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359
Molecular Farming of Medicinal Plants
in Face of Environmental Challenges
20
Priya Patel, Priyanka Shah, Manisha Hariwal, Shweta Verma,
Rahul Yadav, and Sanjay Kumar
Abstract
The uses of medicinal plant as a medicine and secondary metabolites are about a
century old, but genetic engineering of these medicinal plants for production of
pharmaceuticals is much more recent. Molecular farming aids in increasing the
pharmaceutical compounds which are easily available and significantly cost-
effective. Recently the cost of biopharmaceutical availability is limited, but
plant-based pharmaceuticals are available in stores, and it is cheap to produce
the plant-based compounds which help scale up the industry. Here we discussed
the recent development of molecular farming in this field and possible environ-
mental challenges.
Keywords
Medicinal plant · Molecular farming · Edible vaccine · Pharmaceuticals
20.1 Introduction
Any eukaryote that is a member of the biological kingdom Plantae is referred to as a
plant. In the strictest sense, plants are embryophytes, which comprise mosses,
liverworts, hornworts, and vascular plants. Less formal references have referred to
green alga as plants. The incredible network of life on this planet bestows humanity
countless blessings. Healthy wild ecosystems generate the air we breathe, the foods
we eat, the pure water we drink, the medicines that heal and protect us, and the
materials that make up our shelter and clothes. Natural disasters like hurricanes,
floods, and landslides are lessened by wild ecosystems, which also help to regulate
P. Patel · P. Shah · M. Hariwal · S. Verma · R. Yadav · S. Kumar (✉)
Department of Botany, Banaras Hindu University, Varanasi, India
#
The Author(s), under exclusive license to Springer Nature Singapore Pte
Ltd. 2023
D. Singh et al. (eds.), Stress-responsive Factors and Molecular Farming
in Medicinal Plants,
https://doi.org/10.1007/978-981-99-4480-4_20
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our climate. They guard us against pests and illnesses, e.g., species like spiders, for
instance, literally filter insects from the air, and plant roots remove pathogens and
contaminants from streams and different water sources. For all these priceless
benefits, people, communities, and economies depend on intact, diverse native
wild areas.
360 P. Patel et al.
20.2 Medicinal Plants
Around us, medicinal plants naturally flourish. For a very long time, medicinal
plants have been man’s best friend. Any plant that has compounds that can be
utilized to cure a variety of diseases or serve as a precursor for the manufacture of
effective pharmaceuticals is considered to be a medicinal plant. Early civilizations
only used medicinal plants to treat their various illnesses, and over time, what began
as simple herbal remedies all over the world developed into complete medical
systems like Ayurveda, Chinese, Korean, Japanese, European, and Unani systems
of medicine. These systems place a strong emphasis on holistic healing, which
includes both prophylaxis and therapeutics. The use of medicinal plants for a variety
of purposes has reignited interest since they provide affordable and reliable medical
treatments. By producing medical goods, medicinal plants have had a tremendous
impact on the lives of the native inhabitants of these areas. For many years, people
have employed medicinal plants to cure health problems and prevent disease,
including epidemics. Since a bygone era, people have known the fundamentals of
how medicinal plants can treat a variety of ailments (Sharma et al. 2020a).
In recent years, there has been an increase in scientific and economic interest in
the medicinal plants that inhabit natural environments. Worldwide, between 50,000
and 80,000 flowering plants are used medicinally (Marinel li 2005). In the United
States, of the top 150 population drugs, at least 118 are based on natural sources:
74% come from plants, 18% from fungi, 5% from bacteria, and 3% from vertebrate
species such as snakes or frogs.
Scientific and commercial interests in medicinal plants that exist in natural
environments have grown. At least 118 of the top 150 prescription medications in
the United States are derived from natural sources. By 1997, two medications
produced from a wild plant indigenous to Madagascar had boosted the possibility
of remission from the 10% that a child with leukemia had in 1960 to the 95% that it
had in 1997. Althoug h the world has a great variety, the overuse of medicinal plants
has put many species in danger of going extinct. In contrast, medicinal plants
frequently have to withstand harsh environmental conditions; are susceptible to
fungal, bacterial, and viral diseases; and have evolved and developed systems to
produce secondary metabolites in order to live. However, we still know very little
about the rich variety that lives in our medicinal plants. To meet the soaring demand,
however, the output of secondary metabolites in plants grown in the field is fre-
quently poor at times. Less than 1% of all tropical plant species had undergone
screening for potential medicinal uses as of 1995. The burden on the wild plant
populations, from which many medicinal plants are taken, is growing as medicinal
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plants gain more scientific and economic attention. Numerous species used for
medicine are now endangered due to overharvesting. Indigenous peoples who
have relied on traditional remedies for years or millennia occasionally no longer
have access to them due to commercial exploitation. All these factors have made it
more necessary than ever to study and preserve medicinal plant (and animal) species.
