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144 Herbal Pharmacopeia
Singh, R. K., Joshi, V. K., Goel, R. K., Gambhir, S. S., & Achaiya, S. B. (1996). Pharmacological actions of
Pongamia pinnata seeds - A preliminary study. Indian Journal of Experimental Biology, 34(12), 1204–1207.
Singh, S., & Sedha, S. (2016). Medicinal Plants and Their Pharmacological Aspects. Food & Pharma
International, 1(4). https://doi.org/10.5530/fpi.1.4.1
Siow, Y. L., Gong, Y., Au- Yeung, K. K. W., Woo, C. W. H., Choy, P. C., & Karmin, O. (2005). Emerging issues
in traditional Chinese medicine. In Canadian Journal of Physiology and Pharmacology, 83(4). https://
doi.org/10.1139/y05-029
Sostres, C., Gargallo, C. J., & Lanas, A. (2013). Nonsteroidal anti- inammatory drugs and upper and lower gas-
trointestinal mucosal damage. In Arthritis Research and Therapy, 15(3). https://doi.org/10.1186/ar4175
Sultana, S., Akhtar, N., & Asif, H. M. (2013). Phytochemical screening and antipyretic effects of hydro-
methanol extract of Melia azedarach leaves in rabbits. Bangladesh Journal of Pharmacology, 8(2).
https://doi.org/10.3329/bjp.v8i2.14708
Sung, W. S., & Lee, D. G. (2007). In vitro antimicrobial activity and the mode of action of indole- 3-carbinol
against human pathogenic microorganisms. Biological and Pharmaceutical Bulletin, 30(10). https://doi.
org/10.1248/bpb.30.1865
Tlili, N., Elfalleh, W., Saadaoui, E., Khaldi, A., Triki, S., & Nasri, N. (2011). The caper (Capparis L.):
Ethnopharmacology, phytochemical and pharmacological properties. Fitoterapia, 82(2). https://doi.org/
10.1016/j.tote.2010.09.006
Tolo, F. M., Rukunga, G. M., Muli, F. W., Njagi, E. N. M., Njue, W., Kumon, K., Mungai, G. M., Muthaura, C.
N., Muli, J. M., Keter, L. K., Oishi, E., & Ko- Tsekpo, M. W. (2006). Anti- viral activity of the extracts
of a Kenyan medicinal plant Carissa edulis against herpes simplex virus. Journal of Ethnopharmacology,
104(1–2). https://doi.org/10.1016/j.jep.2005.08.053
Tran, N., Pham, B., & Le, L. (2020). Bioactive compounds in anti- diabetic plants: From herbal medicine to
modern drug discovery. Biology, 9(9). https://doi.org/10.3390/biology9090252
Vane, J. R., & Botting, R. M. (1995). New insights into the mode of action of anti- inammatory drugs.
Inammation Research, 44(1). https://doi.org/10.1007/BF01630479
Veerakumar, S., Amanulla, S. S. D., & Ramanathan, K. (2016). Anti- cancer efcacy of ethanolic extracts from
various parts of Annona squamosa on MCF- 7 cell line. Journal of Pharmacognosy and Phytotherapy,
8(7). https://doi.org/10.5897/JPP2016.0398
Verma, S., & Singh, S. P. (2008). Current and future status of herbal medicines. In Veterinary World, 1(11).
https://doi.org/10.5455/vetworld.2008.347-350
Wagner, H., & Ulrich- Merzenich, G. (2009). Synergy research: Approaching a new generation of phytophar-
maceuticals. In Phytomedicine, 16(2–3). https://doi.org/10.1016/j.phymed.2008.12.018
Wangchuk, P., Keller, P. A., Pyne, S. G., Taweechotipatr, M., Tonsomboon, A., Rattanajak, R., &
Kamchonwongpaisan, S. (2011). Evaluation of an ethnopharmacologically selected Bhutanese medicinal
plants for their major classes of Phytochemicals and biological activities. Journal of Ethnopharmacology,
137(1). https://doi.org/10.1016/j.jep.2011.06.032
Webster, D., Taschereau, P., Lee, T. D. G., & Jurgens, T. (2006). Immunostimulant properties of Heracleum
maximum Bartr. Journal of Ethnopharmacology, 106(3). https://doi.org/10.1016/j.jep.2006.01.018
World Health Organization. (1978). The promotion and development of traditional medicine : report of a WHO
meeting [held in Geneva from 28 November to 2 December 1977]. In World Health Organization techni-
cal report series (Issue 622).
