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Ayurvedic Knowledge Inspired Approach to Modern Drug Discovery 373
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CHAPTER 14
Ayurvedic Formulations and
Their Clinical Uses
KARTHIK VARMA A. C.,* SASIKUMAR KUTTAPPAN,
GEORGE JOSEPH, SHINTU JUDE AND AUGUSTINE AMALRAJ
R&D Centre, Aurea Biolabs (P) Ltd, Kolenchery, Cochin-682 311, Kerala, India
*Email: ackvarmaapm@gmail.com
14.1 Introduction
Traditional systems of medicine have always gained the accolade from ancient
days onwards because of the wide range of pharmacological activities. Herbs and
spices have special socio-economic importance and are a traditional system of
medicine.
1
The diverse range of phytochemicals is at the root of the modern
nutraceutical industry for their multi varied uses.
2
Plant-derived classes of phy-
tochemicals include polyphenols, flavonoids, tannins, minerals, vitamins, etc.
3
Ayurveda has marked its potential as a traditional Indian system of
medicine, which is mainly composed of polyherbal formulations for treating
various disorders. Literature suggests that Ayurveda uses almost 1200 spe-
cies of plant followed by 900 for Siddha and 700 for Unani.
4
The majority of
the Asian population relies on the use of traditional systems of medicine.
5
Ayurveda is described as the ‘‘science of life’’ owing to its effects on the
mental, physical, spiritual, and social wellbeing of human beings.
6
Ayurvedic systems of medicine concentrate of the development of a
product covering the three doshas and the majority of them are not clinically
evaluated for their indented use. A modern system of medicine concen trates
on the use of specific bioactive components, which are attributed to the
desired pharm acological act ivities.
Chemistry, Biological Activities and Therapeutic Applications of Medicinal Plants in Ayurveda
Edited by Augustine Amalraj, Sasikumar Kuttappan and Karthik Varma A. C.
r The Royal Society of Chemistry 2023
Published by the Royal Society of Chemistry, www.rsc.org
374
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This chapter tries to present an overview on the need for clinical trials, the
phytochemicals used in ayurvedic medicines, the hurdles in the clinical
trials, and the future prospective for the need of clinical trials for product
development.
7
14.2 The Need for Randomized Clinical Trials (RCT)
and Compatibility With Ayurveda
A randomized clinical trial (RCT) is one of the predominant study designs that
are commonly employed to evaluate the pharmacokinetics and pharmacody-
namics profile of any single molecule or for a polyherbal formulation. A typical
RCT undergoes various steps like drafting of the study design, which includes
protocol development, enrolment of subjects, and drafting of the primary and
secondary outcomes.
7
A study conducted by Manohar has identified two major
concerns in designing the RCT for Ayurveda products: (1) complex diagnostic
assessment in ayurveda that significantly differs from allopathic diagnosis and
(2) multiple complexity of treatments offered in Ayurveda.
8
Charaka Samhita,
one of the classical texts in ayurveda describes that ten important patient as-
sessments are required in addition to clinical assessment, which include
prakriti (physico-mental constitution), agni (metabolic profile), samhanana
(anthropometry), etc.
9
Similarly, Patwardhan et al.
10
pointed out that a clinical
trial in allopathy is restricted tothe evaluation of the effect of a single herb, but
in ayurvedic practices of medicine the drug interventions are complex and
often involve evaluation of multiple medications, physical therapies, and diet
and lifestyle.
10
Results from a study also showed that the study designs in
Ayurveda are further complicated by the dynamic assessment of progression
and regression of disease in real-time clinical practice that requires a periodic
assessment and modification of therapeutic interventions even during the
course of the trial.
11
Fonnebo et al.
12
pointed out that studies claiming little/no
efficacyof alternativemedicine therapies furthersupported this argument,and
reports of substantial benefits in real-time practice show there is a mismatch
between current RCT evaluation of Ayurveda therapies and drugs.
12
Some of
the other struggles in designing Ayurvedic trials also include:
i. One of the major hurdles in designing the study design involves
standardization of bioactive components in polyherbal formulation.
