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12.2 Pharmacological Approaches 251
5. For two weeks, the animals received treatment once a
day, five times a week. Each dosage group uses five to
eight animals.
6. After the animals are sacrificed two hours post-last
treatment, their tails underwent histological processing, which includes paraplastic embedding and fixation in 4% formalin. Hematoxylin-eosin is used to stain
longitudinal sections of the thickness of around 5 m.
Evaluation: For every animal, 10 successive scales are
assessed; the results are given as a percentage of orthokeratosis per scale. For every medication dose or control group,
five to eight animals are used, yielding 50 to 80 unique
orthokeratosis values per test group. For every animal and
group, the mean and standard error of the mean are found.
With a fixed class interval of 10%, the values (ranging from
0 to 100% orthokeratosis) can be grouped into classes (class
1: 0–10%; class 2: 10.1–20%; class 10: 90.1–100% orthokeratosis). The frequency distribution is constructed from each
animal’s orthokeratosis values per dosage group (50–80
scales). The following formula is used to calculate the frequency per class in percentage terms:
Class of frequency =
____________________
total no. of scales
X 100
no. of scales in the class
2. Healing of Skin Wounds
Skin wound healing is a multiphase process [14]. The
impact of medications on wound recovery is investigated
by the assessment of mechanical strength at different
points in time following skin incision. The wound size is
measured to assess the treatment drug’s effect. The following formula is used to measure the size of the wound:
Wound closure rate(%)
Area(day 0) − Area(day n)
________________________
=
Area(day 0
X 1 0 0
)
where the initial wound area is designated as Area (day 0)
and the area on day n following treatment is designated as
Area (day n). Healing of wound skin analysis through histopathology also [42].
Procedure:
1. Ten to 20 male rats weighing 150–200 g are utilized in
groups for every dose.
2. The fur on the dorsal skin is removed under anesthe-
sia, and an incision is made in the dorso-lumbar region
that is about 3 cm long and extends from the craniocaudal direction down to the fascia.
3. Wound clips are then used to seal the wound right
away. The herbal extract is administered subcutaneously to the rats starting on the day following surgery.
4. The clips are taken out at the latest on the 10th postop-
erative day or the day prior to the tensile strength test.
5. On days 3, 6, 9, or 12 following surgeries, the rats are
euthanized under anesthesia to assess the wound tensile strength.
Evaluation: At each time interval, statistical analysis is
done to compare the wound averages of tensile strength in
the drug-treated groups with controls. The changes that
occur after receiving drug therapy are indicated as a percentage of vehicle-treated controls to illustrate the healing
process.
12.2.2.2 In Vitro Models
12.2.2.2.1 Isolated Organs
An organ or a piece of it collected from a recently euthanized
animal and immersed in a tissue bath containing a physiological salt solution (PSS) kept at 37 °C is evaluated [43]. The
bubbles rising from the bottom of the bath oxygenate the
tissue bath. Using a device known as a transducer, researchers can record the contraction, inhibition, or relaxation of
tissue contraction brought about by the presence of herbal
drugs with or without the reference antagonists or agonist
compounds. These changes in contraction, relaxation, or
inhibition indicate pharmacological activity. The isolated
organs rat fundus strip, rat jejunum, guinea pig ileum, rat
uterus, rat duodenum, and rabbit heart are frequently
employed in pharmacology. The study of isolated organs has
shown to be quite beneficial in examining the pathways of
pharmacological activity of herbal drugs and other pure substances. They have nevertheless hardly ever been applied as
a screening technique with herbal drugs [44].
12.2.2.2.2 Culture Methods
External agents like bacteria, viruses, fungi, and parasites
are the source of infectious and parasitic disorders. A proliferation of aberrant cells results in cancers. Advances in
both basic and practical research have allowed for the in
vitro cultivation of these agents. The ability of herbal drugs
to suppress the growth of bacteria, fungi, viruses, parasites,
and cells is assessed using culture-based techniques.
Typically, they are grown in a specified synthetic medium
with serum added at 37 °C. The presence of herbal drugs
that hinder the growth or culture of bacteria, fungi, viruses,
or parasites is a sign of biological activity. The concentration of plant extracts that inhibit, accordingly, 90 and 50%
of the development of living material can be calculated as
the inhibitory concentrations 90 (IC90) and 50 (IC50).
Screening medications with antibacterial, antifungal, antiviral, antiparasitic, and antitumor properties has made
extensive and effective use of culture techniques [45].
252 12 Pharmacological Screening of Drugs from Natural Sources
12.2.2.2.3 Enzyme Inhibition and Receptor Binding Assay
The blocking effect of herbal drugs on particular enzymes
implicated in the development of a disease is quantified
using enzyme inhibition tests. The receptor-binding techniques assess a compound’s capacity to identify a receptor
in a certain way. The former technique has been employed
in the primary examination of herbal drugs [46] as a tool
for discovering novel therapeutic substances [47–49], and
as a way to look at the molecular mechanism of action of
medications [50]. Although the latter approach has been
utilized in commercial drug development for several years
and has been known for several years in pharmacology, it
has not yet been widely adopted. Any medication acting via
a mechanism irrelevant to the assay will be excluded from
these extremely stringent mechanism-based tests.
12.3 Conclusion
Natural products are important sources of new drugs. New
drug discovery involves in vitro studies and preclinical
studies to evaluate the efficacy of new herbal drugs. It is
important to select the correct screening method for assessing new herbal drugs. There are many diseases and conditions for which specific screening methods are unavailable,
such as Leishmaniases, Malaria, and Hepatitis. So, there is
a need to develop new animal models and in vitro techniques for the screening of new herbal drugs.
