University
Coimbatore, India S. Mahadevan
Department of Botany
Subramaniam Kalidass Government Arts College (Autonomous)
Department of Animal Science Coimbatore, India
Manonmanium Sundaranar University
Tirunelveli, India Ramasamy Manikandan
Botanical Survey of India
and
Southern Regional Centre, TNAU Campus
Institute of Food Security and Sustainable Agriculture Coimbatore, India
(IFSSA)
Universiti of Malaysia Kelantan
Jeli, Kelantan, Malaysia
Contributors xvii
CONTENTS
1.1 Introduction.......................................................................................................................................................................... 1
1.2 Botany, Distribution, and Diversity...................................................................................................................................... 2
1.3 Ethnic Uses........................................................................................................................................................................... 3
1.4 Chemistry of High Hotness.................................................................................................................................................. 3
1.5 Nutritive Value...................................................................................................................................................................... 4
1.6 Commercial Applications..................................................................................................................................................... 4
1.7 Agro-Technology.................................................................................................................................................................. 5
1.8 Conclusion............................................................................................................................................................................ 5
References...................................................................................................................................................................................... 6
1.1 INTRODUCTION analysis of the internal transcribed 1, 5.8S, and internal tran-
scribed 2 sequences lead to a distinct clade for all the acces-
Capsicum assamicum, an extremely pungent chilli, is endemic sions of Bhut jolokia, while C. frutescens and C. chinenese
to northeast (NE) India, particularly in the states of Assam, occupied discrete lineages. Further, a unique 13 base pair
Nagaland, and Manipur. The NE region, lying between 20.59° deletion was observed in all the accessions of Bhut jolokia,
latitude and 78.96° longitude, has a unique environment with making it distinct from all other chilli species. The morpho-
a high degree of humidity, which has led to the development logical features of Bhut jolokia, such as profusely branched
of extreme pungency in this chilli. It is known by different habitat, yellow green corolla, pale blue anther, orange red
names and Bhut jolokia is the name as it is called in Assam, color, and sub-conical to conical fruits with rough, uneven,
while it is called Naga chilli in Nagaland. dented skin, and anatomical details of the stem make its
The identity of this species has been a point of contro- distinct from C. frutescens and C. chinense (Purkayastha
versy since its discovery, regarding its phylogenetic position. et al. 2012a). Moreover, phylogeny, based on median join-
Mathur et al. (2000) reported the Bhut jolokia to be a vari- ing network analysis, revealed clear distinction of the Naga
ety of Capsicum frutescens L., while in the Guinness Book King Chilli from its closest relatives (C. chinense and C.
of World Records (2006), Bhut jolokia has been recorded frutescens) and the absence of a star-like network of hap-
as belonging to the species of C. chinense (Purkayastha lotypes indicates the expansion of an ancient population of
et al. 2012b). On the other hand, Bosland and Baral (2007) this chilli species. Besides, the differential proteomic anal-
reported Bhut jolokia to be a natural hybrid of C. frutescens ysis of Bhut jolokia revealed 22 differential protein spots,
and C. chinense based on Random Amplified Polymorphic which appeared only in this species, but not in C. frutescens
DNA (RAPD) analysis. But the RAPD technique has several and C. chinense. Thus, Bhut jolokia has been established as
limitations, such as non-reproducibility of results, compe- a distinct species within the genus Capsicum and christened
tition between different DNA fragments for amplification as C. assamicum Jubilee Purkayastha & L. Singh sp. nov.
(Williams et al. 1993; Halldén et al. 1996), and identical (Purkayastha et al. 2012a). This was further validated by
mobility of fragments with different sequences (Xu 2006), Kehie et al. (2016), who also observed distinct 13 base dele-
which limits its uses for interpopulation or interspecies tions in the 5.8S gene in all the accessions of the Naga King
comparisons. Purkayastha et al. (2012b) undertook molecu- Chilli, unlike other Capsicum species. These works clearly
lar studies of Bhut jolokia to determine the distinctness of establish Bhut jolokia or Naga King Chilli as a distinct spe-
this species from C. frutescens and C. chinenese through cies of chilli endemic to northeast India. This chilli has been
sequencing of the ribosomal RNA gene-internal transcribed patented under the Geographical Indication Registry by the
region along with its phylogenetic analysis. The phylogenetic Government of Nagaland (Kehie et al. 2014).
