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Clinical evaluation of Emblica Officinalis Gatertn (Amla) in healthy human subjects: Health benefits and safety results from a randomized, double-blind, crossover placebo-controlled study

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The preventive efficacies and safety of Emblica Officinalis Gatertn (Amla), a most important and extensively studied plant in the traditional Indian Ayurvedic system of medicine, are presented. Eligible healthy adult subjects (n = 15) were randomized to receive either amla or placebo (500 mg per day) during an 18-week study. The efficacy parameters evaluated were the vascular function, blood hematology, oxidative and inflammatory biomarkers, glucose and lipid profiles, urinalysis, and liver hepatotoxicity. The amla intake showed significant improvements in the primary efficacy parameter of blood fluidity. There were also improvements in the secondary endpoints including lowering of von Willebrand factor (vWF), reduced 8-hydroxy-2'-deoxyguanosine (8-OHdG) as well as thrombin (TM) biomarkers of oxidative stress along with a significant improvement in HDL-cholesterol and lowering the LDL-cholesterol levels. No substantial changes were observed in liver hepatotoxicity, urinalysis, and hematology after consumption of amla compared to baseline or placebo. In addition, no adverse events, changes safety parameters or tolerance issues were observed after consumption of amla. In conclusion, amla supplementation showed acceptable palatability, improved endothelial functions and reduced oxidative stress.
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Contemporary Clinical Trials Communications 17 (2020) 100499
Available online 27 November 2019
2451-8654/© 2019 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Research paper
Clinical evaluation of Emblica Ofcinalis Gatertn (Amla) in healthy human
subjects: Health benets and safety results from a randomized,
double-blind, crossover placebo-controlled study
Mahendra Parkash Kapoor
a
,
*
, Koji Suzuki
b
,
c
, Timm Derek
d
, Makoto Ozeki
a
, Tsutomu Okubo
a
a
Taiyo Kagaku Co. Ltd., Nutrition Division, 1-3 Takaramachi, Yokkaichi, Mie, 510-0844, Japan
b
Department of Molecular Pathobiology, Mie University, 2-174 Edobashi, Tsu City, Mie, 514 8507, Japan
c
Suzuka University of Medical Sciences, Suzuka City, Mie, 510-0221, Japan
d
Taiyo International Inc., Minneapolis, Minnesota, 55416, USA
ARTICLE INFO
Keywords:
Amla (Emblica Ofcinalis Gaertn)
Clinical trial
Vascular functions
Hematology
Lipid prole
ABSTRACT
The preventive efcacies and safety of Emblica Ofcinalis Gatertn (Amla), a most important and extensively
studied plant in the traditional Indian Ayurvedic system of medicine, are presented. Eligible healthy adult
subjects (n ¼15) were randomized to receive either amla or placebo (500 mg per day) during an 18-week study.
The efcacy parameters evaluated were the vascular function, blood hematology, oxidative and inammatory
biomarkers, glucose and lipid proles, urinalysis, and liver hepatotoxicity. The amla intake showed signicant
improvements in the primary efcacy parameter of blood uidity. There were also improvements in the sec-
ondary endpoints including lowering of von Willebrand factor (vWF), reduced 8-hydroxy-20-deoxyguanosine (8-
OHdG) as well as thrombin (TM) biomarkers of oxidative stress along with a signicant improvement in HDL-
cholesterol and lowering the LDL-cholesterol levels. No substantial changes were observed in liver hepatotox-
icity, urinalysis, and hematology after consumption of amla compared to baseline or placebo. In addition, no
adverse events, changes safety parameters or tolerance issues were observed after consumption of amla. In
conclusion, amla supplementation showed acceptable palatability, improved endothelial functions and reduced
oxidative stress.
1. Introduction
The metabolic syndrome is dened as having two of the following:
hyperglycemia, hyperlipidemia, high blood pressure, low HDL-
cholesterol, or abdominal obesity and has become an epidemic during
the last few decades [1]. In recent years there has been a growing in-
terest and awareness of the role of functional dietary supplements to
help with the prevention of lifestyle-related diseases [2,3]. Emblica
Ofcinalis Gatertn, commonly called amla, has traditionally been used
for different medicinal purposes including: rheumatic pains, gonorrhea,
asthma, hemorrhage, jaundice, dyspepsia, nausea, constipation, diar-
rhea, eye disease, brain health, intestinal ailments, diabetes mellitus,
coronary heart diseases, and various cancers [4,5]. Modern science has
shown amla to have hypoglycemic, anti-inammatory, anti--
hyperglycemic, anti-hyperlipidemic, and antioxidant properties in ani-
mal and human studies [68]. These properties may be due to the amla
fruit containing high levels of vitamin C, tannins, polyphenols, bers,
minerals, proteins, and amino acids [4,9]. Standardized amla formula-
tion usually contains the complex tannins and ellagitannins such as
corilagin, geraniin, chebulagic acid, and elaeocarpusin, etc., which are
the most active components and have high antioxidant activity [9].
Apart from the useful antioxidant activity, they have anti-thrombosis
properties to promote vascular health by improve blood uidity,
anti-coagulant, and antiplatelet activity, which can cause a warming
sensation. Amla also supports natural immunity and digestive functions.
It is not completely understood, which amla components are responsible
for each activity and they may be mediated through multiple different
mechanisms [3,1012]. The combined anti-inammatory, anti-th-
rombosis, anti-coagulant, and anti-platelet activities of amla make it
attractive target for the prevention of a variety of vascular disorders [13,
14].
Further, there is limited evidence to support the longevity-promoting
* Corresponding author.
E-mail address: mkapoor@taiyokagaku.co.jp (M.P. Kapoor).
Contents lists available at ScienceDirect
Contemporary Clinical Trials Communications
journal homepage: http://www.elsevier.com/locate/conctc
https://doi.org/10.1016/j.conctc.2019.100499
Received 31 July 2019; Received in revised form 6 November 2019; Accepted 21 November 2019
Contemporary Clinical Trials Communications 17 (2020) 100499
2
Table 1
Anthropometric physiological and vascular parameters of subjects of amla supplementation clinical trial.
