1. Ethnobotany is the study of relationships between people and plants. It aims to document traditional medicinal plant uses. Many early works studied indigenous plant medicines. 2. Herbal medicines provide various health benefits like cardioprotection, hepatoprotection, nephroprotection, and protection against cancer, Alzheimer's, and diabetes. Specific plants like turmeric, neem, onions, broccoli, milk thistle, grapes provide these benefits through active constituents. 3. While herbal medicines have deep historical roots, inconsistencies in active constituents between plants makes effects unpredictable. Standardization through quality controls and guaranteed marker compounds in extracts provides consistent activity and clinical results.

1. ETHNOMEDICINE: MERITS OF
USING HERBAL MEDICINES

2. Introduction
 Ethno + Botany
 Ethno from ethnology – Study of culture
 Botany- Study of plant
 Study of relationship that exist between people and plants
 Basic aim is to document, describe and explain complex relationshipps between
cultures and uses of plants
In 19th century Leopold Glueck published work on traditional
medicinal uses of plants by rural people in Bosnia, which is considered to
be the first modern ethnobotanical work.
The term Ethnobotany was coined by American Botanist John Harshburger in
1896 in an attempt to study native plants used by primitive and aboriginal people.

3. Medicinal Plant: Definition
 According to WHO: any plant which contains substances that can be
used for therapeutic purposes, or which are precursors for
chemopharmaceutical semi-synthesis (Antibiotics).
 This definition distinguishes between the already known medicinal
plants whose therapeutic properties or characters are precursors of
certain molecules which have been established scientifically, with that
of other plants used in traditional medicine which are regarded as
medicinal, but have not yet been subjected to a thorough scientific
study.

4. Herbal
Product –
Health benefit
Cardio
Protection
Hepato
Protection
Nephro
Protection
Anti-Cancer
Alzheimer’s
disease
Anti Diabetic Quercetin: Onion
Curcumin: Turmeric
Sulforaphane: Brocolli
Resveratrol: Grapes
Azadirachtin:
Neem
Silibinin: Silybum marianum

5. 1. Curcumin role on Anticancer1
Curcumin — a yellow pigment found primarily in turmeric (a flowering plant of the
ginger family best known as a spice used in curry) — is a polyphenols with anti-
inflammatory properties and the ability to increase the amount of antioxidants that the
body produces.
 Supplementation with curcumin reliably reduces markers of inflammation and
increases the levels of endogenous antioxidants in the body.
 Research suggests that curcumin can help to cure inflammatory conditions,
Cancer (colon cancer) metabolic syndrome, arthritis, anxiety, and hyperlipidemia.

6. 2. Azadirachtin role on Anti-diabetics2
 Azadirachta indica (Neem) is a medicinal plant, used
in Ayurveda for treating various diseases, one of which is
diabetes mellitus. It is known to possess
antiinflammatory, antipyretic, antimicrobial,
antidiabetic and diverse pharmacological properties.
In the study carried out by Kar et al 95% alcoholic
extract of neem leaf in the dose of 250 mg/kg twice daily
orally for one week reduced blood sugar level by 55%
and urine sugar by 100% (p<0.05) in alloxan induced
diabetes in rats.
 Azadirachtin a triterpenoid is responsible for this
propery.

7. 3. Quercetin role on Hepatoprotection3
 Quercetin is a flavonoid found in fruit and vegetables. It has a wide range of benefits, which
people can get by including a variety of fruit and vegetables in their diet.
 Quercetin is a pigment in many plants, fruits, and vegetables.
 Quercetin has powerful antioxidant properties and help protect against certain health
conditions, including Liver, kidney, heart disease.
 Foods and drinks that contain Quercetin include:
 onions
 peppers
 buckwheat
 capers
 Brassica vegetables (cabbages).

8. 4. Sulforaphane role on Nephroprotection4
 It is dietary isothiocyanate
 Synthesized from precursor found in
cruciferous vegetables – genus Brassica
 Such as cauliflower, broccoli,
cabbage, brussel spourts other Genera
Radish.
 Chemotherapeutic properties – Anti-
cancer & Anti- angiogenic in various
organ.
 Free radicals scavenging properties
from Liver, Kidney, Heart etc.,
 Daily consumption of broccoli
(2.17g dry wt).

9. 5. Silibinin role on Alzheimer diseases5
 Silibinin (flavonoid) has antioxidative stress and antiapoptotic effects and reduces
cognitive impairment in models of Alzheimer's disease (AD).
 Silymarin and its major constituent, Silibinin, are extracts from the medicinal
plant Silybum marianum (milk thistle) and have traditionally been used for the treatment
of Alzheimer diseases.
 Silibinin (INN), also known as silybin (both from Silybum, the generic name of
the plant from which it is extracted), is the major active constituent of silymarin, a
standardized extract of the milk thistle seeds, containing a mixture
of flavonolignans consisting of silibinin, isosilibinin, silychristin, silidianin, and others.

