Herbal Biomolecules in Healthcare Applications

By Subhash C. Mandal

Herbal Biomolecules in Healthcare Applications presents extensive detailed information on all the vital principles, basics and fundamental aspects of multiple herbal biomolecules in the healthcare industry. This book examines important herbal biomolecules including alkaloids, glycosides, flavonoids, anthraquinones, steroids, polysaccharides, tannins and polyphenolic compounds, terpenes, fats and waxes, proteins and peptides, and vitamins. These herbal biomacromolecules are responsible for different bioactivities as well as pharmacological potentials. A systematic understanding of the extraction, purification, characterization, applications of these herbal biomolecules and their derivatives in healthcare fields is developed in this comprehensive book. Chapters explore the key topics along with an emphasis on recent research and developments in healthcare fields by leading experts. They include updated literature review of the relevant key topics, good quality illustrations, chemical structures, flow charts, well-organized tables and case studies. Herbal Biomolecules in Healthcare Applications will be useful for researchers working on natural products and biomolecules with bioactivity and nutraceutical properties. Professionals specializing in scientific areas such as biochemistry, pharmacology, analytical chemistry, organic chemistry, clinics, or engineering focused on bioactive natural products will find this book useful.

• Provides a study of different type of biomolecules from herbal extracts and their bioactivities as well as their application in the healthcare industry
• Contributions by global leaders and experts from academia, industry and regulatory agencies, who have been considered as pioneers in the application of herbal biomolecules in the diverse healthcare fields
• Includes updated literature review along with practical examples and research case studies

• Language: English
• Publisher: Academic Press
• Release date: Oct 5, 2021
• ISBN: 9780323900805

Book preview

Preface

Subhash C. Mandal¹, Amit Kumar Nayak² and Amal Kumar Dhara³, ¹Division of Pharmacognosy, Department of Pharmaceutical Technology, Jadavpur University, Kolkata, India, ²Department of Pharmaceutics, Seemanta Institute of Pharmaceutical Sciences, Mayurbhanj, India, ³Pharmacy Department, Contai Polytechnic, Government of West Bengal, Contai, India

Modern drifts toward the utilization of herbal products in different healthcare aspects (numerous healthcare uses) necessitate (demand) the replacement of the synthetic molecules (biomolecules) with the herbal biomolecules because of their biocompatibility, biodegradability, economic extraction process, and availability from the natural sources. The reality behind the rise in significance of these naturally derived herbal biomolecules is that the herbal sources are renewable if grown in a sustainable manner and these can tender the continual supply. Amongst these, the herbal biomolecules are well-thought-out as excellent candidates in healthcare uses because of their bioactivity and characteristics. In recent years, several research endeavors have already been made on the applications of various kinds of herbal biomolecules in the healthcare field such as effectual ingredients in drug delivery, wound healing, antimicrobial, and nutraceutical. Important herbal biomolecules explored and exploited in healthcare uses are alkaloids, glycosides, flavonoids, anthraquinones, steroids, polysaccharides, tannins and polyphenolic compounds, terpenes, fats and waxes, proteins and peptides, vitamins, etc. These herbal biomacromolecules are responsible to show different bioactivities as well as pharmacological potentials such as antidiabetic, antioxidant, anticancer, antiinflammatory, analgesic, antipyretic, antidiarrheal, antiulcer, antidepressant, diuretic, antidiuretic, cardioactivity, osteogenic, antiemetic, antimicrobial, wound healing, immunomodulatory, etc. For exploiting the healthcare applications, diverse chemical and physicochemical characteristics of these herbal biomolecules are also responsible and some of these are molecular weights and structure, degree of deacetylation, solubility, stability, etc. In this perspective, a systematic understanding of the extraction, purification, characterization, and applications of these herbal biomolecules and their derivatives in healthcare fields demands to be thoroughly understood.

The book Herbal Biomolecules in Healthcare Applications provides a systematic insight into the inclusive herbal biomolecular chemistry, extraction, purification, toxicity studies, characterization, standardization, bioactivity, and applications in the healthcare fields. This volume is a collection of six different sections (namely, introduction; extraction and purification; chemistry, phytopharmacology, and characterization; families; bioactivity and applications; and standardization, regulatory, and clinical trials) containing 28 chapters by the academicians and researchers of biomedical as well as pharmaceutical fields across the world. A concise account of the contents of each chapter has been described to provide a glimpse of the book to the readers.