Parameters Placebo intake (mean sem) Amla intake (mean sem) ANCOVA (Among
Groups)
Before (W1, W2) or
(W10, W11)
2 Weeks (W3, W4)
or (W12, W13)
4 Weeks (W5, W6)
or (W14, W15)
Post (3 Weeks)
(W7,W9,W9) or
(W16,W17,W18)
Before (W1, W2) or
(W10, W11)
2 Weeks (W3, W4) or
(W12, W13)
4 Weeks (W5, W6)
or (W14, W15)
Post (3 Weeks)
(W7,W9,W9) or
(W16,W17,W18)
Weight (kg) 70.6 2.97 70.4 3.03 70.4 3.01 70.9 2.87 70.6 3.04 70.8 2.98 70.4 3.02 71.1 3.00 2W: P ¼0.42
4W: P ¼0.89
Post: P ¼0.51
P ¼0.31 P ¼0.48 P ¼0.44 P ¼0.43 P ¼0.70 P ¼0.17
BMI (kg/m
2
) 25.1 0.63 25.1 0.67 25.0 0.63 25.2 0.66 25.0 0.64 25.3 0.64 25.2 0.62 25.3 0.66 2W: P ¼0.43
4W: P ¼0.21
Post: P ¼0.59
P ¼0.23 P ¼0.47 P ¼0.36 P ¼0.47 P ¼0.24 P ¼0.18
Body Fat (%) 30.5 1.99 30.3 1.93 30.2 2.03 30.5 1.97 30.2 1.97 30.5 2.04 30.9 1.94 30.6 1.97 2W: P ¼0.29
4W: P ¼0.038*
Post: P ¼0.39
P ¼0.52 P ¼0.60 P ¼1.0 P ¼0.22 P ¼0.007* P ¼0.18
SBP (mmHg) 136.6 8.02 148.4 6.62 143.9 5.82 148.4 6.76 135.6 8.53 134.11 8.05 142.2 5.23 147.9 6.17 2W: P ¼0.30
4W: P ¼0.78
Post: P ¼0.84
P ¼0.26 P ¼0.50 P ¼0.20 P ¼0.42 P ¼0.53 P ¼0.29
DBP (mmHg) 86.0 5.03 93.0 4.91 91.6 4.35 91.9 4.19 83.9 4.85 84.7 3.95 89.9 4.26 94.4 3.26 2W: P ¼0.57
4W: P ¼1.0
Post:P ¼0.10
P ¼0.39 P ¼0.50 P ¼0.43 P ¼0.43 P ¼0.45 P ¼0.15
Pulse Rate (Beats/
min)
68.9 2.11 64.6 2.10 65.7 2.29 65.3 2.29 72.7 3.11 70.7 3.94 65.0 2.29 66.8 2.86 2W: P ¼0.64
4W: P ¼1.0
Post: P ¼0.69
P ¼0.27 P ¼0.43 P ¼0.39 P ¼0.61 P ¼0.18 P ¼0.33
Blood Fluidity (
μ
L/
sec)
2.77 0.09 2.74 0.07 2.43 0.25 2.65 0.10 2.63 0.06 2.89 0.09 2.89 0.08 2.86 0.19 2W: P ¼0.012*
4W: P ¼0.024*
Post:P ¼0.036*
P ¼0.81 P ¼0.27 P ¼0.41 P ¼0.018* P ¼0.039* P ¼0.069
Vascular Age
(Waveform index)
0.04 0.15 0.24 0.09 0.21 0.16 0.11 0.13 0.04 0.11 0.15 0.14 0.12 0.09 0.24 0.12 2W: P ¼0.10
4W: P ¼0.82
Post:P ¼0.041*
P ¼0.33 P ¼0.46 P ¼0.70 P ¼0.08 P ¼0.56 P ¼0.29
M.P. Kapoor et al.
Contemporary Clinical Trials Communications 17 (2020) 100499
3
effects of Emblica Ofcinalis, but preliminary evidence suggests potent
antioxidant activity that may explain these effects. In brain cells amla
has high antioxidant activity [15]. Renal injury occurs when reactive
oxygen species exceed the antioxidant reserve of renal tissue. Amla
contains high concentrations of antioxidants ascorbic acid, gallic acid
and phenolic compounds [16] suggesting that antioxidant activity of
amla may be benecial for the prevention of age-related renal disease
and improvement of urinalysis parameters [7,17]. Also, amla extracts
are reported to have the ability to modulate basal oxidative markers and
enhance endogenous antioxidant defenses in a hepatocyte cell line
(HepG2) [18]. Overall, amla has promise to help multiple systems due to
its antioxidant activity.
The present randomized, placebo-controlled, double-blind crossover
study sought to determine the preventive effect of amla on vascular
functions, blood hematology, hemorheology, glucose and lipid proles,
oxidative stress and inammatory biomarkers. Additionally, this study
aimed to examine the safety prole of amla including urinalysis and
hepatic risk parameters in healthy Japanese volunteers. An improve-
ment in blood uidity as the primary objective, and reduction of von
Willebrand factor (vWF), 8-hydroxy-20-deoxyguanosine (8-OHdG), and
thrombin (TM) biomarkers of oxidative stress were secondary parame-
ters along with a signicant improvement in HDL-cholesterol and
lowering the LDL-cholesterol levels were hypothesized.
2. Materials and method
2.1. Ethics statement
The study protocol was reviewed and approved by the Medical
Ethical Committee of Mie University, Japan and registered (H-AO-
00012006) at the hospital clinical trial registry network. Before partic-
ipation, all participants gave written informed consent to the protocol
approved by the Ofce of Research Promotion and Integrity of Mie
University. Study-related procedures were carried out by the approved
guidelines and ethical standards established in the Helsinki Declaration.
2.2. Subjects and criteria for their selection
Twenty four volunteers (n ¼24) aged between 36 and 67 years were
recruited to participate in the study and underwent screening mea-
surements to determine eligibility for participation in the full protocol.
Fifteen subjects (n ¼15; M7, F8) were recruited after screening based on
triglycerides levels, cholesterol levels, and the blood uidity in whole
human blood estimated using a microchannel array ow analyzer (MC-
FAN; [19]. The following inclusion and exclusion criteria were used for
the subjects to participate in the study. Healthy subjects with somewhat
elevated blood triglycerides levels (>130 mg/mL to <250 mg/mL),
lower HDL cholesterol level (<54 mg/mL), and average values of blood
uidity (2.62.8
μ
L/s) were recruited for the study. Subject were
excluded if (i) have an allergy and/or allergic disease including atopy,
(ii) symptoms of cerebrovascular disorder, (iii) a history of myocardial
infarction, (iv) atrial brillation and severe arrhythmia, (v) high renal
Fig. 1. (a) Schematic presentation of the study protocol and procedures, and (b) Illustration of procedural details for evaluation of amla efcacies in randomized,
double-blind, crossover placebo-controlled trial in healthy human subjects.
M.P. Kapoor et al.
Contemporary Clinical Trials Communications 17 (2020) 100499
4
dysfunction (serum creatinine >4.0 mg/dL), (vi) advanced liver func-
tion disorder, (vii) diabetes mellitus, (viii) anemia (hemoglobin <7
mg/dL), (ix) pregnant or lactating women, (x) consumption of medica-
tions or supplements affecting blood uidity, (xi) other exclusions,
judged by study medical practitioner during examination. Clinical
characteristics of the subjects at baseline are presented in Table 1.
2.3. Study design and sample collection protocol
The study was a randomized, placebo-controlled, double-blind,
crossover study (Fig. 1a), and a schematic illustration of the study prole
is presented in Fig. 1b. Randomization was conducted using StatsDirect
system by a researcher who was not involved in taking measurements
and analysis (1:1; block randomization with random block size between
3 and 6). Subjects were randomly assigned into the amla or placebo
group after two weeks (W1, W2) of controlled diet. No signicant dif-
ferences in the study parameters (age, height, body weight, body mass
index (BMI), total fat mass, etc.) were observed between the treatment
and placebo groups at baseline. The treatment group (T; n ¼8) received
amla capsules after each meal, while the placebo group (P; n ¼7)
received identical placebo capsules. After four weeks on the respective
treatment (W3 to W6) a three-week washout period (W7 to W9) was
implemented before crossover the other treatment. Two subjects (M1,
F1) from decided to withdraw from the study due to personal reasons.
After crossover, both groups consumed a controlled diet for two weeks
(W10, W11) and then groups received the other treatment for four
weeks (W12 to W15). At the end of the supplementation period, a post-
intake period for three weeks (W16 to W18) was completed.
