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1. 2. 3.
4.
5.
2,3,7,8-Tetrahydroxy[1]benzopyrano
[5,4,3-cde][1]benzopyran-5,10-dione
(ellagic acid)
3,4,5-trihydroxybenzoic acid (gallic acid)
5,13-bis(3,4,5-trihydroxyphenyl)-4,12,14-
trioxapentacyclo[11.7.1.02,11.03,8.015,20]
henicosa-2(11),3(8),9,15,17,19-hexaene-
6,9,17,19,21-pentol (prodelphinidin A1)
2-(3,4-dihydroxyphenyl)-3,5,7-
trihydroxychromen-4-one (quercetin)
[2,3-dihydroxy-5-[[(2R,3R,4S,5R,6S)-3,4,5,6-tetrakis[[3,4-dihydroxy-5-
(3,4,5-trihydroxybenzoyl)oxybenzoyl]oxy]oxan-2-yl]
methoxycarbonyl]phenyl] 3,4,5-trihydroxybenzoate (tannic acid)
Figure 9.6 Chemical structures of active compounds of Triphala, part III.
212 Chapter 9
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immunomodulatory activity of Triphala was elucidated by testing the various
functions of neutrophil-like adherence, and avidity index in animal studies
(Table 9.5). The activity index was found to be amp lified after Triphala
treatment in in vivo studies. Moreover, neutrophil function was also in-
creased, which reduced the corticosterone level in the Triphala-treated
group.
26
Therefore, Triphala shows strong neutrophil stimulation and pre-
vents stress induction in neutrophils in the Triphala-supplemented group.
In another report, the Triphala-immunised group prevented noise/stress-
induced changes in the cell-mediated immune response in rats.
46
In a pre-
clinical study, the imm unostimulatory action of Triphala was evaluated.
Consumption of Triphala by healthy volunteers validated significant im-
munostimulatory effects on cytotoxic T cells (CD3
CD8
1
) and natural killer
cells (CD16
1
CD56
1
). However, Triphala did not affect the cytokine level in
volunteers.
47
On the other hand, the individual Triphala components have
also exhibited immunomodulatory action. T. chebula fruit extract demon-
strated an increase in rat spleen lymphocyte proliferation and boosted the
cytokines such as IL-2, IL-10 and TNF-a in an animal study.
48
The metha-
nolic extract of T. bellirica affected the mouse immune system, specifically
both the cellular and humoral immune response in in vitro. This extract
Table 9.4 Triphala’s significant bioactives and therapeutic targets involved in vari-
ous types of cancers.
31,45
Therapeutic target and bioactives of Triphala in cancer
Organ types Bioactives of Triphala Protein targets
Breast 1,2,3-Benzenetriol BACE1
Colorectal Ellagic acid Cellular antigen p53 (TP53)
Gastric Quercetin EGFR
Lung F2
Pancreatic Prodelphinidin A1 Insulin-like growth factor-1 receptor (IGF1R)
Prostate — Interleukin 6 (IL-6)
— — Matrix metalloproteinase-2 (MMP2)
— — MMP-9
— — RAD51
Table 9.5 The protein targets and important bioactives of Triphala involved in
immunomodulatory disorders.
51
Immunomodulatory
disorders Important bioactives Protein targets
Autoimmune diseases
(51)
4-O-Methygallic acids Cyclooxygenase-2 (COX-2)
— Bellericanin IL-1b
— Chebulagic IL-2
— Ellagic acid IL-4
— Gallic acid IL-6
— — Interferon gamma (IFN-g)
— — Tumour necrosis factor alpha
(TNF-a)
Therapeutic Potential of Triphala in Ayurveda and its Phytochemical Studies 213
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stimulated phagocytic activity and T-lymphocyte proliferation.
49
Suja et al.
50
demonstrated the immunostimulatory action of E. officinalis fruit extract on
humoral and cell-mediated immune responses with macrophages and
phagocytes.
50
In a nutshell, the above studies illustrate that Triphala and its
three individual components have the potential to stimulate immune
systems.
9.4.3 Cardiovascular Health and Triphala
Cardiovascular disease is a major health condition affecting the heart and
blood vessels, and often elevated cholesterol levels (hypercholesterolaemia)
are the leading risk factor.
52
Animal experiments have shown that hy-
percholesteremia can be managed by Triphala (Table 9.6). In a study, rats
were fed low-density and very low-density lipoprotein, high-density lipo-
protein and free fatty acid diets for 48 days. The results demonstrated that
total cholesterol was decreased in the Triphala - administered group.