In Ayurveda practices the system involves the mixing of the herbs in a
fixed ratio and is not based on the percentage of bioactives.
ii. Studies have also established hurdles in the estimation of ‘‘active’’
molecules in body fluids in the pharmacokinetic studies in phase I of
drug development in ayurvedic practices.
iii. Dose fixation is also one of the biggest hurdles in Ayurveda as many of
the formulations use crude herbs instead of using concentrated ex-
tracts – the use of crude raw herb can have a high degree of variation
based on the geographic and seasonal variation.
Ayurvedic Formulation and Their Clinical Uses 375
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iv. Ayurvedic practices involve supplementation of the drug based on the
body nature of particular individuals and not on a group of the
population.
v. Another drawback in the traditional systems of medicines is the
method of treatment as many traditional systems of medicine con-
centrate on a holistic approach which involves treating the mind,
body, and soul at the same time.
14.3 Ayurvedic Medicinal Plants in Preclinical and
Clinical Trials
The boom and efficacy of traditional plant-based systems of medicine, in-
cluding ayurvedic drugs, is gaining much importance nowadays because of
their efficacy. Traditional ayurvedic medicines are evaluated for their efficacy in
various health disorders like bronchial asthma, rheumatoid arthritis, ischemic
heart disease, etc.
13–16
The most common herbs which are evaluated in ayur-
vedic systems of medicine include turmeric, ginger, boswellia, pepper, ashwa-
gandha, shatavari, etc. for their biological activities. The majority of the
ayurvedic drugs are polyherbal formulations whose combined synergistic ac-
tion contributes to the bioefficacy of the product. The US National Centre for
Complementary and Alternative Medicine has given funding for several re-
search studies based on the ayurvedic system of medicine, out of which the
most evaluated include turmeric, ginger, black pepper, and boswellia. Most of
the ayurvedic preparations are based on the concept of polyherbal
formulations.
14.3.1 Polyherbal Formulations
Triphala, one of the most well-known formulations in ayurvedic prepar-
ations made using the fruits of Terminalia chebula, Terminalia bellirica, and
Emblica officinalis was clinically evaluated for its positive role in controlling
constipation and gastric problems. The study showed promising effects on
the role of the formulation in controlling the symptoms associated with
constipation and gastric problems.
17
Human studies involving a triphala
water decoction found it to be as effective as chlorhexidine gluconate
germicidal mouthwash in the prevention of dental cavities. Studies revealed
that Triphala at a dosage of 6% mouthwash promoted a significant
reduction in oral streptococcus colonies.
18
Triphala mouthwash was also
found to reverse precancerous oral lesions associated with tobacco usage
in the young Indian population.
19
The most promising effect of Triphala
is in weight management. In a 12 week, double blind, randomized,
placebo-controlled trial, human subjects treated with triphala was found to
decrease their body weight by approximately 5 kg compared to the placebo
group.
20
Triphala also exhibits a promising role in reducing the blood glu-
cose levels. A human clinical study on non-insulin dependent diabetes
376 Chapter 14
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mellitus subjects showed that supplementation of 5 g of Triphala for a
duration of 45 days significantly lowered blood glucose levels.
21
Trikatu, another promising herbal formulation comprising black pepper,
long pepper, and ginger, is also used for many disorders in ayurvedic for-
mulations. A human study conducted by Saxena et al. evaluated that Trikatu
Churna was found to be effective in the management of sthaulya. Twenty-
four subjects who were supplemented with Trikatu churna had effectively
lowered signs and symptoms of sthaulya.
22
Guduchyadi ghrita medhya rasayana, an ayurvedic formulation containing
Tinospora cordifolia, Achyranthes aspera, Embelia ribes, Convolvulus prostra-
tus, Acorus calamus, Terminalia chebula, Saussurea lapp a, and Asparagus ra-
cemosa showed positive effects in clinical evaluations by improving the
mental health, memory, stress, and depression conditions and can further
lead to slowing down of the aging process.
23
A clinical study of Suvarna Bindu Prashan evaluated its use in twenty
healthy male and female children within the age group of three to four years
for a duration of six months. The group, which received the test product,
showed significant improvement in the scores of eating habits, behavior,
mood, temperament, and in the scores of events of illness.