Yamai, M., Tsumura, K., Kimura, M., Fukuda, S., Murakami, T., & Kimura, Y. (2003). Antiviral activity of a
hot water extract of black soybean against a human respiratory illness virus. Bioscience, Biotechnology
and Biochemistry, 67(5). https://doi.org/10.1271/bbb.67.1071
Yang, C. M., Cheng, H. Y., Lin, T. C., Chiang, L. C., & Lin, C. C. (2007). The in vitro activity of geraniin and
1,3,4,6-tetra- O- galloyl- β-d- glucose isolated from Phyllanthus urinaria against herpes simplex virus type
1 and type 2 infection. Journal of Ethnopharmacology, 110(3). https://doi.org/10.1016/j.jep.2006.09.039
Yatoo, M. I., Saxena, A., Gopalakrishnan, A., Alagawany, M., & Dhama, K. (2017). Promising antidiabetic
drugs, medicinal plants and herbs: An update. In International Journal of Pharmacology, 13(7). https://
doi.org/10.3923/ijp.2017.732.745
Zaika, L. L. (1988). Spices and herbs: Their antimicrobial activity and its determination. Journal of Food
Safety, 9(2). https://doi.org/10.1111/j.1745-4565.1988.tb00511.x
Zakay- Rones, Z., Thom, E., Wollan, T., & Wadstein, J. (2004). Randomized study of the efcacy and safety
of oral elderberry extract in the treatment of inuenza A and B virus infections. Journal of International
Medical Research, 32(2). https://doi.org/10.1177/147323000403200205
Zuo, G. Y., Li, Z. Q., Chen, L. R., & Xu, X. J. (2005). In vitro anti- HCV activities of Saxifraga melanocen-
tra and its related polyphenolic compounds. Antiviral Chemistry and Chemotherapy, 16(6). https://doi.
org/10.1177/095632020501600606
Biotechnological Approaches
7
for Herbal Drug Discovery
Sohail Ahmad, Maria Faraz, Iftikhar Ahmad,
and Arshad Farid
Gomal Center of Biochemistry and Biotechnology, Gomal University,
D.I.Khan, Pakistan
Samy Selim
Department of Clinical Laboratory Sciences, College of Applied Medical
Sciences, Jouf University, Sakaka, Saudi Arabia
7.1 INTRODUCTION TO HERBAL DRUG DISCOVERY
Herbs are employed globally in the form of drugs to cure or prevent diseases. Historical evidence
of the usage of medicinal plants can be traced to around 5,000 years ago in China and India. The
evidence shows that plants have been an essential component of medicine [1]. The employment of
plants as drugs started at earliest Paleolithic, considering that early people have been exploiting most
of the existing plant species for medication for not less than sixty thousand years. It has been estimated that approximately 80% of the entire global population depends on plant- based medication for
their primary healthcare needs and also that medicinal plants provide about 80% of the raw materials
used in the traditional medical system [2]. Secondly, the public’s need for, interest in, and the use of
plant- based remedies, is increasing on a daily basis. The market of natural products formulated with
herbs has increased due to side effects of allopathic medicines [3, 4]. Concerning the use of medicinal plants, [5] posited that people, especially those in developing countries, prefer to use plants to
treat illnesses and disorders because such practices are culturally acceptable. They are approaching
the plants as a source of new solutions for health needs and saving people’s lives from incurable
infectious diseases. As noted from the yearly statistics, the usage of medicinal plants is rising; recent
studies have recorded that around one- third of the America’s population have adapted to using herbal
products [6]. Drug discovery can be dened as the efforts to identify and develop new drug molecules
from natural sources or through processes of synthesis. When compounds produce pharmacological
activity with low toxicity in preclinical studies, they are put through clinical trial as new drugs [7].
Plants constitute the richest and most widely available source for drug discovery. From 94 species, for example, Fabricant and Farnsworth isolated 122 structurally dened compounds [8].
According to the most recent taxonomic revisions, angiosperms now are considered to consist of
about 295,383 species, while global terrestrial vascular plants including angiosperms, gymnosperms, ferns, and lycophytes are inferred to be about 308,312 species, which may be regarded as
the efcient resource for nding lead molecules/drugs [9]. The global population is expanding; in
order to fulll this demand, scientists are nding for clues in our planet’s supply, plants. A decrease
in biological diversity may lead to increases in specic plant species due to changes in the environment. The red list of the International Union for Conservation of Nature contains data on over
79,800 species. Of these, more than 23,000 species are at risk of extinction status; this accounts for
13% of bird species, 33% of reef- building corals 25% of mammals, 34% conifers, and 41% of
amphibians [10].
