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84 Herbal Pharmacopeia
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5
Bioactive Compounds
inHerbal Remedies
Raheela Sarwar
Center of Biotechnology and Microbiology, University of Peshawar,
Peshawar, Pakistan
Muhammad Maisam
Institute of Molecular Biology and Biotechnology, The University of
Lahore, Lahore, Pakistan
Muhammad Waseem Khan
Institute of Pharmaceutical Sciences, Khyber Medical University,
Peshawar, Pakistan
Youngbo Xue
School of Pharmaceutical Sciences (Shenzhen), Sun Yat- Sen University,
Shenzhen, China
Said Hassan
Institute of Biotechnology and Microbiology, Bacha Khan University
Charsadda, Charsadda, Pakistan
5.1 INTRODUCTION
The World Health Organization (WHO) estimates that nearly 50,000 people worldwide lose their
lives to infectious diseases every day, accounting for almost one- third of all deaths [1]. Antibiotics
are an important and signicant therapeutic discovery for the management of infections; yet their
arbitrary usage has resulted in virulent types of strains becoming more resistant to them [2]. The
prevalence of multidrug resistance is heightened by the pathogen resistance caused by antibiotic
efux mechanisms [3]. Despite the availability of multiple pathogen- specic and broad- spectrum
medications to control microorganisms, the constant emergence of new pathogen- resistant strains
necessitates the exploration of novel antimicrobial agents [4].
Multidrug resistance, which frequently extends to related antimicrobial compounds and makes
ordinary microorganisms become opportunistic pathogens, is a major challenge for the contemporary world. The indiscriminate use of antibiotics, which can bioaccumulate and harm host immunity,
is alarming in both developing and developed countries [5]. Consequently, there is a pressing need
for alternative antimicrobial strategies, with a growing focus on plant sources due to their perceived
safety compared to conventional chemotherapeutics [6]. Ancient phytotherapy is gaining interest for
its enhanced therapeutic potential and reduced side effects, evolving from traditional folk medicine
to modern allopathic treatments as endorsed by the WHO [7]. Historically, herbs have been known
for their antimicrobial properties, containing secondary metabolites (SMs) such as essential oils
(EOs), alkaloids, terpenoids, avonoids, and their glycosides, etc. Modern research continues to
89
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document and explore the effectiveness, protection, and potential, of various herbs, many of which
possess antimicrobial and immunomodulatory activities [8–10].
Plant- based antimicrobial chemicals are more advantageous than allopathy medications in many ways,
including fewer side effects, economic, improved patient tolerance, eco- friendliness, acceptable for longterm use, higher utilization efciency, renewable nature, and prolonged bioavailability [11]. Furthermore,
new research indicates that they can effectively manage non- communicable diseases by preventing the
growth of pathogens through the use of herbal extracts in combination with protein inhibitors. This has
led to global interest in developing novel antimicrobial agents as alternatives to traditional chemotherapy
[12]. Research indicates that these medications may lessen the harmful effects of synthetic pharmaceuticals on people's health when treating and managing cancer. An additional innovative strategy makes
use of the synergistic effects of bioactive plant extracts and antibiotics to create more potent complexes
that either kill target microorganisms or prevent the formation of their cell walls [13].
The world’s population is expected to surpass 7.5 billion people in the next 10 to 15 years, making
the management of multidrug- resistant pathogens even more imperative. Nowadays, approximately
70–80% of people use herbal medicines for basic healthcare since they are culturally appropriate and
have minimal side effects [14]. Between 60 and 90% of people in developing nations obtain their family healthcare from medicinal plants. Herbal medicines were practiced historically by Egyptian,
Middle Eastern, Indian, and Chinese civilizations as early as 3000 BC [15]. Medicinal herbs like
Cimicifuga species are being used today in Korea, Japan, and China to treat inammation, pain, and
fever. Native Americans treated irregular menstruation, malaria, renal issues, menopause, and sore
throats with herbal remedies [16]. In contrast to synthetic pharmaceuticals that contribute to environmental issues through industrial waste, medicinal plants are essential to pharmacological research and
drug development since they can be used as models for novel drugs as well as direct therapies [13].