24
Chyawanprash,
one of the most widely used ayurvedic formulations with the ingredients
Withania somnifera, Emblica officinalis, Piper longum, Tribulus terrestris, As-
paragus racemosa, Bacopa monnieri and Tinospora cordifolia is regarded as an
omnipotent formulation for boosting the immunity and many other disease
ailments. There are many studies indicating the various health benefits of
Chyawanprash. In a double-blind placebo-controlled study, the subjects
showed significant improvement in Hamilton-D (HAM-D) scores compared
to the placebo.
25
Similarly, the nootropic effect of Chyawanprash signifi-
cantly improved the cognitive functions in college students. Parameters like
alertness, attention, and concentration were improved in the study popu-
lation.
26
The immune boosting studies of Chyawanprash were confirmed by
reducing disease symptoms of seasonal influences, modulated IgE and im-
munity markers levels, improved pulmonary functions, reduction in cortisol
levels, and improvement in quality of life (QoL).
27
Chyawanprash was
evaluated in children of 5–6 years in age, in a 6-month long randomized ,
open labeled, prospective, multi-center, clinical study in children and it was
shown to lead to significant improvement in immunity, energy levels,
physical strength, vigor, and quality of life assessed through KIDSCR EEN
QOL-27 questionnaires in children.
28
Studies have also confirmed various
other biological activities like adaptogenic,
29
diabetes management,
30
health
promotion, etc.
31
HFPM-01 a novel ayurvedic formulation containing herbs like Boswellia
serrata, Zingiber officinale, Withania somnifera, Curcuma longa, and Pluchea
lanceolate as the key ingredients was evaluated for its efficacy in controlling
osteoarthritis (OA) of the knee. The study showed that the herbal form u-
lation was found to be effective in controlling the symptoms associated with
knee pain and thereby controlling the OA
32
(Table 14.1).
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Table 14.1 Clinical evaluation of important ayurvedic formulations/herbs.
Herb/formulation Target of study Ref.
Triphala Gastric problems 17
Anti-microbial mouthwash 18 and 19
Weight management 20
Blood glucose level management 21
Triphala Sthaulya 22
Guduchyadi ghrita medhya
rasayana
Mental health 23
Suvarna Bindu Prashan Overall well-being 24
Chyawanprash Cognitive function 25
Nootropic effect 26
Immune boosting 27
Adaptogenic 29
Diabetes management 30
Health promotion 31
HFPM-01 Osteoarthritis 32
Bacopa Monnieri Improving memory 33
Increasing brain function 34
Promoting longevity 35
Protective effects on b-amyloid toxicity 36
Cognitive performance 37
Alzheimer’s disease
46
46
Asparagus racemose Rejuvenating tonic 54
Digestive disorders 55
Female sexual health 56
Curcuma longa Rheumatoid arthritis 57
Chronic anterior uveitis 58
Anti-inflammatory 59–65
Skin disorders 66–69
Eye health 70–73
Nervous system 74–79
Cardiovascular system 80–84
Gastro-intestinal disorders 85–92
Urogenital system disorders 93–95
Metabolic disorders 96–100
Intoxication 101
Malignant diseases 102–106
Withania somnifera Stress and anxiety 107–110
Sexual health 111–116
Cognitive performance 122–124
Pain 125
Remove fatigue 126–127
Schizophrenia 128
Diabetes management 129
Obsessive compulsive disorder 130
Insomnia 131
General well-being 132
Piper Nigrum Gastric problems 133
Boswellia Serrata Sandhigata vata 135
Brain tumors 136
Zingiber officinale Nausea and vomiting 137
Migraine 138
Knee osteoarthritis 139
378 Chapter 14
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14.3.2 Most Studied Herbs in Ayurveda
There are many herbs which are used in traditional systems of medicine
including ayurvedic practices for the treatment of various disorders as they
possess potential pharmacological activities when used individually and
when used in combination (Table 14.1). Bacopa monnieri (Brahmi) is one of
the most promising and widely evaluated herbs for its promising potential in
neuroprotective and cognitive effects. It has been used for over 3000 years in
ayurvedic practices for improving memory,
33
increasing brain function,
34
promoting longevity,
35
its protective effects on b-amyloid toxicity,
36
and
cognitive performance,
37
etc. The bioactive components responsible for the
pharmacological activities include steroidal saponins (bacoside A includes
bacosides A2 and A3; bacoside B includes bacopasides N1, N2, IV and V,
bacopasides I–VIII, bacopaside X, and bacopasaponins A–G and triterpe-
noidal saponins. Several human studies involving different extracts, differ-
ent study dosages, subjects’ criteria, and study duration confirmed the
efficacy of the bioactive components in various studies.