10. 6. Resveratrol role on Cardio protection6
Resveratrol is a stilbenoid, a type of natural phenol, and a phytoalexin
produced by several plants in response to injury or when the plant is under attack
by pathogens, such as bacteria or fungi.
Sources of resveratrol in food include the skin of grapes, blueberries,
raspberries, mulberries, and peanuts.
Resveratrol has antioxidant and anti-inflammatory properties to protect
you against diseases like CVD, cancer etc.,
 Resveratrol supplements are possibly safe when taken by mouth in doses up
to 1500 mg daily for up to 3 months.

11. A brief History
 Prehistoric times
 Plants, including many now used as culinary herbs and spices, have been used as
medicines from prehistoric times.
 Spices have been used partly to counter food spoilage bacteria, especially in hot
climates and especially in meat dishes which spoil more readily. Angiosperms
(flowering plants) were the original source of most plant medicines.
 Human settlements are often surrounded by weeds useful as medicines, such as
nettle, dandelion and chickweed.
 A mushroom was found in the personal effects of Ötzi the Iceman, whose body
was frozen in the Ötztal Alps for more than 5,000 years. The mushroom was
probably used to treat whipworm.
 In ancient Sumeria, hundreds of medicinal plants including myrrh and opium are
listed on clay tablets. The ancient Egyptian Ebers Papyrus lists over 800 plant
medicines such as aloe, cannabis, castor bean, garlic, juniper, and mandrake.

12.  Medevial Ages
 In the Early Middle Ages, Benedictine monasteries preserved medical
knowledge in Europe, translating and copying classical texts and
maintaining herb gardens. Hildegard of Bingen wrote Causae et Curae
("Causes and Cures") on medicine.
 In the Islamic Golden Age, scholars translated many classical Greek texts
including Dioscorides into Arabic, adding their own commentaries
Herbalism flourished in the Islamic world, particularly in Baghdad and in
Al-Andalus.
 Among many works on medicinal plants, Abulcasis (936–1013) of Cordoba
wrote The Book of Simples, and Ibn al-Baitar (1197–1248) recorded
hundreds of medicinal herbs. Avicenna included many plants in his 1025 The
Canon of Medicine.
 Abu-Rayhan Biruni, Ibn Zuhr, Peter of Spain, and John of St. Amand wrote
further pharmacopoeias.

13.  Modern period
 The Early Modern period saw the flourishing of illustrated herbals across Europe,
starting with the 1526 Grete Herball. John Gerard wrote his famous The Herball or
General History of Plants in 1597, based on Rembert Dodoens, and Nicholas Culpeper
published his The English Physician Enlarged.
 Many new plant medicines arrived in Europe as products of Early Modern
exploration and the resulting Columbian Exchange, in which livestock, crops and
technologies were transferred between the Old World and the Americas in the 15th and
16th centuries.
 Medicinal herbs arriving in the Americas included garlic, ginger, and turmeric; coffee,
tobacco and coca travelled in the other direction In Mexico, the sixteenth century
Badianus Manuscript described medicinal plants available in Central America.

14.  Popular Cultures
 India and China have been on the forefront when one refers to the history of
herbal drugs. The traditional systems of medicines viz. Ayurveda, Siddha, Unani,
Western Herbal Medicine, Traditional Chinese Medicine and Homeopathy have
roots in medicinal herbs. Herbal medicines have been produced by a number of
renowned researchers and due to its accessibility to traditions it is still practiced
even by lay practitioners.
 Ayurveda, the ancient healing system flourished in India in the Vedic era. The
classical texts of Ayurveda: Charaka Samhita and Sushruta Samhita were
written around 1000 B.C. The Ayurvedic Materia Medica includes 600 medicinal
plants along with therapeutics. Herbs like turmeric, fenugreek, ginger, garlic
and holy basil are integral parts of Ayurvedic formulations. The formulations
incorporate a single herb or more than two herbs (polyherbal formulations).
 The history of traditional Chinese medicine is renowned and the herbal system,
is very well preserved. It originated about 3000 years ago and is a popular
science in western countries. Traditional Chinese medicine favors the use of
medicinal herbs in their natural form rather than by extraction.