Plants- derived secondary metabolites, including EOs, alkaloids, avonoids, steroids, and their
glycosides, are vital for metabolism but do not directly inuence the host’s metabolic functions [17].
Historically, botanicals have also been employed as anthelmintic, stomachic, anti- inammatory,
diuretic, and anti- malarial treatments. Additionally, they are employed in conventional and allopathic therapy to prevent neurological, autoimmune, and cardiovascular diseases [18, 19].
The assessment of herbal remedies’ clinical potential requires the discovery of new compounds
and an understanding of their mechanisms of action. People turned to ethnopharmacognosy, discovering thousands of plant- based phytochemicals as safer and more effective substitutes for chemically manufactured medications due to side effects and microbial resistance [20]. Novel therapeutic
approaches are desperately needed since misring NF- κB stimulation is associated with a number
of illnesses. Despite the high cost of innovative therapies, plant- based products offer effective alternatives. Clinical trials are required to conrm the safety, efcacy, pharmacokinetics, bioavailability,
and medication interactions of these bioactive compounds, even though traditional claims suggest
advantages [21]. The central theme of this chapter is to explore the potential health benets of bioactive compounds and herbal medicines for humans.
5.2 TRADITIONAL PHYTOMEDICINE
Traditional medicine relies on the indigenous knowledge, practices, and skills of various cultures
to prevent, diagnose, and treat physical and mental illnesses, guided by their unique theories and
beliefs [22]. Traditional medicine has long been the most economical and readily available resource
for primary healthcare. People initially utilized plants for their nutritional values; however, with the
discovery of their therapeutic qualities, these natural resources became vital for the treatment of
many illnesses and the enhancement of general health in many human societies [23].
Currently, several branches such as Ayurveda, homeopathy, and Unani Siddha are all aspects of
the Indian medical system. Approximately 8,000 plant species have been codied as herbal medicines through folk knowledge and traditions [24]. According to pollen research, 3,500 years ago,
Ancient Egyptians had used various herbs for medicinal purposes, specically for heart, circulatory,
and pain ailments, with this practice dating back 4,000 years. Thousands of instructions found in
Bioactive Compounds in Herbal Remedies 91
Egyptian papyrus demonstrated the therapeutic, preservation, and cosmetic benets of castor oil and
coriander [25]. Approximately 500 rare items, processed by methods such as shade drying, grinding,
and treating with wine or vinegar, are part of the over 12,000 commonly used by folk therapists [26].
Greek and Roman scholars, including Hippocrates, Celsus, Theophrastus, and Dioscorides, documented a wide array of medicinal applications for herbal plants [27]. Elsewhere in Europe,
Romanians also have a rich history of employing medicinal herbs; for instance, in the 5th century
BC, Herodotus noted the use of Leonurus cardiaca (Motherwort) by individuals north of the Danube
River. Romanian pharmacopoeia started incorporating herbal products in the 19th century, and in
1904, the city of Cluj established its inaugural institute specializing in medicinal herbs [22, 28].
Traditional Chinese medicine (TCM), which now has a history of over 3,000 years, exemplies the
application of ancient, accumulated knowledge in holistic healthcare today. China’s rural areas are the
main regions, where approximately 5,000 traditional herbal treatments are commonly utilized. The
Divine Farmer’s Classic of Herbalism, originating in China about two millennia ago, is recognized as
the eldest herbal manuscript in existence [29]. Numerous herbal pharmacopoeias and monographs on
specic herbs have been constructed from the knowledge found in this work. Medicinal herbs are used
in therapeutic procedures by African tribes, native American societies, and other traditions developed by
TCM, Ayurveda, and Siddha [15]. In countries such as India (Ayurveda or Siddha), Japan (Kampo
medicines), China (TCM), and Southern Asia (Unani remedies), these traditional methods continue to
be widely used despite the emergence of well- documented synthetic pharmaceuticals in the West [24].
For example, India continues to practice traditional systems such as homeopathy, Ayurveda, naturopathy, Siddha, yoga, and Unani. Ayurveda, meaning “the Science of Life,” encompasses a comprehensive and holistic strategy for the maintenance of good health. The origins of traditional Indian
medicine are found in Vedic Sanskrit texts dating from 1600 to 3500 BC [26]. The roots of ancient
medical knowledge stem from Indian physicians who empirically recorded the therapeutic and
medicinal properties of plants within their medical framework. These insights are indeed a valuable
resource, providing the basis for the advancement of natural drug research and development.