All subjects were asked to refrain from smoking, drinking alcohol or
caffeine-containing beverages and excess consumption of coffee and tea
(>2 cups/day) because caffeine may have a synergic effect with amla
and the ability to modulate study parameters. All subjects were asked to
abstain from any strenuous physical activity during the study. Subjects
came to the laboratory in the morning after an overnight fast at the
beginning of W1 where physical measurements (body weight, height,
body fat, BMI, etc.), as well as fasting blood and urine samples, were
conducted to determine baseline values. Before blood sample collection,
a medical practitioner examined the subjects for the state of breathing as
well as the presence or absence of epigastric/abdominal pains, diarrhea/
constipation, vomiting, nausea, anorexia, and other subjective symp-
toms. Blood samples were drawn by a registered nurse in a seated po-
sition from an antecubital vein with anticoagulation by heparin solution
after resting in a chair for at least 5 min.
Similarly, the fasted blood and urine samples were collected after at
the end of W4, W6 and W9. Likewise blood and urine samples were
collected at the beginning of W10 and then, at the end of W13, W15 and
W18. Blood samples were snap-frozen in liquid nitrogen and stored at
80 C until analysis.
2.4. Test supplementation and dosages
The commercial proprietary formulation of amla (SunAmla-PD1;
Taiyo Kagaku Co. Ltd., Japan) as a dry powder was investigated in this
study. It is prepared as a water extract of amla fruit pulp that has been
hydrolyzed with pectinase followed by centrifugation with the super-
natant spray dried. Study capsules were 250 mg hard gelatin capsules
containing amla formulation (125 mg) and dextrin (125 mg), while
placebo capsules were only dextrin (250 mg). Both supplements were
identical in size and appearance. They are considered safe and well-
tolerated at the reported dose. Subjects received (4 capsules/day) dur-
ing both the treatment and placebo period. The total dose of amla was
500 mg per day (ellagitannins 1.21.5%; ellagic acid 0.10.2%; gallic
acid, 1.52.0%; total polyphenols, 1014%). The major active compo-
nents of ellagitannins are corilagin, geraniin, elaeocarpusin, and che-
bulagic acid. Subjects were instructed to ingest two capsules every day
immediately after breakfast and dinner during the four-week
supplementation periods (W3 to W6) and (W12 to W15). Subjected were
asked to comply with their supplementation and maintain a prescribed
lifestyle during the study. A mandatory daily log of meal timing,
including approximate calorie intake, supplementation intake, and total
working, resting and sleeping hours were completed during the study.
2.5. Measured study parameters
The measured items were body temperature, pulse rate, blood
pressure, vascular function, blood uidity, hematological parameters,
and biochemical parameters. Axillary body temperature was measured
using a mercury thermometer of high precision. Automatic sphygmo-
manometer (Terumo; ES-P2000A) was used to measure blood pressure
and pulse rate after resting at the sitting position at a stable position and
height. Both systolic and diastolic blood pressures, body temperature,
and pulse rate were measured three times consecutively, and the mean
of the three measurements was recorded. Vascular age was measured
using the acceleration pulse wave measurement system (Arnett PDU-M
100; Yumedica Co. Ltd. Osaka, Japan), and was conducted before the
blood sample collection. The acceleration pulse waveform data as
waveform index-I was measured twice, and the mean value of the
waveform was used to estimate the blood vessel age. The measurement
of blood uidity as a primary efcacy parameter was done immediately
after blood samples were drawn. Blood was collected in a separate tube
for the measurement of blood passage time for the calculation of blood
uidity.
Hematological test parameters along with the specic tests of blood
coagulation including Red blood cell count (RBC), White blood cell
count (WBC), Hematocrit (Ht), Hemoglobin (Hb), Blood uidity,
Platelet counts (Plt), Platelet aggregation ability (PAA), Prothrombin
time (PT), Activated partial thromboplastin time (APTT), Mean
corpuscular hemoglobin (MCH), Mean corpuscular volume (MCV),
Mean corpuscular hemoglobin concentration (MCHC) were measured by
using an automatic cell counter (Beckman Coulter Co. Ltd.).
Other blood biochemical parameters including: GOT (AST), GPT
(ALT), and γ–GTP (Randox kits), total protein (Biuret method), albumin
(Bromocresyl green method), albumin/globulin (A/G ratio), blood
glucose (Hexokinase glucose-6-pyruvate dehydrogenase method), tri-
glycerides (Glycerin-1-phosphate-oxidase method), total cholesterol
(Enzyme method), HDL-cholesterol (Homogeneous method), LDL-
cholesterol (Friedewald equation), HbA1c (Chromatographic method),
ALP (Spectroscopic method), uric acid (Enzymatic spectrophotometry
method), total bilirubin (Microassay method), urea nitrogen (BUN) and
creatinine (Enzyme method), Na, K, Ca, P (Flame photometry) and Cl
(titration method) were measured. In addition, the secondary efcacy
parameters thrombin receptor (TM), von Willebrand factor (vWF), 8-
hydroxy-20-deoxyguanosine (8-OHdG), thiobarbituric acid reactive
substances (TBARS), adiponectin (ELISA kit) were also measured.
Urinalysis, a physical and chemical examination of the urine, was
performed by collecting 5 mL of midstream urine by the subjects in a
sample tube. A dipstick (test strips based on necessary wet micro-
chemistry reactions) was used to detect the pH, specic gravity, urobi-
linogen, sugar, a ketone body, and occult blood. Qualitative and semi-
quantitative results are expressed as either adverse or varying degrees
of positive, indicating different amounts present.
2.6. Blood hemorheology assay using MC-FAN
Blood uidity in whole blood collected from subjects was estimated
using a microchannel array ow analyzer (MC-FAN; WBA-Neo, Tokyo,
Japan). These results were employed for the initial screening and
recruiting the subjects for this study. Briey, the microchannel passage
time for the 100
μ
L physiological saline as control was initially
measured, followed by 100
μ
L heparinized blood obtained from the
subjects. The revised values of the blood passage measure for the blood
uidity estimation was corrected and expressed as a function of the
M.P. Kapoor et al.
Contemporary Clinical Trials Communications 17 (2020) 100499
5
Table 2
Changes in hematological and anticoagulant activity parameters in amla and placebo intake groups throughout the trial duration.