145
146 Herbal Pharmacopeia
7.1.1 History of Herbal Drug Discovery
The history of discovering plant- based compounds is deeply rooted in the traditional use of herbal
medicines across various cultures throughout history [11]. Herbal medicine have been empirically
utilized for years in the treatment of diseases, showcasing their longstanding presence in healthcare
practices [12]. These herbal remedies have been recognized for their ability to maintain health and
treat various ailments since ancient times [13]. Despite the advancements in modern medicine, traditional herbal remedies have continued to attract attention as potential alternative therapies for a
wide range of diseases [14]. The process of herbal drug discovery has evolved with the integration
of novel technologies and approaches. The development of novel therapeutic agents now involves
concepts such as ADMET (absorption, distribution, metabolism, excretion, and toxicity) and considers interaction proles between herb–herb and herb–synthetic compounds [15]. Additionally,
computational frameworks have been developed to explore the contributions of herbal ingredients in
treating conditions such as cancer by modulating immune responses and metabolic processes [16].
These advancements highlight the integration of modern scientic methodologies in the exploration
of herbal medicine. The popularity of herbal medicines results from increased concerns about the
efcacy and safety of conventional allopathic drugs, leading to the increased usage of herbal remedies for both mild and severe illnesses [17]. The therapeutic value of herbal medicines has been
acknowledged by both healthcare providers and patients, with a recognition of their potential to
offer superior benets with fewer side effects compared to modern medications [18]. The cartilageprotective, anti- inammatory, or antioxidant effects of herbal products use has shown promise in
the treatment of conditions such as osteoarthritis [19]. The efcacy and safety of herbal medicine
is ensured by its quality control and standardization. The development of techniques such as ngerprint analysis is helpful in standardizing and controlling the quality of herbal medicines, thereby
enhancing their reliability and consistency [20]. Furthermore, the evaluation of standardized herbal
extracts has demonstrated potential in terms of enhancing the effectiveness of chemotherapy while
reducing its associated side effects, thereby demonstrating the incorporation of herbal medicine in
advanced treatment approaches. With regard to major world health challenges such as the recent
COVID- 19 pandemic, there is a call for precision herbal medicine that integrates local community
knowledge and omics systems science technologies to enable more targeted and effective herbal
treatments. This approach emphasizes the importance of leveraging traditional wisdom alongside
modern scientic advancements to enhance the discovery and application of herbal remedies in
addressing contemporary health issues.
7.2 CURRENT TRENDS IN HERBAL DRUG DISCOVERY
The eld of herbal drug discovery is currently experiencing a signicant surge in research and interest on a global basis. The eld is revolutionized through the use of new technologies in research.
Different kinds of new techniques and other isolation and extraction techniques came into play
which have changed the scenario of conventional drug discovery. Below are some of the details of
the modern technologies that have played a crucial role in herbal drug discovery.
7.2.1 Molecular anD genetic stuDy levels
Even if there is little in the way of a written account detailing the medicinal importance of several
plants, it is still necessary to investigate, record, and organize the conventional wisdom on herbal
medicine. Metabolites and bioactivities encoding by genes can be explored, as can the investigation of a particular plant metabolite and the evaluation of its treatment efcacy, the interaction of a
plant bioactive with a drug target interaction in the human body and its effect on relevant biological
pathways, disease- modifying potential, and related toxic effects, using contemporary genomics,
Biotechnological Approaches for Herbal Drug Discovery 147
proteomics, bioinformatics, and metabolomics approaches [21, 22]. Using these contemporary
methods, scientists are trying to conrm the conventional perception of herbal therapy and reported
inuence of sickness on it. Initiatives of various genome sequencing and transcriptional proling
studies pertaining to herbal plants are underway, offering genetic and molecular data for metabolite
proling and investigating potential synthetic pathways associated with plant products [23].
7.2.2 Molecular PHarMacognosy
Molecular pharmacognosy is the study of how to produce effective components at the molecular
level and how to classify, identify, cultivate, and safeguard crude pharmaceuticals. It involves a
number of stages: (a) Sorting the real from the fake to resolve the variety confusion issue: as medical applications and dosages expand, homonyms of plant and animal and materials with identical
appearances are emerging. The same medications in different areas are mistaken by these materials,
causing variety and confusion. Because of this, it's important to separate the real from the fake when
it comes to their places of origin and dissemination. The only way to assure quality is to do this.
(b) Quality assessment: To conrm standard varieties and the aspects that may have an inuence on
them, crude drugs study with numerous origins and genuine quality should be conducted. This study
should address a range of factors: place of origin, harvesting, processing, storage, and the inuence of transportation upon active ingredients. Furthermore, in order to fulll the growing need for
medication, superior cultivars should be studied and cultivated to ensure quick development, good
quality, and high production.