18. Why isn’t the herbs as medicines so popular
 Two medicinal plants of the same species may look similar, yet be substantially
different in the levels of active constituents that they contain.
 Botanical medicines made from plants that differ markedly in their chemical
constituents cannot produce the same therapeutic effects.
 Since the practitioner or consumer will be unable to assess the difference, they
cannot compensate for it. The consequence will be inconsistent clinical results.
So How do we make it popular?

19. Standardization
 The standardized herbal extract is a preparation, which contains a
certain fixed proportion of the active constituent.
 Standardized extracts retain the chemical complexity typical of the
natural plant, but offer the added advantage of guaranteed levels of
certain key constituents.
 A constituent of a medicinal herb, which is used for quality control
and assurance of the herbal product, is known as marker compound.
 Extracts subjected to rigorous quality controls during all phases of
the growing, harvesting and manufacturing processes.

20. Clinical advantages:
 High quality extracts with consistent activity.
 Consistent activity allows for more accurate prescribing.
 Consistent activity allows for consistent clinical results.
 Extensive quality control ensures the quality and safety of standardized extracts.

21. Need of Quality control:
It ensures:
 That the correct botanical species is used.
 That only high quality raw materials are used.

 That no other plant material has been used.
 That the plant material is not contaminated with pesticides, heavy metals,
or other noxious agents, that the final extract complies with international
limits for microbial content and that the final product is of a consistent
high standard preparation.

22. Markets and Marketing Issues
 Larger number of people seeking remedies and health approaches free of the side-
effects caused by synthesized chemicals
 In Germany and France which together represent 39% of the $14 billion global retail
market, herbal remedies known as phytotherapeutics are well established, and the
quality criteria applied to regulation and manufacturing are comparable to those for
chemical drugs.
 The principal primary market for these raw materials is to industries that
manufacture: Essential oils, Liquid extracts and tinctures, Herbal teas, Concentrated
soft extracts (for further industrial application), Concentrated dry extracts (for further
industrial application), Plant-derived pure pharmaceutical drugs.

23.  Their dietary herbal supplement market is estimated at US$4 billion and
has been growing at 6–8% per annum.
 The market share of herbal products made in developing countries
remains comparatively low.
 Scientific knowledge of the products produced in the developing countries,
and of their systems of traditional medicine, is limited and this also
restricts the market for their herbal products.

24. Medicinal plant analysis: HPLC
 By way of comparing HPLC ‘fingerprints’ with reference standards, plant
material and botanical extracts can be identified unequivocally. However,
HPLC also provides detailed information about the composition of the
sample.
 HPLC is therefore widely used in the quality control of standardized
botanical extracts, to ensure the presence of key constituents in specified
amounts (qualitative and quantitative analysis).

25.  Pharmacokinetic studies are an integrated part of the development program of
a new drug. They are intended to define the time course of drug and major
metabolite concentrations in plasma and other biological fluids in order to
obtain information on absorption, distribution, metabolism, and elimination.
 Bioavailability: the proportion of a drug or other substance which enters the
circulation when introduced into the body and so is able to have an active effect.
 When there are safety concerns pharmacokinetic data are useful to provide
safety margins. If there is a constituent with known therapeutic activity and a
narrow therapeutic range, pharmacokinetic data will be required.

26. Reverse pharmacology
Reverse pharmacology, is defined as the science of integrating documented clinical
experiences and experiential observations into leads, through transdisciplinary
exploratory studies, and further developing these into drug candidates through
robust preclinical and clinical research.

27. Reverse Pharmacology
 Conventional Pharmacology
 Reverse Pharmacology

28. Scope
The scope of reverse pharmacology is to understand the mechanisms of action at
multiple levels of biological organization and to optimize safety, efficacy and
acceptability of the leads in natural products, based on the relevant science.

29. Dimensions
 Experiential documentation: Pharmacoepidemiology-standardized formulation
with HPLC pattern standardized formulation with HPLC pattern.
 Exploratory human/animal studies exploratory human/animal studies—
Relevant models of activity relevant models of activity— Human dose
determination human dose determination.
 Experimental programs - Levels of biological organization. - Rapid drug
development path. - Leads: Comb. Leads: Combinatorial Chemistry & high-
throughput pharmacologic screening HTPS.

30. Examples
 Mucuna pruriens (Velvet beans) for Parkinson’s disease.
 Constituents are: L-dopa, apart from other phytochemical substances.
 The seed powder of the leguminous plant, Mucuna pruriens were being used in
traditional Ayurvedic Indian medicine for diseases including parkinsonism.
 The studies on the constituents of Mucana pruriens revealed that L-DOPA itself
mediates neurotrophic factor release by the brain and CNS. Thus, L-DOPA is a
lead molecule towards development of drugs for Parkinsons disease.