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13
Biosynthetic Pathways of Phytopharmaceuticals
Poonam Nilesh Chougule
Pharmacognosy, Ashokrao Mane College of Pharmacy, Peth-Vadagaon, Kolhapur, India
13.1 Introduction
13.1.1 Biosynthetic Pathway
13.1.2 History
13.1.3 Gross Idea
13.2 Introduction to Primary and Secondary Metabolites
13.2.1 Primary Metabolites
13.1.4 Milestones
13.2.2 Roles and Significance
13.2 Introduction to Primary and Secondary Metabolites 257
1. Carbohydrates
Function: Main source of energy for cellular
Examples: Glucose, fructose, sucrose, starch, and
2. Lipids
Function: Energy storage and structural components
Examples: Fats, oils, phospholipids, and steroids.
3. Amino Acids
Function: Building blocks of proteins.
Examples: Alanine, valine, lysine, and serine.
4. Proteins
Function: Enzymes, structural components, trans-
13.2.2.1 Primary Metabolites
Examples: Enzymes, hemoglobin, and collagen.
5. Nucleic Acids
Function: Genetic information storage and transfer.
Examples: DNA and RNA.
6. Nucleotides
Function: Monomers that make up nucleic acids.
Examples: ATP and guanosine triphosphate (GTP).
7. Metabolic Intermediates
Function: Molecules that participate in various meta-
Examples: Pyruvate, acetyl-CoA, and citrate.
8. Coenzymes
Function: Assist enzymes in catalyzing reactions.
Examples: NADH and FADH2 (flavin adenine
9. Vitamins
Function: Coenzymes or precursors of coenzymes.
Examples: Vitamin C (ascorbic acid) and vitamin B
10. Organic Acids
Function: Involved in energy metabolism and cellular
Examples: Citric acid and malic acid.
11. Electrolytes
Function: Maintain osmotic balance and participate
Examples: Sodium (Na+), potassium (K+), and
13.2.2.2 Secondary Metabolites
1. Alkaloids: these substances that contain nitrogen fre-
2. Terpenoids: with a range of functions, terpenoids are
3. Phenolic substances: flavonoids and tannins are
4. Polyketides: frequently produced by bacteria and
5. Glycosides: these substances are made up of one sugar
13.3 General Metabolic/Synthetic Pathway Which Shows from CO2 to Different Primary and Secondary Metabolite Formation 259
Functions: Electron carriers in cellular respiration
8. Glucosinolates
Examples: Found in cruciferous vegetables (e.g. broc-
Functions: Defense against herbivores, may have
9. Saponins
Examples: Glycyrrhizin (found in licorice), and quil-
Functions: Often have detergent-like properties; may
10. Resins and Latex
Examples: Gum Arabic and rubber.
Functions: Defense against herbivores and sealing
11. Floral Scent Compounds
Examples: Volatile compounds that contribute to the
Functions: Attract pollinators.
12. Cannabinoids
Examples: tetrahydrocannabinol (THC) and canna-
1. Alkaloids
Examples: Morphine, quinine, caffeine, and nicotine.
Functions: Often have pharmacological effects, acting
2. Terpenoids (Isoprenoids)
Examples: Essential oils (e.g. menthol), carotenoids
Functions: Involved in plant defense, pigmentation,
3. Phenolic Compounds
Examples: Flavonoids (e.g. quercetin), tannins, and
Functions: Antioxidants, UV protection, defense
4. Glycosides
Examples: Cardiac glycosides (e.g. digoxin) and cya-
Functions: Defensive compounds, and toxins against
5. Polyketides
Examples: Antibiotics (e.g. erythromycin) and aflatoxins.
Functions: Antibacterial, antifungal, and other defen-
6. Phytosterols
Examples: Sitosterol and stigmasterol.
Functions: Structural components of cell membranes
Functions: Found in Cannabis plants; may have psy-
13. Phytocompounds with Antioxidant Properties
Examples: Resveratrol and curcumin.
Functions: Antioxidant properties and potential
13.3 General Metabolic/Synthetic
Pathway Which Shows from CO2 to
Different Primary and Secondary
Metabolite Formation
7. Quinones
Examples: Ubiquinone (coenzyme Q) and plastoquinone.
260 13 Biosynthetic Pathways of Phytopharmaceuticals
1. Carbon fixation (Calvin cycle): The process starts
2. Glycolysis: In the cytoplasm, G3P, a three-carbon
3. Citric acid cycle (Krebs cycle): Pyruvate reaches
9. Plants use photosynthesis as their primary
metabolism: Photosynthesis is a part of primary
10. Nucleotide biosynthesis: Amino acids and CO2 are
4. Electron transport chain: Because of the electrons
5. Gluconeogenesis: This process allows for the
6. Amino acid production: The citric acid cycle and
7. Lipid biosynthesis: An essential building block for
8. Secondary metabolites: Certain organisms generate
13.4 Enzymes
1. Oxidoreductases: initiate and catalyze reduction-oxi-
2. Transferases: aid in the movement of functional
3. Hydrolases: initiate processes involving hydrolysis.
4. Lyases: in order to create double bonds or the opposite,
5. Isomerases: these enzymes catalyze atoms to rearrange
6. Ligases: utilizing ATP energy, join two molecules.