This urgency is increased by the worldwide acceleration in the loss of
species and
habitat. Around 15,000 medicinal plant species may already be in danger of going
extinct worldwide. According to experts, at least one significant major drug
disappears from the planet every 2 years. Over time, it has become clear that plant
improvement is crucial, particularly for increasing yields of high-value, low-volume
chemicals with potential as medicines. By enhancing plant strains and secondary
metabolite productivity, conventional genetic te
chniques have aided in a variety of
ways. Nevertheless, there is a demand for better methods and protocols for improv-
ing medicinal plants, and here is where plant biotechnology has found a market.
20 Molecular Farming of Medicinal Plants in Face of Environmental Challenges 361
20.3 Medicinal Plant and Biotechnology
Medicinal plant biotechnology is still a new field, but it has already increased the
production of secondary metabolites and helped preserve exceptional strains. A
superior medicinal plant metabolite was selected, multiplied, improved, and
subjected to enhanced molecular analysis thanks to biotechnological interventions.
The development of new therapeutic plants and increasing the yield of secondary
metabolites have both benefited from genetic transformation. Utilizing rDNA tech-
nology and drawing inspiration from developments in genomics and proteomics,
several new varieties of medicinal plants have been created that are remarkably
resistant to diseases and the whims of the environment and produce completely
unique novel compounds that are not found in nature’s repertoire. While DNA
microarrays are increasingly used as high-throughput screening tools for the simul-
taneous analysis of many genes and gene expression in order to learn more about the
complex regulatory molecular pathways, upscaling the production of secondary
metabolites in bioreactors has greatly reduced costs. The recently developed disci-
pline of bioinformatics of medicinal plants is another area with a ton of room for
investigation. In plants, edible vaccinations have alrea dy been created, and they will
soon be available for purchase. In the upcoming years, we might see a number of
more high-end designer medicinal plants with a variety of features that could combat
both climate change and function as a panacea.
The life-saving profit of this valuable’s trove is extensive:
• According to the National Cancer Institute, at least 70% of new drugs introduced
in the United States in the last 25 years are derived from natural sources
(Steenhuysen
2007).
• Plant-derived anticancer drugs, such as Taxol, first isolated from the Pacific yew,
save at least 30,000 lives per year in the United States (Lawton and Daily
1997).
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• Thanks to two drugs derived from alkaloids of Madagascar’ s rosy periwinkle, the
likelihood of remission for a child suffering from leukemia increased by 85%
between 1960 and 1997 (Lawton and Daily
1997).
• New compounds, such as one recently discovered in a plant in Madagascar, are
likely to provide novel antibiotics and help curb the epidemic of antibiotic-
resistant diseases (Wang et al.
2006).
• New classes of antiviral drugs derived from plants such as star anise provide
unprecedented hope for combating potential epidemic viral diseases such as flu
(Laurance
2005).
• Drugs to fight life-threatening diseases such as diabetes, HIV, and diarrhea—and
even substances to protect crops from slugs—are being developed from plants,
microorganisms, amoebae, and other species from African countries such as
Egypt, Somalia, Libya, and Gambia (Barnett
2006).
362 P. Patel et al.
Of course, using wild species to treat illness and stave it off is nothing new. More
than 5000 different plant species have been employed by healers in China for at least
4000 years (Tuxill
1999). More than 80% of the 1.4 billion people in South Asia lack
access
to modern healthcare and instead rely on traditional medicine that uses local
species. In truth, many indigenous and local populations are vast repositories of
traditional knowledge that can aid in the development of biotechnology,
pharmaceuticals, agriculture, and healthcare.