Parameters
Placebo intake (mean sem) Amla intake (mean sem) ANCOVA (Among
Groups)
Before (W1, W2) or
(W10, W11)
2 Weeks (W3, W4) or
(W12, W13)
4 Weeks (W5, W6) or
(W14, W15)
Post (3 Weeks)
(W7,W9,W9) or
(W16,W17,W18)
Before (W1, W2) or
(W10, W11)
2 Weeks (W3, W4) or
(W12, W13)
4 Weeks (W5, W6) or
(W14, W15)
Post (3 Weeks)
(W7,W9,W9) or
(W16,W17,W18)
WBC (/
μ
L) 5860 419 5929 480 5840 383 5946 419 5961 383 5724 452 6005 471 6239 530 2W: P ¼0.52
4W: P ¼0.92
Post: P ¼0.67
P ¼0.86 P ¼0.92 P ¼0.81 P ¼0.11 P ¼0.87 P ¼0.43
RBC (x10
4
/
μ
L) 484.7 13.6 486.6 12.8 480.5 12.0 481.5 13.8 481.3 13.3 478.5 12.5 475.5 12.1 486.1 12.8 2W: P ¼0.38
4W: P ¼0.78
Post: P ¼0.24
P ¼0.59 P ¼0.25 P ¼0.35 P ¼0.61 P ¼0.31 P ¼0.42
Hemoglobin (g/dL) 14.6 0.42 14.2 0.39 14.1 0.37 14.5 0.42 14.7 0.41 14.5 0.38 14.3 0.38 14.4 0.41 2W: P ¼0.56
4W: P ¼0.79
Post: P ¼0.23
P ¼0.05* P ¼0.015* P ¼0.80 P ¼0.04* P ¼0.002* P ¼0.004*
Hematocrit (%) 44.5 1.21 44.5 1.51 44.1 1.09 44.1 1.29 44.1 1.21 44.0 1.17 43.7 1.12 44.6 1.20 2W: P ¼0.92
4W: P ¼1.0
Post: P ¼0.16
P ¼0.86 P ¼0.20 P ¼0.18 P ¼0.84 P ¼0.42 P ¼0.39
Platelets Count
(x10
4
/
μ
L)
28.4 2.46 28.5 2.41 28.1 2.17 29.2 2.55 28.9 2.64 28.1 2.45 28.3 2.23 28.7 2.53 2W: P ¼0.48
4W: P ¼0.82
Post: P ¼0.46
P ¼0.92 P ¼0.57 P ¼0.37 P ¼0.18 P ¼0.47 P ¼0.82
PT (Sec) 11.6 0.47 10.9 0.17 11.9 1.30 10.47 0.12 11.6 0.33 10.9 0.23 10.3 0.22 10.38 0.29 2W: P ¼0.11
4W: P ¼0.01*
Post: P ¼0.013*
P ¼0.13 P ¼0.87 P ¼0.07 P ¼0.025* P ¼0.007* P ¼0.008*
APTT (Sec) 31.7 1.13 32.6 1.44 35.8 2.28 32.3 1.71 32.4 1.58 32.3 1.56 33.5 1.75 31.9 1.56 2W: P ¼0.73
4W: P ¼0.60
Post: P ¼0.81
P ¼0.67 P ¼0.15 P ¼0.81 P ¼0.59 P ¼0.64 P ¼0.83
Platelet
Aggregation (%)
96.7 2.50 100 0 100 0 93.7 5.04 86.5 4.81 99.7 0.28 94.0 4.49 95.1 2.51 2W: P ¼0.30
4W: P ¼0.20
Post: P ¼0.28
P ¼0.095 P ¼0.23 P ¼0.33 P ¼0.027* P ¼0.20 P ¼0.16
MCV () 91.7 0.98 92.0 0.99 91.9 0.97 91.7 0.90 91.9 1.07 91.5 0.92 91.8 0.90 91.7 0.98 2W: P ¼0.04*
4W: P ¼0.15
Post: P ¼0.52
P ¼0.16 P ¼0.38 P ¼1.0 P ¼0.05* P ¼0.52 P ¼0.37
MCH (pg/cell) 30.4 0.39 29.7 0.32 29.7 0.35 29.9 0.27 30.3 0.27 29.8 0.31 29.7 0.32 29.9 0.36 2W: P ¼0.57
4W: P ¼0.48
Post: P ¼0.89
P 0.001* P 0.001* P ¼0.003* P 0.001* P 0.001* P ¼0.017*
MCHC (g/dL) 33.1 0.21 32.5 0.12 32.4 0.16 32.6 0.18 33.1 0.15 32.3 0.20 32.3 0.15 32.6 0.20 2W: P ¼0.08
4W: P ¼0.03*
Post: P ¼0.28
P 0.001* P 0.001* P ¼0.005* P 0.001* P 0.001* P ¼0.03*
M.P. Kapoor et al.
Contemporary Clinical Trials Communications 17 (2020) 100499
6
actual whole blood passage time over physiological saline solution
passage time of 12 s at a pressure of 20 cm of water.
Further, platelet aggregation ability based on thrombus formation in
blood treated with activating agent thrombin was determined by screen
ltration pressure (SFC) detected using an aggregometer by measuring
the decrease in ow rate as a function of agent concentration according
to the manual of the manufacturer as described in Ref. [19]. Briey, 200
μ
L of blood collected from subjects was mixed with 22
μ
L of thrombin at
the concentration of 5U/mL of thrombin. The platelet aggregation
ability was measured and expressed as % of inhibition against thrombin
agonists.
2.7. Estimation of anticoagulant activity
Anticoagulant activities of the amla or placebo supplementation
were determined by prothrombin time (PT) and activated partial
Fig. 2. Illustration of oxidative and inam-
matory biomarkers assay (A) 8-hydroxy-2
0-
deoxyguanosine; 8-OHdG, (B) von Wille-
brand factor; vWF, (C) Thrombin; TM and
(D) Thiobarbituric acid reactive substances;
TBARS during the amla supplementation
duration. The result depicts the comparison
between the groups (a to b denote signi-
cance of p-value p <0.05; a to ab denote
nearly signicance of p-value p <0.07;
measured by one-way ANOVA), and among
the groups (* denote signicance of p-values
p <0.05; **denote signicance of p-values
p <0.01; measured by ANCOVA).
Table 3
Assessment of characteristic oxidative and inammatory biomarkers and their statistical comparison to review the potential of amla preventive effects among healthy
human subjects.
Parameters
Placebo intake (mean sem) Amla intake (mean sem) ANCOVA
(Among
Groups)
Before
(W1, W2) or
(W10, W11)
2 Weeks
(W3, W4) or
(W12, W13)
4 Weeks
(W5, W6) or
(W14, W15)
Post
(3 Weeks)
(W7,W9,W9) or
(W16,W17,
W18)
Before
(W1, W2) or
(W10, W11)
2 Weeks
(W3, W4) or
(W12, W13)
4 Weeks
(W5, W6) or
(W14, W15)
Post
(3 Weeks)
(W7,W9,W9) or
(W16,W17,
W18)
TM (FU/mL) 1.98 0.22 1.86 0.21 2.10 0.21 1.96 0.26 2.05 0.23 1.80 0.27 1.64 0.15 2.02 0.27 2W: P ¼0.67
4W: P ¼0.16
Post: P ¼0.86
P ¼0.68 P ¼0.76 P ¼1.0 P ¼0.11 P ¼0.12 P ¼0.92
vWF (mU/mL) 9.05 0.71 8.54 0.51 8.73 0.60 8.02 0.56 10.2 0.94 8.52 082 8.22 0.41 8.09 0.48 2W: P ¼0.27
4W: P ¼0.58
Post: P ¼0.18
P ¼0.56 P ¼0.75 P ¼0.28 P ¼0.011* P ¼0.045* P ¼0.056*
TBARS (
μ
M) 4.56 1.11 4.96 0.93 5.54 0.73 4.55 0.51 5.41 1.33 3.18 0.43 3.72 0.67 4.99 0.95 2W: P ¼0.19
4W: P ¼0.46
Post: P ¼1.0
P ¼0.80 P ¼0.54 P ¼1.0 P ¼0.14 P ¼0.34 P ¼0.80
8-OHdG
(ng/mL)
0.25 0.02 0.24 0.03 0.24 0.01 0.19 0.02 0.27 0.02 0.23 0.03 0.21 0.01 0.22 0.02 2W: P ¼0.22
4W: P ¼0.002*
Post: P ¼
0.003*
P ¼0.77 P ¼0.60 P ¼0.06 P ¼0.033* P ¼0.036* P ¼0.031*
Adiponectin
(ng/mL)
1.33 0.19 1.47 0.21 1.50 0.21 1.51 0.23 1.41 0.23 1.32 0.17 1.47 0.19 1.40 0.17 2W: P ¼0.47
4W: P ¼0.24
Post: P ¼0.11
P ¼0.69 P ¼0.63 P ¼0.61 P ¼0.86 P ¼0.83 P ¼1.0
M.P. Kapoor et al.