Dendrobium catenatum Lindl., Orchidaceae, Panax ginseng C.A. Mey, Araliaceae, and Bupleurum
chinense DC, Apiaceae, like medications, have been subjected to DNA barcoding techniques in
recent years. To prevent adulteration and harmful situations, a precise and prompt scientic identication of the herbal plant is essential [24]. Plant species identication using taxonomy is conventional, time- consuming, and sometimes imprecise; by contrast, the contemporary DNA barcode
method is quick and accurate. Herbal plants are identied using DNA barcodes such as matK, rbcL,
trnH- psbA, ITS, trnL- F, 5S- rRNA, and 18S- rRNA [25].
For the effective conrmation of herbal products, conjunction with transcriptomics utilization
can be achieved by DNA barcoding, metabolomics, and proteomics. The main source of bioactive
substances and metabolites is a vast number of plant species belonging to the Lamiaceae family.
Because there are a few raw plants in this species, products are frequently tampered with. The
examination of proposed DNA barcode loci (matK, trnH- psbA, and trnL) for their PCR amplication in order to identify several Lamiaceae species revealed that matK locus reliably identies
all selected species, followed by trnH- psbA and trnL [26]. For Mentha, Ocimum, and Plectranthus
medicinal plants, DNA barcode- based verication may lessen associated unfair trades and
adulterations.
For the purpose of addressing the quality, efcacy, safety concerns, and precise identication of
the medicinal plants species of a traditional multi- ingredient herbal Chinese medicine can be possible
by shotgun metabolomic sequencing. Microscopy, thin- layer chromatography, and high- performance
liquid chromatography [27] was undertaken as a complementary method. Combinations of ten herbal
raw materials make up Longdan Xiegan Wan (LDXGW) a conventional Chinese medicine derived
from a herbal prescription from the Qing Dynasty (17th century). These materials include Gentianaceae
(roots); Gentiana crassa subsp. Rigescens (Franch. ex Hemsl.) Halda, Bupleurum chinense DC.,
Apiacea (roots); Akebia trifoliata (Thunb.) Koidz., Alismataceae (rhizoma and roots); Lardizabalaceae
(stem); Alisma plantago- aquatica subsp. orientale (Sam.) Sam., Plantago asiatica L., Plantaginaceae
(stir- fried seeds with salt solution); Angelica sinensis (Oliv.) Diels, Apiaceae (stir- fried roots with
yellow rice wine); Scutellaria baicalensis Georgi, Lamiaceae (roots); Gardenia jasminoides,
Rehmannia glutinosa (Gaertn.) DC, Plantaginaceae (roots); Glycyrrhiza uralensis Fisch., Fabaceae
(roots stir- fried with honey); J. Ellis, Rubiaceae (stir- fried fruits).
148 Herbal Pharmacopeia
7.2.3 coMbination tHeraPy
A single metabolite or family of chemicals is not present in herbal extracts made from plant parts. It
is nonetheless a complicated blend of several bioactive substances. Consequently, it becomes imperative to investigate the primary ingredients in the blend that have a therapeutic effect. Understanding
the therapeutic properties of each bioactive metabolite in a herbal combination would increase our
comprehension of its therapeutic efcacy and lower the possibility of adverse effects brought on by
the presence of additional bioactive specialized compounds [28]. Herbal remedies are thought to
be safer and less likely to have negative effects than manufactured medications. However, taking it
without a prescription and in an unfavourable combination can potentially prove fatal. It is expected
that the use of comparative genomics to identify a synthetic pathway linked to a bioactive agent
would be easy once the genomic and proteome information of the majority of herbal plants have
been screened and made available in biological databases [29, 30].
For a very long time, people have had a rm belief in the traditional herbal method. To assess the
efciency and safety of herbal medicine, it is essential for clinical studies to be carried out. The
World Health Organization published the recommendations for these tests and is in favor of conducting herbal medicine clinical trials. Numerous instances bolster the idea of combination treatment, indicating that two herbs taken together may have a synergistic impact on the illness [31].
However, the interaction of different compounds present in these two herbs may confer negative
health effects. Additionally, the effectiveness of herbal treatments varies depending on the person or
group. Consequently, the pharmacogenomics principles have to be consistently implemented for
herbal remedies as well as their phytopharmaceutical derivatives. The complex and varied components found in herbal remedies are affected by several factors: the type of plant used, when it was
harvested, and whether or not it was contaminated or adulterated with microorganisms. However,
following clinical examination, high- throughput investigation and contemporary biotechnology
technologies have made it feasible to assess the efcacy of herbal medication and suggest appropriate treatments.