1
2 Phytomedicine
TABLE 1.1
Few Ethnic Uses of Capsicum assamicum in Treating Human Aliments
Sl. No. Ailments Mode of Application Mode of Action
1. Asthma Regular consumption of raw fruits in Dilation of blood vessels by capsaicin, thereby
low quantities relieving chronic congestion
2. Gastrointestinal abnormalities Regular consumption of raw fruits in Stimulation of saliva and gastric juice by capsaicin
low quantities as well as protection of mucous membrane
3. Toothache/muscle pain Hot infusions of fruits. But it should Alleviation of pain by capsaicin
not be applied on injured tissues
4. Removal of puss from boils/arthritis/headache Paste of leaves applied locally Removal of puss from boils/pain alleviation
4 Phytomedicine
FIGURE 1.6 Dried fruits of Bhut jolokia. FIGURE 1.7 Capsigrenade (a), capsispray for personal protection
(b), and mob dispersal (c).
explored judiciously with proper post-harvest handling Kehie, M., Kumaria, S., Devi, K.S., and Tandon, P. 2016. Genetic
and good market network, can bring about an economic diversity and molecular evolution of Naga King Chilli
upsurge for the farmers of this region. With the increase inferred from internal transcribed spacer sequence of nuclear
ribosomal DNA. Meta Gene 7: 56–63.
in p opularity and demand for this native chilli of NE
Kehie, M., Kumaria, S. and Tandon, P. 2014. Manipulation of cul-
India, the first King Chilli Festival was organized in the ture strategies to enhance capsicin biosynthesis in cell cultures
Tamenglong District of Manipur in 2018 to attract tourists of Capsisum Chinense Jacq. cv Naga King Chilli. Bioprocess
as well as entrepreneurs for setting up post-harvest pro- Biosyst. Bioprocess Eng. 37: 1055–1063.
cessing units for export of this chilli in the form of value- Mathur, R., Dangi, R.S., Das, S.C., and Malhotra, R.C. 2000.
added products. The hottest chilli variety in India. Current Science 79:
Due to the rising demand of this chilli, both in the domes- 287–288.
Meghvansi, M.K., Sidiqui, S., Khan, H., Gupta, V.K., Vairale, M.G.,
tic and international markets, this chilli is being cultivated
Gogoi, H.K., and Singh, L. 2010. Naga chilli: A potential source
on a wide scale in different regions of northeast India. of capsaicinoids with broad-spectrum ethnopharmacological
The chilli is being sold in the open market at the price of applications. Journal of Ethnopharmacology 132: 1–14.
Rs. 300– 400 per kg in Assam depending upon the season and Pandey, V., Pandey, H.K., Dayal, D., Joshi, U.C., Pant, T., and
size of the fruit. They are also sold loose at 3–4 fruits for ten Ahmed, Z. 2009. Studies on antioxidant constituents of some
rupees. This reflects the high demand of this chilli for domes- domesticated capsicums in the middle hill conditions of west-
tic consumption, since the supply is not adequate as the ern Himalayas. Horticultural Science 36: 26–30.
cultivation is restricted to only a few areas owing to the suit- Purkayastha, J., Alam, S.I., Gogoi, H.K., and Singh, L. 2012a.
Capsicum assamicum sp. Nov. (Solanaceae) from Assam,
ability of the agro-climate. Since the availability of the chilli Northeastern India. Ozean Journal of Applied Science 5: 55–66.
is restricted to only a few months of the year, the demand is Purkayastha, J., Alam, S.I., Gogoi, H.K., Singh, L., and Veer, V.
high in the market. Moreover, extraction of capsaicin is lim- 2012b. Molecular characterization of ‘Bhut jolokia’ the hot-
ited to the time of availability of the fruit, for which, R&D test chilli. Journal of Biosciences 37: 757–768.
efforts are being made by the Defence Research Laboratory, Roy, A. 2016. Bhut jolokia (Capsicum chinense Jacq.): A review.
Tezpur for in vitro production of capsaicin through cell sus- International Journal of Pharmaceutical Sciences and
pension culture. Breakthroughs have been made at laboratory Research 7: 882–889.
Sanatombi, K., and Sharma, G.J. 2008. Capsaicin content and
scale, which need to be scaled-up, for which further studies pungency of different Capsicum spp. Cultivars. Notulae
are being carried out. Botanicae Horti. Agrobotanici Cluj-Napoca 36: 89–99.
Singh, M.S. 2009. Standardization of sowing time and plant popula-
tion of Bhut Jolokia (Capsicum chinense). MSc Thesis. Assam
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Borgohain, R., and Devi, J. 2007. The hottest chilli: A new horizon centa of Capsicum annuum cv. Karayatsubusa. Plant and Cell
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assamagribusiness.nic.in Talukdar, J., Saikia, A., and Borah, P. 2015. Survey and detection
Bosland, P.W. 1996. Capsicums: Innovative uses of an ancient crop. of the diseases of Bhut jolokia (Capsicum chinense Jacq.) in
In Janick, J., (Ed.), Progress in New Crops. ASHS Press, Assam. Journal of Crop and Weed 11: 186–192.
Arlington, VA, 479–487. Tiwari, A., Kaushik, M.P., Pandey, K.S., and Dangi, R.S. 2005.
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Guinness Book of World Records. 2006. http://en.wikipeia.org/wiki/ Williams, J.G.K., Hanafey, M.K., Rafalski, J.A., and Tingey, S.V.