20.4 Threats for Medicinal Plants: Destruction of Habitat,
Bioprospecting, and Overharvesting
Due to habitat degradation, bioprospecting for new sources, and overharvesting of
recognized medicinal species, medicinal plants are under growing risk. United Plant
Savers now identifies 19 native medicinal plants from North America as being “at
peril.” In the groups, 22 more plant species have been identified. The Forest Service,
the National Centre for the Preservation of Medicinal Herbs (NCPMH), other herb
societies, the Global Convention on Biological Diversity, the Convention on Inter-
national Trade in Endangered Species (CITES), and scientists also keep track of,
keep records of, and work to conserve imperilled medicinal species around the
world.
The benefits that herbal medicine provides are the main reason why it is becoming
more and more popular throughout the world. The benefits that herbal medicine
provides are the main reason why it is becoming more and more popular throughout
the world. According to estimates from the World Health Organization, approxi -
mately 80% of people worldwide live in underdeveloped nations and rely mostly on
herbal therapy to treat their medical conditions (Sharma et al.
2020a). Typically,
medicinal plants are taken from the wild, which destroys the ecosystem and depletes
the genetic variety that cannot be replaced. The following benefits can be obtained
via systematic cultivation of medicinal plants as opposed to collecting them from
the wild: (1) optimizing yield and producing a high-quality product, (2) no issue with
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identity confusion, (3) less variation in genes and phenotypes, (4) contaminants are
handles as a problem, (5) the issue of extract fluctuation and instability is lessened,
(6) availability in significant quantities without causing environmental harm. How-
ever, occasionally the chemical spectra of medicinal and aromatic plants (MAPs)
grown for their uses deviate significantly from those of their wild counterparts.
Traditional plant-breeding techniques have been
heavily used to increase
agronomical and medicinal features in order to achieve top germplasm with
improved quality, and molecular marker-assisted breeding has been applied with
significant returns on investment. However , it has been felt that the only way to
significantly increase MAPs in order to satisfy the industry’s future need is to use
biotechnological treatments.
20 Molecular Farming of Medicinal Plants in Face of Environmental Challenges 363
20.5 Habitat Destruction
Less than 1% of all tropical plant species had been examined for possible medicinal
uses as of 1995. Environments are being destroyed faster than scientists can study
them. Experts believe that the Earth is losing at least one important medicine
candidate every 2 years at the current extinction rates.
20.6 Bioprospecting and “Biopiracy”
The medicinal plant industry is quite lucrative. According to a 1995 analysis, each
new plant-derived medication is worth, on average, $449 million to society and $94
million to pharmaceutical businesses (Lawton and Daily
1997; Mendelsohn and
Balick 1995). According to other projections, nonprescription medicinal plant sales
in the United States range from $1.5 to $5.7 billion yearly, with $24.4 billion in
global sales. In 1985, the market for prescription and over-the-counter plant-based
medications was estimated to be worth $84.3 billion globally and $19.8 billion in the
United States (Pearce and Moran 2013).
The availability of historically used, easily accessible, and reasonably priced
medicinal plant resources to populations that have relied on them for ages may
decrease as a result of this profitability. The term “biopiracy” has been coined to
describe the practice of private companies patenting traditional remedies from the
wild and selling them at a vast profit, often allowing little or none of that profittogo
back to the country or indigenous and local communities of origin (Barnett
2006).
Occasionally, after a medicine is patented, indigenous and local communities that
have utilized it for millennia may no longer be able to use it or gain from it. For
instance, the neem tree, a relative of mahogany from South Asia, has produced
highly powerful and lucrative germicides, fungicides, and other substances. At least
50 patents for goods made from this species had been given to American and foreign
businesses by 1995. International humanitarian organizations and environmentalists
have opposed these patents (Torrance 2002).
The World Intellectual Property Organization (WIPO) established a Traditional
Knowledge Task Force in 2001 in response to an Indian proposal in response to the
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patenting of traditional goods like neem and turmeric (used for wound healing). This
task force was made up of representatives from the United States, China, EU, Japan,
and India. The task force conducted a thorough search of international patent
databases and discovered that the US Patent and Tradema rk Office’s databases
alone contained more than 5000 patent references on 90 medicinal plants. Seven
plants with Indian ancestry were the subject of 80% of the patents issue
d for these
90 therapeutic plants. More than 45% of patents on medicinal plants were found to
fall under traditional knowledge systems, according to a thorough analysis of
762 patents on medicinal plants conducted by the Patent and Trademark Office.