38–45
Multiple clinical
studies have also highlighted the potential of Brahmi in Alzheimer’s
disease.
46–49
Asparagus racemosa (A. racemosa) is one of such herbs, which was used
in traditional ayurvedic practices even in the ayurvedic system of medicine.
A. racemosa commonly referred to as shatavari is referred to in many tradi-
tional systems of medicine. In traditional systems of medicine, shatavari is
referred to as the ‘‘Queen of Herbs’’ owing to the miraculous benefit of the
herb to females.
50
The plant is well known in ayurvedic practices in terms of
anti-aging, female sexual health, dyspepsia, tumors, etc.
51
In ayurve dic
practices, shatavari is regarded as ‘‘Rasayana’’ which implies that the drug is
Table 14.1 (Continued)
Herb/formulation Target of study Ref.
Active rheumatoid arthritis 140
Diabetes mellitus 141
Heavy menstrual bleeding 142
Primary dysmenorrhea 143
Muscle pain 144
Irritable bowel syndrome 145
Ocimum sanctum Diabetes mellitus 146
Gouty arthritis 147
Hypertension 148
Immuno modulation 149
Cognitive function 150
Emblica officinalis Diabetes mellitus 153–155
Hyperacidity 156
Pulmonary tuberculosis 157
Cardiac health 158
Idiopathic oligoasthenoteratospermia 159
Vitiligo 160
Dental disorders 161–162
Ayurvedic Formulation and Their Clinical Uses 379
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used for promoting wellness and vitality.
52
The use of asparagus species was
mentioned in the ancient ayurvedic literature Charaka Samhita.
53
Charaka
Samhita written by Charak and Ashtang Hridyam by Vagbhata, the two main
classical texts on Ayurvedic practices, list A. racemosa as part of the formulas
to treat women’s health disorders. In many traditional systems of medicine,
shatavari is used in epilepsy, vata disorders, and digestive disorders,
54
as a
rejuvenating tonic,
55
and in female sexual health,
56
etc.
Another important herb, which is most commonly used in ayurvedic prac-
tices include turmeric, which is commonly referred to as Haridra in ayurvedic
practices. Turmeric is used in many ayurvedic formulations from vedic dates
onwards. The bioactive components responsible for the pharmacological ac-
tivities include the so-called phenolic curcuminoids. The role of curcuminoids
is clinically validated for many disorders including rheumatoid arthritis,
57
chronic anterior uveitis,
58
in anti-inflammation,
59–65
skin disorders,
66–69
eye disorders,
70–73
the nervous system,
74–79
cardiovascular system,
80–84
gastro
intestinal disorders,
85–92
urogenital system disorders,
93–95
metabolic
disorders,
96–100
intoxication,
101
and malignant diseases.
102–106
Withania somnifera is very revered herb of the Indian Ayurvedic system of
medicine, which is referred to as Rasyana in ayurvedic literatures. In tradi-
tional languages like Sanskrit (a language of ancient India), ashwagandha
means ‘‘horse’s smell’’ (ashwa ¼horse and gandha¼smell), and when con-
sumed it is believed to provide horse-like power.
107
The bioactive components
that contribute to the pharmacological activities include the so-called with-
anolides. Many clinical studies have highlighted the different biological ac-
tivities as well. The majority of the clinical studies have focused on the positive
effect of ashwagandha in symptoms related to stress, anxiety, and having
aphrodisiac activities. Different randomized studies have studied the positive
effect of different dosages and extracts of ashwagandha and their role in
clinical biomarkers associated with stress and anxiety.