Contemporary Clinical Trials Communications 17 (2020) 100499
7
thromboplastin time (APTT) assays. The assays were performed with 50
μ
L blood serum collected from the subjects added with 100
μ
L of PT or
50
μ
L of APTT and 50
μ
L of CaCl
2
to measure coagulation time (sec) by a
CA50 coagulometer (SYSMEX, Kobe, Japan) according to the manu-
facturer instructions.
2.8. Data processing and statistical analysis
All data values are expressed as means sem unless otherwise
stated. Data analysis was performed by one-way analysis of variance
(ANOVA) with study duration followed by Tukeys post hoc test, as well
as using analysis of covariance (ANCOVA) to access the pre-post dif-
ferences between both amla and placebo supplementations. All differ-
ences were considered signicant at p 0.05. At the beginning of the
study, a sample size of at least 12 subjects was estimated to be required
to detect relevant physiological changes in study parameters between
groups, at a 5% signicance level with 90% power, assuming the drop
out of 10%. Further, a post hoc power calculation was conducted to
conrm the statistical power was adequate. An independent two-tailed
Students t-test was performed to verify the statistical signicance.
3. Results
In accordance with the established criteria of subject selection based
on blood rheology, we enrolled subjects with average values of blood
uidity (range 2.62.8
μ
L/s), because of the tendency for the blood
uidity to increase after test supplementations. The subjects who
completed the study trial (n ¼13; M6, F7) had a mean age of 51.9 2.8
years.
3.1. Physiological and vascular parameters
Most of the physiological parameters changes with the time duration.
Weight and BMI were in the normal range, and no signicant differences
were found. Also, no signicant difference was observed for SBP, DBP,
and pulse rate over the study. On the other hand, the blood uidity was
higher after the amla treatment compared to baseline. Signicance
differences by ANCOVA were observed in blood uidity after two weeks
(P ¼0.012), four weeks (P ¼0.024), and even after withdrawal (P ¼
0.036) of the amla treatment. Vascular age measured from the waveform
index-I was only found to signicant after the withdrawal of the amla
intake (P ¼0.041) compared to placebo (Table 1).
3.2. Hematological parameters and anticoagulant activity
The hematocrit, red blood cell, and white blood cell counts did not
show signicant changes during the placebo or amla period. The he-
moglobin showed signicant changes within both placebo and amla
period compared to baseline, and also remained signicant after the
withdrawal of amla intake (P ¼0.004). However, the hemoglobin levels
were not signicantly different between the amla and placebo periods.
No signicant difference was noticed in platelets counts for both placebo
and amla intakes during the trial period, whereas compared to baseline
the MCH and MCHC showed very signicant changes within both pla-
cebo and amla intake duration (P <0.001), and even after the with-
drawal of the intake of both treatments (P <0.05). Whereas, MCV
Fig. 3. (a) Metabolic pathways of amla: Urolithins are the major tentative metabolites of ellagitannins of amla formulation associated with different health benets,
and (b) Amla inhibits the vWF stimulated thrombin (TM) generation by the reduction in vWF secretion.
M.P. Kapoor et al.
Contemporary Clinical Trials Communications 17 (2020) 100499
8
showed the signicance difference (P ¼0.04) between both placebo and
amla treatments at two weeks of supplementation (see Table 2).
The platelet aggregation showed signicant stepwise improvement
within the amla intake (P ¼0.027) after two weeks of supplementation,
but no difference were observed between placebo and amla intake for
platelet aggregation. Anti-coagulant activity parameter PT showed a
statistically signicant reduction (P <0.01) for the amla intake
throughout the trial and also after the post-treatment period. Further, a
signicant difference between the placebo and amla treatment groups
after four weeks of supplementation (P ¼0.01) and also after the post
treatment period (P ¼0.013) was observed. The anticoagulant activity
parameter APTT showed no signicant changes within and between the
placebo and amla treatment groups.
3.3. Blood biochemical parameters and biomarkers
Fasting blood glucose levels signicantly changed after four weeks
(P ¼0.03) and tended to after the withdrawal (P ¼0.06) of amla intake.
Both the fasting glucose and triglyceride levels remained in the normal
range during the amla and placebo intake periods. No signicant dif-
ference in HbA1c, triglycerides, and total cholesterol levels were
observed during both the placebo and amla periods. HDL cholesterol
levels were signicantly higher after two weeks (P ¼0.03) and remained
higher than baseline values when comparing to the placebo or amla
intakes. The LDL cholesterol levels decreased but did not reach statis-
tical signicance (P ¼0.09) after two weeks of amla supplementation
compared to placebo. The Ca, Na, K, P levels in the blood signicantly
changed with amla, while chloride levels signicantly changed in both
placebo and amla intake periods (see Table ST1; supplementary
information).
Of secondary efcacy parameters, the concentration of 8-hydroxy-20-
deoxyguanosine (8-OHdG) was signicantly decreased compared to
baseline during the amla intake period and even after the withdrawal (P
<0.05) of amla supplementation. Further, compared to placebo, a sig-
nicant difference (P <0.01) was also observed after four weeks and
even after post-intake of amla (Fig. 2a). Also, the von Willebrand factor
(vWF) was signicantly lowered (P <0.05) during the amla intake
period (Fig. 2b). While a non-signicant decrease in the thrombin (TM)
receptor concentration and thiobarbituric acid reactive substances
(TBARS) was observed (Fig. 2c and d) and remained in the normal range
during the amla intake period. No signicant changes were observed in
adiponectin (see Table 3).
3.4. Evaluation of hepatic risk parameters
The test results of the hepatic factors, which are helpful to determine
the liver functions are illustrated in Table ST2 (see supplementary in-
formation). During the amla and placebo period no difference in the
levels of AST (GOT). The ALT (GPT) level was lower after two weeks (P
¼0.02) of amla intake and remained at lower than baseline levels. Also,
a lower ALP and γ-GPT levels were noticed during the trial periods, but
were not statistically decreased. All critical hepatic risk parameters
remained in the normal range throughout for both amla and placebo
periods. Total bilirubin signicantly decreased after two weeks of amla
intake (P ¼0.04) compared to baseline, while no signicant differences
were found in total protein, albumin, albumin/globulin ratio, creatinine,
uric acid, and urea-nitrogen levels assays.