Traditional medicine has a long history in China and India in the use of herbal medicine for therapeutic purposes. With a combined history spanning over two millennia, the two oldest medical systems are traditional Chinese medicine (TCM) and Ayurveda. These two systems have a number of
similarities. The main therapeutic ingredients utilized in each of these systems are medicinal plants.
Indians have long been aware of the benets of herbal remedies in treating a variety of skin conditions. Numerous similar herbal remedies are also suggested by the Ayurvedic and Unani medical
systems for the treatment of various illnesses. For instance, in India, there are a total of just 119
herbal plants that can be used to treat 39 skin conditions [32]. Many medicinal plants are processed
using methods provided by Ayurveda and TCM, and in order to make full use traditional knowledge,
more research on the extraction and preparation of herbal extracts is needed [33].
Additionally, it's necessary to look for related plant species that can serve as high- quality substitutes for endangered or expensive herbal extract sources. There are several instances of herbal formula creation in the traditional medical system which incorporate extracts from numerous herbal
plants. When two plant compounds or drugs are combined, they may work synergistically to enhance
therapeutic outcomes. For example, Xiaozhang Tie is a herbal remedy which is used to treat ascites
related to cirrhosis. Various methods, such as proteomics, biochemistry, histopathology, and immunohistochemistry, were employed to determine the potential therapeutic targets linked to this herbal
remedy [34]. By interfering with the l- arginine and nitric oxide pathways, Xiaozhang Tie raises
serum arginine levels and lowers the levels of nitric oxide in the bloodstream.
7.2.4 conservation anD ProPagation strategies
Research has indicated that the pace of extinction of plant species is far higher than anticipated. We
will eventually run out of many signicant medical plants if this rate continues. Data from the World
Biotechnological Approaches for Herbal Drug Discovery 149
Wildlife Fund and the International Union for Conservation of Nature indicate that between 50,000
and 80,000 kinds of owering plants are used for medicinal purposes. Due to human population
growth destroying their natural habitats, the overutilization of plant species, and unfavorable climate
changes, some 15,000 plants are currently in danger of going extinct [35]. One of the primary causes
of medicinal plant extinction in countries such as India, Kenya, China, and Nepal is habitat loss.
Regarding the preservation, propagation, inventorying, and status monitoring of medicinal plants,
several guidelines and recommendations have been evaluated. Globally, the rate at which medicinal
plants are disappearing can be slowed down by the maintainable utilization of natural resources.
Brazil, China, India, and South Africa have witnessed declines in their ora and fauna because of the
high demand brought on by the increases in population. Enhancing the quantity, caliber, and effectiveness of pharmaceuticals can be achieved through the use of plant tissue culture, micropropagation, and synthetic seed development techniques [35, 36]. The mass production of desired bioactive
compounds can be achieved through the fermentation of tissue culture and of medicinal plants.
Tissue culture can also be used to generate a large number of secondary metabolites and to multiply
uncommon medicinal plants more quickly. Cultivating the herbal plant in vitro or ex vitro can be
achieved by synthetic seed technology when regular seeds are unable to germinate. It is also possible
to shorten the time needed for large- scale manufacturing to breed the desired herbal plant using
genetic modication [37, 38].
It is necessary to conduct exploratory research on medicinal plants and nd novel bioactive molecules in order to evaluate and characterize possible lead compounds for drug development. Using
plant cell cultures, heterologous biosynthesis, and synthetic biotechnology techniques the largescale, economical synthesis of secondary metabolites can be achieved [39]. The functional expression of plant biosynthetic cascades requires a deeper comprehension of the genetic control of
pathways and protein production. Understanding the information of pathway reconstruction and the
gene involvement in synthesis are important for the de novo manufacture of a plant compound.
Various in- vitro studies have been conducted for the culturing of medicinal plants using the
technique of micropropagation. Different techniques of micropropagation are available for culturing the plants. The synthesis of secondary metabolites is benecial in rare conservation of endangered and vulnerable specie of medicinal plants can be achieved by in vitro culture procedures.
Numerous medicinal plants, such as like Aloe vera (L.) Burm.f., Xanthorrhoeaceae; Artemisia
annua (L.), Asteraceae; Catharanthus roseus (L.) G. Don, Apocynaceae; Withania somnifera (L.)