Chapter 1, Introduction to Herbal Biomole-cules, describes different herbal biomolecules such as alkaloids, glycosides, coumarins, flavonoids, tannins, terpenoids, essential oils, fixed oils, phenols, coumarins, and carbohydrates and their therapeutic activities such as anticancer activity, antidiabetic activity, immunomodulatory effect, wound healing property, and antimicrobial activity with standardization and regulatory considerations for the uses of herbal biomolecules in healthcare.

Chapter 2, Extraction of Herbal Biomolecules, provides an overview of traditional and modern extraction techniques that are used for the extraction of herbal biomolecules.

Chapter 3, Purification of Herbal Biomolecule, intends to provide a comprehensive view of various methods used to extract, isolate, and identify herbal biomolecules, namely, UV-visible spectroscopy, Fourier transform infrared spectroscopy, Gas Chromatography analysis, high-performance liquid chromatography–electrospray ionization tandem mass spectrometry (HPLC–ESI-Ms/MS) analysis and so forth. The methods presented in this chapter are illustrated in the herbal plant crude extract model.

Chapter 4, Chemistry of Herbal Biomolecules, focuses on the chemistry of various herbal biomolecules such as carbohydrates, oils, resins, alkaloids, glycosides, tannins, and their classified derivatives.

Chapter 5, Variation of Biomolecules in Plant Species, spotlights on the variation of various herbal biomolecules such as nucleic acids, proteins, carbohydrates, lipids, alkaloids, terpenoids, phenolics, and glycosides, all of which play important roles in the therapeutic effects in herbal healthcare. To better understand the variation of herbal biomolecules, factoring influencing the variation and analytical methods to quantify the variants are also discussed.

Chapter 6, Phytopharmacology of Herbal Biomolecules, deals with important plant biomolecules that have been found to be effective against important diseases pertaining to cardiovascular, central nervous system, antimicrobial, antiinflammatory, oncology, and hepatic ailments.

Chapter 7, Analytical Characterization of Herbal Biomolecules, highlights the critical roles of analytical techniques in characterizing the complex structures and the composition of the herbal biomolecules and advancing our understanding of healthcare and diseases

Chapter 8, Bioactivity Characterization Herbal Molecules, overviews the possibilities for bioactivities for medical applications using herbal molecules. The different sections of this chapter display various important aspects related with characterization and specific applications of herbal molecules in diseases related with dental care, respiratory and gastrointestinal diseases as well as bioactivities of herbal molecules, such as analgesic, antimicrobial and antiinflammatory activities.

Chapter 9, Herbal Carbohydrates in Healthcare, encompasses the healthcare uses of carbohydrates extracted from medicinal and food plants.

Chapter 10, Herbal Oil in Healthcare, describes sources, chemical compositions, therapeutic potentials, and uses of various herbal oils for healthcare applications.

Chapter 11, Essential Oil and Their Bioactive Molecules in Healthcare, covers sources, chemistry, methods of extraction and analysis, biological activities, trade, and commercial applications of essential oils along with the risks and dangers of essential oils in much greater detail.

Chapter 12, Herbal Glycosides in Healthcare, addresses different types of herbal glycosides such as anthraquinone, cardiac, coumarin, cyanogenic, flavonoid, glucosinolates, phenol, and saponin glycosides and their healthcare applications in high-level depth.

Chapter 13, Herbal Alkaloids in Healthcare, presents an overview of the useful alkaloids derived from plants against some chronic diseases such as cancer, diabetes, obesity, hypertension, tuberculosis, and cardiovascular complications.

Chapter 14, Herbal Flavonoids in Healthcare, highlights the description of herbal medicine, sources of herbal flavonoids, classification of herbal flavonoids, and their chemical structure, application in the healthcare system.

Chapter 15, Herbal Terpenoids in Healthcare, explores the pharmacological activities of terpenoids and their mechanism insights toward healthcare.

Chapter 16, Herbal Coumarins in Healthcare, covers a general description of coumarins, bioactivities of coumarins such as analgesic activity, antiadipogenic activity, antiangiogenic activity, anticancer activity, anticardiovascular activity, anticoagulant activity, antidiabetic activity, antiedema activity, antihypertensive activity, antiinflammatory activity, antimicrobial activity, antioxidant activity, antispasmodic activity, antiviral activity, central nervous system-related activities, activity against COVID-19 virus, hepatoprotective activity, and immunomodulator activity.

Chapter 17, Plant Biomolecule Antimicrobials: An Alternative Control Measures for Food Security and Safety, describes different kinds of plant biomolecules, their applications, and antimicrobial activity that might help researchers to develop new treatments against different plant and animal diseases for food security and safety.