Because of the controversy surrounding the rights of nations and indigenous
communities to traditional medicines and local native species and products, the
Global Convention on Biological Diversity specifically recognize
s the property
rights of indigenous and local communities over commercial exploitation of tradi-
tional remedies and other native species (Barnett
2006).
364 P. Patel et al.
Overharvesting Indigenous people
s’ access to traditional treatments is being
restricted while overharvesting of certain species also threatens the habitats of
some economically valuable wild species. This danger has long been recognized.
The World Conservation Union (IUCN) estimates that overharvesting may be
endangering the existence of over 15,000 medicinal plant species globally. The
Wildlife Commerce Monitoring Network (TRAFFIC), which was established more
than 30 years ago by the World Wildlife Fund and the IUCN, was created to track
and regulate international trade in wild species, particularly those used as medicines.
US National Park Service and TRAFFIC has documented the hazards posed by
overcollection to wild species on american public lands in serveral reports.
20.7 Medicinal Plants in Industrialized Societies
In mainstream medicine, plant-based remedies have been largely superseded by
“chemical” medications in the latter half of this century. This advancement is
consistent with the prevalent understanding of the disease, the conviction in
human-initiated progress, and the pursuit of pure medicinal compounds with a single
active principle . However, a closer look reveals that up to 60% of prescription
medications in Eastern Europe and over 25% of all medications in OECD nations
are made from unaltered or just minimally altered higher plant products. They cover
crucial therapeutic areas like quinine and artemisinin against malaria, digitalis
derivatives for heart failure, anticancer drugs like vinblastine/vincristine, Taxol,
and etoposide and steroids (prednisone) and muscle relaxant (used for abdominal
surgery and anesthesia). All of these are made from wild yam. Cost-effectively
synthesizing these agents is not possible. As a result, the reliable availability of
plant material, whether from cultivation or the wild, is necessary for their manufac-
ture. This is the situation with the non-cultivable wild yam Dioscorea composita
(hemp), which is sold in large quantities from Mexico and other nations (Fig.
20.1).
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20 Molecular Farming of Medicinal Plants in Face of Environmental Challenges 365
Fig. 20.1 Industrial use of medicinal plant
20.8 Effect of Climate on Medicinal Plant
Since the beginning of time, medicinal and aromatic herbs have been essential in
reducing human suffering from illnesses, disorders, and afflictions. The main factors
contributing to the reduction of wild medicinal plant species are natural disasters and
human activities, such as overharvesting, destructive harvesting, floods, declining
forest cover, pollution from overpopulation, urbanization, and industrial activity.
Unlike all other living creatures in the biosphere, medicinal and aromatic plants are
not immune to the effects of climate change. Some medicinal plants that are unique
to specific geographic areas or ecosystems are consequently put at risk and are
especially vulnerable to climate change. Additionally, these issues with climate
change will undoubtedly constitute a more serious or urgent threat and have the
ability to put increasing pressure on species of medicinal plants. The impact of
global climate change on medicinal plants is extremely likely, especially given their
importance in traditional medical systems and as plants with commercial value
(Sharma et al. 2020b) (Table 20.1).
20.9 Examples of Endangered Species
Species like the following have been noted as being in danger of extinction in
the wild:
• Ulmus rubra (slippery elm): In North America, particularly in Appalachia, the
sticky lining of the slippery elm’s bark has long been utilized as a calming remedy
for gastrointestinal problems, coughs, and skin irritations. The seasonal use of
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366 P. Patel et al.