3.5. Urinalysis parameters
Urinalysis of the most common chemicals before and after the pla-
cebo and amla intake periods were collected. The pH range was slightly
acidic (5.56.1) and the specic gravity range of urine was always less
than 1.02 during the trial periods, but no signicant changes were
noted. Quantitative assay of urobilinogen showed normal levels for all
subjects (n ¼13) throughout the study. Quantitative protein and sugar
levels were also normal except somewhat doubt (no immediate concern)
was registered for one subject during the post-supplementation periods
of placebo (protein, n ¼1) and amla (sugar, n ¼1), respectively. The
placebo group had nine subjects with normal occult blood in urine and
four subjects with some borderline doubt but in healthy condition (n ¼
9, A1-judgment; n ¼4, A2-judgment) at baseline and remained un-
changed during the placebo period. The amla intake group registered
twelve subjects without abnormalities and one with no immediate
concerns at baseline, however, eight subjects without abnormalities and
ve subjects with no immediate concerns were reported at the end of
amla treatment possibly due to crossover nature of the study trial (see
Table ST3; supplementary information).
3.6. Adverse events and examination opinions
No signicant conditions or adverse events were found in the
physician examination implemented on the rst day of both study pe-
riods through the completion of the study. Some minor conditions were
reported mainly during the placebo intake. One subject reported diar-
rhea feelings during the placebo intake of the trial. While, one subject
reported for the loose bowel movements after two weeks, and other
reported constipation after four weeks of placebo supplementation.
Also, one subject reported cold after 24 weeks of placebo intake
duration of the trial. One subject reported edema before the start of amla
intake; however, no other conditions were reported during the amla
intake period (see Table ST4; supplementary information).
Furthermore, no anomalies were observed in the subjective symptom
surveys or daily activity diaries wherein the subjects recorded any
concerning information during the study, such as unusual circumstances
or the side effects. There was 100% compliance with the placebo and
amla intakes during the trial for all subjects who completed this study.
Also, the diet and meal intake were not noteworthy, and there were no
subjects with eating and lifestyle habits that deserve special mention.
4. Discussion
Vegetables and fruits form essential elements of a healthy diet;
however, ellagitannins and ellagic acid are the polyphenol often
underestimated in our diets [20,21]. Interest in ellagitannins is still
growing [22]; therefore, it is important to identify safer and more
cost-effective strategies for managing common health issues. The pre-
sent study was designed to evaluate the safety and efcacy of ellagi-
tannins (hydrolyzable to ellagic acid and gallic acid) rich amla (500
mg/day) compared to a placebo in healthy humans. Risk factors such as
hypertension, dyslipidemia, and atherosclerosis are emerging as critical
components associated with the pathophysiology of accelerated
impaired endothelial functions [2,12,13]. The oxidative stress in the
vascular endothelium cell is primarily associated with thrombosis, while
increased platelet aggregation is yet another signicant risk factor for
cardiovascular diseases [2325]. The high blood lipid proles and
platelet aggregation in blood vessels can lead to hypertension. Inhibition
of platelet aggregation by oral supplementation of amla is attributable
primarily to the abundance of low molecular weight (<1000 Da)
hydrolysable ellagitannins (i.e. chebulagic acid, pedunculagin, geraniin,
corilagin, elaeocarpusin, etc.), gallic acid, ellagic acid, and their me-
tabolites which are illustrated in Fig. 3a. Hydrolysis of ellagitannins
yields galloyl-glucose residues, which are eventually transformed into
gallic acid, pyrogallol and resorcinol [26,27], along with HHDP moiety,
which undergoes lactonization and spontaneous rearrangement to stable
ellagic acid. Due to very poor bioavailability of ellagitannins, they are
found relatively low concentrations in the gastrointestinal (GI) tract
including feces; therefore the ellagitannins have not been reported in the
human systematic circulation system or urine. Urolithins are the pri-
mary metabolites of ellagitannins of amla in human plasma and urine
mostly present as a conjugated form with glucuronic acid or sulfate.
Urolithin-A metabolite was recently reported to possess several
M.P. Kapoor et al.
Contemporary Clinical Trials Communications 17 (2020) 100499
9
biological activities such as anti-inammatory effects [27]. Thus, ella-
gitannins of amla are associated with health benets that are mediated
by the bioconversion of ellagitannins by gut microbiota.
Earlier studies demonstrated the benecial antioxidant activity and
cytoprotective effect of amla formulations on dyslipidemia and lipid
peroxidation [23,28]. Amla has an anti-thrombotic and anti-oxidative
effect. It may also help control vascular injuries in humans due to hy-
perglycemia that has been positively associated with oxidative stress,
which is one of the principal mechanisms involved in the damage of
endothelial function. In this study, amla supplementation showed a
benecial effect on endothelial function by modulating thrombin and
endothelial vWF, along with a signicant improvement in biomarkers of
oxidative stress, including TBARS and 8-OHdG. The vWF is a critical
adhesive protein that captures platelets from circulation, which usually
changes to an elongated form that provides an adhesive surface for
platelets via binding to glycoprotein [29]. Oral supplementation of amla
inhibits the vWF stimulated thrombin generation by the reduction of
vWF secretion in the circulatory system and, thus prevent the vWF
mediated adhesion of platelets to brin (Fig. 3b), which is a prerequisite
for the thrombin to expose anionic phospholipids at the plasma mem-
brane of platelets to facilitate the adhesion. The vWF appears to be an
essential factor in the generation of thrombin and subsequent conver-
sion of plasma protein brinogen into brin [30]. Therefore, amla
intake reduces the thrombin formation in vWF decient platelet-rich
plasma (Fig. 3b and c). The oral administration of amla reduced
TBARS levels in plasma, suggesting amla consumption could also
ameliorate oxidative stress due to aging-related mitochondrion
dysfunction. A signicant decrease in the cellular oxidative stress
biomarker 8-OHdG excretion, an oxidized nucleoside of DNA, represents
a decrease in oxidative DNA damage as a result of amla supplementation
compared to the placebo. The overall ability to reduce oxidation induced
DNA damage and repair of DNA lesions is believed to depend on the time
phase relationship. However, an inuence of metabolic rate (oxygen
consumption) on the 8-OHdG excretion cannot be excluded due to its
standard dual function in base excision repair (BER; the cellular mech-
anism that repairs damaged DNA) as well as in the oxidation of DNA
[31]. Further, it is also postulated that metabolites of ellagitannins and
polyphenols of amla could be radially adsorbed by cell tissues during
regular supplementation, and thus enhancing antioxidant protection
against oxidation-induced DNA damage and mutation.
Although there is minimal human evidence on amla in the scientic
literature, it appears to be very promising as it could lower blood glucose
in both healthy people and diabetics [6]. In animal research, amla ap-
pears to be able to reduce triglycerides, improve the cholesterol prole,
and benet cardiovascular health. Most of these actions are attributed to
its antioxidant properties, which are partially derived from a reasonably
high vitamin C content in addition to the ellagitannins. Amla is bene-
cial in preventing age-related kidney diseases when administration
resulted in signicantly decreased levels of lipids [32]. Benets appear
to extend to humans, and the present study demonstrated that four
weeks of oral supplementation of standardized amla effectively alters
the lipid levels by decreasing LDL cholesterol, total triglycerides, and
total cholesterol levels along with a concomitant increase of HDL
cholesterol, whereas placebo did not have any considerable effect on any
of the study parameters. The results were comparable to studies reported
previously [32]. Lipid-lowering properties and endothelial function
management activity of amla may be attributed to the polyphenol
content and ellagitannins of the formulation. It is also postulated that
the ellagitannins present in amla delay the oxidation of vitamin C, while
the synergic effect of pectin has also been reported to decrease the
cholesterol levels in humans [12] along with the avonoid components
of amla are mainly responsible for a potent hypolipidemic effect.