Chapter 18, Antidiabetic Herbal Biomolecules, addresses the general panorama of diabetes mellitus, the conditions associated with its development, and also presents some phytochemicals with the ability to intervene in a beneficial way of glucose metabolism.

Chapter 19, Herbal Biomolecules: Anticancer Agents, presents the herbal biomolecules, such as phenols, flavonoids, tannins, stilbenes, curcuminoids, coumarins, lignans, quinones, alkaloids, etc., as anticancer agents to treat various cancers.

Chapter 20, Herbal Biomolecules Acting on Central Nervous System, examines these herbal biomolecules and their effects on the central nervous system (such as stimulant, depressive, antidepressant, cognitive, toxic, and dependence effects) and mechanism of actions.

Chapter 21, Herbal Biomolecules as Nutraceuticals, overviews various plant-based bioactive nutraceuticals based on their food sources, their pharmacological activities, and chemical constituents.

Chapter 22, Herbal Immunomodulators, reviews the immunomodulatory activities of various herbal bioactive compounds as effective biomedicines in various immune-dysregulatory disorders.

Chapter 23, Herbal Antilithiatic Biomolecules, presents an overview of different antilithiatic biomolecules from herbal sources and their molecular mechanism of action to have a better understanding of how these antilithiatic biomolecules exert their effects as biomedicines.

Chapter 24, Herbal Aphrodisiac Biomolecules in the Management of Male Reproductive and Sexual Problems: Connecting Nature With Clinics, describes important herbal aphrodisiacs with their effects and the potent molecules/compounds that manifest their aphrodisiac activity.

Chapter 25, Herbal Biopolysaccharides in Drug Delivery, presents a brief review on the uses of herbal biopolysaccahrides as excipients in the formulations of different drug delivery dosage forms.

Chapter 26, Standardization of Herbal Biomolecules, addresses the authentication and assurance of the quality of herbal biomolecules as medicines along with a discussion on the safety and toxicity profiling of herbal medicines.

Chapter 27, Regulatory Considerations of Herbal Biomolecules, discusses the importance of global regulatory considerations in the marketing of herbal drugs/biomolecules and the importance of USFDA, ICH, EMEA, WHO, policies in regulating herbal biomolecules as new drug approval.

Chapter 28, Clinical Trials of Herbal Biomolecules, reviews the clinical evaluations and effects of bioactive compounds of different herbal medicines.

In the end, we the editors convey our sincere thanks to all the distinguished authors for contributing significant chapters, which facilitated bringing out this volume on time. We especially thank Elsevier Inc., and Erin Hill-Parks for their invaluable supports in organizing the intelligent editing of the book. We also would put on record our special thanks to Tracy I. Tufaga, Editorial Project Manager, for her priceless support right from the beginning to the completion of this book. We would also thank Narmatha Mohan, Sr. Copyright Coordinator for the support in obtaining permission for the publication of this book. We gratefully acknowledge all the permissions we received for reproducing the copyright materials from different sources. Finally, we cannot overlook the sacrifices and supports from our family members during the preparation of the book. All our friends, colleagues, and students who have helped in the process of editing this book deserve our great appreciation. Contributing authors, the publishers, and we the editors will be extremely pleased if our endeavor fulfills the needs of academicians, researchers, students, pharmaceutical experts, biomedicine experts, and herbal drug formulators.

Chapter 1

Introduction to herbal biomolecules

Amal Kumar Dhara¹ and Amit Kumar Nayak²,    ¹Department of Pharmacy, Contai Polytechnic, Contai, India,    ²Department of Pharmaceutics, Seemanta Institute of Pharmaceutical Sciences, Jharpokharia, Mayurbhanj, India

Abstract

The uses of herbal biomolecules as phytomedicines in healthcare have been practiced from the early stage of human civilization to the modern age. Plethora of plants with significant value are available worldwide. According to World Health Organization (WHO), about 80% of world population receives phytomedicine for their primary healthcare. Herbal biomolecules are chemicals that have definite biological activities including alkaloids, glycosides, coumarins, flavonoids, terpenoids, carbohydrates, oils, etc. Active biomolecules from herbal resources have been popularly used for the treatment of various diseased conditions, such as cancers, diabetes, malaria, mental illness, microbial infections, cardiovascular disorders, etc., and have also been extensively used as antioxidants, immunomodulators, neutraceuticals, anticancer agents, antidiabetics, etc. In addition, many herbal biomolecules have been exploited as functional biomaterials in different biomedical applications like drug delivery, antimicrobial applications, tissue engineering, wound healing, etc. To attain the optimal health benefits with the uses of herbal biomolecules, standardization of phytoconstituents with the application of modern analytical techniques as well as uses of sophisticated analytical equipments are very much essential. The global market for herbal biomolecules as phytomedicines is increasing day by day. Strict regulation and systematic scientific research will definitely brighten the future prospects of herbal biomolecules.