Table 20.1 Medicinal plant status in relation to climate change
S. no. Name Local name Status Uses
1. Withania
Somnifera
Ashwagandha Vulnerable Treatment for ulcers and cardiovascular
ailments
2. Swertia
chirayita
Chirayita Vulnerable Very effective in malarial fever and
edema
3. Rauwolfia
serpentina
Sarpgandha Endangered Antihypertensive, root extract used in
various central nervous disorder and
epilepsy
4. Aconitum
ferox
Vatsanabha Vulnerable Poisonous, used for treatment of
leprosy, fever, cholera, sore throat, and
gastric disorder
5. Gloriosa
superba
Kalihari Endangered Used in gout, infertility, ulcers,
arthritis, and kidney problems, used in
arrow poison
6. Centella
asiatica
Brahmi,
gotukola
Endangered Treatment in chronic dysentery used as
antiseptic
7. Dalbergia
latifolia
Satisal Vulnerable Used for fuel and timber,
bark used in
treatment of ulcer, acne, and pimple
8. Saussurea
obvallata
Brahmakamal Endangered Bitter in taste and used in fever,
urogenital disorders, and liver problems
9. Nelumbo
nouchali
Bagabhet Endangered Used as nutraceutical
slippery elm and other herbal product s by locals has changed, but now millions
more people want them. Trees are stripped of their bark and then left to wither
since slippery elm wood has little market value. For every 50 pounds of dried
bark, 12 trees are sacrificed. Bark in 50-pound containers can sell for up to $150.
The National Center for the Preservation of Medicinal Herbs (NCPMH), the US
Forest Service, and the US Park Service have all designated this species as “at
risk.”
• Taxus species (Yew): Taxus brevifolia and Taxus chinensis are two types of yew
trees that are used to make the well-known, lucrative, and successful cancer
medication Taxol. Several yew species have been designated as needing protec-
tion from overharvesting for international trade by CITES.
• Cimicifuga racemosa (black cohosh): a member of the buttercup family that has
been used for centuries to cure a numbe r of ailments, including menopause,
rheumatism, and pain. The supply of black cohosh is derived almost entirely
from wild gathering. The US Forest Service and other organizations have listed
the species as being endangered due to overharvesting and habitat destruction.
• Panax quinquefolius (American ginseng): In North America, sales of both wild
and cultivated ginseng total more than $25 million annually, with wild ginseng
being the more sought-after variety. Given how much more profitable wild
ginseng is than cultivated ginseng, there is a significant deal of worry regarding
the extinction and threatened status of the species in the wild. This species is
subject to CITES regulation.
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• Hydrastis canadensis (goldenseal): This member of the buttercup family has a
long history of usage as a tonic and in the treatment of conditions like
hemorrhoids. More than 60 million golden seal plants are taken each year without
being replaced, according to the NCPMH and CITES, and many states already
classify the species as uncommon, threatened, or endangered.
20 Molecular Farming of Medicinal Plants in Face of Environmental Challenges 367
To
stop
overhar
vesting
from
t
he
wild,
CITES
regulates
inte
rnational trade in this
species as well as many others.
20.10 Medicinal Plant Information Databases
Documents and databases geared for readers in a variety of fields, such as botany,
chemistry, horticulture, medicine, social sciences, veterinary science, and econom-
ics, contain information about therapeutic plants. More and more of this material is
now available in electronic form as a result of recent advancements in information
technology and telecommunications. Reviewing the variety of primary, secondary,
and tertiary electronic publications that are available, as well as the main online
databases and offline electronic goods that include knowledge on medicinal plants, is
done. Concomitant with the growing interest worldwide in the conservation, culti-
vation, and use of medicinal, aromatic, and other related groups of plants, there has
been a fourfold increase in the volume of literature published on these plants during
the past two decades (Bhat
1994).
Sources of Information on Medicinal Plants (a) Primary sources, (b) Secondary
information database. (c) Tertiary information database.
20.11 Molecular Farming
Plant molecular farming (PMF) is a new branch of plant biotechnology, where plants
are engineered to produce recombinant pharmaceutical and industrial proteins in
large quantities. Plant molecular farming is the practice of growing plants for
pharmacological or industrial purposes rather than to produce feed, food, or fiber.
Plant molecular farming is the recombinant production of medicines, functional
proteins, industrial enzymes, and functional secondary metabolites in plants
(PMF). According to Basaran and Rodriguez-Cerezo (2008), the phrases molecular
farming, biofa rming, molecular pharming, recombinant or plant-made industrials,
plant bioreactors, plantapharma, plant biofactories, and phyto-manufacturing, and
pharmaceutical gardening are all interchangeable (Basaran and Rodriguez-Cerezo
2008). Molecular pharming is a new biotechnology tool that uses plants as the host to
generate substantial amounts of industrial proteins and recombinant medicines like
vaccines and antibodies (Fig.
20.2).
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