Although several mechanisms [5,33] such as interference with choles-
terol absorption, an increase in lecithin-cholesterol acyltransferase ac-
tivity, and inhibition of HMG-CoA reductase activity are reported in
literature for the alteration in the lipid proles upon supplementation of
amla formulations; however conclusive pieces of evidence are not yet
clear [8]. Further, the decreasing trend of total cholesterol could also be
a determinant of the increased blood uidity, since erythrocyte mem-
brane structure that usually decreases the membrane uidity in the su-
percial layer with any signicant alteration of membrane cholesterol
and TBARS.
Further, the white blood cell counts, a surrogate marker of inam-
mation, which usually correlates positively with platelet counts showed
no evidence on their possible association with aforementioned risk
factors indicate the possibility of a shared mechanism that drives a
detrimental effect of amla intake on the improvement in the blood
rheology [25]. Therefore, it may be suggested that hematocrit and WBC
could be the determinants of the blood uidity a primary efcacy
parameter of this study. Moreover, the albumin is also a vital protein
regarding blood uidity as it could have a negative correlation with
blood passage, but the measured values of albumin were at normal levels
in the present study indicates the possibility of the relevance of a weak
plasma lipid concentration for blood uidity. Thus, a signicant increase
in blood uidity with amla compared to placebo could be attributed to
soft and balanced oxygen transport to the cells. Also, vascular age
derived from the waveform index can reect vascular resistance, as the
pathogenesis of small size vessels may affect the vascular age. Since,
hemorheology is estimated using MC-FAN which is an in vitro assay that
uses articial blood vessels (lumen measures <10 mm; assumed to
correspond to small-sized capillary vessels), and signicant post-trial
changes observed between amla and placebo intake suggests the
improvement in vascular resistance and reduced impairment of hem-
orheology with increased blood uidity possibly due to sympathetic
activation on vascular functions. The prothrombin time was signi-
cantly lowered upon amla intake compared to placebo without signi-
cant alteration in APTT (almost no interfering with coagulation complex
assembly on phospholipid surface). Also, levels of both PT and APTT
remained within the normal range, suggested that amla on limits the
platelet aggregation due to reduced thrombin, and help accelerate the
anticoagulant activity, which could result from a moderate increase in
blood uidity. No considerable differences were noticed in any blood
test item MCV, MCH, and MCHC between placebo and amla groups as
changes were small and within the normal range, suggesting that
observed changes were not medically relevant. Also, no signicant dif-
ferences were noted in urinalysis ndings between placebo and amla
groups. Also, the blood tests related to liver and renal/kidney functions
(blood urea nitrogen, AST, ALT, γ-GPT, creatinine, uric acid, phosphate,
calcium, sodium, potassium, and chloride) were standard in all subjects.
Although a few adverse events were noted during the trial, they were
reported during the placebo and were common conditions likely unre-
lated to study participation. No symptoms considered to be a side effect
were observed during the amla treatment period. These results indicate
the tolerance and safety of a daily 500 mg dose of amla in healthy
humans. The ndings above indicate that amla and its components
(ellagitannins, polyphenols and their metabolites) could be recognized
as a potent antioxidant with the determinant function of vascular ho-
meostasis, regulating several physiologic properties, including vascular
permeability as well as antithrombotic properties that could prevent the
arterial thrombosis.
Despite the positive ndings of this study, there were few limitations.
The rst is MC-FAN can detect somewhat lower platelet aggregation
related hemorheological data due to its in vitro characteristics that use
articial blood vessels and absence of an inuence of vascular factors
such as endothelial cells or smooth muscle, which must be considered
when interpreting the results. Another limitation that this is a relatively
small study of only fteen subjects and despite a strong study design, a
larger study is necessary to conrm the health benets of amla.
5. Conclusions
In this clinical study, we conrm that the proprietary amla
M.P. Kapoor et al.
Contemporary Clinical Trials Communications 17 (2020) 100499
10
formulation showed a signicant improvement in endothelial function
as well as a reduction in biomarkers of oxidative stress. Also, the results
suggest that amla intake may increase plasma antioxidant potential and
decrease oxidative stress, which can help promote oxidative homeo-
stasis. All of these benets are possible without inuencing hepatic or
renal function, or diabetic indices in healthy humans. Lastly, the results
from this human clinical study conclusively established that amla has an
acceptable sensory and safety prole while providing enormous poten-
tial for the management of a healthy lifestyle.
Acknowledgments
The authors thank all study subjects for their voluntary participation.
All authors acknowledge and thank their respective Institutes and Uni-
versities. The authors have no conicts of interest to declare.
Appendix A. Supplementary data
Supplementary data to this article can be found online at https://doi.
org/10.1016/j.conctc.2019.100499.
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M.P. Kapoor et al.
... Previous reports have extensively documented the pharmaceutical potential of amla. These include antioxidant, antimicrobial, anti-inflammatory, adaptogenic, analgesic and antipyretic, antitumor, antiulcerogenic, and hepatoprotective activities, either in combined formulation or amla alone (Almatroodi et al., 2020;Earpina et al., 2020;Gaire & Subedi, 2014;Kapoor, Suzuki, Derek, Ozeki, & Okubo, 2020). Ayurvedic and traditional medicines in Thailand have long documented its use as an antitussive remedy. ...
... Previous researches have shown that amla has many useful pharmaceutical properties, such as antiinflammatory, antipyretic, antimicrobial, antitumor, antiulcerogenic, analgesic, adaptogenic, and hepatoprotective activities. Both combined formulations and amla used alone have demonstrated these activities (Almatroodi et al., 2020;Earpina et al., 2020;Gaire & Subedi, 2014;Kapoor et al., 2020). The antitussive properties of this substance have been documented in Ayurvedic and traditional medicinal practices in Thailand. ...
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This study aimed to investigate the consumption of amla as a food by conducting a thorough literature analysis and a field survey with unstructured, in-depth interviews. Amla or Indian gooseberry (Phyllanthus emblica L.) is rich in phytochemicals, and their pharmaceutical potentials have been extensively reported. However, their utilization as foods is not well documented. Thai recipes use whole or minced fresh amla fruits as an ingredient in some spicy dishes, such as chili pastes, soups, and salads. Like other Asian countries, amla could be processed into products such as juice, preserves, pickles, and dried amla. Ten amla dishes and products were selected for evaluation of their ascorbic acid contents and antioxidant properties (total phenolic compounds, total flavonoids, DPPH, and FRAP assays). High-heat processing resulted in a marginal reduction of ascorbic acid in amla dishes and products. Processing methods also affected antioxidant activities, and they varied depending on processing conditions and product types. The processing of amla into juice slightly decreased antioxidant activities. Thai foods that used amla as an ingredient exhibited less antioxidant activity than those made of fresh amla. The antioxidant activities of pickled and preserved amlas were substantially diminished due to their high salt and sugar content. On the contrary, dried amla demonstrated enhanced antioxidant activities as a result of its reduced moisture content and the presence of concentrated phytochemicals. Given its substantial phytonutrient content and lack of utilization, the results obtained from this research contribute to the promotion of amla as a valuable food ingredient.