Dunal, Solanaceae; and Rauvola serpentina Benth. ex Kurz, Apocynaceae, have all been successfully propagated through the use of effective protocols. Secondary metabolites from medicinal
plants are produced by callus induction and growth, shoot proliferation, cell culture, and the use of
transgenic techniques (Agrobacterium rhizogenes). Sanguinarine from Papaver somniferum (L.),
Papaveraceae, shikonin from cell cultures of Lithospermum erythrorhizon Siebold & Zucc.,
Boraginaceae, and berberine from Coptis japonica (Thunb.) Makino, Ranunculaceae, and berberine from Coptis japonica (Thunb.) Makino are examples of such techniques. Conservation of therapeutic plants including Saussurea costus (Falc.) Lipsch., Asteraceae; Ginkgo biloba (L.),
Ginkgoaceae; Gymnema sylvestre (Retz.) R.Br. ex Sm., Apocynaceae; Tinospora sinensis (Lour.)
Merr., Menispermaceae; and Oroxylum indicum (L.) Kurz, Bignoniaceae is carried out through the
use of tissue culture techniques [40]. Normally, a plant creates secondary metabolites in response
to a variety of adverse environmental stressors, including nutrition deciency, predator contact, and
pathogenic interaction. One substantial, environmentally acceptable, and vital method for conserving medicinal plants and their germplasm is tissue culture. It is a process for producing secondary
metabolites in plants [41].
7.2.5 PHarMacogenoMics
Since they have been used for a considerable period, many herbs that we use as spices and condiments in our daily diet do not need to be under medical care. Before receiving permission and
150 Herbal Pharmacopeia
license to be sold, herbal medications must also adhere to a few regulatory requirements. It is necessary to outlaw the use of unauthorized herbal treatments in order to prevent poisoning and other
major health problems [42, 43].
When using herbs conventionally, side effects from herb–herb and herb–drug interactions pose a
serious risk to public health. Numerous chemical components included in herbal mixtures may target various hormones, enzymes, receptors, and other molecules in our biological systems, potentially producing a wide range of pharmacological responses [44, 45]. When a herb has the potential
to impact the distribution, metabolism, excretion, absorption, or absorption of concurrently administered herbs or medications, this can have a negative effect.
Pharmacogenomics is study of how a person’s genes affects and how they react to medications,
which is the combination of genomics (the study of genes and their function), and the science of
pharmaceuticals, to create safe, effective treatments and dosages that are specic to an individual’s
genetic composition. By using pharmacogenomics, one may forecast possible adverse consequences
of herb–drug interactions based on an individual’s prole of absorption, distribution, metabolism,
and excretion [45, 46].
A deeper comprehension of the interactions between herbs and drugs, as well as genetic differences, is essential for the safe use of herbal drugs. Herbs and CYP450 enzymes, including CYP3A4,
CYP1A2, CYP2C9, and CYP2C19, can interact to either favorably or unfavorably affect a drug’s
metabolism [47]. Numerous CYP450 enzyme- related polymorphisms have been documented in the
human population. There are people who have vast metabolisms and others who have inadequate
metabolisms. If a herb has a negative effect on a medicine’s metabolism, a drug with a poor metabolizer may have hazardous effects because of inadequate drug elimination. Analogously, a herb’s
benecial effects on medication metabolism may lessen the therapeutic response. Grapefruit juice is
one of the strong inhibitors of the cytochrome P450 CYP3A4 enzyme. While grapefruit juice can
sometimes interact fatally with medications like terfenadine or astemizole, it also boosts the bioavailability of pharmaceuticals by inuencing drug metabolism [48]. Herb–drug interactions are
becoming more common; however, it’s still unclear how they work in various genotypes of many
plants.
For more efcient and successful therapy, it is important to evaluate the genetic basis of the various medication responses in different genotypes. Additionally, pharmacokinetic pathways and other
polymorphisms associated with the transporter gene are how herbs interact with transporters [47].
The metabolism of warfarin in people with the CYP1A1 and CYP2B1 genotype strongly induces
the Danshen–Gegan formula (DGF). This results an increase in the absorption of warfarin in the
intestine because of this decrease of warfarin binding to plasma protein [49]. Another example is
berberine [6], which is easily obtained from medicinal plants belonging to various plant families that
grow mostly at high altitudes. These families include the Annonaceae (e.g., Xylopia L.),
Berberidaceae (e.g., Berberis L.), Menispermaceae (e.g., Tinospora Miers), Papaveraceae (e.g.,
Argemone L.), Ranunculaceae (e.g., Coptis Salisb.), and Rutaceae (e.g., Zanthoxylum L.). Some of
these plants are used in several traditional folklore formulations in Ayurvedic and Chinese medicine
to treat hyperglycemia, high blood pressure, and hyperlipidemia. Berberine can interact negatively
with cyclosporine A and enhance its bioavailability due to suppression of the CYP3A4 enzyme,
requiring a lower dose. Moreover, berberine may interact negatively with tolbutamide, thiopental,
and warfarin, worsening blood toxicity. Azithromycin and clarithromycin are examples of macrolide
antibiotics that may interact with berberine and cause cardiac problems [50].