Historical, cultural, and allopathic factors contribute to the reliance of many people in developing
nations on folk specialists who use medicinal plants for their healthcare [30].
Ancient practices involving herbal plants depict the history of bioactive compounds [31]. Though
bioactive chemicals were unfamiliar to most in the past, their varied applications merited exploration.
The generation of plant bioactive substances usually occurs as secondary metabolites (SMs), which
are discussed below. The eld of natural products has recently drawn signicant attention because of
several factors, including the discovery of distinct chemical structures and their purposes in naturally
occurring SMs, unexplored remedial applications, advancements in analytical techniques, the effectiveness of newly discovered bioactive substances in biochemical research, and the isolation, purication, and characterization of natural compounds [32]. Herbal therapy is extensively used throughout
the world since it is safe, non- toxic in nature, has few adverse effects, and is affordable [22].
5.3 MODERN PHYTOMEDICINE
The development of innovative medication formulations hinges signicantly on medicinal plants.
Throughout history, plant- derived medications have been integral to modern medicine, whether in
their full form or through the use of specic plant components, as evidenced by traditional systems
[20]. The worldwide emergence of multidrug- resistant pathogens threatens the clinical efciency of
existing antibiotics, making the study of infectious diseases a global concern and a leading cause of
death. Throughout the annals of history, herbal medicines have treated a wide array of infectious diseases, utilizing the unparalleled chemical diversity found in plant extracts, whether as standardized
natural products or as pure compounds, promising limitless avenues for new pharmaceuticals [33].
A diverse set of methods, including synthetic chemistry, combinatorial chemistry, bioinformatics,
and the extraction and purication of bioactive compounds from medicinal herbs and other natural
sources, has been used to produce compounds for drug development [34]. Before the 19th century,
plant medicines were used mainly in crude forms as tinctures, infusions, syrups, and decoctions, and
92 Herbal Pharmacopeia
externally as ointments and washes. Researchers in developing countries conduct extensive studies of
native plants, which are sold in local marketplaces. The WHO advises incorporating traditional herbal
medicines with Western medicine for effective healthcare in developing countries and achieving primary healthcare goals [35]. Patients in developed countries with chronic diseases are increasingly
using herbal treatments as alternatives to synthetic drugs. Approximately one hundred novel medications derived from higher plants are available in the US drug market. Among these are Moderil, Velban,
Canescine, Raudixin, and Leurocristine, which were approved between 1950 and 1970 [33, 34].
Testicular, lung, and lymphoma cancers were successfully treated with the phytophyllotoxin that
was extracted from Podophyllum emodi [36]. Serpentine, a 1953 herbal medication made from
Rauwola serpentina root, lowers blood pressure and hypertension [37]. Treatment recommendations for childhood lymphocytic leukemia, lung, uterine, and breast cancer include vincristine isolated from Catharanthus roseus. Similarly, several plant- based medications, known for their
anticancer, antidiabetic, antibacterial, and antimicrobial properties, are commonly used to treat conditions like jaundice, hypertension, diabetes mellitus (DM), mental health issues, tuberculosis, and
skin disorders [38]. Factors that contribute to the increasing interest in herbal medicines by the
members of developed countries include [39]:
1. Efciency: Herbal drugs are supposed to be efcient and gentle and usually act on precise
body organs or systems. They are considered to cure particular diseases against which conventional drugs do not work.
2. No Side Effects: Herbal medications, having been utilized for an extended period, are generally
believed to be free from the potential risks and side effects associated with synthetic treatments.
3. Economical: Herbal medicines are generally cheaper than synthetic drugs and contribute
key constituents for new drug synthesis. Researchers worldwide are investigating medicinal plants to nd more phytochemicals and lead compounds for treating diseases.