Keywords

Herbal biomolecules; phytomedicine; healthcare; standardization; regulatory affairs

1.1 Introduction

From the dawn of human civilization, plants have played a significant role in healthcare. On Earth, God gifted plants, with medicinal activities, contribute significantly in treating different diseases [1,2]. Primitive people also used herbal biomolecules without knowing or understanding the science behind the treatment of diseases and how they act [3]. They also did not know about the proper method of cultivation, collection, and storage and as a result, some important medicinal plants gradually exhausted and also became extinct. Different parts of plants like leaves, bark, roots, flower, fruits, seeds, etc., as well as whole plants are used for the treatment [3–6].

The oldest treaties dealing Ayurveda are Susruta and Charak Samhita both complied between 500 and 300 BCE. Chemical characterization, isolation and purification of many plants were started with CE 1800. The Chinese crude drug, Ma Huang, has been used in China for over 5000 years for the treatment of fever and respiratory ailments. With time, different plant parts are being utilized for the treatment of a variety of diseased conditions as they contain many biomolecules, that is, biologically active compounds, for examples, alkaloids, glycosides, phenolic compounds, terpenoids, flavonoids, tannins, carbohydrates, vitamins, organic acids, etc. [7,8]. Herbal biomolecules are not only used for the treatment of diseases, but also widely and popularly used as neutraceuticals, immunomodulators, pharmaceutical excipients, drug delivery carriers, etc. [6,9–15].

In herbal preparations (crude extract), varieties of biomolecules are present, which are capable to enhance the action of each other and thereby, provide better therapeutic effect rather than the single isolated active constituent [16–19]. These phytocomplexes may also be responsible for fewer side effects as compared to single compound [20,21]. Day by day, the tendency to use herbal biomolecules as healthcare medicines is increasing and gaining huge popularity. Gemmotherapy is one of the recent advancements in the field of therapeutic techniques, where buds and sprouts were usually collected at the peak time of annual germination and are effectively employed as therapeutics for the management of various health issues and treatment of various ailments [22,23]. Table 1.1 shows some important phytoconstituents used in modern medicines.

Table 1.1

1.2 Herbal biomolecules

Varieties of herbal biomolecules like alkaloids, glycosides, coumarins, flavonoids, tannins, terpenoids, essential oils, fixed oils, phenols, coumarins, carbohydrates, etc., are present in the plants (Fig. 1.1) [3,6,9,21]. All of these herbal biomolecules are extensively used in healthcare applications around the globe [55,56]. Most of them also possess definite physicochemical and pharmacological properties.

Figure 1.1 Various herbal molecules.

1.2.1 Alkaloids

Alkaloids are basic, nitrogen containing heterocyclic organic compounds of plant origin with marked physiologic action [57,58]. About 10,000 alkaloids are available in different plants and also, in some animal species. The nitrogen atoms are responsible for alkalinity of the alkaloids. Almost every parts of plant contain alkaloids, but they differ in amount. Alkaloids of plant origin have been reported to be used for recreational as well as therapeutic purposes [57]. Opium was considered as a gift from God [59]. Narcotine was the first in this category, obtained from opium and isolated by Derosne, in 1803. Chemically, alkaloids are classified depending on the nature of heterocyclic ring present in their structure. The important nitrogen containing ring structure are [57–61]: pyrrolidine (stachydrine), pyridine (lobeline), piperidine (ricinine), quinoline (quinine), isoquilonine (papaverine), tropane (hyoscyamine), indole (strychnine), imidazole (pilocarpine), and purine (caffeine). They are also classified according to their biosynthetic origins. The following are some important herbal alkaloids used as phytomedicines in modern therapy (Table 1.2).