7.2.6 coMPutational resources for Drug Discovery
Over the past few years, the eld of computing hardware, software, and algorithm development has
developed very signicantly. These initiatives have had a noteworthy inuence in creating databases
Biotechnological Approaches for Herbal Drug Discovery 151
comprised of biogenic and synthetic drug- like compounds as well as the computer- aided drug discovery process [51]. Numerous databases, including PubChem, ChEMBL, and ZINC, offer details
on hundreds of chemical compounds that are sourced from various plants or natural sources [52].
Detailed information of herbal compounds, including compound name and source, IUPAC name,
chemical composition, molecular weight, lipophilicity, hydrogen bond donor and acceptor, biological targets, bioactivity assay, efcacy, toxicity, related literature, and other datasets are available in
databases that have free access [53, 54]. In the creation of new drugs, these plant metabolites can be
applied as a lead molecule in order to target traditional medical situations.
Herbs or medication molecules act on hormones, enzymes, receptors, lipids, carbohydrates,
DNA, and RNA in order to produce therapeutic effects. Proteins are typically employed as possible
pharmacological targets [55]. Rational medication design benets greatly from the traditional understanding of herbs and their pharmacological uses. Algorithms and computational tools have been
crucial in the drug design process. Currently, a number of servers and software tools are available
for modeling and validating the 3D structure of the target protein [56]. The calculation of the extent
and content of the binding site or cavity in the target protein can be achieved using theoretical computing. Targeting the protein can also be done using the analogue of a substrate molecule. Information
on the protein–ligand complex is available in Protein data bank database for a large number of proteins, which may be observed to determine the binding- related details of a substrate, cofactor, previously identied inhibitor, or antibody [57, 58].
The structural distinction seen in herbal substances is considered to be a valuable starting points
for the progress of new drugs. Most of the lead compounds come from natural sources. Lead compounds do not meet the requirements for medications, notwithstanding the possibility of there
being some therapeutic benets against illness [59, 60]. The recognition of old herbal components
is a source for the discoveries of new medication. Binding interaction, specicity, selectivity,
absorption, distribution, metabolism, and toxicity are factors for the optimization of herbal lead
compounds. Several chemical changes occurs in the lead molecule during the lead optimization
process in order to meet the various requirements to be considered as a potential medication [59].
A herbal compound needs to be chemically modied to make it easier for liver enzymes to metabolize it, especially if it has excellent absorption, distribution, and binding afnity for the drug target
but has a poor metabolism and toxic substructure. Removing or substituting harmful groups with
alternative groups can reduce the toxicity of herbal substances [61, 62]. An anti- inammatory medication called lumiracoxib has serious liver toxicity. Diclofenac, another safe and efcient medication, was created by substituting chlorine for uorine and eliminating the methyl group from the
meta position of phenylacetic acid in lumiracoxib [63]. Aromatic nitro, aromatic amines, bromoarenes, hydrazines, polyhalogenated groups, and hydroxylamine like toxic groups are not added
to candidate medications throughout the drug discovery process. If they already existed in the original lead compounds, they are eliminated. Several theoretical guidelines to structure- property and
structure- activity help in determining what modications to the lead molecule are necessary to
improve effectiveness, pharmacokinetics, and pharmacodynamics [62]. According to the binding
energy of the docked complex, molecular docking software is particularly useful in sifting through
a large number of compounds to nd those that may be potentially effective against a target [64].
Predicting the compound’s binding posture and the associated interaction with the target protein’s
amino acids is now feasible thanks to docking and structural visualization technologies. This
method is being used by pharmaceutical corporations for the creation of new drugs, and there are
several examples of successful computer- aided drug design [23, 65]. Computational approaches for
the development of medications include some examples, such as saquinavir for the target HIV- 1
and HIV- 2 protease (AIDS), zanamivir for the target neuraminidase (inuenza), aliskiren for the
target renin (hypertension, high blood pressure), and captopril for the target angiotensin- converting
enzyme (hypertension) [66] (Figure 7.1).
152 Herbal Pharmacopeia
FIGURE 7.1 Drug discovery and development pipeline.