108–110
Another clinical
area in which extensive research was carried out on ashwagandha include the
sexual function and fertility in both men and women. Significant improve-
ment in parameters like sperm count, motility, and morphology was found in
males and a positive impact in the female population was also observed.
111–116
The use of ashwagandha extract was evaluated for its potential to be used in
improving athletic performance, which was modulated by multiple mech-
anisms of action.
117–121
The use of ashwagandha was also evaluated in im-
proving the cognitive performance,
122–124
pain,
125
to remove fatiguness,
126,127
schizophrenia,
128
diabetes management,
129
obsessive compulsive disorder,
130
insomnia,
131
and general well-being,
132
etc.
Black pepper/long pepper belonging to the piper family are most common
among the spices which are widely used in the spice and food industry. The
piperine is one of the key bioactive components, which is most commonly
used as a bioavailability enhancer in traditional ayurvedic practices and
most modern nutraceutical industries. The majority of the clinical studies of
the piperine is concentrated on enhancing the bioavailability of active
components like curcuminoids, resveratrol, etc. In a single dose case
380 Chapter 14
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indicative study, the effects of black pepper on the gastric mucosa were as-
sessed using double-blind intragastric administration of the spice (1.5 g) to
healthy human subjects, with aspirin (655 mg) as the positive control. The
study proved that administration of piperine increases in parietal secretion,
pepsin secretio n, and potassium loss and black pepper administration and
mucosal micro bleeding was also seen.
133
Boswellia serrata is a common herb used in ayurvedic practices for treating
inflammatory disorders. The herb is used as a combination and/or as a single
herb. The bioactive components responsible for the pharmacological activ-
ities include the so-called boswellic acids.
134
Sandhigata vata commonly re-
ferred to as osteo arthritis in modern medicine is a sort of inflammatory
condition particularly affecting the joints. In a clinical study 56 patients
fulfilling the diagnostic criteria of Sandhigata vata were divided into two
groups, in which one group was supplemented with a 500 mg capsule of
Shallaki, 6 g per day (in three divided doses) with lukewarm water (n ¼ 29),
and the second group was given a capsule Shallaki as above, along with local
application of Shallaki ointment on the affected joints (n¼23). After the two
months supplementation, symptomatic improvement was observed in both
study groups.
135
In another case indicative study 12 patients with brain tu-
mors and progressive edema were treated with B. serrata (H15) extract. The
MRI showed a significant reduction of edema in two of the seven patients
with glioblastoma.
136
Ginger (Zingiber officinale) belonging to the Zingiberaceae family is a well-
known ingredient in traditional systems of medicine, which is most com-
monly used for digestive disorders. The pungency of ginger and the
pharmacological activities are mainly attributed to the active components
gingerols and its dehydrated form shogaols. There are a number of clinical
studies which used either raw ginger powder or ginger in the form of a
concentrated extract. Studies have concentrated on the use of ginger for
various disorders like nausea and vomiting,
137
migraines,
138
knee osteo-
arthritis,
139
active rheumatoid arthritis,
140
Type 2 diabetes mellitus,
141
heavy
menstrual bleeding,
142
primary dysmenorrhea,
143
muscle pain,
144
irritable
bowel syndrome,
145
etc.
Ocimum sanctum an aromatic shrub in the family Lamiaceae is believed to be
cultivated throughout the Asian countries. In ayurvedic texts, tulsi is known as
‘‘The Incomparable One,’’ ‘‘Mother Medicine of Nature’’ and is revered as an
‘‘elixir of life’’ that is without an equal in terms of both its medicinal and
spiritual properties.
146
Multiple clinical studies have highlighted its diverse
range of biological activities. The biological activities of tulsi and its different
extracts have been widely evaluated in various sorts of metabolic disorders
like diabetes mellitus,
146
gouty arthritis,
147
hypertension,
148
etc. The im-
munomodulatory potential of tulsi extract was evaluated in healthy patients,
subjects with asthma, and those with viral infections.
149
The phenolic com-
pounds in tulsi leaves have a high degree of anti-oxidant potential which ac-
counts for the antioxidant potential of the herb. The leaf extract was clinically
evaluated for its potential to be used in neuroprotective disorders.
150
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