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2 Plant-Based Compounds as
Alternative Adjuvant Therapy for
Multidrug-Resistant Cancer
E. C. Aniogo, Blassan P. George, and Heidi Abrahamse
CONTENTS
2.1 Introduction.......................................................................................................................................................................... 7
2.2 Multidrug Resistance Mechanisms...................................................................................................................................... 7
2.3 Classifications of Plant-Derived Compounds....................................................................................................................... 8
2.3.1 Carotenoids............................................................................................................................................................... 9
2.3.2 Phenolics................................................................................................................................................................... 9
2.3.3 Nitrogen-Containing Compounds............................................................................................................................ 9
2.3.4 Organosulfur Compounds........................................................................................................................................ 9
2.4 Bioactive Plant-Derived Compounds with Antitumor Activity Against Multidrug-Resistant Cells.................................... 9
2.5 Conclusion and Future Prospects....................................................................................................................................... 11
Acknowledgments........................................................................................................................................................................ 11
References.................................................................................................................................................................................... 11
membrane. Today, there are 48 identified human ABC genes abnormal cells with increased survival proteins to protect
grouped into seven subclasses (A–G) based on their sequence themselves and inhibit cell death. These, in addition to reduced
of homology and genomic organization (Chorawala et al. 2012; apoptosis and other forms of cell death, have underpinned drug
Eid et al. 2015). In clinical transport-associated multidrug resistance. Other factors like tumor microenvironments, where
resistance, the MDR1 gene, which encodes for P-glycoprotein cancer cells reside, and intratumoral genetic heterogeneity with
(P-gp; MDR1, ABCB1), is the widely studied. The P-gp has two proximity to stromal cells can function in paracrine manner to
highly hydrophobic integral membrane and nucleotide-binding support the survival of cancer cells. For example, various tumor
domains that make up its structure. This structure enables them landscapes create numerous microenvironmental niches, and
to efficiently efflux cytotoxic drugs through a “pump” and each niche with genetically identical cancer cells will respond
“flippase” model of transport from the inner leaflet to the outer differentially to the same treatment due to different biophysi-
leaflet of the lipid bilayer into the extracellular space (Sharom cal properties, such as: vascularity, Potential of Hydrogen (PH),
2014). Other ABC transporters: the multidrug resistance- hypoxia, and extracellular matrix organization of the niche
associated protein 1 (MRP-1, ABCC1) and the breast cancer- (Rybinski and Yun 2016). Tumor-initiating cells otherwise
resistant protein (BCRP, ABCG2) have been implicated as known as cancer stem cells may also play a role in tumor resis-
major efflux transporters responsible for cancer resistance in tance. These cells utilize the expression of ABC transporters,
chemotherapy (Mao and Unadkat 2015). The MRP1 is similar altered DNA damage response, and expression of pro-survival
in structure with the P-gp/MDR1 and contains an added amino proteins to evade and better tolerate drug exposure. The cancer
terminal in the domains attached to the core that can recognize stem cells are thus refractory to drug treatment and often con-
both neutral and anionic hydrophobic natural products and tribute to cancer relapse, recurrence, and resistance (Abdullah
transports glutathione (Eid et al. 2015). The ABCG2 gene and Chow 2013).
located at 4q22 encodes human BCRP. Structurally, the BCRP
contains an ATP-binding domain and six transmembrane 2.3 CLASSIFICATIONS OF PLANT-DERIVED
segments in a homodimer of two-half transporters. The BCRP
COMPOUNDS
is highly expressed and widely distributed in the gastrointestinal
tract, excretory tissue, and blood-tissue barriers (Fletcher et al. Phytochemicals are bioactive compounds found in plants.
2016). Many of these compounds are in synergy with several nutri-
Genetic responses that lead to changes in cellular pro- ents, vitamins, and minerals found in foods to possess disease
cesses have been identified as another drug resistance mecha- preventive effects (Kapinova et al. 2018). These effects are
nism. Alterations in cell cycle, increased DNA damage repair, expected to be integrated into the human diet, thus, a grow-
reduced apoptosis, and altered drug metabolism are among the ing emphasis has been placed on dietary plant products as
cellular changes that affect the ability of cytotoxic drugs to kill an alternative approach toward the prevention and treatment
cancerous cells (Cree and Charlton 2017). Rapid downregula- of cancer, especially breast cancer (Bak et al. 2016). Based
tion of a target gene expression and mutations are common in on the chemical structure and biological properties, phyto-
cancer cells, which enables them to escape upon DNA dam- chemicals can be classified as phenolics, carotenoids, alka-
age, and become susceptible to increased DNA repair mecha- loids, nitrogen-containing, and organosulfur compounds, as
nisms for the replication process to continue. Thus, producing discussed in Figure 2.1 (Kapinova et al. 2018).