7.3 CONNECTION BETWEEN HERBAL DRUG DISCOVERY
ANDBIOTECHNOLOGY
The relationship between herbal drug discovery and biotechnology is a multifaceted and evolving
eld that encompasses various aspects of research, development, and application. Herbal medicine, derived from plants and natural sources, has been a signicant part of traditional medicine
systems globally and continues to gain recognition for its therapeutic potential [67]. The integration of biotechnological interventions in herbal medicine plays a vital role in improving the
conservation, cultivation, and utilization of medicinal plants [68]. Biotechnology offers tools and
techniques that can aid in the sustainable production, standardization, and quality assessment of
herbal products, thereby contributing to the advancement of herbal drug discovery [69]. The emergence of network pharmacology as a research paradigm has provided a systematic approach to
exploring the complex interactions between herbal compounds and biological systems, facilitating
evidence- based drug discovery [70]. This approach allows for a comprehensive understanding of
the mode of action of herbal remedies, supporting identication of potential therapeutic targets for
various conditions, including obesity, neurodegenerative diseases, and cancer [71]. Thus, using the
network pharmacology approach, it is possible to reveal the interactions of several compounds in
the complex of herbal medicine and develop new targeted therapies. Considering the fact that precision medicine—the use of the genomic information to personalize the medical treatment—has
become a trendy topic, more and more attention is paid to the prospects of using herbal medicine
for personalized medicine. When using concepts and data from omics technologies, including
genome and metabolomics, with traditional knowledge on natural products comprising herbs, the
quality and safety of traditional cured herbs can be boosted, especially when applied to current
Biotechnological Approaches for Herbal Drug Discovery 153
global concerns like COVID- 19 [20]. This approach emphasized the positive way of synergy
between the old knowledge of herbs and the new biotechnological approach to the solution of
present- day health complications. Additionally, the incorporation of herbal drugs with orthodox
practice has been testied to help in the control of many diseases such as cancer. That being said,
paradoxical to its immunosuppressive effects, herbal medicine has been recognized to have a positive inuence on the immune microenvironment alongside the metabolic pathways that relate to
cancer development [72]. The inclusion of herbal medicine into conventional health systems, in
other centres of academic oncology, shows that the concepts offered by traditional herbal practices
can be incorporated into existing medical practices [73]. The use of herbal medicine to cure such
ailments as mouth ulcers, gynecologic cancer, and Behcet’s disease demonstrates how—and in
what ways—some Internet- sourced herbal remedies were used in other branches of medicine [74,
75]. Most patients use herbal treatment to manage symptoms in addition to conventional medical treatment, showing why it is essential for healthcare workers to understand and have a basic
knowledge of herbal medicine. The general patterns and temporal trends of herbal medicine use
among patients with different diseases can help healthcare providers design individual patientcentered treatment plans that combine American Medical Association (AMA) and Western biomedical medications [76].
7.4 APPLICATIONS OF BIOTECHNOLOGICAL TOOLS FOR HERBAL
DRUGDISCOVERY
Thus, the application of biotechnological methods to study herbal drugs is an innovative approach
to studying natural compounds through the synergistic blend of traditional practices and modern
discoveries. When the two elds of technology are combined with herbal medicine, new opportunities, such as the development of new drugs, the quality control of medicines, and the use of
individualized patient- orientated medicines can be enhanced by researchers. This integration also
applies the use of articial intelligence and machine learning algorithms in quickening the process of drug discovery [77]. These technologies allow the forecasting of molecular interactions,
the potential drug identication targets and the ne- tuning of an herb’s chemical composition,
effectively making the process of developing new herbal medicines more efcient [78]. In addition, network pharmacology studies has become a viable method in integrating herbal drugs and
natural products in the processes of complex drug discovery [79]. Applying network pharmacology
to analyze and comprehend the multitarget nature of herbal ingredients and their biological effect,
it is possible to discover new targets of disease interventions, like cancer, neurodegenerative diseases, and other diseases and infections. This IT approach facilitates the study of herb–medicine
relations along with the simultaneous action of numerous compounds in the formulation, and lays
down the framework for improving present- day herbal drugs. In addition to articial intelligence
and network pharmacology, computational technologies are considered a major determinant of
enhancing herbal drug discovery [80]. The uses of these tools are unlimited, encompassing the
virtual screening of phytochemicals with pharmacokinetics of herbal compounds [81]. Thus, computational models provide an opportunity to speed up the process of selection of bioactive compounds, to ne- tune a drug delivery system, and to the assessment of the safety and efcacy of the
components of herbal products. This computational method is benecial not only in accelerating
the drug discovery process but also in increasing the accuracy and speed of the formulation of
herbal medicines. Furthermore, the use of bio- modern techniques, including metabolic proling,
genomic sequencing and the bioactivity screening of the natural product, has been enhanced to
boost drug discovery and development [82]. They help the researchers to replicate, discover the
chemical constitution of bioactive organisms, and identify drug leads from natural products. Thus,
integrating such biotechnological tools with the conventional system of using herbal medicine will