Table 1.2

1.2.2 Glycosides

Herbal glycosides are secondary metabolites, which on hydrolysis yield one or more sugar portions along with a nonsugar moiety [21]. The nonsugar moiety is called aglycone or genin, whereas sugar part is known as glycone [66]. The sugar and nonsugar moiety are linked by the glycosidic linkase [67]. The aglycone part is responsible for pharmacological action, whereas sugar part is responsible for solubility, cell permeability, and other pharmacokinetic properties [66,67]. Different types of glycoside are found in different plants and possess particular type of characteristics. Examples are: anthraquinone glycosides, saponin glycosides, cardiac glycosides, isothiocyanate glycosides, cyanophore glycosides, etc. [66–70]. Herbal glycosides are widely used as phytomedicine for the treatment of a variety of diseased conditions [68–70]. Some important glycosides, their herbal sources, and therapeutic activities are presented in Table 1.3.

Table 1.3

1.2.3 Terpinoids

These are naturally occurring organic compounds having several isoprene units, also called terpenes [80,81]. There are different types of terpenoid depending upon the number of isoprene units, for example, monoterpinoids (built up of two isoprene units), sesquiterpinoids (three isoprene units), diterpinoids (four isoprene units), triterpinoids (six isoprene units), and tetraterpinoids (eight isoprene units).

About 20,000 terpinoids obtained naturally are isolated and characterized for their therapeutic as well as other effects [80,81]. The herbal terpinoid biomolecules are widely used as aromatic substance and are obtained from eucalyptus, cinnamon, cloves, camphor, menthol, thymol, etc. Examples of some therapeutically important terpinoids are [82,83]: cadinene (aroma soap), caryophylline (antiseptic mainly used in tooth paste/mouth wash), zingiberine (stomachic/carminative), guaiazulene (antiinflammatory), guaianolide (antioxidant), etc.

Artemisinin is one of the most important widely used effective terpenoids exclusively used for the treatment of malaria [84,85]. It is obtained from the plant, Artemisia annua, belonging to the family Asteraceae. Artemisinin and its derivatives are very much effective against chloroquine resistant as well as chloroquine sensitive falciparum malaria [32]. They exhibited a better result in relieving fever due to Plasmodium vivax and also in the treatment of cerebral malaria as compared to other drugs.

1.2.4 Volatile oils or essential oils

The essence or odor of the plant is due to volatile oils and hence, called essential oils [86]. These oils evaporate on exposure at ordinary temperature and the plants contain odorous components. The wide varieties of plants contain volatile oils and the main families include [86–89]: Umbelliferae, Compositae, Rutaceae, Labiatae, Pinaceae, Myrtaceae, etc. In those plants, volatile oils form in specialized secretory cells, such as glandular hairs, modified parenchyma cells, in tubes (vittae), in lysigenous or schizogenous cavities. Chemically, volatile oils are composed of a wide variety of compounds [86]. The terpinoid or volatile oil molecules contain five carbon moieties and are called as isoprene (C5H8) units. These compounds may be alcohols (geraniol), aldehydes (citral), ketones (L-menthone), esters (oil of wintergreen), etc. [87–89]. Different types of herbal volatile oils are found, some of which have therapeutic actions, and others are used as flavoring or as perfumes in different pharmaceutical preparations [86].

1.2.5 Flavonoids

Another important naturally occurring and therapeutically significant plant constituents are flavonoids and other phenolic compounds [90]. Flavonoids are found in vegetables, fruits, grains, roots, flowers, bark, stems, tea and wine. It has been reported that about 8000 flavonoids (phenolic compounds) are obtained from the herbal sources and exhibited antioxidant, antimutagenic, immunomodulator, antiinflammatory, anticarcinogenic, antibacterial and many other important activities [90–92]. They are also widely used as important constituents of neutraceuticals, pharmaceuticals, and cosmetic preparations. Flavonoids are subgrouped according to their structures like: flavones, flavanones, flavonols, flavanonols, catechins, anthocyanins, and chalcones [93]. In Table 1.4, various herbal flavonoids, their sources, and therapeutic activities are presented.

Table 1.4

1.2.6 Coumarins

Coumarins are naturally occurring biomolecules, which are mainly oxygen containing heterocycles having benzopyrone framework [101,102]. Coumarins can be classified as [101]: simple coumarins, dihydrofurocoumarins, furocoumarins, pyranocoumarins, biscoumarins and phenylcoumarins. Coumarin was first isolated as natural product, in 1820 [102]. Because of its sweet odor, it has been used in perfume since 1882. Plants produce this metabolite as chemical defense [103]. Coumarins are generally found in the outer covering of fruits, seeds, flowers, leaves, roots, and stems, but in fruits the largest concentration is usually observed [104]. Various types of pharmacological activities showed by the coumarins include [101–104]: antitubercular, antiinflammatory, antimutagenic, anticancer, antifungal, vasodilator, antithrombotic, CNS stimulant, anticoagulant, etc.