5.4 SYNTHESIS AND PURPOSE OF BIOACTIVE COMPOUNDS
All living beings, from the simplest bacteria to the most complex plants, process various chemical
compounds essential for their sustenance and survival. Compounds in biological systems are classied into primary metabolites, which support growth and development (including amino acids,
carbohydrates, lipids, and proteins), and secondary metabolites (SMs), which enhancing a plant's
survival and environmental interactions [40]. SMs are compounds produced post- growth, contributing to survival rather than growth, characterized by unique chemical structures, and frequently
forming as mixtures of related compounds. The production of SMs varies among species due to
evolutionary selection and unique ecological necessities. Flowering plants, for example, release
fragrances to attract pollinators, while diseases and herbivores produce toxins to inhibit neighboring
plant growth [41]. Within the realm of SMs, some substances interact with biological systems and
are termed bioactive. Thus, a simple way to dene bioactive compounds in plants is SMs that cause
toxicological or pharmacological effects in animals and humans [42].
Bioactive compounds generally fall into a few distinct families, each with unique structural features derived from their biosynthetic assembly. There are four key pathways for the synthesis of bioactive compounds or SMs [43]: (a) mevalonic acid, (b) shikimic acid, (c) non- mevalonate (MEP), and
(d) the malonic acid pathway. The malonic acid and shikimic acid pathways are responsible for the
synthesis of phenolic compounds. Alkaloids are derived from aliphatic amino acids (via the tricarboxylic acid cycle) and aromatic amino acids (via the shikimic acid pathway). The synthesis of terpenes
occurs through the MEP and mevalonic acid pathways [42, 44]. Moreover, hybrid biosynthesis is
valuable in agriculture for their signicant gains in biomass and seed yield, a phenomenon known as
hybrid vigor or heterosis [45]. In crops like Chinese cabbage, maize, and Arabidopsis, hybrids have
larger leaves and taller plants due to increased leaf cell number and size. Hybrid mimics overcome the
F1/F2 hurdle, allowing for high- yielding crops from kept- seed planting [46].
Bioactive Compounds in Herbal Remedies 93
5.5 BIOACTIVE COMPOUNDS AND ITS CLASSIFICATION
IN MEDICINAL HERBS
Bioactive compounds are crucial to the therapeutic potential of plants, offering a rich and varied
assortment of chemical constituents that contribute to their medicinal properties. The categorization of bioactive compounds is still inconsistent, often relying on their intended applications rather
than multiple standard categories. For example, classications based on biosynthesis, designed for
simplicity in describing biosynthetic pathways, do not correspond to the extent of pharmacological
classication. Based on their chemical structures, plant bioactive compounds are divided into the
following main classes [47]:
5.5.1 Phenolic comPounds (Pcs)
Among plant SMs, phenolic compounds (PCs) represent one of the most signicant categories.
These compounds are identied by the presence of one or more phenol groups, a hydroxyl (-OH)
function group linkages to aromatic rings, such as benzene or other complicated aromatic ring
structures [48]. This chemically heterogeneous class of plant phenolics includes compounds that
are water- soluble, organic solvent- soluble, and insoluble polymers. UV radiation activates several
simple PCs. The presence of abundant PCs in plants profoundly inuences their color, avor, and
taste [49]. Pharmaceutical properties including antioxidant, anti- inammatory, and antihepatotoxic
actions are exhibited by PCs biosynthesized from the shikimate pathway. PCs derivatives encompass benzoic acid derivatives, simple phenylpropanoids, isoavones, anthocyanins, lignin, tannins,
and avonoid compounds that begin with phenylalanine [50].
Flavonoids, the most prominent class of naturally occurring phenols, occur primarily in higher
plants and are essential for oral pigmentation, defense, and nitrogen xation [51]. In the stage of
symbiotic infection, it is secreted by the roots with the assistance of Rhizobia. Flavonoids can be
categorized into several classes based on the oxidation level of the central ring [52]. Scientists have
isolated more than 5,000 avonoids from various plants, classifying them into avanonols, anthocyanidins, avanones, avans, and isoavonoids according to their chemical structures (Figure 5.1)
[53]. Other avonoid groups with minor components include dihydrochalcones, dihydroavonols,
coumarins, avan- 3, 4-diols, aurones, and chalcones. Syringic acid, a phenolic substance produced
FIGURE 5.1 Common herbal avonoids and their chemical structures.