31. Zingiber officinale (Ginger): for nausea/vomiting
 Modern-day uses for ginger in Eastern medicine include the use of the herb to treat nausea
(including motion sickness and morning sickness of pregnancy).
 The main components of ginger are the aromatic essential oils, antioxidants, and the pungent
oleo-resin. These aromatic or pungent compounds have been identified as the
phenylalkylketones, known as gingerols, shogaols, and zingerone.
 The anti-emetic effects of ginger are due to Zingerone’s (a diterpenoid) local effect on the
vagal receptors in the stomach.

32. Reverse pharmacology and Ayurveda
 Central Council for Research in Ayurveda and Siddha (CCRAS) has recently
adopted the golden triangle approach for some new indications of old drugs, as well
as for Ayurveda.
 The golden triangle approach is a combination of Dravyagunavignyan, systems
biology, and reverse pharmacology for the discovery of potent and cost-effective
remedies.

33.  In Ayurveda, drugs have been classified based on action of the drug is widely
accepted.
 In modern medicine, drugs have been classified according to pharmacological
actions (molecular targets to which drug binds).
 Medicinal plants like Ashwagandha, Brahami, Tulsi, Guggul, Kutki, Kalmegha,
Gokshura and Shatavari have been targeted for their application in modern
science. Active constituents of the plants have been identified and highly purified
extracts are being marketed.

34.  The reverse approach in pharmacology has been quite successfully applied
in the past. The drawback was the long time frame from the observational
therapeutics to a new drug.
 For example, Rauwolfi a serpentina (sarpagandha) was convincingly
demonstrated to be anti-hypertensive by Sen and Bose in 1931.
 However, a drug reserprine, emerged only after 20 year of work by Vakil,
Bein, Muller and Schlitter.
 This occurred because the path of reverse pharmacology was quite
discontinuous.

35.  The paradigm of reverse pharmacology is actually a rediscovery of the
path, which founded modern pharmacology.

36. Ethnopharmacology
 Ethnopharmacology is the scientific study correlating ethnic groups, their health, and
how it relates to their physical habits and methodology in creating and using
medicines.
 Example: isolation of quinine from Cinchona.

37. Ethnopharmacology and Traditional Medicine
 Numerous drugs have entered the international pharmacopoeia via the study of
ethnopharmacology and traditional medicine.
 Traditional medical traditions can offer a more holistic approach to drug design and
myriad possible targets for scientific analysis.
 Powerful new technologies such as automated separation techniques, high-throughput
screening and combinatorial chemistry are revolutionizing drug discovery.
 Traditional knowledge can serve as a powerful search engine, which will greatly facilitate
and rediscover intentional, focused and safe natural product drug discovery.
 Good botanical practices which can improve the quality control procedures of
monitoring impurities, heavy metals and other toxins in the raw material can make
ethnopharmacology research more meaningful.

38.  Drug discovery in the current scenario has become unproductive to the point where
the economic future of the industry is questionable. The research and development
thrust in the pharmaceutical sector needs to focus on development of new drugs,
innovative processes for known drugs and development of plant-based drugs through
investigation of leads from the traditional systems of medicine.
 Traditional medicine can provide novel inputs into the drug development process.
However, bioprospecting—the search for economically valuable natural resources—
by pharmaceutical companies, or on their behalf, has not been conspicuously
successful in recent years.

39. These include:
 Ethnopharmacological field work which involves: interviewing healers; interpreting traditional
terminologies into their modern counterparts; examining patients who are consuming herbal
remedies; and identifying the disease for which an herbal remedy is used.
 Interpretation of signs and symptoms mentioned in ancient texts and suggesting the proper use of
old traditional remedies in the light of modern medicine.
 Clinical studies on herbs and their interaction with modern medicines.
 Advising pharmacologists to carry out laboratory studies on herbs that have been observed
during field studies.
 Work in collaboration with local healers to strengthen the traditional system of medicine in a
community

40. Advantages
 Antiviral Herbal medicinal products have been used as a source of putative candidate
drugs in many diseases. However, in case of viral diseases, the development of antivirals
from natural sources is less explored, probably because within the virus there are few
specific targets where the small molecules can interact to inhibit or kill the virus.
 The currently available antiherpes drugs are nucleoside analogs that did not cure the
lifelong or recurrent infections and the use of these drugs often leads to the development
of viral resistance coupled with the problem of side effects, recurrence and viral latency.
 However a wide array of herbal products, used by diverse medicinal systems throughout
the world, showed a high level of antiherpes virus activities and many of them have
complementary and overlapping mechanisms of action, either by inhibiting viral
replication, or by viral genome synthesis.