1.2.7 Carbohydrates

Carbohydrates are the herbal biomolecules comprising of carbon, hydrogen and oxygen [105]. The ratio of the last two elements is same as in water (i.e., H2O—2:1). They occur widely in nature and provide means of storage and transport of energy. Carbohydrates are also known as the main constituents of cell wall. Most natural carbohydrates exist as polysaccharides [106]. Polysaccharides can be classified on the basis of their electric charge as well as chemical compositions [10,107,108]. On the basis of their electric charge, polysaccharides can be classified as: (1) cationic polysaccharides, for example, chitin and chitosan [109,110], (2) anionic polysaccharides, for example, hyaluronic acid [111], alginic acid [112–120] and chondroitin sulfate [121], and (3) nonionic polysaccharides, for example, dextran [122], starches [123–127], and cellulose [128]. Proteoglycans, glycolipids and glycoconjugates are another class of polysaccharides, which are grouped according to the different glycosides linked with glycan. Polysaccharides along with oligosaccharides usually serve many essential purposes, for example, building blocks of the life; mediate important biological signals like immune recognition [129], cell communication [130], and mitogenesis [131]. Many researchers reported diverse therapeutic properties of polysaccharides including antitumor activity [132], antioxidant activity [133], wound healing [134], and immunostimulatory activity [135]. In Table 1.5, various important herbal polysaccharides, their sources, and therapeutic activities are presented.

Table 1.5

1.3 Therapeutic activities of herbal biomolecules

Herbal biomolecules exhibit a variety of therapeutic activities [6–9,21]. Some of which are described briefly:

1.3.1 Anticancer activity of herbal biomolecules

Cancer is characterized by unrestricted multiplication of cells in the human body [144,145]. Consequently, tumor formation of malignant cells occurs with the tendency to be metastatic [146]. The damage of DNA in the cancer cells is primarily responsible for abnormal cell division. The treatment strategy depends on the stage and severity of cancers including chemotherapy, biological therapy, surgery, hormonal therapy, radiation therapy, etc. [146]. However, in all the situations, there are some undesirable effects, such as nausea, vomiting, fatigue, appetite loss, fever, alopecia, and many other issues, which ultimately affect the patient’s quality of life.

In an international survey, it was found that deaths as well as new cases of cancers are increasing day by day. It was estimated that by 2030, there will be 17 million cancer cases per year [147]. Due to emergence and rapid increase of cancer cases, herbal biomolecules are extensively being used as highly effective novel anticancer agents for both prevention and treatment of cancers [148,149]. At present, about 60% drugs obtained from herbal sources are potentially used for the management of cancers [150]. Examples of some important anticancer phytoconstituents include [151–154]: podophyllotoxin, etoposide, podophyllinic acid, and teniposide—Podophyllum peltatum (Berberidaceae); taxanes and taxol—Taxus brevifolia (Taxaceae); docetaxel and Taxol—Taxus baccata (Taxaceae); rhinacanthin-C and rhinacanthin-D.—Rhinacanthus nasuta (Acanthaceae); Vinblastine and vincristine—Catharanthus roseus (Apocynaceae); aloe-emodin, emodin and aloin—Aloe barbadenis (Liliaceae); alliin, allicin alliin and alliinase—Allium sativum (Liliaceae); with anolides and withaferin—Withania somnifera (Solanaceae); lentinan—Lentinus edodes (Agaricaceae), etc.

1.3.2 Antidiabetic activity of herbal biomolecules

Diabetes mellitus is a chronic disorder associated with metabolic dysfunction characterized by hyperglycemia [155]. The increase in blood sugar level may be attributed due to impairment in insulin secretion and/or improper insulin action [156]. In case of untreated diabetic individuals, most of the vital organs like heart, kidneys, eyes, etc. are affected. Incidence of diabetes mellitus is exponentially increasing. International Diabetes Federation (IDF) studied that there are 425 million of diabetic individual worldwide and the rate of increasing incidences of diabetes is so high that by 2045 the number will go up to 625 million [157].

α and β cells of islets of Langerhans in the pancreas are responsible for the secretion of glucagon and insulin, respectively [155]. They jointly maintain the homeostasis of body [158]. For the treatment of type 2 diabetes mellitus, various categories of hypoglycemic agents are used clinically, either single or in combination [159]. However, due to undesirable effects of currently available drugs, biomolecules from plant sources (i.e., herbal biomolecules) have gained potentiality in treating diabetic patients. In addition, other advantages associated to antidiabetic therapy by herbal molecules include better efficacy, lesser or no side effects as well as cost effective [160]. Examples of some important herbal biomolecules having hypoglycemic action and how they exert their hypoglycemic effects are presented in Table 1.6.