... Amla (Indian gooseberry) is a rich source of Vitamin C, which is absolutely necessary for providing nutrition to the immune system and enhancing immunity power. Amla extracts have also been proven in clinical studies to reduce oxidative stress and inflammation and support overall immune health [13]. During the COVID-19 pandemic, Amla played a notable role in immunity and is commonly found in formulations like Chyawanprash. ...
... Scientific evidence shows that ascorbic acid, tannins, polyphenols, fiber, minerals, proteins, and amino acids are compounds contained in P. emblica fruit, which are essential components in promoting health and are used as medicinal components [15,16]. ...
... Flavonoids (quercetin) and alkaloids (phyllantine and phyllantidine) are reported in this plant [97]. These are widely recognized as "Amla churn" and are reported to lower the cholesterol and enhance memory [98]. Both the body and brain cholesterol levels can be effectively lowered by including amla in the diet [99]. ...
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Phyllanthus emblica L., known as Indian gooseberry (Euphorbiaceae), has been used in traditional Indian medicine for its benefits in treating various diseases. Antioxidant and neuroprotective activities of Phyllanthus emblica L. provide great benefits in medicine. Antioxidants can help lower the risks of many diseases, including neurological conditions, by preventing reactive oxygen species (ROS) and lipid peroxidation. Research on herbal plants as alternative treatments is increasing; hence, the current research trend aims to examine new treatments for these conditions. Scientific research has extensively explored herbal medicine for neurological disorders. Both in vitro and in vivo studies have demonstrated the therapeutic potential of the antioxidant activity of P. emblica in addressing various neurological disorders. This article provides an overview of the roles of antioxidant and neuroprotective activities of P. emblica in treating various neurological and neurodegenerative disorders. It also paves the way for future research in this field by involving chemical compounds as references for understanding the mechanisms of neuroprotective action of P. emblica
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Medicinal plants, having great elementary and therapeutic importance, are the gift to mankind to acquire healthy lifestyle. Emblica officinalis Gaertn. or Phyllanthus emblica Linn. (Euphorbeaceae), commonly known as Indian gooseberry or Amla, has superior value in entirely indigenous traditional system of medicine, including folklore Ayurveda, for medicinal and nutritional purposes to build up lost vitality and vigor. In this article, numerous phytochemicals isolated from E. officinalis and its ethnomedical and pharmacological potentials with molecular mechanisms are briefly deliberated and recapitulated. The information documented in the present review was collected from more than 270 articles, published or accepted in the last five to six decades, and more than 20 e-books using various online database. Additional information was obtained from various botanical books and dissertations. The extracts from various parts of E. officinalis, especially fruit, contain numerous phytoconstituents viz. higher amount of polyphenols like gallic acid, ellagic acid, different tannins, minerals, vitamins, amino acids, fixed oils, and flavonoids like rutin and quercetin. The extract or plant is identified to be efficacious against diversified ailments like inflammation, cancer, osteoporosis, neurological disorders, hypertension together with lifestyle diseases, parasitic and other infectious disorders. These actions are attributed to either regulation of various molecular pathway involved in several pathophysiologies or antioxidant property which prevents the damage of cellular compartments from oxidative stress. However, serious efforts are required in systemic research to identify, isolate and evaluate the chemical constituents for nutritional and therapeutic potentials.
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The endothelium, a thin single sheet of endothelial cells, is a metabolically active layer that coats the inner surface of blood vessels and acts as an interface between the circulating blood and the vessel wall. The endothelium through the secretion of vasodilators and vasoconstrictors serves as a critical mediator of vascular homeostasis. During the development of the vascular system, it regulates cellular adhesion and vessel wall inflammation in addition to maintaining vasculogenesis and angiogenesis. A shift in the functions of the endothelium towards vasoconstriction, proinflammatory and prothrombic states characterise improper functioning of these cells, leading to endothelial dysfunction (ED), implicated in the pathogenesis of many diseases including diabetes. Major mechanisms of ED include the down-regulation of endothelial nitric oxide synthase levels, differential expression of vascular endothelial growth factor, endoplasmic reticulum stress, inflammatory pathways and oxidative stress. ED tends to be the initial event in macrovascular complications such as coronary artery disease, peripheral arterial disease, stroke and microvascular complications such as nephropathy, neuropathy and retinopathy. Numerous strategies have been developed to protect endothelial cells against various stimuli, of which the role of polyphenolic compounds in modulating the differentially regulated pathways and thus maintaining vascular homeostasis has been proven to be beneficial. This review addresses the factors stimulating ED in diabetes and the molecular mechanisms of natural polyphenol antioxidants in maintaining vascular homeostasis.
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Phyllanthus emblica Linn. Or Emblica officinalis Gaertn. commonly known as Indian gooseberry or Amla is one of the most important medicinal plants in Indian traditional systems of medicine (Ayurveda, Unani and Siddha). It is a well-known fact that all parts of amla are useful in the treatment of various diseases. Among all, the most important part is fruit. Amla fruit is widely used in the Indian system of medicine as diuretic, laxative, liver tonic, refrigerant, stomachic, restorative, anti-pyretic, hair tonic, ulcer preventive and for common cold, fever; as alone or in combination with other plants. Phytochemical studies on amla disclosed major chemical constituents including tannins, alkaloids, polyphenols, vitamins and minerals. Gallic acid, ellagic acid, emblicanin A & B, phyllembein, quercetin and ascorbic acid are found to be biologically effective. Research reports on amla reveals its analgesic, anti-tussive, antiatherogenic, adaptogenic; cardio, gastro, nephro and neuroprotective, chemopreventive, radio and chemo modulatory and anticancer properties. Amla is also reported to possess potent free radical scavenging, antioxidant, anti-inflammatory, anti-mutagenic, immunomodulatory activities, which are efficacious in the prevention and treatment of various diseases like cancer, atherosclerosis, diabetes, liver and heart diseases. In this article, we discuss the nutritional value, biochemical constituents, traditional uses, medicinal value of amla and its use as a household remedy. We also emphasized the mechanisms behind the pharmacological activities based on the recent research reports and tried to summarize the results of research done from the past 5 years with proper specifications on the future prospects in a pharmacological perspective.
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The endothelium causes relaxations of the underlying vascular smooth muscle, by releasing nitric oxide (NO). The endothelial cells also can evoke hyperpolarization of the vascular smooth muscle cells (endothelium-dependent hyperpolarizations, endothelium-derived hyperpolarizing factors-mediated responses). Endothelium-dependent relaxations involve both pertussis toxin-sensitive Gi and pertussis toxin-insensitive Gq coupling proteins. The endothelial release of NO is reduced in diabetes and hypertension. Arteries covered with regenerated endothelium lose the pertussis-toxin sensitive pathway for NO-release. This dysfunction favors vasospasm, thrombosis, penetration of macrophages, cellular growth and the inflammatory reaction leading to atherosclerosis. Endothelial cells also release endothelium-derived contracting factors (EDCF). Most endothelium-dependent contractions are mediated by vasoconstrictor prostanoids (endoperoxides and prostacyclin), which activate thromboxane-prostanoid (TP)-receptors of the underlying vascular smooth muscle cells. EDCF-mediated responses are augmented by aging, hypertension and diabetes. Thus, endothelial dysfunction is the first step toward coronary arteriosclerosis. (Circ J 2009; 73: 595 - 601)