41. Story of Aspirin:
 Many believe that willow is the natural source of aspirin. However, willow species contain
only a low quantity of the prodrug salicin which is metabolized during absorption into
various salicylate derivatives.
 If calculated as salicylic acid, the daily salicin dose is insufficient to produce analgesia.
Salicylic acid concentrations following an analgesic dose of aspirin are an order of
magnitude higher.
 Flavonoids and polyphenols contribute to the potent willow bark analgesic and anti-
inflammatory effect. The multi-component active principle of willow bark provides a
broader mechanism of action than aspirin and is devoid of serious adverse events.
 In contrast to synthetic aspirin, willow bark does not damage the gastrointestinal mucosa.
An extract dose with 240 mg salicin had no major impact on blood clotting. In patients
with known aspirin allergy willow bark products are contraindicated.
OH
HO
O CH3
OH
Acetyl Salicylic acid
(Aspirin)

42. Recent developments
 Artemisia and Artemisia-based products for COVID-19 management:
current state and future perspective
 Artemisia-based products have demonstrated a broad spectrum of biological
ability including antiviral properties. Besides its antiviral activity, Artemisia
annua have shown to contain appreciable amounts of minerals such as zinc,
gallium and selenium among others.

43.  Artemisia species are an excellent source of essential oils such as pinene, thujyl
alcohol, cadinene, phellandrene, thujone, etc. and have been reported to achieve
remarkable success for several biological activities including, analgesic, anti-
coccidial, anti-diabetic, antifungal, antiviral, anti-herpes virus, and lots more.7
 Artemisia spp. had earlier been reported to consist of essential phytochemicals
that contribute to its inhibitory role against viruses.8
 A. annua, a highly effecacious species demonstrated its ability to inhibit SARS-
CoV-2 penetration and replication.9
 Wormwood (Artemisia annua) inhibits the growth of the virus and could be an
additional therapeutic against COVID-19.

44. New Approaches towards improving
Pharmaceutical properties of medicinal plants

45.  Genetic engineering of a secondary metabolic pathway aims to either increase or decrease the
quantity of a certain compound or group of compounds i.e., secondary metabolite pathway
manipulation based on the application of systems biology approaches (integrated metabolomics,
proteomics and transcriptomics).
 Metabolic engineering is not only widely applied in industrial fermentation for strain
improvement and metabolite overproduction but has also found many applications in functional
genomics, biological research (signal transduction), and medical research (such as drug
discovery and gene therapy).
Metabolite Pathway Engineering in Plants

46.  To aid in development and defense against stress, plants synthesize hundreds of thousands of
compounds, many of which are produced through species-specific and complex biosynthetic
pathways.
 Shikimic acid pathway, non-mevalonate (MEP) pathway and mevalonate (MVA) pathway lead
to diverse classes of compounds, which include the terpenoids, monoterpene indole alkaloids,
isoquinoline alkaloids, flavonoids and anthocyanins.
Wilson et al. (2014) Current Opinion in Biotechnology

48.  Secondary metabolites are synthesized in small quantities in plants.
 Although some valuable plant natural products with simple structures are easily chemically
synthesized (e.g., aspirin and ephedrine), many have complex structures with multiple
chiral centers, making chemical synthesis both difficult and commercially infeasible.
 These compounds are often produced through the exploitation of native biological
pathways using natural harvest (e.g., codeine, morphine and dietary food compounds),
semi-synthesis (e.g. paclitaxel), heterologous production where a specific protein is
introduced in cell which it doesn’t prepare (e.g. vanilla) or plant cell culture techniques.
Why We need Metabolite pathway engineering in Plants?

49.  Metabolic engineering for increasing natural product yield can be approached using two primary
strategies, depending upon the desired outcome.
 For food crops, increasing the production of an entire class of compounds is often beneficial, leading to
enhanced ability of a plant to adapt to the environment or increasing the overall nutritional value of a food
product.
 On the other hand, it is often necessary to target specific compounds within a biosynthetic pathway,
allowing for increased yield of a single product for medicinal or nutraceutical applications. By upregulating
or silencing of specific pathway genes, cooperative or competing pathway genes, or transcription factors, as
well as introduction of heterologous genes to allow for production of non-native compounds
Metabolite pathway engineering approaches

52. Conclusion
 Revitalization of the natural products is bringing newer challenges with
respect to quality control and standardization along with cost effectiveness.
 The renewed interest in the development of natural products requires the
confluence of the modern techniques and harmonization of regulations related
to their research and development between various fields of science.

53. References
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