Table 1.6

1.3.3 Immunomodulatory effect of herbal biomolecules

In our body, immune system maintains homeostasis, which is influenced by several factors (endogenous and exogenous) and causes either immunostimulation or immunosuppression. The agents involved in the process to normalize or modulate the pathophysiology of immune response are called immunomodulators [180]. The immunomodulatory biomolecules may be obtained from natural sources or synthesized chemically [181,182]. Due to serious adverse effects of synthetic compounds, researchers are emphasizing the uses of biomolecules obtained from natural sources. Plant sources are the important sources and herbal constituents are being currently used by both developing as well as developed countries to improve host defense mechanism and are the basis of treatment of various diseases. From the literature survey, it has been noticed that a large number of herbal biomolecules like polysaccharides, flavonoids, lectins, peptides, etc., are extensively used experimentally in the immune system [181,182]. Example of some immunomodulators from plant sources are: Piperine—Piper longum [183], Lycorine—Lycoris radiata [184], Luteolin—Lonicera Japonica [185], Ginsang—Panax ginseng [186], Triptolide—Tripterygium wilfordii [187], etc.

1.3.4 Wound healing property of herbal biomolecules

Many medicinal plants have been mentioned to be used in wound healing [4,188]. The uses of Aloe vera for the treatment of burns, ulcers as well as surgical wounds have already been practiced over 500 years by the Egyptians, Romans and also, by the peoples of America, Asia as well as Africa [189]. In these studies, a wide variety of plants showed wound healing properties, for example, Altenanthera sessilin, Napoleona imperialis, C. roseus, Clerodendrum serratum, Sesamum indicum, Ginkgo biloba, Mortinda citrifolia, etc. [190]. In a research, Maan et al. [191] studied the wound healing activity of a commonly available plant, Azadirachta indica [191]. The extracts of stem bark in different solvents exhibited the wound healing properties like wound contraction, increase in hydoxyproline and total protein content of extracts treated animals.

1.3.5 Antimicrobial activity of herbal biomolecules

Due to emergence of antimicrobial resistance, scientists around the globe are always trying to find an alternative source [18,49,87–89]. Our nature is well decorated with plethora of plants, which contain varieties of herbal biomolecules [18,31,46]. In the reported literature, many researchers have already demonstrated the antibacterial property against susceptible as well as resistant pathogens [192]. Plants with antibacterial property are found throughout the world; however, India is the major source in this respect [46]. According to reported literature, different plants with antibacterial activity have already been reported and some of these are [46,193]: Casia fistula, Murraya exotica, Urgenia indica, Canscora diffusa, Hyptis suuaveolens, etc.

Herbal biomolecules are not only significant in treating human being, but are equally important for the control of plant diseases [194]. So far, food safety and security is concerned with the preservation of foods, prevention of insect contamination, better crop yield and maintaining quality of foods, plant extracts play important role [195]. Preservation of foods by chemical substances may cause toxicity on our health and thus the uses of herbal biomolecules as natural preservatives are safer, biodegradable as well as ecofriendly in nature [196–198].

1.4 Standardization of herbal biomolecules

Every substance/product should have a definite standard and conform the prescribed quality [199]. This is the most important criteria if the substances/products are used for healthcare applications. Many industries are involved in manufacturing/processing of the herbal preparations [200,201]. However, due to lack of proper regulatory laws, standard protocols and mechanism, the quality of herbal formulations were compromised. Standardization of herbal drugs should start from the cultivation and collection of raw materials to the ultimate clinical applications [202,203]. World Health Organization (WHO) has given priority on qualitative and quantitative characterization of herbal biomolecules, quantification of the biomarkers and/or chemical markers and the finger-print profiles [204].

Standardization methods of phytoconstituents should cover the different aspects including pharmacognostic evaluations, identity of the constituents, organoleptic and phytochemical evaluation, tests for xenobiotics, biological activity and toxicity studies [202–204]. From the phytochemical studies, activity of herbal biomolecules can be assessed, whereas from fingerprint study, quality of phytochemicals can be ensured. The quantification of marker compounds provides the additional parameter for the assessment of herbal sample quality [205].