25
In
another study, an atherogenic diet along with Haritaki was fed to animals.
The results showed a significant decrease in total cholesterol, triglycerides
and total protein, and increased high-density lipop rotein cholesterol was
found in the Haritaki-treated group as compared to the control group.
53
Triphala addresses disparities in the gastrointestinal tract and cardio-
vascular system and should be extensively reviewed in the context of these
common diseases.
9.4.4 Nervous System and Triphala
Chronic stress or depression and anxiety cause serious effects on the body
and mind, and are identified as major causes of disability worldwide.
54
Stress is an imbalance caused by apparent threat that is counteracted by an
adaptive response to re-establish homeostasis and is associated with many
chronic disorders. In vivo studies have reported that Triphala provides pro-
tection against cold-induced stress and reversed stress-induced behavioural
and biochemical alterations such as elevated lipid peroxidation and corti-
costerone levels.
55
Triphala also prevented noise-induced stress in ani-
mals.
46
Triphala successfully prevented noise-induced metabolic changes by
facilitating the cell-mediated immune and antioxidant status.
46,56–59
Thus,
Table 9.6 Tabular data representing the therapeutic linkage between score-1 bioac-
tives and the target group of Triphala in cardiovascular diseases.
31
Cardiovascular diseases Important bioactives Protein targets
Atherosclerosis 1,2,3,4,6-Penta-galloylglucose F2
Cerebral vasospasm 1,2,3,6-Tetrakis-(O-galloyl)-beta-
D-glucose F10
Hypertension Bellericagenin A1 FABP4
Infarction Quercetin SERPINE1
Myocardial ischaemia Prodelphinidin A1 —
Thrombosis — —
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high levels of stress or depression in humans may be tackled with Triphala
treatments in clinical practice, based on its reported adaptogenic activity
(Table 9.7).
9.4.5 Metabolic Syndrome and Triphala
Metabolic syndrome is a pathological condition characterised by central
obesity, elevated blood pressure, increased lipid levels, and high blood
glucose.
60–63
The overall prevalence of metabolic syndrome is estimated to
be one-fourth of the global adult population.
61
The scientific literature has
also endorsed the potential of Triphala as a therapeutic agent for weight loss
and reduction of body fat (Table 9.8). In an animal study, diet-induced obese
mice were fed with Triphala for 10 weeks.
64
Triphala administration sub-
sequently decreased the percentage of body fat, body weight and energy
intake. Triphala also decreased total cholesterol, triglycerides and low-
density lipoprotein cholesterol in the experimental group compared with
the controls.
65
In a clinical study (n ¼749), Triphala-treated groups showed
significantly reduced low-density lipoprotein-cholesterol, total cholesterol
and triglyceride. Five RCTs have shown that Triphala administration sig-
nificantly reduces body weight, body mass index (BMI) and waist circum-
ference in obese patients. Moreover, Triphala significantly reduces the
fasting blood glucose level in diabetic patients, but not in healthy indi-
viduals. Given the global obesity epidemic, more treatment options are ne-
cessary to reduce the associated healthcare burden.
65
Triphala plays a key role in inhibiting starch digestion and absorption,
thus reducing postprandial hyperglycaemia. A similar process is carried out
by miglitol and acarbose (diabetes pharmaceutical drugs), which cor-
respondingly target these glycolytic enzymes. In addition, Patel et al.
66
dis-
covered that Triphala decreases the blood glucose level in alloxan-induced
diabetic as well as normal rats.
66
Triphala powder (5 g) was supplemented to
diabetes mellitus patients for 45 days in a clinical study. The results eluci-
dated a significant decrease in blood glucose level.
67
Interestingly, both
fasting and postprandial blood glucose were reduced, which may be due to
active ingredients such as menthol and sorbitol. However, ellagitannins and
gallotannins, the other constituents of Triphala, also improve the immune
responses for glucose uptake by enhancing both PPAR-alpha and -gamma,
Table 9.7 The therapeutic network addressing the nervous system of Triphala’s
bioactives and protein targets.
31
Nervous system disorders Important bioactives Protein targets
Alzheimer’s 1,2,3,4,6-Pentagalloylglucose ALDR
Diabetes 1,2,3,6-Tetrakis-(O-galloyl)-beta-
D-glucose BACE1
Parkinson’s Epigallocatechin-3-gallate CA2
Retinopathy Quercetin PLAT
— — SERPINE1
Therapeutic Potential of Triphala in Ayurveda and its Phytochemical Studies 215
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without inducing adipogenesis.