Monographs of different pharmacopoeias have been developed internationally where the standard of herbs and herbal preparations have been mentioned. Examples of pharmacopoeias are: United States Herbal Pharmacopoeia, Standards for Herbal Medicine, Chinese Herbal Pharmacopoeia, British Herbal Pharmacopoeia, and The Ayurvedic Pharmacopoeia of India (API). WHO developed comprehensive guidelines for the evaluation and clinical research of herbal medicines where both efficacy and safety parameters were critically considered [204]. Standardization of polyherbal formulations is also very important in order to avoid the batch to batch variation and to obtain the desired therapeutic efficacy [206,207]. Important standardization methods for herbal preparations include [205,208]:

1. Fluorescence quenching;

2. Thin layer chromatography (TLC) and high performance thin layer chromatography (HPTLC);

3. High performance liquid chromatography (HPLC);

4. Use of fingerprinting and bio marker compounds;

5. Liquid chromatography-mass spectroscopy (LC-MS);

6. Liquid chromatography-nuclear magnetic resonance (LC-NMR);

7. Gas chromatography-mass spectroscopy (GC-MS);

8. Gas chromatography-flame ionization detector (GC-FID);

9. Genetic marker;

10. DNA fingerprinting;

11. Supercritical fluid chromatography (SFC).

Phytopharmaceutical industry is growing vertically worldwide and the new herbal formulations are also coming into the market to fulfill the demand. However, the efficacy and safety of herbal preparations depend on the method of standardization [204]. Although some modern and sophisticated methods of standardization have developed, more innovative methods are required to be developed to ensure zero defect products to the patients.

1.5 Regulatory consideration

With time, the use of herbal biomolecules has increased. Many important diseases are being treated by herbal biomolecules from medicinal plants, such as tuberculosis, cancers, etc. To fulfill such demand, many herbal companies are now manufacturing various herbal formulations but unfortunately, some dishonest manufacturers are using the substandard or adulterated plant constituents due to scarcity of raw materials as well as for more profit [209]. Thus there is doubt about quality, safety, and efficacy of herbal formulations and there is a need for quality control, that is, implementation of regulatory measures. The different regulatory authorities like United States Food and Drug Administration (USFDA), International Council for Harmonization (ICH), WHO, etc., prescribe the standards which should be followed by the manufacturers. Paclitaxel, one of the most important herbal biomolecules also known as an anticancer agent, was approved in 1992 and was also enlisted under WHO essential medicines list [209]. USFDA is one of the leading regulatory authorities. Any manufacturer intended to manufacture and sale the product in the market should submit New Drug Application (NDA) to the appropriate authority and obtain approval for the same. USFDA may approve the product after satisfying the different criteria like purity, safety, strength, efficacy, quality, and specific uses [209].

1.6 Future prospective and challenges

The scope of herbal biomolecules in the current scenario is very significant. A large population of different developed and under developed countries relies on traditional medicine [209,210]. In China, Africa, and India, about 40%, 90%, and 70% of the total population receive herbal medicines respectively for their day to day healthcare. Most serious diseases including cardiovascular disease, cancer, prostate problems, diabetes, depression, inflammation, and even AIDS are currently treated with phytomedicines containing herbal biomolecules [210].

For a long time, nature has supplied highly effective herbal biomolecules, such as chloroquine mefloquine, amodiaquine, artemether, arteether, artemisinin and dihydroartemisinin, vinblastine, etoposide, paclitaxel, irinotecan, topotecan, cryptolepine, harunganin, maprouneacin, cucrcumin, phenoxidiol, etc. [211]. There is an increasing demand for herbal drugs, and according to projected estimation of WHO, the global herbal market will grow from $62 billion (current value) to $5 trillion by 2050. India and China are the leading producers of herbal biomolecules and the major export market includes United States, Japan, European Union, Canada, Singapore, Brazil, Indonesia as well as Mexico [212].

Despite all the opportunities, there are some challenges with herbal biomolecules regarding safety, efficacy, appropriate equipment for the manufacturing and the assessment of quality, inadequate regulatory mechanism, etc. [213,214]. Some important challenges in this respect include: (1) challenges associated to the assessment of safety and efficacy, (2) challenges associated to the regulatory status of herbal medicines, and (3) challenges associated to quality control of herbal medicines.

We are blessed with the grace of nature. The plethora of plants are available, most of which have medicinal value. Those precious herbs are to be preserved so that they can’t be extinct. Proper cultivation, collection, storage, standardization for safety and efficacy, stringent regulatory mechanism, and rational use of herbal biomolecules can assure better healthcare for a large number of people around the globe.

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