68
Hence, these polyphenols may also be
promoted to reduce blood glucose and insulin level s in diabetic patients.
9.5 The Way Ahead for Triphala
The major diseases in the present era are more like syndromes rather than
simple diseases. Synthetic molecules are double-edged swords, offering
benefits laced with adverse effects. To treat these patients, pharmacy prac-
tice is experiencing a change from synthetic chemicals to refined single
herbs and polyherbal compounds. Eventually it will find its way to herbo-
mineral compounds. The knowledge of Ayurvedic Rasashastra (Indian
Iatrochemistry) based metal nanomolecules made using Triphala and other
herbs will pave the way to a new age of drugs.
The total of 177 bioactives of the formulation Triphala act in unison to
eradicate disease, and do not harm healthy tissues at the same time, which
is unique to this formulation. Whether or not the change in the proportion
of the three plants reflects making it a therapeutic, antiaging, or im-
munomodulator substance remains to be explored. Apart from powder-filled
capsules or compressed tablets and decoctions (quath), other dosage forms
like Triphala-ghrita, oil and guggul may be explored for targeted drug delivery
for complex and morbid diseases. The Mashi dosage form can be developed
further using various carbon nanotube development methods for diagnostic
and therapeutic purposes. The Ayurveda-described Triphala bio-iron, bio-
zinc and bio-copper are a challenging area of drug development for the anti-
inflammatory, anticancer, anti-Alzheimer, antiaging, etc. activities. The
known phytoconstituent profile of Triphala may prove to be beneficial for
exploration of its genetic effects in non-communicable diseases. Simple
in vitro experiments, preclinical and clinical trials of Triphala, and its ad-
vanced dosage forms such as Triphala Guggul with various accompaniments
including water, honey, sugar, ghee and oil for indicated disease conditions
would subs tantiate the therapeutic potential of this formulation.
Table 9.8 The relationship between metabolic disorders and the Triphala
network.
31
Therapeutic target and bioactives of Triphala in metabolic syndrome
Metabolic diseases Important bioactives Protein targets
Diabetes Ellagic acid ALDR
Endometriosis Quercetin AKR1B1
Hypercholesterolaemia Bellericagenin A1 FABP5
Hyperlipidaemia — IGF1R
Gout — —
Psoriasis — —
Lung fibrosis — —
Obesity — —
Osteoarthritis — —
Ulcerative colitis — —
216 Chapter 9
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Abbreviations
AKT Ak strain transforming
BMI Body mass index
CD-3 Cluster of differentiation-3
DB Database
Dravyagunavigyan Indian Pharmacology
EGFR Epidermal growth factor receptor
ERK Extracellular signal-regulated kinase
FTIR Fourier transform infrared spectroscopy
IL-2 Interleukin-2
P53 Tumour protein P53
PKB Protein kinase B
PPAR Peroxisome proliferator-activated recept or
Rasa shastra Indian iatrochemistry
RCT Randomised control trial
TNFa Tumour necrosis factor alpha
UNPD Universal Natural Products Database
VEGF Vascular endothelial growth factor
VGEFR Vascular endothelial growth factor receptor
Acknowledgements
The authors acknowledge all the known and unknown sources used in this
chapter.
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220 Chapter 9
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CHAPTER 10
Pharmacological Potential and
Phytochemical Evaluation of
Emblica officinalis: A Wonder
Herb in Ayurveda
GURMEET SINGH,* SHRIDEVI GOTHE, NADANA VINAYAGAN
AND SMRITI CHAWALA
Centre for Ayurveda Biology and Holistic Nutrition, The University of
Trans-Disciplinary Health Sciences and Technology (TDU), Bengaluru,
Karnataka 560064, India
*Email: gur meet.singh@tdu.edu.in
10.1 Introduction
Emblica officinalis (E. officinalis) is conventionally called as Amla or Indian
gooseberry, a superfood of Ayurveda. Its use as a medicine predates Ayurveda
as it finds a prominent place for its health-promoting effects in Indian
mythological literature such as Vedas, Upanishads and Puranas. These ref-
erences suggest that because of its medicinal importance, the amla tree had
wide cultural and religious significance as well as being revered, with its fruit
considered sacred and it being attributed with the quality of giving longevity
to those who consumed it regularly. Amla is considered to be the beloved
tree of Lord Vishnu and so is worshipped. The Indian mythological epic
Mahabharat mentions that the Amla berry originated from a drop of Amrit,
the heavenly nectar of immortality, that fell from the home of the gods.
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
221
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